Neurology

Neurology

Back to Main NeuroImage Human Brain Mapping 2002 Meeting Order to appear: 700 A TMS study of the functional significance of ipsilateral motor cortic...

19MB Sizes 4 Downloads 394 Views

Back to Main NeuroImage Human Brain Mapping 2002 Meeting

Order to appear: 700

A TMS study of the functional significance of ipsilateral motor cortical activation after stroke Heidi Johansen-Berg , MFS Rushworth

, PM Matthews

Centre for Functional Magnetic Resonance Imaging of the Brain, University of Oxford, John Radcliffe Hospital, Headley Way, Oxford, OX3 9DU Department of Experimental Psychology, University of Oxford, South Parks Road, Oxford, OX1 3UD Subject: Neurology Abstract Introduction: Functional imaging studies have shown that movement of an affected limb after stroke is associated with increased activity in ipsilateral motor cortical areas (e.g. Cramer et al, 1997 Stroke 28, 2518-2527). However, the functional significance of these ipsilateral activations is unclear. We used functional magnetic resonance imaging (FMRI) to detect movement-related brain activity in control subjects and patients after stroke. We tested the functional significance of ipsilateral activations by using transcranial magnetic stimulation (TMS) to transiently interfere with processing in the ipsilateral primary (MC) and dorsal premotor (PMC) cortex while subjects performed the same movement tasks. Methods: Subjects: 16 right-handed controls (8 female, age 23 to 65) were tested. The 10 oldest controls (5 female, age 48.3 +/- 11.9) were compared to 7 right-handed patients after first ischaemic stroke (2 female, age 54 +/- 7.5, 2 with right hemiparesis, 5 with left hemiparesis). Movement tasks: Visually-cued finger tapping including simple (index finger) and complex (random, 4 fingers) movements. FMRI: A 3T Varian/Siemens MRI system was used to acquire axial echo-planar volumes and a T1-weighted anatomical image for each subject. Subjects performed alternating 30 second periods of movement tasks and rest. Image analysis used tools from the FMRIB Source Library (www.fmrib.ox.ac.uk/fsl). Volumes of interest (VOIs) corresponding to MC and PMC were defined. The maximum percent signal change within VOIs was used to calculate laterality indices (LI=C-I/C+I where C=contralateral and I=ipsilateral % change). TMS: A 70mm figure-of-eight coil connected to a Magstim Rapid delivered single TMS pulses over ipsilateral MC or PMC at 50, 100 or 150ms after the movement cue and at 115 to120% of motor threshold. Frameless stereotaxy was used to locate the coil trajectory on each subject's MRI scan. Results: Movements activated ipsilateral motor areas and greater activation was seen for complex movements (F=26.56, p<0.001). In normal subjects TMS over ipsilateral MC or PMC slowed movements when applied at specific times after the movement cue(Effect of time, F=20.5, p<0.001; Interactions: task and site, F=10.3, p=0.006; task and time F=5.1, p=0.02). These effects were stronger for left hemisphere TMS (Effects of side, F=9.8, p=0.007). TMS effects in patients were enhanced in a manner that depended on stimulation site and time (Figure 1; Interaction between subject group, site and time of stimulation, F=4.1, p=0.04).

Back to Main

Back to Main

Figure 2: In normal subjects early effects of PMC stimulation were only seen in complex movements (dotted lines) and not during simple movements (solid lines) For example, the response acceleration with 50ms PMC stimulation seen in controls with simple finger tapping was reduced in patients (Figure 1b), while response interference in controls with ipsilateral PMC stimulation was only seen during complex movements (Figure 2). Over the heterogenous patient group, the magnitude of effects of PMC TMS correlated with laterality of PMC FMRI activation during the simple task (r=-0.793, p=0.017). Conclusions: The effects of TMS over ipsilateral primary and premotor cortex are altered in patients. A greater dependence on ipsilateral motor areas for patients could be shown at least for simple movements of the affected limb. The clinical relevance of increased ipsilateral motor cortex FMRI activity after stroke was suggested by the good correlation between relative FMRI activation laterality and the extent of TMS interference. © 2002 Elsevier Science (USA). All rights reserved.

Back to Main NeuroImage Human Brain Mapping 2002 Meeting

Order to appear: 701

Functional brain reorganisation for hand movement in patients with multiple sclerosis: defining distinct effects of injury and disability Hasini Reddy , Sridar Narayanan , Mark Woolrich , Tomoyuki Mitsumori , Douglas Arnold , Paul M. Matthews Centre for Functional Magnetic Resonance Imaging of the Brain, University of Oxford, UK Dept of Neurology and Neurosurgery, McGill University, Montreal Canada Subject: Neurology Abstract Introduction Previous work has demonstrated potentially adaptive cortical plasticity that increases with the extent of brain injury in patients with multiple sclerosis (MS) (1,2). However, animal studies showing use-dependent changes in motor cortex organisation suggest the possibility that functional changes also may occur in response to disability, independently of increased brain injury (3). We therefore wished to test whether brain injury and disability lead to distinguishable patterns of activation with hand movement in patients with MS. By employing a passive as well as an active movement task (4,5), we also wished to test whether these changes were independent of voluntary recruitment and thus likely to reflect true functional reorganisation. Methods Fourteen patients (EDSS 0-7.5) with relapsing remitting MS were selectd on the basis of pathology load and hand functional impairment for 3 study groups: 1. low diffuse central brain injury (DCBI, as assessed by the magnetic resonance spectroscopy measure of relative Nacetylaspartate concentration, a marker of axonal integrity) and normal hand function (n=6); 2. greater DCBI and normal hand function (n=4); and, 3. greater DCBI and impaired hand function (n=4). 3T fMRI was used to map brain activation with a 4- finger and both 1-finger passive and active flexion-extension movement tasks for the three groups. Results Considering all of the patients, we found increased activity in ipsilateral premotor and motor cortex (IMC) and in the ipsilateral inferior parietal lobule with increasing disability. These changes appear to define true functional reorganisation, independent of voluntary movement, as fMRI activations in IMC (r=0.87, p<0.001) and in the contralateral motor cortex (r=0.67, p<0.007) were highly correlated between active and passive single finger movements. We attempted to disambiguate any distinct effects of disability and brain injury by direct contrasts between patients differing predominantly in one or the other. A direct contrast of patients matched for DCBI, but differing in disability (Group 3- Group 2) showed greater bilateral primary and secondary somatosensory cortex activation with greater disability alone. A contrast matched for disability, but differing in DMWI (Group 2- Group 1) showed a different pattern of changes with relative ipsilateral premotor cortex and bilateral SMA activity. Conclusions From these observations we conclude that the pattern of brain activity with finger movements changes both with increasing DCBI and with disability in patients with MS and that these changes are distinct. Those related directly to disability may reflect responses to altered patterns of use. As injury- and disability-related activation changes are found even with passive finger movements, they must reflect true brain reorganisation. 1. Lee et al. Ann Neurol 47 (2000) 606-613 2. Reddy et al Brain 123 (2000) 2314-2320 3. Ziemann et al Brain 124 (2001) 1171-1181 4. Reddy et al. Exp Brain Res 138 (2001) 484-491 5. Reddy et al. J Neurol Neurosurg Psych (2002) In press.

Back to Main

© 2002 Elsevier Science (USA). All rights reserved.

Back to Main

NeuroImage Human Brain Mapping 2002 Meeting

Order to appear: 702

Discordance between progressive delayed brain atrophy and clinical recovery after middle cerebral artery infarction detected by intraindividual in vivo 3D MRI volumetry Matthias Kraemer , Thorsten Schormann , Ruediger J. Seitz Department of Neurology, Heinrich-Heine University, Duesseldorf, Germany Department of Neuroanatomy, Heinrich-Heine University, Duesseldorf, Germany Subject: Neurology Abstract Introduction Middle cerebral artery (MCA) infarctions cause severe neurological deficits like hemiparesis and aphasia. Usually, the maximum of neurological symptomatology is reached in the first hours after stroke onset, followed by clinical improvement in the subsequent weeks and months. From imaging studies it is known that the infarction lesion develops within the first days after stroke due to peri-infarct edema, excitotoxicity, inflammation and programmed cell death [1]. However, little is known about the relation of clinical and structural consequences of cerebral infarcts. In this study we investigated the long-term development of brain volume alterations in humans suffering from MCA infarction compared to the clinical outcome within the same time period. Methods Ten Patients (aged 34 to 62 years) were scored (Rankin Score, Bartel Index, European Stroke Score (ESS)) when admitted to hospital and 32 months later. Volumetric MRI scans were acquired 27 days and 32 months after stroke. Using a 3D morphometric image analysis method [2] brain volume differences were assessed. Matching of the different MRI scans of the same patient was done by application of a three step procedure including (i) coarse and (ii) fine linear alignment resulting in exact linear matching of different brains. In the final third step a non-linear transformation was performed by application of a multiresolution full multigrid movement model, which resulted in a matching of brains down to subvoxel accuracy. Thereafter, volume differences were calculated and visualized in gray-value coded volume fields. Results In all brains investigated widespread regions of cerebral atrophy were detected exceeding the infarct region and including brain regions not affected by the infarct. Atrophy was observed in widespread areas of white matter adjacent to the infarcted area, in subcortical structures like nucleus caudatus and thalamus and even contralaterally in the cerebellum and homotopic cortical structures. As changes were

Back to Main

observed contralaterally and in the posterior artery territory, localization of volume changes clearly indicated that the atrophic process was independant of the MCA territory. Clinical examination of patients revealed significant improvement of neurological deficits from an average ESS of 65/100 shortly after infarct to 93/100 after 32 months. Conclusion Our data show a diverging enlargement of the postischemic brain lesion in the presence of a clinical improvement in patients suffering from MCA infarction. Specifically, our non-invasive intraindividual 3D volumetric MRI analysis revealed for the first time a widespread post-ischemic brain atrophy, while the neurological symptoms improved at the same time. We hypothezise that the observed divergence may be due to functional post-stroke plasticity leading to a shift of function to brain regions not affected by ischemia. Supported by SFB 194 References [1] Dirnagl,U., Iadecola,C., Moskowitz,M.A., Pathobiology of ischaemic stroke: an integrated view, Trends Neurosci., 22 (1999) 391-397. [2] Schormann,T., Zilles,K., Three-dimensional linear and nonlinear transformations: an integration of light microscopical and MRI data, Hum. Brain Mapp., 6 (1998) 339-347.

© 2002 Elsevier Science (USA). All rights reserved.

Back to Main

Back to Main

Back to Main

NeuroImage Human Brain Mapping 2002 Meeting

Order to appear: 704

Optical Intrinsic Signal Imaging in the Preictal Phase of Seizures James W.Y. Chen

, Sameer Sheth , Michael Guiou , Masahito Nemoto , Arthur W. Toga

Laboratory of NeuroImaging, UCLA School of Medicine, Los Angeles, CA 90095, USA Department of Neurology, VAGLAHS, Los Angeles, CA 90073, USA Subject: Neurology Abstract It was noted in our previous study that seizure related optical intrinsic signal (OIS) changes imaged at 850 nm could precede the onset of electrographic and/or behavior seizures by up to 1 minute (Neurology 2000 55: 312-315). It was noted that intensity of light reflectance changes in the immediate preictal phase preceding seizure onset was small, but it showed similar decreased light reflectance as in fully developed seizures. In this study, this preictal phase related OIS changes were further investigated by using the same penicillin induced acute seizure model in rats. In Spraque-Dawley rats (n=5), surgery and OIS imaging were performed under anesthesia. Please refer to our previous publication (Neurology 2000 55: 312-315) for experiment method. OIS imaging was obtained with an optical filter of 610 nm. EEG and OIS signals were synchronized and collected on a PC computer simultaneously. The EEG sampling frequency was 1000 Hz, and the camera frame rate was 1 frame per 3 seconds, with 2.5-second exposure time. Seizures were induced by dripping 100 units of penicillin solution topically over the burr hole 2 mm in front of the EEG electrode. A ratio analysis was performed on the optical images. Shortly after penicillin application, the region near penicillin application showed a central spot with increased light reflectance (~ 10% changes from the baseline). This region encompasses an elliptical area of about 2 x 1.5 mm2. The surrounding halo region outside the central spot, a superimposed elliptical area of about 3 x 2.5 mm2, showed decreased light reflectance (~ 5% changes from the baseline). During seizure induction, the area of the central spot gradually attenuated over 20 to 30 minutes, which could also be perceived as an intrusion of the central spot by the surrounding halo. The completeness of this intrusion, or the reversal of the light reflectance changes in the central spot from the increased to the decreased, correlated well with seizure onset recorded on EEG. After seizure onset, the whole region showed decreased light reflectance changes (~10% from the baseline) and encompassed an elliptical area of about 4 x 3.5 mm2. The nearby drainage veins outside this elliptical area showed increased light reflectance changes after seizure onset. The rest of cortex did not show significant changes from the baseline. The findings suggest that in acute seizure model induced by penicillin, OIS imaging could detect changes in the seizure induction phase, which was 20 to 30 minutes before spikes were detectable on EEG. In addition, the reversal of the light reflectance changes in the central spot correlated well with seizure

Back to Main

onset, which might be employed in the future as an optical marker for identifying seizure onset. The increase of light reflectance in the nearby veins after seizure onset suggests that blood flow increases in the ictal region after seizure onset. Supported by the VA CDA grant and NIMH grant MH52083.

Go to Main Abstract page

© 2002 Elsevier Science (USA). All rights reserved.

Back to Main

NeuroImage Human Brain Mapping 2002 Meeting

Order to appear: 705

In vivo voxel-based morphometry (VBM) in multiple system atrophy (MSA) Karsten Specht , Martina Minnerop , Michael Abele , Jürgen Reul , Thomas Klockgether fMRI Section, Dept. of Neuroradiology, Medical Centre Bonn, Germany Department of Neurology, University of Bonn, Germany Subject: Neurology Abstract Introduction Multiple system atrophy (MSA) is a sporadic, adult-onset disease characterized by neurodegeneration in the basal ganglia, brainstem, cerebellum and intermediolateral cell columns of the spinal cord. The ultrastructural hallmark of MSA is the presence of oligodendroglial cytoplasmic inclusions. Clinically, MSA patients present with various combinations of parkinsonism, cerebellar ataxia and autonomic failure (orthostatic hypotension, urinary incontinence). Magnetic resonance imaging (MRI) in MSA patients reveals a number of morphological abnormalities including volume loss of the cerebellum, brainstem and basal ganglia as well as signal changes in the cerebellar peduncles, brainstem and basal ganglia (Schulz et al. 1994, 1999; Schrag et al. 2000). In the first instance, we used in vivo voxel-based morphometry (VBM) to study the brains of MSA patients. VBM is an objective and automated procedure that compares neuroanatomical differences on a voxel by voxel basis thereby allowing to study brain morphological changes in an unbiased way (Good et al. 2001). Methods We examined 10 healthy controls (3 male, 7 female; mean age: 54.2yrs) and 12 MSA patients (6 male, 6 female, mean age: 60.5 yrs). 8 patients fulfilled the diagnostic criteria of probable MSA, and 4 patients the criteria of possible MSA (Gilman et al. 1998). All subjects were scanned with a high resolution T1weighted mpr sequences, as well as a multi-echo T2 weighted turbo spin multi-echo sequence (TE 15, 75, 135 ms). The data were normalized and segmented using a standardized SPM protocol (Good et al. 2001). The final segmented images are indicating the probability of being grey or white matter, respectively. The smoothed and segmented images were analysed with several two sample t-tests, separately for grey and white matter, as well as for each sequence and echo time. Results Significantly decreased grey matter volume was found within the cerebellum, the tectum, substantia nigra, putamen, along the anterior commissure, in the anterior cingulate gyrus and the hippocampus. In addition, there were significant differences along the pyramidal tract with an increase of T1 signal as

Back to Main

well as an increased signal in the T2 images with long echo times. Discussion Our results confirm and extend present knowledge of significant volume loss of cortical and subcortical brain structures in MSA. For the first time we observed signal changes along the pyramidal tract that cannot be simply explained by pure tract degeneration. It is hypothesized that these changes reflect myelin abnormality due to ultrastructural pathology of oligodendroglia. References Schrag et al.: Clinical usefulness of magnetic resonance imaging in multiple system atrophy. J Neurol Neurosurg Psychiatry 1998; 65:65-71 Schulz et al.: Multiple system atrophy: natural history, MRI morphology, and dopamine receptor imaging with 123IBZM-SPECT. J Neurol Neurosurg Psychiatry 1994;57;1047-56 Schulz et al.: Magnetic resonance imaging-based volumetry differentiates idiopathic parkinson’s syndrome from multiple system atrophy and progressive supranuclear palsy. Ann Neurol 1999;45:65-74. Gilman et al.: Consensus statement on the diagnosis of multiple system atrophy. Clinical Autonimic Research 1998,8:359-362. Good et al.: A voxel-based morphometric study of ageing in 465 normal adult human brains. Neuroimage 2001;14:21-36.

Go to Main Abstract page

© 2002 Elsevier Science (USA). All rights reserved.

Back to Main NeuroImage Human Brain Mapping 2002 Meeting

Order to appear: 706

A Segmentation Method of Human Brain White Matter Using Diffusion Distance at 3.0 T MRI Tetsuo Sato , Hiroshi Toyoda , K Kashikura , Khader Hasan , Andrew Alexander , Yoshiharu Yonekura Biomedical Imaging Research Center, Fukui Medical University Graduate School of Medicine, Kyoto University W.M. Keck Laboratory for Functional Brain Imaging and Behavior, University of Wisconsin Subject: Neurology Abstract We have developed a novel method to assess white matter connectivity using diffusion tensor distance between neighborhood voxels and apply the method to in vivo brain measurements at 3.0 T MRI. Diffusion tensor distance is defined as the length from the center to the surface of the diffusion tensor. Using the iterative algorithm, we can segment typical white matter trajectories such as corpus callosum and internal capsule. Introduction In vivo detection of the structure of deep brain white matter using diffusion weighted MRI techniques has become more important [1][2][3]. In this study, directional diffusion measurements are used to infer regional white matter connectivity. This connectivity is determined as a function of distance between the origin of the tensor and the surface for each neighboring voxel direction. This approach is different from other methods that use the principal eigen vectors [4][5][6][7] or full tensors [8][9]. Methods Data acquisition DWI were acquired on a 3.0 T Signa MRI system (GE). Echo planar images were acquired in two subjects in the axial plane at 38 and 46 slice locations. The maximum b value was 1000 sec/mm2. Other parameters were TR=8000 msec, TE=107 msec, slice thickness=3 mm, image matrix=128x128 pixels, in plane resolution=1.875 mm Projected distance of the diffusion tensor In this study, the projected tensor distance xtDx is used as a measure of connectivity potential in specific directions x. The x directions correspond to those of the 26 neighboring voxels in 3D. Normalized distance potential The normalized distance potential is defined by multiplying the projected distance from the reference to the neighborhood and from the neighborhood to the reference as follows. {xitDixi/Trace(Di)}{xjtDjxj/Trace(Dj)} where xi is the unit vector to the neighboring voxel, Di is the diffusion tensor, Trace is the trace of the diffusion tensor of the reference voxel. Segmenting white matter In Figure 1, the searching algorithm is performed for all eight 2-D neighborhoods (26 neighborhoods in 3D). In this case, we start from the center as a reference. Right-up, up, down, left-down voxel are the subsequent references. We continue searching until visiting the previous reference. The starting point is on major fiber trajectories such as corpus callosum and internal capsule. Results Results of the algorithm are shown in Figure 2. Discussion The results of the algorithm tested here are promising for segmenting specific white matter trajectories such as corpus callosum and internal capsule. But they are dependant on the thresholding values. Further studies need to be performed to determine the most appropriate thresholding criteria statistically and automatically. This will be important before it can be used in clinical studies such as comparing between several subjects. References [1] Le Bihan D. NMR Biomed 1995 Nov-Dec;8(7-8):375-86. [2] Poupon C et al. Neuroimage 2000 Aug;12(2):184-95. [3] Jones DK et al. Magn Reson Med 1999 Jul;42(1):37-41. [4] Conturo TE et al. Proc Natl Acad Sci USA 1999 Aug 31;96(18):10422-7. [5] Mori S et al. Ann Neurol 2000 Mar;47(3):412-4. [6] Mori S et al. Proc of 8th Annual ISMRM 2000:83. [7] Basser PJ et al. Magn Reson Med 2000 Oct;44(4):625-32. [8] Weinstein D et al. Proc. of IEEE Visualization 1999:249-53.

Back to Main

[9] Lazar M et al. Proc. of 8th Annual ISMRM 2000:482.

Go to Main Abstract page

© 2002 Elsevier Science (USA). All rights reserved.

Back to Main

NeuroImage Human Brain Mapping 2002 Meeting

Order to appear: 707

Functional Anatomy of Crossed Cerebellar Diaschisis Kenji Ishii , Michikazu Nakamura , Tadashi Nariai , Masahiro Mishina , Masashi Ohyama , Keiichi Oda , Kiichi Ishiwata PET Center, Tokyo Metropolitan Institute of Gerontology Department of Neurology, Tenri Hospital Department of Neurosurgery, Tokyo Medical and Dental University 2nd Internal Medicine, Nippon Medical School Subject: Neurology Abstract Objective: The purpose of this study is to investigate the pathophysiological mechanism of crossed cerebellar diaschisis (CCD) using voxel-based analyzing technique for functional neuroimaging. Methods: Among 237 consecutive PET studies with 15O labeled gases in the PET Center of Tokyo Metropolitan Institute of Gerontology, we picked up 58 chronic stroke cases who had cerebrovascular lesion in unilateral cerebral hemisphere. All the patients had quantitative measurements of cerebral blood flow (CBF), cerebral metabolic rate of oxygen (CMRO2), oxygen extraction fraction (OEF), and cerebral blood volume (CBV) under the inhalation of C15O2, 15O2 and C15O with continuous/serial arterial blood sampling and static PET scan. The following analysis was performed by SPM99. The CBF images were normalized to a standard anatomical space. In order to match the lesion side, the CBF images with left cerebral lesions were flipped. Regions of interests were placed on both cerebellar hemispheres and the asymmetry index (AI) was calculated in each subject by the following formula. AI = 100 x (unaffcted cerebellum - affected cerebellum) / unaffected cerebellum Then, a voxel-based statistical analysis was performed to search which part of the brain has significant reduction of CBF correlated with the AI as covariate. The analysis was done on whole 58 patients altogether, and also on 24 patients with left cerebral lesions and on 34 patients with right cerebral lesions separately. Exactly the same analysis was done for CMRO2 images. Results: Results from the analysis of CBF and CMRO2 were similar. Significant correlation with AI was found in the lateral frontal and lateral parietal cortex surrounding the central sulcus, thalamus, and striatum contralateral to the affected cerebellar hemisphere. A majority part of the temporal lobe and the occipital lobe were not involved. Interestingly, primary sensory-motor area and the region where the corticospinal tract passes have relatively spared from the correlation (Fig. 1). The AI correlate cerebral region was

Back to Main

much wider in the right cerebral hemisphere than in the left. Discussion: Our results support the hypothesis that the CCD was caused by the dysfunction of cerebro-pontocerebellar network. The primary sensory-motor cortex and the corticospinal pathway may not be directly involved in the CCD, but it locates adjacent to the 'hot spots' that cause CCD. This well explains the previously reported findings that the paresis frequently accompanies with CCD but there was no strict correlation of the severity of paresis and that of CCD. The cerebro-cerebellar connection was not symmetric, but the left cerebellum seems to have wider functional connectivity with cerebral hemisphere compare to the right.

Go to Main Abstract page

© 2002 Elsevier Science (USA). All rights reserved.

Back to Main NeuroImage Human Brain Mapping 2002 Meeting

Order to appear: 708

Statistical Parametric Mapping for Cerebral Metabolism of Glucose and Clinical Symptoms in Progressive Supranuclear Palsy Masahiro Mishina , Masashi Ohyama , Kenji Ishii , Kazuko Mitani , Yuichi Komaba Shin Kitamura , Yasuo Katayama , Michio Senda ¶

, Kiichi Ishiwata , Shirou Kobayashi ,

Departments of Neurology, Neurological Institute, Nippon Medical School Chiba-Hokusou Hospital Positron Medical Center, Tokyo Metropolitan Institute of Gerontology The Second Department of Internal Medicine, Nippon Medical School Departments of Neurosurgery, Neurological Institute, Nippon Medical School Chiba-Hokusou Hospital ¶Institute of Biomedical Research and Innovation Subject: Neurology Abstract Introduction: In the patients with progressive supranuclear palsy (PSP), cerebral metabolism of glucose is reduced in basal ganglia, brainstem and cerebral cortex using positron emission tomography (PET) with 2-[18F]fluoro-2-deoxy-D-glucose (FDG) and regions of interest (ROIs) analysis. Recent image analysis applications, such as statistical parametric mapping (SPM), allow us to analyze all available metabolic information, without a priori hypotheses based on anatomic ROIs. Such analyses revealed occipital hypometabolism in the patients with Parkinson's disease and diffuse Lewy body disease. The purpose of this study is to investigate the patterns of cerebral metabolism of glucose and the relationship between clinical symptoms and the metabolism in PSP using FDG PET and SPM99. Methods: We studied 14 patients with PSP on the basis of the NINDS-SPSP clinical research criteria (mean age ± SD, 75.7 ± 6.4), consisting one definite PSP, nine probable PSP and four possible PSP. The control group consisted of 14 volunteers (age, 61.6 ± 10.5). The clinical severity of parkinsonism and dementia for PSP was evaluated with a Unified Parkinson's Disease Rating (UPDRS, n = 14) and a revised version of Hasegawa dementia scale (HDS-R, n = 10)1, respectively. The FDG uptake was acquired by static scans from 45 to 57 minutes after injection of 150 MBq of [18F]FDG. Using a locally made FDG template, the FDG images were spatially normalized into a standard stereotaxic anatomical space. The data were smoothed with a 24-mm Gaussian filter to account for residual inter-subject differences and corrected for differences in FDG uptake by cerebellar normalization. Using analysis of covariance (ANCOVA) and age as nuisance parameter in order to remove the effect of aging, the differences between groups were displayed as SPM {Z} with a voxel threshold probability of 0.005 and an extent threshold of 100 contiguous voxels per cluster. The maps for correlations between the covariates for clinical severity and FDG uptake in PSP were also calculated with the same threshold. Results: Relative FDG uptake for PSP was significantly reduced as compared with normals in midbrain, inferior frontal gyrus, insular area, head of caudate nucleus, anterior putamen, anterior globus pallidus, medial nucleus of thalamus, hypothalamus and anterior cingulate gyrus (Figure, A). There was positive correlation between the UPDRS scores and relative FDG uptake in culmen of cerebellar vermis (Figure, B). The SPM for HDR-S scores demonstrated that the progression of dementia in PSP was related with reduction of FDG uptake in the left inferior fontal gyrus and left parahippocampal gyrus (Figure, C). Discussion: Neuropathological studies showed that PSP was characterized by neuronal loss, fibrillary gliosis and a large number of neurofibrillary tangles affecting several subcortical structures, but with relative sparing of the cerebral cortex. The group analysis also showed hypometabolism in PSP was prominent in subcortical area. The SPM for UPDRS scores could not reveal the hypometabolic area involving the severity of parkinsonism, but demonstrated higher glucose metabolism in the culmen as the parkinsonism was advanced. We speculate that this finding reflect the compensation for the motor impairment. References: 1. Wolfe N, et al. J Gerontol 1992;47(4):289-91.

Back to Main

Go to Main Abstract page

© 2002 Elsevier Science (USA). All rights reserved.

Back to Main

NeuroImage Human Brain Mapping 2002 Meeting

Order to appear: 709

Simultaneous EEG and fMRI in epileptic discharges: BOLD response and localization Christian-G. Benar, Abdullah Al-Asmi, Bruce Pike, Francois Dubeau, Jean Gotman Montreal Neurological Institute, McGill University, Montréal, Québec, Canada Subject: Neurology Abstract INTRODUCTION: Simultaneous recording of EEG and functional MRI permits to localize noninvasively the sources of interictal epileptic discharges. Our interest here is two-fold: improve the statistical detection of activated areas and seek new insights in the mechanisms of interictal discharges. We started by investigating the BOLD hemodynamic response (HR) to the epileptic events on a set of patients. Then, we compared for each patient the fMRI activated areas with dipole models of the same type of events recorded outside the scanner. METHODS: Recording: 1.5T MR scanner (Siemens Vision, Erlangen, Germany), 21-channel EEG with EMR32 amplifier (Schwarzer, Munich, Germany). We acquired 7 to 10 runs of 120 frames, each frame consisting of 25 BOLD 64*64 images, with a TR of 50ms, a voxel size of 5x5x5mm, and a repetition time of 3s. ANALYSIS: EEG was processed offline to remove the scanner artifact (FEMR sofware, Schwartzer, [1]). Epileptiform discharges were marked by experts. Statistical analysis was performed using the methods of Worsley et al. [2], with a model of the hemodynamic response based on Glover [3]. ROIs were defined as clusters of significant voxels. On 5 patients with clear activation, the BOLD signal was oversampled by a factor of 3 and the average HR for each ROI was computed on isolated events. Dipole modeling was performed using the Curry software (Neuroscan, Sterling, USA) on EEG data recorded outside the scanner. RESULTS: We observed a large variability in shape and duration of the HR response both intra and across patients. The amplitude of the average HR ranged between 0.5% and 3.5% and the duration between 20s and 45s (Fig. 1), which is above the 20s length of the model. The average distance between a dipole and the closest activation region was 22.4 ± 12.2 cm (cf. Fig 2 for an example of coregistration). CONCLUSION: Our results could be used for improving the statistical detection, but also to attempt correlation with clinical features such as type of lesion. Dipole localization was consistent with the fMRI findings, which suggests we are measuring different aspects of the same phenomenon. This is encouraging concerning the relevance of fMRI studies on epileptic patients. REFERENCES [1] Hoffmann A et al. 2000. Mag. Res. Med. 44(5):791-8.

Back to Main

[2] Worsley, K.J et al. 2000. NeuroImage 11:S648 [3] Glover G.H. 1999. Neuroimage 9(4):416-29.

Back to Main

Go to Main Abstract page

© 2002 Elsevier Science (USA). All rights reserved.

Back to Main

NeuroImage Human Brain Mapping 2002 Meeting

Order to appear: 710

Brain SPECT abnormalities in Alzheimer's disease revealed by atrophy correction Hiroshi Matsuda , Hidekazu Kanetaka , Takashi Ohnishi , Takashi Asada , Etsuko Imabayashi , Seigo Nakano , Asako Katoh , Fumiko Tanaka National Center Hospital for Mental, Nervous, and Muscular Disorders, National Center of Neurology and Psychiatry, Japan Department of Neuropsychiatry, Institute of Clinical Medicine, University of Tsukuba, Japan Subject: Neurology Abstract Introduction. The limited spatial resolution of SPECT scanners does not allow an exact measurement of the local radiotracer concentration in brain tissue because partial volume averaging effects (PVEs) underestimate activity in brain structures of small size. Thus, actual regional cerebral blood flow (rCBF) values can be underestimated in Alzheimer's disease (AD). It is unclear whether the reduction of rCBF observed in AD patients reflects an actual reduction of rCBF or the PVEs on SPECT measurements. The objectives of the current study were to determine which brain structures had higher PVE correction and whether low rCBF areas without correction remained low after correction. Materials and Methods. We analyzed 30 patients with mild probable AD (NINCDS-ADRDA criteria, MMSE score; 20.8 + 1.8) and age-matched 62 healthy volunteers. The rCBF was measured using the previously reported method [1]. The SPECT data were coregistered to MR images. The MR images were segmented in SPM99 without prior spatial normalization. A three-dimensional convolution of segmented gray and white matter MR images with the point spread function of the SPECT device was performed to obtain coefficients of dispersion for each voxel. These convolved gray matter and white matter images were normalized to have a maximum count of 1.0. Regions of interest (ROI) were automatically extracted from this white matter MR image as areas over 95% of maximum count density and overlaid on co-registered SPECT images. Multiplication of the normalized white matter MR images by the maximum SPECT count for these white matter ROIs yielded white matter SPECT images. The gray matter SPECT images were obtained by subtraction of this white matter images from original SPECT images. Lastly, the gray matter SPECT image was divided by the normalized gray matter MR image on a voxel-by-voxel basis. A global gray matter CBF value after PVE correction was set to the same value as that before PVE correction [2]. Results,

Back to Main

The SPM99 analysis showed significant absolute rCBF reductions before PVE correction in the right posterior cingulate gyrus, bilateral inferior parietal lobules, bilateral hippocampi, right precuneus, bilateral amygdala, right parahippocampal gyrus, left anterior cingulate gyrus, right superior temporal gyrus, right insula, and right frontal gyri. While PVE correction revealed significant rCBF reductions in the bilateral inferior parietal lobules, right precuneus, right subcallosal gyrus, bilateral cunei, bilateral parahippocampal gyri, left anterior cingulate gyrus, left posterior cingulate gyrus, left precentral gyrus, left middle temporal gyrus, right insula, and bilateral frontal gyri. Medial temporal areas showed the biggest differences in results after PVE correction. Discussion. The PVE correction revealed significant rCBF decrease in bilateral parahippocampal gyri without significant decrease in hippocampus in mild AD. This finding may suggest the compensatory response of reinnervation in hippocampus to the neuronal loss in the entorhinal cortex in the course of AD [3]. This correction seems to be essential to SPECT images in subjects with brain atrophy. References. [1] Matsuda H et al. Eur J Nucl Med 1995; 22:633-637 [2] Mueller-Gaetner HW et al. J Cereb Blood Flow Metab 1992;12:571-583 [3] Hyman BT, et al. Ann Neurol 1987;21:259-267

Go to Main Abstract page

© 2002 Elsevier Science (USA). All rights reserved.

Back to Main NeuroImage Human Brain Mapping 2002 Meeting

Order to appear: 711

Imaging post-stroke somatosensory recovery: Two serial fMRI case studies. Leeanne M Carey , David F Abbott , Aina Puce , Graeme D Jackson , Ari Syngeniotis , Geoffrey A Donnan National Stroke Research Institute, Austin & Repatriation Medical Centre, Australia Brain Research Institute, Austin & Repatriation Medical Centre, Australia Brain Sciences Institute, Swinburne University of Technology, Australia School of Occupational Therapy, LaTrobe University, Australia Subject: Neurology Abstract Background: Knowledge of the evolution of cerebral changes associated with post-stroke motor and somatosensory recovery is limited. To date there have been no whole-brain serial studies of neural plasticity associated with somatosensory recovery. We therefore serially investigated the cortical and subcortical areas active in discrimination of a controlled touch stimulus in two stroke patients who had experienced marked sensory loss with variable recovery. Methods: A 42 and a 47 year-old man (Patients 1 and 2) with posterior cerebral artery territory infarcts involving the thalamus of the left or right hemisphere, were investigated. Serial high-resolution whole-brain functional MRI (fMRI) studies were conducted at two-to-five weeks, three months and six months post-stroke using a controlled dynamic touch discrimination stimulus to the fingertips. Touch discrimination impairment and recovery were quantified using the Tactile Discrimination Test [1] and WEST-handTM monofilaments [2]. fMRI activation was detected using statistical parametric maps and region of interest analysis. Results: At the initial study there was little or no activation in expected sensory regions during stimulation of the affected hand, consistent with severe loss of touch sensation. At the 3-month study, Patient 1 showed a return of activation in primary somatosensory cortex (SI) contralateral to the stimulus and bilateral secondary somatosensory cortices (SII) following marked recovery of touch sensation (but a mild residual deficit). These sites remained active at the 6-month study and improvement was maintained. A greater number of activated voxels were present in SI and SII for the affected relative to the ‘unaffected’ hand at 3- and 6-month studies. There was no evidence of significant activation in the thalamus of either hemisphere at the p < 0.0001 (uncorrected) threshold or lower thresholds at any of the studies. In comparison, Patient 2 still had severe sensory loss at the 3- and 6-month studies. This patient demonstrated thalamic activation at the 3-month study and bilateral SII activation at the 6-month study. There was no significant activity in contralateral SI at the 3-month study and only very minor activation at the 6-month study. Stimulation of the ‘unaffected’ hand was associated primarily with activation of contralateral SI and bilateral SII in all studies and, for Patient 2, thalamic activation at the early study. Conclusions: We have demonstrated the presence of different patterns of activation over time in stroke patients with variable somatosensory recovery. The potential for return of activation in brain regions normally involved in touch discrimination, ie. primary and secondary somatosensory cortices, was demonstrated in the patient who showed early, marked improvement. These changes occurred primarily between 2-weeks and 3-months post-stroke, indicating a re-emergence of activation during the period of somatosensory recovery. In contrast, activation was limited primarily to thalamus and bilateral SII in the patient who showed relatively poor recovery. There was little evidence of early plasticity. References: 1. Carey LM et al. 1997. J Neurol Rehabil 11:219-32. 2. Weinstein S. 1993. J Hand ther Jan-Mar:11-28.

Back to Main

Go to Main Abstract page

© 2002 Elsevier Science (USA). All rights reserved.

Back to Main

NeuroImage Human Brain Mapping 2002 Meeting

Order to appear: 712

Effects of right hemispheric lesions on cortical activation patterns during auditory tasks: fMRI study Michela Adriani , Anne Bellmann Thiran , Philippe Maeder , Reto Meuli , Eleonora Fornari , Rolf Frischknecht , Claire Bindschaedler , François Rivier , Jean-Philippe Thiran , Stéphanie Clarke Division de Neuropsychologie, CHUV, Lausanne Service de Radiodiagnostic et Radiologie Interventionnelle, CHUV, Lausanne Service de Rhumatologie et Médecine Rééducative, CHUV, Lausanne Institut de Traitement des Signaux, EPFL, Lausanne; Switzerland Subject: Neurology Abstract Evidence from activation studies (Maeder et al., 2001) suggests that sound recognition and localization are processed in two anatomically and functionally distinct cortical networks that are each present in both hemispheres. Sound recognition and/or localization may be, however, disrupted by purely unilateral damage (Clarke et al. 2000; Bellmann et al. 2001), suggesting that processing within one hemisphere may not be sufficient or may be disturbed by the contralateral lesion. We report here on psychophysical performance and activation patterns in cases of right unilateral hemispheric lesions. Semantic recognition of environmental sounds was tested with a standardized battery of 50 sound samples, and sound localization by simulating different azimuthal positions by varying differences in interaural time. Normal performance was established in 60 normal subjects. Brain activations associated with sound recognition or localization was investigated in 18 normal subjects using fMRI (1.5 Tesla Siemens Vision; Maeder et al. 2001). Three conditions were used: i) comparison of spatial stimuli simulated with interaural time differences; ii) identification of environmental sounds; and iii) rest. Conditions i) and ii) required motor response. Activation patterns were analyzed using SPM99 for individual subjects. Sound recognition and localization activated, as compared to rest, inferior colliculus, medial geniculate body, Heschl gyrus and distinct parts of temporal, parietal and frontal convexity bilaterally. The activation pattern on temporo-parieto-frontal convexity differed in the two conditions. Middle temporal gyrus and precuneus bilaterally and the posterior part of left inferior frontal gyrus were more activated in sound recognition than localization. The lower part of inferior parietal lobule and posterior parts of middle and inferior frontal gyri were more activated (bilaterally) in sound localization than recognition. Four patients, 3 male 1 female, aged 46 to 64 years, with focal ischemic lesions in the right hemisphere

Back to Main

(cases 1-3 in the territory of the medial cerebral artery, case 4 orbitofrontal) were tested with the same psychophysical and fMRI paradigms as normal subjects, 2 to 13 months after lesion. All patients were deficient in sound localization and case 4, but not cases 1-3, in sound recognition. Auditory information activated spared parts of the right hemisphere. In the non-damaged left hemisphere parts of the temporo-parieto-frontal cortex were activated, but less than in normal subjects. Recognition or localization, versus rest, activated Heschl's gyrus and varying extent of surrounding cortex. The specialized processing pathways for sound recognition and localization were, however, not activated by specific tasks as in normals. These results show that right unilateral hemispheric damage disturbs significantly auditory processing within the contralateral, spared hemisphere. In particular specific auditory information, leading to localization or recognition, is no longer processed selectively within specialized networks. These processing disturbances within cortical networks of the spared hemisphere are accompanied by deficient performance in at least one of the auditory functions. References Clarke S, Bellmann A, Meuli R, Assal G & Steck AJ. Neuropsychologia, 38 (2000) 797-807. Maeder P, Meuli RA, Adriani M, Bellmann A, Fornari E, Thiran JP, Pittet A, Clarke S. NeuroImage, 14 (2001) 802-816. Bellmann A, Meuli R, Clarke S. Brain, 124 (2001) 676-687.

Go to Main Abstract page

© 2002 Elsevier Science (USA). All rights reserved.

Back to Main NeuroImage Human Brain Mapping 2002 Meeting

Order to appear: 713

Sensorimotor Reorganization After Early Cortico-Spinal Tract Injury: Different Contributions of the Unaffected Hemisphere Wolfgang Grodd , Martin Staudt

, Christian Gerloff , Michael Erb , Jutta Stitz , Inge Kraegeloh-Mann

Section Exp. MR of the CNS, Dept. Neuroradiology Dept. Pediatric Neurology, University Childrens Hospital Cortical Physiology Research Group, Dept. of Neurology, University of Tuebingen, Germany Subject: Neurology Abstract Introduction Reorganization after early brain injuries is not only determined by the maturational stage of the CNS at the time of the insult, but also by the type, location, and extent of the lesion. This study examines the impact of different lesion extents in a sample of patients with lesions of uniform type and location (unilateral periventricular defects) and similar timing (early third trimester of pregnancy). Patients and Methods Twelve young adult patients with congenital hemiparesis (10 right-, 2 left-sided) of different degrees and ten age-matched, right-handed controls were studied. The severity of structural damage to hand motor projections of the cortico-spinal tract was assessed on semi-coronal MRI reconstructions along anatomical landmarks of cortico-spinal tract somatotopy [1]. Functional integrity of cortico-spinal projections in the affected hemisphere, as well as any abnormal ipsilateral projections to the paretic hand originating in the unaffected hemisphere were examined by focal transcranial magnetic stimulation (TMS). Cortical activation during simple, repetitive hand movements were studied by fMRI. Results Three subgroups of patients could be identified on the basis of structural MRI, clinical data, and TMS: Group A (n = 4) with minor lesions, mild hand motor impairment, and motor evoked potentials (MEP) in the paretic hand by TMS of the affected hemisphere; Group B (n = 6) with large lesions, moderate to severe hand motor impairment, marked mirror movements, and paretic hand MEP by TMS of the unaffected hemisphere; and an Intermediate Group (n = 2) with intermediate-sized lesions, moderate impairment, and paretic hand MEP by TMS of either hemisphere. Functional MRI of paretic hand movement revealed bilateral activation patterns in the majority of patients, with different topographies of activation in the unaffected hemisphere (ipsilateral to the paretic hand performing the motor task): Compared with controls, Group A showed stronger activation of premotor cortex (white in Figure), whereas in Group B, the primary sensorimotor cortex was activated more strongly (black in Figure), in comparison both with controls and with Group A (SPM99 random-effect analysis).

Back to Main

Conclusion This study identifies the extent of a lesion as a critical determinant for the type of reorganization induced in a sample of patients with similar timing, type, and location of an early brain lesion. In addition, different cortical topographies of recruitment in the unaffected hemisphere were identified for different modes of reorganization in the cortico-spinal system. [1] Staudt M et al: Neuropediatrics 2000;31:257-264

Go to Main Abstract page

© 2002 Elsevier Science (USA). All rights reserved.

Back to Main

NeuroImage Human Brain Mapping 2002 Meeting

Order to appear: 714

Effects of working memory training on brain activity - a case study Helena Westerberg, Hans Forssberg, Torkel Klingberg Karolinska Institutet, Stockholm, Sweden Subject: Neurology Abstract Working memory (WM) is the ability to hold and manipulate information for short periods of time. WM is closely associated with attention (1). Injuries affect the central nervous system (CNS) in different ways, almost always causing deficits in attention (2). Since the ability to pay attention enhances the result of all other rehabilitation, it is a critical issue (2). We hypothesized that attention could be enhanced with a method of intense and adaptive WM training (3). We developed a computerized training programme, which targets different modalities of WM. Here we present the results of WM training for a single male subject (aged 29 years) who suffered severe prefrontal brain injury (Glasgow Coma Scale < 7) 12 month before commencing training. The injury affected the right caudate nucleus and the surrounding white matter tracts. Compared to test-retest data from a control group (n = 8), statistically significant training effects were found not only on the trained WM task, but also on Corsi block tapping, Stroop and Raven tests, all of which are known to rely on the prefrontal cortex. To compare brain activity pre- and post training we used functional magnetic resonance imaging (fMRI) during performance of a visuo-spatial WM task (4), similar to one of the trained tasks. The analysis of this data showed that training resulted in an increased prefrontal activity of the injured hemisphere. References 1 de Fockert, JW et al (2001). Science, 291 2 Robertson and Murre (1999). Psychological Bulletin 3 Klingberg, T et al. (2001) Submitted 4 Fry, A and Hale, S (1996) Psychological Science

Back to Main

Go to Main Abstract page

© 2002 Elsevier Science (USA). All rights reserved.

Back to Main NeuroImage Human Brain Mapping 2002 Meeting

Order to appear: 715

Mapping Cortical Gray Matter Asymmetry Patterns During Normal Adolescence and the Effects of Heavy Prenatal Alcohol Exposure Elizabeth R. Sowell , Paul M. Thompson , Bradley S. Peterson , Sarah N. Mattson , Suzanne E. Welcome , Amy L. Henkenius , Erin C. Lobo , Edward P. Riley , Terry L. Jernigan , Arthur W. Toga University of California, Los Angeles Laboratory of Neuro Imaging, Department of Neurology Columbia College of Physicians & Surgeons Department of Psychiatry and the New York State Psychiatric Institute Center for Behavioral Teratology, San Diego State University Department of Veterans Affairs Medical Center and Departments of Psychiatry and Radiology University of California, San Diego, School of Medicine Subject: Neurology Abstract Introduction: Little is yet known about brain asymmetry patterns in normal development or how they are altered in fetal alcohol syndrome (FAS). We used cortical matching techniques that allowed us to assess differences in gray matter density and brain surface location at homologous anatomic points in the left and the right hemispheres in each subject. In addition to assessing age effects in normals, we tested for differences in gray matter asymmetry between the alcohol-exposed subjects (ALC) and controls. Methods: We studied two independent samples of normally developing children, adolescents and young adults (age 7 to 25 years) totaling 83 subjects from two different research groups and compared them to 21 individuals (age 7 to 22) with heavy prenatal alcohol exposure. Highresolution T1-weighted image data sets for each individual were linearly transformed into standard space, tissue segmented, and sulcal boundaries were drawn on the surface renderings of each individual's brain. Elastic deformation maps were used to encode gyral patterns and drive each individual's cortical anatomy into a group average (i.e., control, ALC). Gray matter density at each point on the cortical surface was estimated for each individual 1,2. Differences in brain surface location between the 2 hemispheres were computed for each subject by computing a flow of each subjects left hemisphere onto a flipped version of their right hemisphere while matching sulcal and gyral patterns. Ratios of gray matter density at analogous surface points in the left and right hemispheres were also assessed within and between groups. Results: Quantitative maps of brain surface asymmetry reveal prominent perisylvian hemispheric differences in which the superior temporal and inferior parietal cortices are shifted backward in the left hemisphere in both normal and alcohol exposed subjects. Cortical surface gray matter asymmetry is most prominent in the posterior inferior temporal lobes (right greater than left), and this effect does not differ between groups of normally developing children, adolescents, or young adults. Alcohol exposed individuals show a significant reduction in this asymmetry, whether studied with surface-based or more traditional volumetric region of interest analyses. This region of cortex, near the junction of Brodmann's areas 21, 22, and 37, primarily subserves language functions that are known to be impaired on average in the alcoholexposed subjects. Discussion: To our knowledge, this is the first report in the literature of brain surface and gray matter density asymmetry patterns in normally developing children and adolescents, and in individuals with severe prenatal alcohol exposure. Here we show that gray matter asymmetry within the posterior inferior temporal lobes is altered in the alcohol exposed subjects. These findings may contribute to a more comprehensive understanding of the neural substrates of cognitive dysfunction after heavy prenatal alcohol exposure.

References 1. Sowell, E.R. et al. Mapping sulcal pattern asymmetry and local cortical surface gray matter proportion in vivo: maturation in posterior perisylvian cortices. Cerebral Cortex 12, 17-26 (2002). 2. Sowell, E.R. et al. Mapping Continued Brain Growth and Cortical Gray Matter Density Reduction in Frontal Cortex: Inverse Relationships

Back to Main

During Post Adolescent Brain Maturation. Journal of Neuroscience 21, 8819-8829 (2001).

Go to Main Abstract page

© 2002 Elsevier Science (USA). All rights reserved.

Back to Main

NeuroImage Human Brain Mapping 2002 Meeting

Order to appear: 716

DELINEATION OF SENSORY RESPONSE IN HUMAN CEREBRAL CORTEX WITH INTRINSIC OPTICAL SIGNALS AS GUIDES FOR NEUROSURGICAL OPERATION Tadashi Nariai , Katsushige Sato , Kimiyoshi Hirakawa , Yoshihisa Ohta , Itaru Yazawa , Shinichi Sasaki , Kenji Ishii , Kohtaro Kamino , Kikuo Ohno Department of Neurosurgery, Tokyo Medical and Dental University Department of Physiology, Tokyo Medical and Dental University Positron Medical Center, Tokyo Metropolitan Institute of Gerontology JAIC College of Mecical and Welfare Technology Subject: Neurology Abstract Purpose: Intrinsic optical signals to somatosensory and auditory response were recorded from human cerebral cortex during brain tumor surgery under general anesthesia. Localization of optical signal was compared with that of MEG, PET and cortical monitoring with subdural electrodes. Methods: The recordings were carried out on twelve patients bearing tumor adjacent to the sensorimotor or the language cortex. The cortical surface was illuminated with voltage-stabilized Xe white-light. The reflected light passed through a bandpass filter (605 nm), and 8 functional images were acquired during 5 sec using the intrinsic optical imaging system (Imager 2001). For somatosensory stimuli, the median nerve, the first and the fifth digits or the first and the third branches of trigeminal nerve were electrically stimulated. For auditory stimulus, binaural click sound was applied. Other mapping modality such as MEG, PET and subdural electrode was applied, depending on the location of tumor. Localization of the optical signal was compaired with that of other modalities using 3D expression of cortical structure reconstructed with patients' own MRI. Results: In all patients but one, the somatosensory optical signals were recorded on the primary sensory but not on the primary motor cortex. The location of optical signals corresponded with that of the dipole estimation of cortical sensory responses in MEG and CBF response detected by PET. The optical signals to the stimulation of the first and the fifth digits, and the first and the second branches of trigeminal nerve were recorded on the different locations among sensory strip. In one patients, who underwent the second operation for recurrent tumor, no signal was recorded presumably due to adhesion of cerebral cortex. In two patients who underwent auditory recording, signal was recorded from supramarginal gyrus. Conclusions: These results indicated that the intrinsic optical imaging is a useful technique to delineate the area of human cortical neuronal activity with superior space resolution. It can also be a key method to compare the neuronal activity detected by electrophysiological technique and that detected by blood flow response.

Back to Main

Go to Main Abstract page

© 2002 Elsevier Science (USA). All rights reserved.

Back to Main

NeuroImage Human Brain Mapping 2002 Meeting

Order to appear: 717

Contralesional Activation in Early Versus Late Stages of Stroke Recovery Georg Deutsch, Beverly Corbitt, Hong Gang Liu, Todd Harshbarger, James Mountz University of Alabama at Birmingham Medical Center Subject: Neurology Abstract Introduction: Evidence for increased activation in the side opposite to the stroke has been reported previously and is often interpreted as indicating reorganization in the undamaged side. We present preliminary evidence that such increased contralesional activation is a temporary phenomenon that may help stimulate the affected side in some patients. Once some recovery from diaschisis takes place in the affected side, the contralesional activation subsides. If this is correct, it suggests a new model of how level of activity changes between the hemispheres lead to recovery of function. Methods: Nine patients with unilateral cortical or internal capsule lesions, 6 left and 3 right hemisphere, were studied during affected motor or cognitive tasks using quantitative Xe-133 SPECT at six weeks, six months and after one year post stroke. Absolute rCBF was calculated from a series of 24 rapid scans conducted during 4 minutes of performance of each task. The transverse slice of maximum change was used to evaluate increases on the lesion side versus the unaffected side for tasks affected by the stroke (e.g., right finger motion and/or semantic processing for left side stroke, left finger motion and/or 3-dimensional figure analysis for right side stroke.) Results: Table 1 lists the percent increase in mean hemispheric rCBF in the slice of maximum change for stroke patients in the first two scanning sessions versus in scans conducted after one year. Table 1. Early stage vs late stage activation in stroke recovery. Percent increase in rCBF during task targeted at affected side, N= 9.

1-6 months Intact hemisphere

1-2 year

Normal values

+16.2 % (11.3) +3.4%(3.4) +6.5% (3.7)

Stroke hemisphere + 1.9% (2.7)

+7.6% (5.9) +12.9% (4.2)

Note that the early stage studies show greater than normal activation of the unaffected hemisphere during a task normally processed by the stroke side. In later stage studies activation in the unaffected

Back to Main

hemisphere is closer to normal and activation on the stroke side also improves (during tasks normally processed by the stroke side.) Discussion: Based on absolute rCBF measurements, regions in the unaffected hemisphere show some striking activation patterns in the subacute period post stroke that appears to diminish with time and as the patient improves. In early stages (6 weeks – 6 months) task activation in areas of diaschisis usually occurs in conjunction with activation of homologous areas of the intact hemisphere. In later stages, activation of regions in the affected hemisphere appears to occur more independently. Thus contralesional activation may not necessarily reflect permanent reorganization. It could be an indicator of temporary increases in regions homologous to diaschitic regions on the stroke side. In the case of motor tasks ipsilateral motor pathways and the intact, contralesional hemisphere in general, may act to stimulate diaschitic regions via interhemispheric fibers. Once some recovery takes place in the affected side, the contralesional activation may subside.

Go to Main Abstract page

© 2002 Elsevier Science (USA). All rights reserved.

Back to Main

NeuroImage Human Brain Mapping 2002 Meeting

Order to appear: 718

Functional imaging with Low Resolution Electromagnetic Tomography (LORETA) in cortical cerebellar atrophy Mio Arai, Hideaki Tanaka, Yuka Kobayashi, Masaki Harada, Akinori Hozumi, Koichi Hirata Depertment of Neurology, Dokkyo University School of Medicine Subject: Neurology Abstract Background: There are some controversies whether spinocerebellar degeneration patients have a certain cognitive dysfunctions especially relate to frontal lobe or only apparent cognitive deficits secondary to motor dysfunction. Purpose: This study aimed to search for the brain electric signature of cortical cerebellar atrophy (CCA) patients to assess the relation between cerebellum and cognitive function. Methods: We studied 14 CCA patients and 14 age-, sex-matched normal controls (NC). Both groups showed no significant difference in cognitive function assessed by Mini-Mental State Examination (MMSE). We evaluated frontal lobe function with the New Modified Wisconsin Card Sorting test (WCST). We recorded spontaneous eyes-closed resting EEG and the midlatency auditory evoked responses (MLRs) with silver/silver chloride EEG electrodes attached with paste to 20 locations of the international 10/20 system using connected ears as reference. Eighty dB 1/s click stimuli were used for MLRs measurement. Stimuli were presented in blocks 250 trials with a second repetition of 250 trials. After recording, 20 artifact-free EEG epochs consisting of 2-seconds were selected for each subject and filtered into 7 frequency bands; delta (1.5-6Hz), theta (6.5-8Hz), alpha1 (8.5-10Hz), alpha2 (10.5-12Hz), beta1 (12.5-18Hz), beta2 (18.5-21Hz), beta3 (21.5-30Hz). The global field power (GFP) was computed each EEG frequency band and each MLRs component to compare between two groups using unpaired ttests. Low Resolution Electromagnetic Tomography (LORETA) was used to compute the threedimensional intracerebral distribution of electric activity for 7 EEG bands and MLRs. Images of two groups were statistically compared using non-parametric randomization tests with correction for multiple testing. Results: WCST scores and EEG revealed no significant differences between CCA and NC. On MLRs, activities of Nb and P1 components in CCA patients significantly decreased at frontal cortex on LORETA compared with NC. Discussion: These results suggest the ascending reticular activating system and the frontal lobe are inhibited in CCA patients. We conclude the cerebellum involve in cognitive function regardless of motor adjunct.

Back to Main

Go to Main Abstract page

© 2002 Elsevier Science (USA). All rights reserved.

Back to Main

Back to Main

Back to Main NeuroImage Human Brain Mapping 2002 Meeting

Order to appear: 720

Influences of focal brain lesions on electrophysiological correlates of error processing Markus Ullsperger , D. Yves von Cramon

, Notger G. Müller

Max Planck Institute of Cognitive Neuroscience, Leipzig, Germany Day Care Clinic for Cognitive Neurology, University of Leipzig, Germany Clinic for Neurology, Charité, Humboldt University, Berlin, Germany Subject: Neurology Abstract Introduction Electrophysiological as well as hemodynamic studies have suggested that structures in the vicinity of the anterior cingulate cortex are involved in performance monitoring, particularly in detection of errors. Bidirectional interactions between the frontomedian system involved in performance monitoring and the lateral prefrontal cortex as well as the orbitofrontal cortex have been proposed, but only few studies have directly addressed the issue whether lesions in these brain regions influence performance monitoring and its neural correlates. Because of its important role in task-set-related processes it would be conceivable that the lateral prefrontal cortex interacts with the error detection process and thus the generation of the error-related negativity (ERN/Ne). According to previous lesion studies it seems plausible that the orbitofrontal cortex plays a role in the emotional evaluation of errors and their consequences which might be reflected in changes of the ERN as well as the error positivity (Pe). Methods In order to address these questions we recorded error-related ERPs in three patient groups with different focal cortical lesions while they performed a speeded flankers task: (A) patients with unilateral lesions of the lateral frontal cortex (n=7, mean age 50.7 years), (B) with bifrontopolar lesions extending into the orbitofrontal cortex (n=6, mean age 38.8 years) , and (C) with unilateral temporal lesions (n=6, mean age 38.4 years) who served as a clinical control group. The behavioral data as well as the amplitudes, latencies and scalp distribution of the ERPs were compared to the results from two age-matched healthy control groups (mean age: 51.1 and 38.4 years, respectively). Results and Discussion All patients were able to perform the task and showed compatibility effects as typically found in flankers tasks. The ERP waveforms at two representative electrodes are depicted in the Figure. Lesions of the lateral frontal cortex resulted in an abolition of the ERN and a reduction of the error positivity (Pe). This suggests that frontolateral lesions rendered the generators of the ERN unable to distinguish between correct and incorrect. It could be speculated, that lesions of the lateral frontal cortex led to difficulties with task-set-related processes, which may have disturbed the establishment of a representation of the correct response. It is conceivable that on the basis of incomplete response representations errors cannot be detected properly. In contrast, bilateral frontopolar lesions involving the neighboring orbitofrontal cortex did not alter the ERN. The only difference from the healthy controls was a more anterior maximum of the error positivity (Pe) in these patients. We concluded that the frontal poles as well as the anterior orbitofrontal cortices play only a minor role in automatic error detection as reflected by the ERN/Ne. As expected, unilateral temporal lesions did not interact with behavioral and electrophysiological correlates of error processing.

Back to Main

Go to Main Abstract page

© 2002 Elsevier Science (USA). All rights reserved.

Back to Main NeuroImage Human Brain Mapping 2002 Meeting

Order to appear: 721

Hand cortical representation areas reorganization induced by stroke: an MEG study Franca Tecchio , Filippo Zappasodi , Patrizio Pasqualetti , Carlo Salustri , Marco Pascoli , Matilde Ercolani , Fabrizio Vernieri , Paolo Maria Rossini IESS-CNR, Roma AFaR-Dip di Neuroscienze, Osp. Fatebenefratelli, Roma IRCCS "S. Giovanni di Dio-Fatebenefratelli", Brescia Neurologia Clinica, Università Campus Biomedico, Roma Subject: Neurology Abstract Understanding of the cerebral mechanisms underling functional recovery in patients affected by stroke is of maximal importance in relation to the high incidence of this disease as cause of chronic and severe disability in the western countries. This understanding is constituted by two sides: deeper evaluation of the effects of the cerebrovascular attack, and the relation between the following cerebral reaction with the patient clinical picture. Magnetoencephalographic (MEG) evaluation of the cerebral responses to the separate electrical stimulation of left and right median nerves has been performed, in 104 patients affected by monohemispheric stroke within the middle cerebral artery territory in chronic stage. Morphological characteristics of the somatosensory evoked fields (SEF) and the topography of the cortical activated generators has been evaluated, in terms of absolute values in both the hemispheres and inter-hemispheric asymmetries. A 3-level score has been defined for the evaluation of the lesion volume and site. Clinical status as been evaluated by National Institute of Health Stroke Scale (NIH) and Bartel Index scores (BI) at the moment of the event and at the MEG recording time. Statistical evaluation of the parameters describing response morphology, latency, position and strength of the cortical activated generators and their interhemispheric asymmetries has been performed in order to define the relation between the cortical functional activation properties and the anatomical and clinical situation of the patients, with particular focus on the recovery level. Results non only provide indications of plasticity phenomena characteristics associated to the brain reaction to the lesion, but indicate different activated region contributions to the cerebral processing of the somatoensory information and their relation with motor functionality. Fig. Superimposition of the all recording channels in the [–20, 100] ms time interval from the two hemispheres, showing SEF abnormalities in two paradigmatic patients with subcortical (deep) or pure cortical lesions. MRI/MEG integration shows acticated sources posiotion in relation to anatomical strucutres. A. Patient affected by a large lesion involving globus pallidus, putament and internal capsule of the right hemisphere. SEFs are strongly depressed from the AH and enhanced from the UH. B. Patient affected by a parietal cortical lesion of the right hemisphere. SEF enhancement from the AH, and abnormal wave shape from the parietal region of the affected hemisphere. Asymmetrical shift of the ECD localization in the AH was compatible with a displacement due to mass effect from perilesional oedema.

Back to Main

Go to Main Abstract page

© 2002 Elsevier Science (USA). All rights reserved.

Back to Main

NeuroImage Human Brain Mapping 2002 Meeting

Order to appear: 722

Reorganisation of specialised auditory networks in a patient with progressive aphasia Stephanie Clarke , Anne Bellmann Thiran , Michela Adriani , Eleonora Fornari , Maeder Philippe , Reto Meuli , Mary Bach , Jean-Philippe Thiran Division de Neuropsychologie, CHUV, Lausanne, Switzerland Service de Radiodiagnostic et Radiologie interventionnelle, CHUV, Lausanne, Switzerland Laboratoire de Traitement des Signaux, EPFL, Lausanne, Switzerland Subject: Neurology Abstract A 60 year old woman with progressive aphasia and left temporal atrophy, was investigated longitudinally including: i) morphological analysis; ii) fMRI; and iii) neuropsychological evaluation. After the first investigation donepezil (10 mg) was introduced. The degree of regional anatomical degeneration was computed by studying morphological changes in two anatomical MR exams (September 2000, October 2001). The images have been put in geometrical correspondence using a non-rigid registration algorithm based on the optical flow method, and the resulting displacement field between both images has been analysed to show anatomical changes of the cortex. For fMRI investigation (1.5 Tesla Siemens Vision), we used a paradigm developed in our group and validated with 18 control subjects1 investigating specific and non-specific processing of auditory information and involving abilities that were not impaired in our patient. Three conditions were used: a) active comparison of sound positions simulated with ITD; b) active identification of environmental sounds; and c) rest. Activation patterns were analysed using SPM99. Results in normal subjects showed non specific activations (whatever auditory stimulation versus rest), but also specific regions of activation for recognition and for localisation: Middle temporal gyrus and precuneus bilaterally and the posterior part of left inferior frontal gyrus were more activated in sound recognition than localisation. The lower part of inferior parietal lobule and posterior parts of middle and inferior frontal gyri were more activated (bilaterally) in sound localisation than recognition. The patient had two fMRI examinations, in September 2000 and October 2001. Results of the patient and the control population were compared in terms of cluster location and number of pixels within clusters. At the first investigation, the patient had a normal activation pattern. At the second investigation, we found a global bilateral lowering of activation in each condition; recognition and localisation still activated partially the left atrophic temporal lobe when compared to rest, but there was no more specific activation for the recognition task in the left

Back to Main

temporal lobe. Moreover, there was a reorganisation of specialised networks outside the atrophic temporal area in both hemispheres. Neuropsychological examination, including auditory testing, showed stable performance between May 2000 and October 2001. Briefly, the patient presented selective deficit of word retrieval while other language parameters, episodic and semantic memory, visual gnosis, praxias, executive functions, as well as auditory localisation and recognition (see 2 for a description of testing procedure) were within normal limits. In conclusion, our results show a contrast between stabilisation of performance and modification of cerebral activation patterns. This modification predominates in the left atrophic temporal lobe, but suggest also more widespread and bilateral reorganisation of specialised networks. References 1 Maeder, P., Meuli, R., Adriani, M., Bellmann, A., Fornari, E., Thiran, J.-P., Pittet, A. & Clarke, S. Neuroimage, 14 (2001) 802-816 2 Clarke, S., Bellmann, A., Meuli, R.A., Assal, G. & Steck, A.J. Neuropsychologia 38 (2000) 797-807

Go to Main Abstract page

© 2002 Elsevier Science (USA). All rights reserved.

Back to Main

NeuroImage Human Brain Mapping 2002 Meeting

Order to appear: 723 Presurgical fMRI: usefulness as percieved by the clinicians Ann Tieleman , Karel Deblaere , Pieter Vandemaele , Jacques Caemaert , Paul Boon , Luc Defreyne , Eric Achten Department of Radiology, UZG, Ghent, Belgium Department of Neurosurgery, UZG, Ghent, Belgium Department of Neurology, UZG, Ghent, Belgium Subject: Neurology Abstract Aim: to evaluate the value of fMRI on therapy management in patients with focal brain lesions. Patients and Methods The medical records of 31 consecutive patients aged between 9 and 64 years, with focal brain lesions referred for fMRI were reviewed. The main reason for referal was that the planned interventional procedure could result in severe functional deficit if adjacent eloquent functional cortex was removed or damaged during surery. For 9/31 subjects, hemispheric dominance was an additional issue. Whole brain EPI scanning was used for fMRI at 1.0 Tesla in 24 patients and at 1.5 Tesla in 7 patients. A variety of motor and language tasks were used in the individual patient, depending upon the localization of the lesion. Data treatment: All data were processed using SPM99. Reported issues: quality of SPM's, proximity and hemispheric dominance (if applicable). We retrospectively conferred with the referring clinicians how often and in which way these fMRI studies contributed to the planning of neurosurgical procedures. Results In total, we conducted 38 motor activation paradigms and 35 language activation paradigms. 9/73 experiments (8.1%) performed in 5 patients were degraded beyond clinical use by artifacts of head motion. Nevertheless, because of the use of multiple paradigms, useful functional activation from motor and/or language tasks was present for all patients but one. After questioning the referring clinicians, the results of the fMRI studies yielded used clinical information in 26 of the 31 patients. In 5, the fMRI results were considered redundant to clinical or structural MRI information, but language lateralisation was considered a bonus in 2 of these. In 16 patients the sensorimotor cortex was identified relative to the lesion. In 5 patients the lesion to activation distance was more than one gyrus and surgery was deamed without risk. Surgery was performed in 4/5 and neurological deficit resulted. In 12 patients the activated regions were immediately adjacent (less than one gyrus) or in the lesion. Surgery was considered too risky in 11. For one patient, surgery planning was adapted to the knowledge acquired and no postoperative deficit resulted. Of 18 patients with lesions in or near possible language related areas , activated language cortex was present in close vicinity to the lesion in 12, implying serious surgical risks. Nevertheless, surgery was tailored to the fMRI results in 3, but resulted in a serious postoperative deficit in one. One patient had a

Back to Main

lesion in the left angular gyrus, but showed right sided activation with a semantic decision task. Surgery was uneventful.The remaining patients had lesions outside the dominant hemisphere and also had uneventful surgery. Conclusion This study indicates that fMRI results did indeed help our surgeons to assess possible surgical risks. In only 3/31 patients, one with a small right sided frontal cavernous hemangioma, one with what proved to be right sided mesial temporal glioses, and one due to technical failure, did elective fMRI not really contribute to the surgical decision making. References 1.E.Achten, G.D.Jackson, J.A.Cameron, et al. Radiology 1999; 210:529-538. 2.Dymarkowski, S.Sunaert, S.Van Oostende, et al. Eur.Radiol.1998; 8:1573-1580. 3.K.Papke, T.Hellmann, B.Renger, et al. Eur. Radiol 1999; 9(2):211-220.

Go to Main Abstract page

© 2002 Elsevier Science (USA). All rights reserved.

Back to Main

NeuroImage Human Brain Mapping 2002 Meeting

Order to appear: 724

Neurophysiological and metabolic evaluation of the organization of cerebral sensorimotor areas in stroke patients: an MEG/fMRI study Franca Tecchio , Cosimo Del Gratta , Filippo Zappasodi , Fabrizio Vernieri , Claudia Altamura , Francesco Tibuzzi , Vittorio Pizzella , Kathya Torquati , Antonio Ferretti , Armando Tartaro , Gian Luca Romani , Paolo Maria Rossini ¶ IESS-CNR, Roma, Italy AFaR- Dip di Neuroscienze Osp. Fatebenefratelli, Roma, Italy Dpt. Of Clinical Sciences and Bioimaging and ITAB, University of Chieti, Italy INFM, L’Aquila, Italy ¶Neurological Clinic Univ.Campus Biomedico, Roma, Italy Subject: Neurology Abstract Stroke is probably the commonest cause of chronic and severe disability in the western countries. For this reason the focus of research is nowadays on the analysis of mechanisms subtending the vascular accidents and the possible functional recovery and rehabilitation. In the present study stroke effects are considered on the organization of the cortical districts controlling sensorimotor functions of the hand, by magnetoencephalographic (MEG) and functional magnetic resonance imaging (fMRI) evaluation in patients suffering by monohemispheric stroke within the middle cerebral artery territory. MEG evaluation of the cerebral responses to the separate electrical stimulation of median nerve, thumb and little finger has been performed. Morphological characteristics of the somatosensory evoked fields (SEF) and the topography of the cortical activated generators has been evaluated, as absolute values in both hemispheres and in terms of inter-hemispheric asymmetries. The same patients were involved in an fMRI study, in which they were electrically stimulated at both median nerves separately, and were asked to perform voluntary movements with both hands separately. Preliminary results show the presence of cerebral plasticity phenomena. Brain areas, usually not reached by a dense input from hand and finger sensory receptors, were identified acting as somatosensory 'hand' centers, while the “usual” ones were functionally disconnected. This involvement of unusual brain areas was observed with both techniques. The cerebral hemodynamic local status was evaluated through the relation between functional neurophysiologic activation and the local cerebral blood flow increase: in the case of preserved neuronal response to sensory stimulation, and absence of activation as characterized by fMRI (see Fig.), we could deduce that the local cerebral vasomotor reactivity was impaired. Fig: high: Superimposition of all the MEG signals recorded from the parietal region in the affected and unaffected hemispheres, in the (–20, 100) ms time interval, time 0 indicating the electrical stimuli of the contralateral median nerve. Although decreased from the affected, the response is clearly identified in both

Back to Main

Back to Main

Back to Main

NeuroImage Human Brain Mapping 2002 Meeting

Order to appear: 725

Pain induced cerebral perfusion changes in persistent vegetative state: a O-15-H2O PET study J. Kassubek , F. D. Juengling , T. Els , M. Herpers , J. Spreer , C. H. Lücking Dept. of Neurology, University-Hospital Freiburg, Germany Division of Nuclear Medicine, University-Hospital Freiburg, Germany Division of Neuroradiology, University-Hospital Freiburg, Germany Subject: Neurology Abstract Introduction: Survivors of prolonged cerebral anoxia suffer various degrees of global cerebral impairment and often remain in a so-called persistent vegetative state (PVS). Although a deeper insight into the way these patients feel external stimuli is of high relevance for their everyday care, it is unclear to which degree central pain processing is preserved in PVS. In this study, PVS patients were investigated by PET to analyze central processing of peripheral pain. Methods: The study was approved by the internal review board / local ethics committee, the experiments were performed in accordance with the Helsinki Declaration of 1975. Seven patients remaining in PVS due to prolonged cerebral hypoxia were investigated. We performed functional PET of the brain using 15Olabelled water and an electrical nociceptive stimulus applied to the left forearm (6 baseline studies, 6 stimulus studies). Additionally, in all patients a brain metabolism study using 18F-FDG was performed. For morphological imaging, multi-sequence MRI was acquired, including a 3-D data set (MP-RAGE). Both PET studies were analyzed by means of Statistical Parametric Mapping (SPM99) and coregistered to individual 3-D MRI. Results: Pain induced activation (hyperperfusion) was found in the posterior insula, postcentral gyrus, and posterior cingulate cortex contralateral to the stimulus and in the insula ipsilateral to the stimulus (p<0.001). Structural MRI showed general cortical atrophy of various degrees. FDG-PET showed a general severe hypometabolism with maximum in the precuneus bilaterally, similar to previous findings (1). Conclusion: Cerebral areas which could be shown to be activated in central pain processing in normal subjects (2)

Back to Main

could be demonstrated to be activated in PVS patients as well. Unexpectedly, thalamic activation could not be found. The insula (bilaterally) seems to play a key role in central pain processing in PVS. References: (1) Laureys S, Goldman S, Phillips C et al. Neuroimage 1999; 9 (4): 377-382 (2) Tölle TR, Kaufmann T, Siessmeier T et al. Ann Neurol 1999; 45 (1): 40-47

Go to Main Abstract page

© 2002 Elsevier Science (USA). All rights reserved.

Back to Main

NeuroImage Human Brain Mapping 2002 Meeting

Order to appear: 726

Impairments in selective attention and anosognosia evaluated with the Counting Stroop Test in patients with mild Alzheimer's disease M. de Leonni Stanonik , R. Kent Hutson , Karl F. Hubner , Gary T. Smith , Charles A. Licata , Shannon K. Campbell , Kenneth A. Rule , John H. Dougherty Jr. Department of Radiology Cole Neuroscience Center University of Tennessee Medical Center, Knoxville Subject: Neurology Abstract Alzheimer's disease (AD) is often unrecognized or misdiagnosed in its mildest stages. PURPOSE: We investigated changes in brain activation in patients with mild AD using functional MRI. METHODS: 23 subjects - 10 patients with probable AD (NINCDS-ADRDA criteria) and 13 cognitively normal agematched volunteers were examined. The Stroop Test-a method of studying selective attention and executive functions was adapted. Subjects see color words (ex:blue) printed in either the color the word refers to or another color. When the print color is different from the color word, subjects take longer to name the print color than when the word and the color match. The Counting Stroop, a Stroop Testvariant specialized for functional imaging uses blocks of neutral and incongruent words. Incongruent words consist of number names (one, two, three, four) written 1 to 4 times in a column. Ex: neutralcat,cat,cat,cat vs. incongruent-three,three,three,three. This activation task triggers the neurobiological substrates responsible for affording humans to choose biologically important stimuli successfully. The Stroop Test consisted of 4 incongruent and 4 neutral blocks. Image acquisition was performed with a 1.5 Tesla MR scanner. High resolution anatomic images were obtained with a T1-weighted 3D SPGR pulse sequence. MR data were analyzed with the SPM99 software. Anosognosia severity was measured using an Anosognosia Questionnaire. RESULTS: While there were individual differences, the group with presumed early AD invariably showed significant absence of activation in the Anterior Cingulate Cortex (ACC). Direct comparisons showed that the ACC activity was higher in the control group. Interestingly, in the AD group activations occurred in the medial frontal lobe (bilaterally), the inferior frontal lobe (bilaterally), the insula (bilaterally), the left caudate nucleus, the thalamus, the medial and inferior occipital lobe, and the right posterior parietal lobe. The normal group showed significantly increased activity in the ACC bilaterally in addition to the right dorsolateral prefrontal cortex, the superior parietal lobule, the inferior parietal lobule, the middle and inferior occipital lobe, and the inferior orbital cortex. Comparisons showed significant differences in the left dorsolateral prefrontal cortex (mild AD), and ACC and posterior parietal cortex bilaterally (normal group). In the assessment of anosognosia, 6 out of 10 AD patients showed moderate to severe anosognosia (mean difference 0.87, p<0.02). Furthermore, a

Back to Main

significant correlation was found between the presence of anosognosia in patients with mild AD and the absence of significant activations in the ACC (r=.85, p<.01). MRI anatomical scans of patients with mild AD did not show significant focal lobar atrophy. CONCLUSION: The absence of activity in the ACC was associated with impairments in selective attention in mild Alzheimer’s group, but not in the control group. Furthermore, correlation of the high anosognosia scores and functional hypoactivity of the ACC was highly indicative of anosognosia in mild AD patients. This is a preliminary study using fMRI to show differences in the ACC between mild AD patients who are aware of AD symptoms and those who are not. This finding suggests that anosognosia may be the result of a specific abnormality of selective attention in this patient population.

Go to Main Abstract page

© 2002 Elsevier Science (USA). All rights reserved.

Back to Main

NeuroImage Human Brain Mapping 2002 Meeting

Order to appear: 727

Ipsilaterised Prefrontal Cortical Activation in Tonic Cold Pain: Yoko Hoshi , Masato Tanosaki , Kazutoshi Shinba , Yosinobu Iguchi , Andrew CN Chen Dept. of Integrated Neuroscience, Institute of Psychiatry, Tokyo, Japan Human Brain Mapping and Cortical Imaging Laboratory, Aalborg University, Denmark Subject: Neurology Abstract [Background] The prefrontal cortex is closely related to chronic pain and experimental noxious stimulation as imaged by recent PET/fMRI studies. However, the prefrontal cortex encompasses a large and heterogeneous set of areas and further study on the specific regional activation is of great significance to understand its role in pain processing. This study employed a tonic pain model by the classical cold pressor test (CPT), which is known to induce both high sensory intensity and emotional aversion. This model may elucidate the affective-motivational and cognitive components, a major role of the prefrontal cortex, in human pain. [Methods] Subjects were 10 healthy right-handed males (mean 29.5 years). CPT (at 2 ± 1 °C) was conducted with the subject immersed their hands, either right (Rh) or left (Lh) hand in a counter-balanced order. Subjects were asked to rate the pain intensity covertly and to endure the pain as long as one can (ceiling time: 3 min). Near-infrared spectroscopy was employed for optical imaging. A multi-channel NIRS imaging system (OMM-2000, Shimadzu Co.) was employed. 6 pairs of illuminating and detecting light guides were placed on the forehead. Measurement was started about 5 minutes before the test and was continued until the end of the test. We compared the Rest condition from the Test (CPT) condition. Oxy-Hb was analysed as an indicator of CBF. Changes between 1 and 2 minutes (peak pain) after the beginning of each task were compared. Statistical analysis by Two-Way (stimulated hand by recording site) repeated measure ANOVA was conducted. Post hoc comparison of means by Tukey test was set at P<.05 for significance. [Results] 9 subjects (one could not endure 3 min) were included in this report. Subjects rated the over-all CPT at 8 (very strong pain) of the 10 scale. For the group, the main findings were following: 1. Similar total magnitude on the prefrontal activation between the stimulation hands (Lh: 29.4 mM vs. Rh: 22.4 micro-M; F=.809, p=.395). 2. For the effect of both hands, significant differences across channels (F=3.792, p=.007). Largest at Ch-1 (6.08 micro-M) and Ch-6 (5.84 micro-M). 3. Significant hand stimulation by channel effect (F=5.606, p<.001), as seen in Fig.. 1. 4. Within the Lh stimulation, Ch-6 (9.64 micro-M) significantly larger than others. 5. Within the Rh stimulation, Ch-1 (8.38 micro-M) significantly larger than the rest. 6. Significantly larger activation in Ch-6 and Ch-5 for Lh vs. Rh stimulation; but no difference in Ch-1 and Ch-2 for Rh vs. Lh stimulation. [Discussion and Conclusion] The finding of ipsilateral dorsal lateral prefrontal activation in response to human pain has never been reported before. This lateralized prefrontal cortical activation is highly differential from the sensori-motor somatotopic orgnisation as reported in most PET/fMRI

Back to Main

Back to Main

Back to Main

NeuroImage Human Brain Mapping 2002 Meeting

Order to appear: 728

Topographic Effects of Event-Related fMRI Responses to Nonpainful vs. Painful Intramuscular Electrical Stimulation Applied to the Hand David M Niddam

, Lars Arendt-Nielsen , Andrew CN Chen , Y-T Wu , T-C Yeh , J-C Hsieh

Human Brain Mapping and Cortical Imaging Laboratory, Center for Sensory-Motor Interaction, Aalborg University, DK-9220, Aalborg, Denmark Integrated Brain Research Laboratory, Dept. of Medical Research and Education, Taipei Veterans General Hospital, 201, Taipei 11217, Taiwan Subject: Neurology Abstract Aims: The current study is the first to use event-related fMRI to investigate the cerebral processing of pain from muscles. The aims were to (1) validate and compare the findings with previous neuroimaging reports on pain from muscle and skin and (2) compare the hemodynamic response functions from nonpainful and painful stimulus levels. Methods: Whole head fMRI were acquired from 6 subjects. Non-painful and painful electrical stimulation (1 ms square wave pulse) was given within abductor pollicis brevis of the left hand. Stimulation was delivered every 12 seconds in 4 runs each consisting of 24 randomized stimuli. Eight whole head scans were acquired between stimulations. Data were analyzed using statistical parametric mapping (SPM99) and the number of voxels above the statistical threshold were extracted for each responding structure together with the hemodynamic response function for the local maxima. Results: Of the areas that responded to both stimulus intensities (bilateral: SII, inferior parietal, middle frontal; contralateral: insula, superior temporal gyrus, SI, thalamus, claustrum) pain resulted in a larger spatial extend than no-pain. Areas exclusively responding to painful stimuli included prefrontal, anterior and posterior cingulate, premotor, posterior parietal, and cerebellar regions. The activity at both stimulus levels included the most consistently responding areas from previous reports on processing of cutaneous pain. Additionally, a larger number of ipsilateral responding areas than those in previous reports were found in the painful condition. The time-activity curves from painful stimulation almost exclusively showed activation patterns while for non-painful stimulation the number of activations and deactivations were evenly distributed in the contralateral hemisphere but prevalence existed for deactivations in the ipsilateral hemisphere. Conclusion: The whole head pattern of activity in response to muscle pain closely resembled that from cutaneous pain. The painful intensity increased the number of bilateral structures responding. Further on, different dynamics were observed between contra- and ipsilateral hemispheres for non-painful stimuli but

Back to Main

not for painful stimuli. Acknowledgment: This study was supported by the Danish National Research Foundation as well as National Science Council (892314B075054, 892314B075159), Taiepi-Veterans General Hospital (89362, 89402, 89400) and Ministry of Education (89BFA221401) of Taiwan.

Go to Main Abstract page

© 2002 Elsevier Science (USA). All rights reserved.

Back to Main NeuroImage Human Brain Mapping 2002 Meeting

Order to appear: 729

Mapping of Differential Topographic Cerebral Processing of Subcutaneous vs. Intramuscular Inputs at the Hand David M. Niddam, Lars Arendt-Nielsen, Andrew CN Chen Human Brain Mapping and Cortical Imaging Laboratory, Center for Sensory-Motor Interaction, Aalborg University, DK-9220, Aalborg, Denmark. Subject: Neurology Abstract Aims: To compare somatosensory evoked potentials (SEP) from skin and muscle using identical stimulus methods. Methods: SEPs from subcutaneous (SC) and intramuscular (IM) electrical stimulation at the thenar site of the hand were examined at three stimulus rates (0.2 Hz, 0.5 Hz and 2.0 Hz) and two intensities (non-painful and painful) by the same type of needle electrodes. Global field power analysis and visual inspection of the waveforms and topographies were used for spatio-temporal isolation of the maximas. For both stimulus intensities a two-way (stimulus method vs. rate) repeated measures ANOVA was carried out to analyze the isolated peak latencies and amplitudes. Results: The two stimulation methods resulted in similar topographies. These were early contralateral bipolar patterns, a late bi-temporal negativity and a vertex positivity (see Fig. 1). The earliest components (0-35 ms) were poorly defined in the IM condition compared to the clear patterns in the SC condition. Four of twelve components (F4/N65, T4/N140, Fc6-C4/N140 and Cp2/P270) differentiated skin and muscle activation in the painful condition, compared to one component (F4/N85) in the non-painful condition. Furthermore, the amplitude of these components increased more at slower stimulus rates after IM than SC stimulation. Finally, in the painful condition 6 components showed a higher amplitude after 0.2 Hz stimulation compared to 0.5 Hz stimulation. In the non-painful condition no differentiation was observed between these two stimulus rates. Conclusion: The different response to variation in stimulation intensity and stimulation rate suggests that cerebral processing of input from skin and muscle are not identical although the same brain structures most likely are activated. This study was supported by the Danish National Research Foundation

Go to Main Abstract page

© 2002 Elsevier Science (USA). All rights reserved.

Back to Main NeuroImage Human Brain Mapping 2002 Meeting

Order to appear: 730

Dissociation of motor motor lateralization between WADA test and functional MRI Roland Beisteiner , Rupert Lanzenberger , Gerald Wiest , Alexander Geissler , Markus Barth , Josef Bruck , Helmut Ringl , Christian Wöber , Andreas Gartus , Christoph Baumgartner Department of Neurology, General Hospital and University of Vienna, Währinger Gürtel 18-20, A-1090 Vienna, Austria Department of Radiology, General Hospital and University of Vienna, Währinger Gürtel 18-20, A-1090 Vienna, Austria Subject: Neurology Abstract We report the first case showing a clear discrepancy between the induction of arm paresis by the intracarotid amobarbital WADA test(1) and functional lateralization of motor arm function by fMRI in a patient with a longstanding extensive left telencephalic lesion. When injecting the left carotid artery, counting was not arrested, speech remained fluent and no change in motor function of the mildly preparetic right arm was observed with 2 tries. Using the same amytal ampulla for contralateral testing yielded almost simultaneously speech arrest and contralateral hemiplegia. FMRI measurements were carried out on a 3 Tesla MR using a GE EPI sequence (TE_eff 55.5 ms, TR 4000 ms, 128*128 matrix, voxel size 1.8 x 1.8 x 3 mm, 25 adjacent axial slices). FMRI risk maps were generated as described earlier(2-4) and a classical SPM99 analysis was performed. Both analysis techniques showed clearly contralateral MI activation (figure). Additional motor evoked potentials and somatosensory evoked potentials confirmed lesioned but not disrupted sensory-motor pathways in the left hemisphere. Results were initially interpreted as neuroplastic shift of intrinsic left hemisphere functions to the right brain with the possible consequences of extended resection of presumably epileptogenic tissue. Due to the fMRI results a rather restrictive neurosurgical approach was eventually selected. A possible reason for the WADA test outcome may be vascular abnormalities seen on the angiogram. We conclude that missing contralateral motor effects in damaged brains may occur with WADA testing but are not per se indicative of a neuroplastic lateralization change. Rather the situation should be checked by fMRI and neurosurgical consequences should be drawn cautiously. Legend Slices showing MI activation (arrows) for left and right hand movements. The first three images from left show SPM results on original functional EPI images. On the right a functional risk map is shown which extracts only most reliably activated voxels. Note stronger activation with healthy left hand movements, no ipsilateral activation with right hand movements but small ipsilateral MI activation with left hand movements (slice 3) located almost identically with the right hand spot. References 1.) Wada J. Igaku to Seibutsugaku (Medicine and Biology) 1949,14: 221-222. 2.) Edward V, Windischberger C, Cunnington R, et al. Human Brain Mapping 2000;11(3):207-213. 3.) Beisteiner R, Lanzenberger R, Novak K, et al. Neuroscience Letters 2000;290:13-16. 4.) Beisteiner R, Windischberger C, Lanzenberger R, et al. NeuroImage 2001;13:1016-1026.

Back to Main

Go to Main Abstract page

© 2002 Elsevier Science (USA). All rights reserved.

Back to Main

NeuroImage Human Brain Mapping 2002 Meeting

Order to appear: 731

Brain Processing of Cool and Warm Perceptions: EEG Spectral Topography and Coherence Analyses Peng Fei Chang, Lars Arendt-Nielsen, Thomas Graven-Nielsen, Andrew CN Chen Human Brain Mapping and Cortical Imaging Laboratory, Center for Sensory-Motor Interaction, Aalborg University, Fredrik Bajers Vej 7 D-3, DK-9220 Aalborg, Denmark. Subject: Neurology Abstract Aims: The perceived qualities of warm and cool stimulations are different, but little is known about the central processing of somatic warm and cool stimuli. This study investigated the EEG activation to somatic warm and cool stimulation. Materials and methods: Thirteen male volunteers participated in two sessions of experiment in counterbalanced order, warm (40-43oC) and cool (11-15 oC) water stimulations. VAS was used for the assessment of warm and cool sensations. Continuous EEG data recorded in 1) baselines, 2) warm/cool stimulation, 3) post-warm/post-cool stimulations were compared and analysed with respect to EEG topography, EEG power spectra and coherence. Results: Similar overall EEG topographic patterns were found associated with both warm and cool sensations. The EEG powers in theta, alpha-1 and alpha-2 bands over the central parietal and occipital lobes decreased significantly during cool stimulation compared to baseline and post-cool stimulation. No significantly changes in EEG activation were found during warm stimulation, even though a similar decrease of alpha-1 activity. During cool stimulation, the EEG coherence in alpha-1 and alpha-2 bands in the contralateral hemisphere (between frontal, temporal, parietal and occipital areas) increased significantly compared to the baseline. However, warm stimulation did not significantly increase the EEG coherence except for the F4-T4 pairing. There was no significant difference in EEG activation was found between the warm and cool stimulations. Highly individual consistency in EEG changes between the warm and cool stimulations implicated that the degrees to which the EEG activation to cool and warm stimulations were different, regardless of no statistical significance. Conclusion: Cool and warm stimulations on the same site evoke a similar EEG topography. The same neural network may be involved in the central processing of cool and warm stimuli. The degrees to which the EEG changes may reflect the different emotional response associated with cool and warm stimulations.

Back to Main

Back to Main

Back to Main

Fig. 2. The EEG coherence in alpha-1 (A) and alpha-2 (B) activities significantly increased at the contralateral hemisphere during cool stimulation. The warm stimulation produced a significant increase of coherence in alpha-2 activities (C) only in the co

Go to Main Abstract page

© 2002 Elsevier Science (USA). All rights reserved.

Back to Main

NeuroImage Human Brain Mapping 2002 Meeting

Order to appear: 732

Differential Cerebral Responses to Auditory Aversive Arousal and Muscle Pain: EEG Topography and Power Spectra. Peng Fei Chang, Lars Arendt-Nielsen, Thomas Graven-Nielsen, Andrew CN Chen Human Brain Mapping and Cortical Imaging Laboratory, Center for Sensory-Motor Interaction, Aalborg University, Fredrik Bajers Vej 7 D-3, DK-9220 Aalborg, Denmark. Subject: Neurology Abstract Aims: Quantitative EEG measurement has been used to assess human pain, and some characteristic EEG activations have been proven to be related to the cerebral processing of human experimental pain. As the human pain is a complex symptom composed of cognitive and emotional dimensions, it is necessary to discriminate the differential effects of arousal, attention and emotion associated with pain on the EEG activation. The aim of this study is to investigate the differential EEG effects of arousal and pain in man. Materials and Methods: Auditory aversive arousal stimulation was delivered by playing noise (80 db for 2 min) recorded in cassette by rubbing balloon, and the muscle pain stimulation was produced by injection of hypertonic saline (5.8%) into the left brachioradialis muscle in 12 male subjects (mean age: 27, range: 21-38 years). Two sessions of experiments were randomly arranged in separate days. A arousal and unpleasantness rating form, and VAS were used as psychophysical assessment. 31-channels EEG data acquired during baseline, stimulation (arousal and pain) and post-stimulation were compared quantitatively. The EEG changes between the baselines and task trials (pain or arousal) were analyzed by two-way RM ANOVA. Ressults: The auditory aversive noise induced moderate arousal and unpleasantness, and the intramuscular injection of hypertonic saline evoked moderate pain with unpleasantness. The muscle pain induced significant decrease of alpha-1 activity at T6, Pc2, Pc6, Pz, P4, O2 and Poz sites compared to the baseline, but the auditory noise did not produce any significant EEG changes compared to the baseline. The alpha-1 EEG powers at P3, Pz, P4, Pc1, Pc2 and Poz, and alpha-2 at Pz and Poz sites significantly decreased during pain compared to the aversive noise stimulation. Conclusion: Muscle pain and auditory aversive arousal produced significantly different EEG activation. The muscle pain induced EEG activation is likely related to the nociceptive inputs but not general arousal per se. Acknowledgement: This study was supported by the Danish National Research Foundation

Back to Main

Back to Main

Fig. 2. The 12 VAS profiles induced by injection of hypertonic saline into the left brachioradialis muscle

Back to Main

Go to Main Abstract page

© 2002 Elsevier Science (USA). All rights reserved.

Back to Main

NeuroImage Human Brain Mapping 2002 Meeting

Order to appear: 733

Motor cortex functionality in Alzheimer’s Disease: a Transcranial Magnetic Stimulation study Patrizio Pasqualetti , Florinda Ferreri Maria Rossini

, Flavia Pauri , Rita Fini , Gloria Dal Forno

, Paolo

AFaR-Dept. of Neuroscience, Fatebenefratelli Hospital, Isola Tiberina, Rome, Italy Dept. of Neurology, University Campus Biomedico, Rome, Italy Dept. of Clinical Neurology, University "La Sapienza", Rome, Italy Dept. of Neurology, The Johns Hopkins University School of Medicine Subject: Neurology Abstract Alzheimer s Disease (AD) is a neurodegenerative process which progressively affects distinct neuronal pools and circuitries subtending cognitive and affective functions. Motor function impairment is a late event in the natural disease progression, manifesting with apraxia, myoclonus, and pyramidal and extrapyramidal dysfunction. Two main features of the motor cortex that could explain such a delayed involvement are scarce burden of neuropathological changes in motor cortex compared to other cortices and a rich dendritic arborization plastically compensating for neuronal loss. The aim of the present investigation was to test motor function by examining specific neurophysiologic parameters such as excitability thresholds, areas and volumes of two upper extremity muscles via Transcranial Magnetic Stimulation in early AD patients, compared to age-matched Controls. A global inter-hemispheric symmetry of the motor cortex parameters was found in the whole sample (p=0.200) and without differences between controls and patients (p=0.641). Conversely, the two groups clearly differed with respect to the studied muscles cortical representations (p=0.012), indicating overall hyperactivation in AD. The centers of gravity of the cortical maps are expressed in a Cartesian system with respect to the hot-spot (the position with largest amplitude). The hot-spot is normally localized in the middle of the map. A deviation from this pattern is measured by the distance between the hot-spot and the center of gravity. If they are coincident, a doubly symmetrical distribution (on both axes) is expected, such as in bivariate Gaussian distributions. A slight medial asymmetry was found in the Controls, while in AD patients we observed a significant combined medial and frontal shift. A bidimensional separation between groups was evident in the multivariate test (p=0.032), but not univariately in the two dimension (p=0.171 for x-axis, p=0.059 for y-axis). In other words, in Controls the weight of the medial excitable sites was slightly heavier than that of the lateral sites, while the hot-spot was statistically coincident with the center of the map in terms of antero-posterior representation. In AD, we found a further medial shift and a clear potentiation of the frontal area with respect to parietal sites. Functionally this could facilitate recruitment of circuitries larger and more widely distributed than normal, allowing longer preservation of

Back to Main

motor programming and execution, despite disease progression Our results confirm the hypothesis of motor cortex hyper-excitability in early AD, possibly explained by dysregulation of intracortical inhibitory circuitries modulated by cortico-cortical and transcallosal connections. Hyperexcitability and fronto-medial migration of the excitable areas may be explained by recruitment and integration of the inhibitory frontal area into the excitatory motor cortex, leading to enlargement of the latter and frontomedial shift of its center of gravity. Such changes are compatible with a functional interpretation: the increased excitability facilitates the recruitment of circuitries larger and more widely distributed than normal, allowing longer preservation of motor programming and execution despite disease progression.

Go to Main Abstract page

© 2002 Elsevier Science (USA). All rights reserved.

Back to Main

NeuroImage Human Brain Mapping 2002 Meeting

Order to appear: 734

Language dominance assessment in the temporal lobe with a fMRI reading paradigm: results in normal subjects and postsurgical TLE patients Karel Deblaere , Walter Backes , Paul Hofman , Pieter Vandemaele , Paul Boon , Jaap Troost , Kristl Vonck , Peter Boon¶, Jan Vermeulen||, Ann Tieleman , Jan Wilmink , Albert Aldenkamp , Eric Achten Neuroradiology, UZG, Ghent, Belgium Neuroradiology, University Hospital Maastricht, The Netherlands Neurology, UZG, Ghent, Belgium Neurology, University Hospital Maastricht, The Netherlands ¶Medical Psycholgy, University Hospital Maastricht, The Netherlands ||S.E.I.N Heemstede, Psychological Laboratory, The Netherlands Epilepsy Centre Kempenhaeghe, The Netherlands Subject: Neurology Abstract Purpose The aim of this study was to asses the reliability of a functional magnetic resonance (fMRI) reading paradigm in determining the language dominant hemisphere and more specific the language dominant temporal lobe. This paradigm was evaluated in both normal subjects and postsurgical temporal lobe epilepsy (TLE) patients. Patients and Methods The reading paradigm was first tested on 9 right-handed healthy volunteers (3 male, 6 female). This test was a part of study of a pre-surgical fMRI protocol on healthy subjects [2]. Subsequently the paradigm was tested on 7 post-surgical TLE patients who were seizure free after surgery (4 male, 3 female). The paradigm was a covert reading task with two conditions: reading of a meaningful text with semantic content (READ) was contrasted with reading of a text with nonsense words (NONSENSE). Epochs of the contrasting conditions were alternated 6 times; the epochs lasted 32 s (8 functional scans,TR=4 s). For functional imaging a single-shot multiple slice T2* sensitive echo planar imaging (EPI) sequence was used. The imaging parameters were TR 4 s, TE 50 ms, flip angle 90°, isotropic voxel size 3.5 mm, matrix dimensions 64 x64, 34 contiguous slices per volume, 96 volumes per run. Image postprocessing and statistical analysis were performed using the software package SPM99 (http://www.fil.ion.ucl.ac.uk).The contrast READ>NONSENSE was calculated and individual statistical results were thresholded at p<0.01.

Back to Main

Results The results of the normal subjects have been reported previously [1,2] and demonstrated task related activation in the bilateral fusiform gyrus and both the middle temporal gyrus (BA 21/22) and the anterior temporal pole (BA 38) predominantly on the left side in all subjects . Five patients had surgery in the non-language-dominant hemisphere (2 left and 3 right). In these, postsurgical fMRI showed clear lateralised and normal semantic activation in the language dominant temporal lobe which was concordant with the presurgical IAT. Two patients had a modified temporal lobectomy at the language dominant side. No activation was found with the reading paradigm in the temporal lobes. One showed no language related activation whatsoever with our paradigm, and the other only some prefrontal and parietal activation. Conclusion The above finding prompts us to investigate further the relation of semantic activation in the temporal lobe in TLE patients with seizure side. A possible hypothesis is that more widespread damage to the epileptic temporal lobe has shifted semantic activation or to different area's, or that the semantic network is now much more diffuse and hence activation more difficult to see. The relationship towards postsurgical language deficits is still under investigation and will also be subject of a prospective study to allow us to compare pre-and postsurgical fMRI results with language outcome. references 1.Achten E, Van Borsel J, Santens P, Lahorte P, Voet T (2000) fMRI of developmental stuttering: a pilot study. ISMRM Book of abstracts p.326 2.K.Deblaere, W.H.Backes, P.Hofman, P.Vandemaele, P.A.Boon, P.Boon, J.Troost, J.Vermeulen, J.Wilmink, E.Achten, A.Aldenkamp (2001) Developing a comprehensive presurgical fMRI protocol for patients with intractable TLE: results of a pilot study. Neuroimage 13; 6:S784 Aknowledgements This study is supported by grant number 99-02 of the National Epilepsy Foundation of the Netherlands

Go to Main Abstract page

© 2002 Elsevier Science (USA). All rights reserved.

Back to Main

NeuroImage Human Brain Mapping 2002 Meeting

Order to appear: 735

Voxel-based morphometry demonstrates regionally restricted basal ganglia degeneration in early stages of Huntington´s disease J. Kassubek , F.D. Juengling , T. Kioschies , K. Henkel , J. Karitzky , B. Kramer , D. Ecker , J. Andrich , C. Saft , A. Aschoff , A.C. Ludolph , G.B. Landwehrmeyer Dept. of Neurology, University of Ulm, Germany Dept. of Nuclear Medicine, University of Ulm, Germany Dept. of Neurology, University of Bochum, Germany Dept. of Radiology, University of Ulm, Germany Subject: Neurology Abstract Introduction: Huntington´s disease (HD) is a monogenetic disorder clinically characterized by progressive involuntary movements (e.g. chorea), cognitive impairment and behavioral disturbances. A neuropathological correlate of these clinical findings in HD is a widespread neuronal degeneration, macroscopically most prominent in the caudate nucleus and putamen. Correspondingly, MRI may demonstrate global, but regionally accentuated (striatal) atrophy in late stages. In this study, the technique of voxel-based morphometry was used to analyze gray matter changes in HD. Methods: Forty-four patients with the clinical diagnosis of HD based on the presence of motor signs and confirmed by genetic testing were included in the study (mean age 48.5 years, mean duration of disease 2.5 years, mean CAG repeats in the abnormal allele 45.5). All patients were in early clinical stages of HD (i.e. ambulatory, independent; stages I and II according to Shoulson et al.) Patients were clinically rated using the Unified HD Rating Scale. High-resolution volume-rendering (3-D) T1w MRI scans (MP-RAGE) were acquired. MRI data were volumetrically analyzed in comparison to an age-matched normal data base (30 subjects) by voxel-based morphometry using statistical parametric mapping (SPM99). Results: Regional decreases of gray matter density, i.e. atrophy, of high significance (p<0.001, corrected) were found. They were localized in the caudate nucleus bilaterally, the dorsal putamina, the hypothalamus, and the operculum bilaterally, furthermore in the left lobus paracentralis. With respect to the caudatum, the entire anatomical structure including caput and cauda was involved; the more ventral parts were relatively spared whereas a marked the atrophy was consistently observed in the posterior (caudal) subregions of the caudates. No significant increases of gray matter density were found.

Back to Main

Conclusions: In this first study using voxel-based morphometry in HD patients, regional brain atrophy was noninvasively mapped. Atrophy was most prominent in basal ganglia, displaying a rostrocaudal and ventrodorsal increasing gradient of volume loss in good agreement with previous post-mortem studies. In contrast to previous volumetric studies in HD [1], the most robust changes were observed in the caudate rather than in the putamen. In addition, hypothalamic alterations were marked, whereas cortical atrophy was less prominent, less widespread and less consistently observed in early stages of HD. References: [1] Rosas HD, Goodman J, Chen YI, Jenkins BG, Kennedy DN, Makris N, Patti M, Seidman LJ, Beal MF, Koroshetz WJ. Neurology 57: 1025-1028 (2001)

Go to Main Abstract page

© 2002 Elsevier Science (USA). All rights reserved.

Back to Main

NeuroImage Human Brain Mapping 2002 Meeting

Order to appear: 736

Correlation between Lesion Location and Performance on the Paced Auditory Serial Addition Test (PASAT) in Relapsing-Remitting Multiple Sclerosis Arnaud Charil , Sridar Narayanan , Keith J Worsley , Alan C Evans , Douglas L Arnold , Alain Dagher McConnell Brain Imaging Centre, Montreal Neurological Institute (MNI), McGill University, Montreal, Canada Department of Neurology and Neurosurgery, McGill University, Montreal, Canada Department of Mathematics and Statistics, McGill University, Montreal, Canada Subject: Neurology Abstract Objective To determine whether MRI-determined lesion location correlated with working memory performance as assessed by the PASAT in multiple sclerosis (MS). We hypothesized that lesions located in the dorsolateral prefrontal cortex (DLPFC), a region involved in monitoring of working memory, could preferentially be responsible for deficits on this task. Methods A total of 49 patients with clinically definite relapsing-remitting MS were chosen from a cohort of patients being followed at the Montreal Neurological Institute MS Clinic. Conventional MRI was performed the same day as the PASAT. During the task single digits are presented on an audio tape at intervals of 3 seconds, and the patient must add each new digit to that preceding. The test result is a number of correct sums out of a possible 60. Cerebral MS lesions were manually segmented using T1,T2- and proton density-weighted images, and registered into a standard anatomical space1. Each individual binary map, that is a volume with only lesion-containing voxels, was blurred using a Gaussian smoothing kernel (fwhm=10mm). This smoothing process averages the binary values of neighboring voxels in 3D space, thus increasing signal to noise ratio. The relation between PASAT scores and the probability at each lesion voxel in standard space was modeled as a simple linear regression with PASAT score as the dependent variable. The parameter of interest in these 3D regression maps was the slope of the effect of lesion probability on PASAT score. At each voxel, an estimate of the slope and its standard deviation were obtained by least squares and t-statistics values were calculated by dividing the estimated slope by its estimated standard deviation. The resulting t-statistic map tested whether, at a given voxel, the slope of the regression was significantly different from zero. The presence of significant peaks in

Back to Main

these 3D regression maps was assessed by a method based on 3D Gaussian random-field theory2, which corrects for the multiple comparisons involved in searching across a volume. According to this method, a threshold of t=5.3 corresponds to a P=0.05. Results and Discussion The group of MS patients aged 21 to 57 (mean=38, SD=7) had a PASAT score ranging from 13 to 60 (mean=43,SD=11). The presence of lesions in the left DLPFC correlated with PASAT scores (Fig.1.t=5.3, P=0.05). This is consistent with the known role of this region in working memory tasks, especially when the information has to be monitored3.

Conclusion We combined statistical and stereotaxic techniques of functional neuroimaging to demonstrate, in a group of relapsing-remitting MS patients, the role of the left DLPFC in the PASAT, a cognitive task that requires monitoring of working memory. This approach can be used to study the pathophysiology of other forms of cognitive impairment in MS. References 1-Collins D, Neelin P, Peters T, Evans AC. J Comput Assist Tomogr 1994;18:192-205. 2-Worsley KJ, Marrett S, Neelin P, Vandal AC, Friston KJ, Evans AC. Human Brain Mapping 1996;4:58-73. 3-Petrides M. Exp Brain Res 2000 Jul;133(1):44-54.

Go to Main Abstract page

© 2002 Elsevier Science (USA). All rights reserved.

Back to Main

NeuroImage Human Brain Mapping 2002 Meeting

Order to appear: 737

Voxel Based and ROI Based Statistical Analysis of PET Parameters as Guides for Surgical Treatment of Intractable Mesial Temporal Lobe Epilepsy Yoshihisa Ohta , Tadashi Nariai , Kenji Ishii , Kiichi Ishiwata , Masahiro Mishina , Kikuo Ohno Neurosurgery, Department of Brain Medical Science, Tokyo Medical and Dental University, Tokyo, Japan Positron Medical Center, Tokyo Metropolitan Institute of Gerontology, Tokyo, Japan Subject: Neurology Abstract Background and Purpose: Positron emission tomography (PET) is a useful tool to locate the epileptic focus of patients with mesial temporal lobe epilepsy (MTLE) by measuring multiple parameters of brain. However, the objective method to determine the area with abnormal parameters in each patient is need to be established with validation by the surgical outcome. In this study, we investigated patients with MTLE using PET measurement of cerebral blood flow (CBF), cerebral glucose metabolism (CMRGlc) and binding of central benzodiazepine receptor (cBDZ-R). We compared the result obtained by voxel based statistical analysis using the statistical parametric mapping (SPM) and that obtained by placing regions of interest (ROIs) on PET images in order to examine if these can offer the predictive information to foresee the surgical outcome of each patient. Methods: Eleven patients with intractable MTLE underwent PET measurement of CBF using [O15]H2O, CMRGlc using [F-18]FDG and binding of cBDZ-R using [C-11] flumazenil. All the PET images were co-registered to patients•f own MRI. All of the patients were treated with anterior temporal lobectomy and their outcome were classified according to Engel•fs classification (Class 1; seizure free 8, Class 3; 90 % reduction of seizure 3) after following them up more than one year. In voxel based analysis, PET data of each patient were analyzed using SPM99, by statistically comparing the voxel value of PET parameters between single patient and twelve normal volunteers. Voxels having significantly decreased value than normal control were mapped on standard brain atlas. P< 0.05 was considred as significant. In ROI based analysis, ROIs were placed on the mesial, basal and lateral temporal cortex over MRI which is co-registered to PET. In order to depict the ROIs with abnormally decreased value of parameters than contralateral side, asymmetry index (AI = (lt-rt) x 2 / (lt+rt)) was calculated and AI outside the mean +/- 2SD range of normal control was considered as abnormal. Results: 1) In both voxel and ROI based analysis, CBF did not have predictive value in determining the side of epileptic focus. 2) In ten out of eleven patients, the resected temporal lobe bore more voxels or

Back to Main

ROIs with abnormally decreased CMRGlc than the contralateral side. However, in only three out of eleven patients, the resected temporal lobes bore more voxels or ROIs with abnormally decreased cBDZR than contralateral side. 3) In all patients, the voxels or ROIs with abnormally decreased CMRGlc extended beyond the resected areaeven in the Class 1 patients. The voxels or ROIs with abnormally decreased cBDZ-R (Fig1) represented the resected area more accurately than CMRGlc study (Fig2). 4) The voxel based analysis with SPM was more specific than ROI analysis to delineate the area with decreased cBDZ-R in epileptic focus. Conclusions: In either voxel or ROI based statistical analysis, the side of epileptic focus was more sensitively detected by CMRGlc analysis than by cBDZ-R analysis. However, voxel based SPM analysis of cBDZ-R was the most specific method to delineate the accurate epileptic focus to the others in the present study.

Back to Main

Go to Main Abstract page

© 2002 Elsevier Science (USA). All rights reserved.

Back to Main

NeuroImage Human Brain Mapping 2002 Meeting

Order to appear: 738

Motor imagery and phantom sensations in paraplegic patients Hatem Alkadhi , Sabina Hotz Bondermaker , Peter Brugger , Gerard R. Crelier , Armin Curt , Marie-Claude Hepp-Reymond , Spyros S. Kollias Institute of Neuroradiology, University Hospital Zurich, Switzerland Institute of Neuroinformatics, University and ETH Zurich, Switzerland Department of Neurology, University of Zurich, Switzerland ParaCare, University Hospital Balgrist, Zurich, Switzerland Subject: Neurology Abstract Introduction: Many patients who have sustained a spinal cord injury (SCI) report sensory phenomena that have many similarities to phantom sensations experienced after limb amputation (1). However, the occurrence and prevalence of these phenomena after SCI has been rarely reported. Motor imagery is defined as conscious mental rehearsal of a motor act without performing any overt movement. Gerardin et al. have recently demonstrated that imagination and execution of movements activate a large overlapping cerebral network, however, a number of cortico-subcortical regions are more specifically devoted to motor imagery (2). The aims of our study were first, to determine the characteristics and prevalence of perceived phantom sensations in SCI patients, and second, to analyze by using functional magnetic resonance imaging (fMRI) the central representations of motor imagery in these patients. Material and Methods: Eight right-handed, chronic SCI patients (3 female, 5 male, mean age 31.3 years ± 6.8, mean period following SCI 32 months) and eight age-matched healthy volunteers participated in the study. Structured interviews about the experience and quality of phantom sensations were carried out in all SCI patients. For all categories, a score was used, where the SCI patients had to choose between 0 and 6. FMRI was conducted on a 1.5 T scanner using a gradient-echo echo-planar pulse sequence providing a resolution of 2 x 2 x 4 mm. The following experiments were performed: (a) repetitive opening and closing of the right hand (controls), (b) to kinesthetically imagine the same movement without actual execution (controls), (c) flexion and extension movements of the right foot (controls), and (d) imagining the foot movements (controls and SCI patients). Single subject (Spearman rank order correlation) and group analysis (linear model) were performed and the volumes of activation, the centers of gravity and the maximum t-values of each activated cluster were quantified.

Back to Main

Results: Of the eight patients investigated, all perceived phantom sensations related to their lower limbs. These included the sensation of size (n=7), position (n=8), weight (n=5), temperature (n=5), of paresthesia (n=8), pain (n=5), and the ability to imagine movements (n=8) and to visualize (n=5). When correlating the scores of each category with the time since SCI, a significant positive correlation was found for size (r=0.818, p<0.05), and a positive trend was present for the position (r=0.674), weight (r=0.680), movement (r=0.636), paresthesia (r=0.655), and visualization (r=0.800). A significant negative correlation was found between the time since SCI and the sensation of pain (r=-0.945, p<0.01). The FMRI experiments showed overlapping regions between real and imagined movements (including bilateral medial and lateral premotor, cingular, and parietal areas), and more specific cortico-subcortical areas, which were more engaged during mental simulation. The latter were found in bilateral prefrontal, and in specific parietal and cerebellar areas. The observed activation patterns during hand and foot motor execution and imagery in the controls were thus similar to those reported in the literature for the hand (2). During imagery of foot movements, SCI patients concomitantly activated the regions activated by the controls for both motor execution and imagination. Particularly, a strong and consistent activation during motor imagery was present in all SCI patients in the contralateral primary motor (M1) foot representation. Furthermore the activation level, particularly in the putamen, pallidum, thalamus, and caudate nucleus was significantly higher in the SCI patients as compared to the activation levels during both real and imagined movements in the controls. In the contralateral M1, Spearman rank order correlation coefficients revealed a significant correlation between the ability of motor imagery (r=0.842, p<0.05), and a highly significant correlation between the ability to visualize (r=0.995, p<0.01) and the maximum signal intensity during foot imagery in the SCI patients. Conclusions: We found a high prevalence of simple and complex phantom sensations in paraplegic patients after SCI. The disconnection of efferent motor and afferent sensory pathways in SCI patients may induce changes of activation patterns during motor imagery in various cortical and subcortical areas. This open-loop situation leads to a concomitant activation of regions normally devoted to movement execution and to movement imagination, and to an increase of the general activation level in various motor-related brain areas. In all patients the degree of movement perception in their deefferented and deafferented lower limbs is significantly correlated with the degree of activation in contralateral M1. This indicates the role of the primary motor cortex for higher cognitive functions. References: (1) Bors E. Amer Med Assoc Archs Neurol Psychiat 1951; 66: 610-631. (2) Gerardin E, et al. Cerebral Cortex 2000; 10: 1093-1104.

Go to Main Abstract page

© 2002 Elsevier Science (USA). All rights reserved.

Back to Main

NeuroImage Human Brain Mapping 2002 Meeting

Order to appear: 739

Normative Data from an fMRI Cognitive Task Battery Alexander Drobyshevsky, Steve Baumann, Walter Schneider Psychology Software Tools, Inc., 2050Ardmore Blvd, Suite 200, Pittsburgh, PA, 15221 Subject: Neurology Abstract A set of “classical” cognitive tasks combined in a task battery was tested on a group of normal healthy subjects in an effort to provide the fMRI community with a standardized database of functional brain activity for established paradigms. Paradigms were selected based on widespread use in the cognitive neuroscience community and robustness of acquired activation (Bandettini, 1992; Tootell, 1996; Benson, 1999; Lang, 1999; Cohen, 1997). The database can be used as a reference for newly established fMRI centers and for developing standardized cognitive and clinical datasets. The battery consisted of the following five tasks: · Motor-Visual - Alternating blocks of a flashing checkerboard and finger pressing are presented according to displayed cues. The task activates multiple visual areas within the occipital cortex and hand areas of the motor strip. · Verb Generation - Subjects were instructed to silently think of a corresponding action verb to a presented noun cue. The task maps speech production areas. · Novel Pictures - The task presents a sequence of various pictures against a repeated control picture. The task activates parietal and occipital areas. · N-Back - The subject sees a series of single letters and presses a button if the current letter has occurred 1-2 letters before. As a control, subjects press a button for underlined letters. This task provides strong activation of areas associated with working memory. · Emotional pictures – Subjects are presented visual images from the IAPS inventory invoking strong emotional responses. As a control, neutral pictures (e.g. furniture) are presented. Limbic structures are activated. Stimuli were presented using the IFIS system (MRI Devices, Inc.) through a 640x480 LCD display and stereo headphones. Healthy subjects who gave informed consent participated in the study. Functional EPI images were obtained on a GE 1.5 T Signa scanner, TR 2.5 sec, 28 axial slices covering the whole brain. Voxel dimensions were 3.8x3.8x4 mm. Anatomical references were obtained from a set of T1-weighted images and an SPGR volume scan. Statistical analysis was performed using the general linear model in Brain Voyager (Brain Innovations, Inc.) and SPM99 statistical packages. Data sets were realigned, normalized to standard space and spatially (FWHM 6 mm) and temporally smoothed before submitting the data to the general linear model. All parametric maps were entered to the second level random effect analysis. For most of the

Back to Main

subjects, flattened activation maps were constructed. The majority of the subjects displayed activity in the areas as predicted in referenced papers. All parametric maps were entered to second level random effect analysis and maps significant on population level were generated. Probabilistic maps were calculated, reflecting spatial extent of activation in predicted areas among different subjects. As a logical continuation, a similar study will be performed on a cohort of patients with various brain pathologies. Results obtained in the study will be made available to the broad research community.

Go to Main Abstract page

© 2002 Elsevier Science (USA). All rights reserved.

Back to Main NeuroImage Human Brain Mapping 2002 Meeting

Order to appear: 740

Event-related fMRI of myoclonic jerks arising from dysplastic cortex John S Archer, Anthony B Waites, Paolo Federico, Graeme D Jackson Brain Research Institute, Austin and Repatriation Medical centre, Melbourne, Australia Subject: Neurology Abstract Introduction Myoclonic jerks can be a manifestation of focal epilepsy, and often occur in the absence of abnormal activity as seen in scalp electroencephalography (EEG) recordings. Event-related fMRI (ER-fMRI) offers a non-invasive means of localising the origin of these jerks. Methods We studied a 26-year-old female with a 19-year history of epileptic myoclonic jerks of the right foot whose scalp EEG appeared normal, even during the jerks. After a structural MR acquisition to determine the anatomy, a series of fMRI runs were performed at 3 Tesla. First, two blockdesigned trials were obtained to map cortical activity associated with voluntary right and left foot movement. Several "free-run" datasets were then acquired during periods of spontaneous jerking, and at varying repetition times (TRs). ER-fMRI analysis was then conducted on each of the datasets, using the occurrence of right foot jerks (determined from video monitoring of the patient during scanning) as events of interest. Results Structural imaging revealed a dysplastic region adjacent to an abnormal sulcus branching anteriorly from the left central sulcus (Fig.1A, dysplastic region marked with an arrow, with the supplementary motor area (SMA) marked with a triangle). Block design fMRI experiments showed normal activation of contralateral medial primary motor cortex and bilateral supplementary motor cortex with voluntary movement of either foot. However, voluntary left foot movement also produced increased right foot jerking and activation of the dysplastic cortex (Fig.1B, with activation in the right foot motor area (square), head of the dysplastic region (ringed) and SMA (triangle)). The fact that left foot voluntary movement caused the frequency of right foot spontaneous jerks to increase raised the possibility that this dysplastic tissue was involved in jerk generation. This was confirmed with the ER-fMRI analysis, which showed activation associated with right foot jerks in the right foot area, the SMA and the dysplastic tissue (Fig.1C). Further, by examining brain activation one second prior to the right foot jerk, activation in the foot area decreased, while activation in the dysplastic tissue and SMA increased (Fig.1D). Discussion These results indicate the utility of ER-fMRI in localising the origin of epileptic myoclonic jerks. Systematically manipulating the event timing provides a tool for probing the generation of such activity. It was found that there was more than one region activating in unison with the spontaneous jerks. In this patient the myoclonic jerks may arise from an interaction between the dysplastic cortex and the SMA. Shifting the timecourse sheds light on the evolution of myoclonic jerks, with both dysplastic cortex and the SMA appearing to lie upstream from the primary foot area. The presurgical use of this technique has allowed a more tailored approach for intracranial monitoring in this patient and may provide an alternative to invasive investigations in this patient population.

Go to Main Abstract page

Back to Main

© 2002 Elsevier Science (USA). All rights reserved.

Back to Main

NeuroImage Human Brain Mapping 2002 Meeting

Order to appear: 741

Individual classification of Alzheimer’s disease and depression by linear subspace analysis of FDG PET G. Zuendorf , V. Holthoff , N. Kerrouche , B. Beuthien-Baumann , K. Herholz University Cologne, Neurological Clinic and Max-Planck-Institute for Neurological Research, 50931 Cologne, Germany Department of Psychiatry and Psychotherapy, Department of Nuclear Medicine, Dresden University of Technology INSERM U320, Cyceron, Caen, France Subject: Neurology Abstract Introduction: Alzheimer's disease(AD) is frequently accompanied by depressive symptoms and major depression by itself may cause cognitive deficits that may be difficult to distinguish from mild AD. Thus, there is a need for a biomarker to differentiate between AD and depression. Previous studies of cerebral glucose metabolism with FDG-PET have shown mainly posterior cingulate, temporo-parietal and frontal impairment in AD and mainly frontal impairment in depression. With multivariate image analysis we now studied whether these conditions can be distinguished by their metabolic patterns. Subspace methods are well known methods for classification in the fields of chemometrics or digit classification. The method used in this work is solely based on techniques from the field of pattern recognition rather than on prior knowledge of the disease specific hypometabolic regions and is completely user independent. Subjects: PET images were available from 90 subjects suffering from AD (NINCDSADRDA criteria of probable AD, age=62.9±7.6 years, MMSE=20.4±5.3), 92 non-demented patients suffering from major depression (DSM-IV, age=48.3±16.0, MMSE=29.1±1.23, Hamilton score=27.3±4.65(HAMD 21-item version)) and 74 normal controls (age 56.6±12.8). Method: After spatial normalisation (SPM99) images were smoothed by an 8mm Gaussian filter, masked to show only voxels inside the brain and scaled to the same mean. The number of voxels retained was about 200000. One subject is represented as a point in a 200000 dimensional Euclidean space. To create subspaces which are supposed to represent images from one diagnostic group better than those from others the mean image of a group is subtracted from the images of this group. Principal component analysis (PCA) of the centred images is then performed for each group separately. The principal components (PCs), explaining the variance within the datasets in decreasing order of importance, form the group specific subspaces. An unclassified image is centred by subtraction of the mean of the different classes and the distances to the different subspaces are calculated. A new image is assigned to the diagnostic group for which this distance is minimal. The dataset was split randomly in two parts. The first part contains 45 images from each group to build the classifier. The rest of the data is used to evaluate the classifier with

Back to Main

an independent sample. Only the first 15 PCs of each group were taken into account for building the subspaces. To make the results as independent from the particular PCA- and evaluation datasets as possible, 50 classifiers were built and the mean classification success was calculated. Results: The classification success in terms of sensitivity and specificity is given in the table. Conclusion: The different groups were distinguished from each other with little overlap. Especially AD subjects could be classified with high accuracy. Thus, FDG PET with multivariate classification provides an objective diagnostic biomarker to distinguish between these conditions. Acknowledgement: This study was conducted by the authors on behalf of the NEST-DD group with support from the European Commission(Framework V). Classification Success AD

Depression Controls

Sensitivity(%) 93.9±3.4 80.1±8.4

84.3±7.3

Specificity(%) 93.2±3.2 96.9±2.1

90.1±4.9

Go to Main Abstract page

© 2002 Elsevier Science (USA). All rights reserved.

Back to Main

NeuroImage Human Brain Mapping 2002 Meeting

Order to appear: 742

Correction of FDG-PET data for Partial Volume Effect in Alzheimer's Disease: comparison of different techniques Anna Prinster , Karim Berkouk , Mario Quarantelli , Sabina Pappatà , Brigitte Landeau , Bruno Alfano , Jean-Claude Baron CNR, Centre for Nuclear Medicine, Naples, Italy INSERM Unit 320, Cyceron, Caen, France Dept of Neurology, Uni. of Cambridge, UK Subject: Neurology Abstract Introduction Decrease in Gray Matter (GM) FDG concentration seen at PET in Alzheimer's Disease (AD) patients is partly related to brain atrophy. Correction of PET-FDG data for partial volume effects (PVE) is desirable to role out this effect. Several methods for PVE-correction have been published based on the knowledge of scanner resolution and of the underlying brain structure (obtained from segmented MRI). These methods correct either only for the effect of surrounding CSF [1], or also for the different concentrations in GM and WM, providing PVE-corrected images [2] or PVE-corrected ROI data [3]. Aim of our study was to compare PVE correction using both approaches on AD and Normal Volunteers (NV) FDG studies. Material and Methods FDG-PET (ECAT HR+) and T1-weighted MRI from 5 AD patients and 5 age- and sex matched NV were used. GM, WM and CSF maps were obtained by probabilistic MRI segmentation [4]. After coregistration of segmented maps [5], PVE corrected FDG concentration maps of GM were calculated taking into account only CSF effect [1] or CSF and WM effects [2]. A pre-defined set of ROI for main cerebral structures (supratentorial lobes and cerebellar hemispheres, defined according to Talairach [6] and fitted onto the GM map of each single study) was then applied on both the original and corrected PET images to derive corresponding uncorrected and corrected (for CSF and for CSF/WM) data. A third approach to PVE correction (CSF/WM based) was implemented using the ROI-based method described by Rousset et al. [3]. Data were normalized by mean cerebellum counts, and for each correction technique, comparison between AD and NV was performed (Student's T-test, significancy 0.05).

Back to Main

Results Mean increase in GM PET values was 17.4% and 21.9% in NV and AD studies respectively when correcting only for CSF, always above 35% when correcting for WM/CSF. After correction for CSF, left temporal and bilateral occipital FDG uptake was significantly reduced in AD patients. When correcting also for WM only left temporal uptake resulted significantly reduced in AD patients, independently of the method used (voxel- and ROI-based). Discussion Few studies have compared FDG-PET data of NV and AD patients after PVE-correction [7,8], only in one case [8] performing correction also for WM. We have shown that PVE correction limited to "cold" tissues leaves residual PVE resulting in artificial decreases in apparent FDG, while correction also for WM of FDG-PET data is feasible and removes further differences between AD and NV due to GM atrophy. Acknowledgments This work is supported by PVEOut, a project co-financed by the EC (contract # QLG3-CT2000-594). References [1] Meltzer CC. J Cereb Blood Flow Metab 1996;16:650-8 [2] Muller-Gartner HW, et al. J Cereb Blood Flow Metab 1992;12:571-83 [3] Rousset OG, et al. J Nucl Med 1998;39:904-11 [4] Ashburner J. NeuroImage 2000; 11:805-21 [5] Friston KJ. Human Brain Mapping 1995; 2:165-189 [6] Talairach, J., and Tournoux, P. 1988. Co-planar stereotaxic atlas of the human brain. Thieme, New York [7] Ibanez V. Neurology 1998;50:1585-1593. [8] Labbe C. Alz. Dis Assoc Disord 1996;10:141-70

Go to Main Abstract page

© 2002 Elsevier Science (USA). All rights reserved.

Back to Main

NeuroImage Human Brain Mapping 2002 Meeting

Order to appear: 743

Diffusion Tensor Imaging Predict Tissue Damage in Ischemic Stroke G LI , L Huang , RTF Cheung , G Cao , SR Liu , QY Ma , ES Yang The Jockey Club MRI Engineering Centre, The University of Hong Kong HKSAR Imaging Center of the First Affiliated Hospital of Medical College, Jinan University, P.R. China Division of Neurology, University Department of Medicine, Faculty of Medicine, The University of Hong Kong, HKSAR GE Medical Systems Asia, HKSAR Subject: Neurology Abstract Diffusion weighted MR imaging (DWI) can delineate acute infarct and is increasingly used in the workup of stroke patients in the acute stage. MR DTI fully characterizes water molecule mobility in vivo and allows an exploration of fiber tract integrity and orientation in the human brain. DTI has been used to reveal reduced fiber coherence (anisotropy) associated with cerebral infarction and in the white matter tracts remote from the lesion (Le Bihan et al. 2001). Very early ischemic lesions appear hypointense in the Apparent/Average Diffusion Coefficient (ADC) maps but hyperintense in the Exponential ADC (eADC) maps (Lansberg MG et al. 2001). Established ischemic lesions of several weeks old would have the opposite appearance in the ADC and eADC maps (Gillard et al., 2001). Fractional Anisotropy (FA) maps can detect disruption or distortion of white matter tracts. Some authors suggested that patients with distortions of white matter tracts would have better clinical recovery than those with fiber tract disruption (Werring et al. 2000, Gillard et al. 2001). In this study, we applied MR DTI to a cohort of patients either within 1 week of their strokes or between 3 and 4 weeks after onset to examine the lesion appearance on the ADC, eADC, and FA maps. 29 stroke patients (11 men) aged between 20 and 80 years underwent MR examination using a 1.5 T whole body GE MR scanner. The following settings were used for DTI echo planar imaging (EPI): TE = minimum ms, TR = 6500 ms, matrix 160x128, FOV = 32x32, slice thickness = 5 mm, total number of diffusion encoding directions = 25 with diffusion b values of 1000 s/mm2. In addition, conventional T1weighted, T2-weighted, FLAIR, and DWI imaging were performed. Within 1 week of onset, the ischemic lesions were hypointense in the ADC maps but hyperintense in the eADC maps between 3 to 4 weeks. (Fig. I and II). FA maps detected distortions of white matter tracts in 16 patients and disruptions of white matter tracts in 13 patients (Fig. III). Our preliminary results demonstrate that lesions are hypointense on the ADC maps and hypeintense on

Back to Main

the eADC maps in very early ischemic stroke patients, (Fig. I), and the other way round after 3 weeks (Fig. II). This may not be found on T1 weight and T2 weight imagings. DTI may detect the pattern changes of white matter to forecast the recovery of the stroke patients. Our primary study indicates that ADC and eADC maps provide a method for the exact diagnosis in very early stroke patients. FA maps can detect the white matter changes in early stroke patients to improve diagnosis and monitor the course of disease, as well as to provide insight into the pathophysiology in the recover course of the disease. This study was supported by The Hong Kong Jockey Club Charities Trust and The Hong Kong University Foundation. We thank GE Medical Systems Asia for the technical support. Le Bihan D et al., JMRI 13;534-546,2001. Gillard JH et al., The British J Radiology74;642-647,2001. Lansberhg MG et al., AJNR Am J Neuroradiol 22;637-644, 2001. Molko N et al., Stoke 32(9);2049-54,2001 Werring DJ et al., J Neurol Neurosurg Psychiatry 69;269-272,2000

Back to Main

Go to Main Abstract page

© 2002 Elsevier Science (USA). All rights reserved.

Back to Main

Back to Main

Back to Main

Demented patients showed a strong inability to wait for the Go stimuli, respect to control Nold, despite the fact that fronto-temporal dementia and relevant frontal vascular involvement were excluded. Their cerebral activity showed a significant increase of the frontomedial alpha ERD, indicative of excessive transmission across thalamocortical pathways and/or an excessive excitability in the frontal-medial cortical regions. The present results support the idea that combined behavioural and neurophysiological settings could provide useful information for the assessment and monitoring of demented patients.

Go to Main Abstract page

© 2002 Elsevier Science (USA). All rights reserved.

Back to Main

NeuroImage Human Brain Mapping 2002 Meeting

Order to appear: 745

Occurrence of speech disorders following surgical resection of the mesial frontal lobe: an fMRI study of the role of the SMA Alexandre Krainik , Stéphane Lehéricy , Hugues Duffau , Mihaela Vlaicu , Philippe Cornu , Laurent Capelle , Jean-François Mangin , Yves Menu , Denis Le Bihan , Claude Marsault Department of Neuroradiology, Hôpital de la Salpêtrière, Paris Department of Radiology, Hôpital Beaujon, Clichy Service Hospitalier Frédéric Joliot, Department of Medical Research, CEA, Orsay Department of Neurosurgery, Hôpital de la Salpêtrière, Paris Subject: Neurology Abstract Purpose: The Supplementary Motor Area (SMA) is located in the mesial frontal lobe, and is involved in language functions. Patients undergoing surgical resection of the SMA may present a transient postoperative neurological deficit including speech disorders. The nature and pathophysiological basis of this speech deficit remains incompletely understood. The objective of this study was to determine whether the deficit results from the resection of the SMA involved in verbal task. Subjects and Methods:12 patients were studied before and after mesial frontal lobe resection of low grade gliomas, and compared to 6 right-handed healthy subjects. Patients had a preoperative fMRI, and an anatomical postoperative MR control. No speech disorder was observed preoperatively. Imaging: The MR protocol was carried out with a 1.5T MR unit using BOLD fMRI. The preoperative examinations included functional axial EG-EPI and anatomical 3D-FSPGR images. The postoperative MR examination included 3D-FSPGR. Tasks: A semantic verbal fluency task was performed by the subjects with a block-designed paradigm. Analysis: Data analysis were performed using SPM99 software. Hemispheric dominance for language was assessed using fMRI laterality index (LIglobal = [L - R]/[L + R], L being the number of activated voxels in the left hemisphere and R in the right hemisphere). A laterality index was calculated in the SMA (LISMA = [D – ND]/[D + ND], D: dominant hemisphere for language, ND: non-dominant). Activated voxels in the mesial frontal lobe were overlaid on coregistered postoperative axial anatomical images to evaluate the extent of the resection of the activated area in the SMA. Results: In healthy subjects, activation in the SMA was bilateral with a mean LISMA of 0.20 (-0.22; +0.75). Patients were divided in 2 groups depending on their clinical outcome. Group 1: Six patients had a transient speech disorder presenting as a global reduction in spontaneous speech ranging from a complete mutism (4 patients) to a less severe speech reduction (2 patients). Comprehension was normal. No paraphasia nor dysnomia was observed. Deficit recovery began during

Back to Main

the first week, and was complete or almost complete within 8 months. All patients had a resection of the area activated in the SMA during the fluency task in their dominant hemisphere ranging from 16 to 93 % (m = 43 %). Mean LISMA was shifted toward the non-dominant hemisphere ranging from -0.55 to +0.02 (m= –0.34) (p= 0.05). Group 2: Six patients had no speech disorder. Four of these patients had a resection of the area activated in the SMA in their dominant hemisphere during the fluency task, ranging from 0 to 12 % (m = 5 %), and 2 patients had a resection of the SMA in their non-dominant hemisphere. Mean LISMA ranged from -0.21 to +0.61 (m= 0.19, not significant). Conclusion: Transient speech disorders occurring after mesial frontal lobe surgery in patients with brain tumors result from the resection of the area activated during language tasks in the SMA dominant for language (p<0.05). This deficit occurred despite evidence of a preoperative recruitment of the SMA in the hemisphere contralateral to the tumor.

Go to Main Abstract page

© 2002 Elsevier Science (USA). All rights reserved.

Back to Main

NeuroImage Human Brain Mapping 2002 Meeting

Order to appear: 746

Follow-up of somatosensory recovery after stoke with fMRI Antti Korvenoja

, Heidi Wikström

, Juha Huttunen , Risto O. Roine¶, Hannu J. Aronen

Department of Radiology, Helsinki University Central Hospital BioMag Laboratory, Helsinki University Central Hospital Department of Clinical Neurophysiology, Helsinki University Central Hospital Department of Radiology, Kuopio University Hospital Subject: Neurology Abstract Introduction The aim of this study was to investigate the potential of fMRI in detecting plastic changes in the brain after an ischemic stroke. Methods The study protocol was approved by the ethical committee of Helsinki University Central Hospital. Altogether six patients were selected for the study and their written consent was obtained. Subjects were studied first in the acute phase (1-10 days after onset of symptoms) and thereafter in the chronic phase (3 months after onset of symptoms). On each time the clinical status was evaluated. The disability caused by symptoms was scored using Rankin scale, Scandinavian Stroke Scale and Barthel index. The functional imaging was performed with Siemens Vision 1.5 T using gradient echo echoplanar sequence (38 slices with 4 mm thickness without gaps, 64 64 matrix, FoV 256 mm, TR 4.0 s, TE 60 ms). Blocked paradigm with electrical stimulation of the median nerve at 4 Hz rate (40 s off, 40 s on) was applied first to the affected side and thereafter to the intact side. Altogether 110 image volumes were acquired during the paradigm. T1-, and T2-weighted structural images as well as FLAIR and diffusion weighted images were obtained as well. Analysis was carried out using FEAT, the FMRIB Easy Analysis Tool. Statistical analysis was carried out using FILM (FMRIB?s Improved Linear Model) with local autocorrelation correction [Woolrich 2000]. Fixed effects analysis between acute and chronic phase first level analyses were performed. Z (gaussianised T/F) statistic images were thresholded using resel (corrected Bonferroni) thresholding with a corrected significance threshold of P=0.01 [Friston 1995, Forman 1995]. Registration to high resolution and/or standard images was carried out using FLIRT [Jenkinson 2001].

Back to Main

Results The patients' symptoms ranged from mild sensory paresis to total paralysis of the affected arm with severe sensory paresis. All patiens showed some degree of clinical recovery at the time of the second examination. The MRIs revealed small lacunar lesions in the deep sensorimotor pathways (i.e., the thalamus, capsula interna, basal ganglia) in 5 patiens while in one the lesion was located in the insula including second somatosensory cortex. In three subjects activation was detected in primary sensorimotor areas for stimulation of affected and healthy hand. Activation was detected in secondary somatosensory areas and in cerebellum as well. There were differential activation effects between acute and chronic phase in two of these patients. Increased activation in the primary sensorimotor cortex for stimulation of both the contra- and ipsilateral side to the lesion was observed. These two subjects had the mildest clinical symptoms. In two subjects there was incomplete or artefact contaminated data. In one subject no activation was detected either in acute or chronic phase. This subject had a complete paresis of the left upper and lower limb, with almost complete recovery of lower limb motor function and somatosensory function but no recovery of the upper limb motor function. Conclusion The results of this feasibility study suggest that plastic changes during recovery from stroke may be observed with fMRI. Patient co-operation may introduce problems especially in case of more severe lesions.

Go to Main Abstract page

© 2002 Elsevier Science (USA). All rights reserved.

Back to Main

NeuroImage Human Brain Mapping 2002 Meeting

Order to appear: 747

Cortical Origin of Mini-Asterixis in Hepatic Encephalopathy Lars Timmermann , Joachim Gross , Gerald Kircheis , Markus Butz , Dieter Häussinger , Alfons Schnitzler Department of Neurology, Heinrich-Heine-University, D-40225 Duesseldorf, Germany Department of Gastroenterology, Heinrich-Heine-University, D-40225 Duesseldorf, Germany Subject: Neurology Abstract Introduction The neurophysiological basis of Mini-Asterixis in hepatic encephalopathy (HE) is unknown. We therefore investigated in 6 patients with mini-asterixis and HE (grade 2-3, according to the West-Haven criteria) due to chronic liver cirrhosis and in 6 age-matched healthy controls the coupling between the surface EMG of hand muscles and motor cortical activity recorded non-invasively with magnetoencephalography (MEG). A second control group (patient controls) consisted of 6 patients with liver cirrhosis but no mini-asterixis or manifest HE. Results During rest, no subject showed significant MEG-EMG coherence. On elevation of the forearm patients with HE-grade 2-3 developed clearly visible mini-asterixis of varying frequencies (6-12 Hz) that was reflected in EMG oscillations. In these patients excessive corticomuscular coherence occurred at the individual tremor frequency between EMG and primary motor cortex (M1) activity (1). In contrast, M1EMG coherence in both control groups was significantly smaller and of higher frequency (> 15 Hz). However, in patients with mini-asterixis the power spectrum of M1 activity was dominated by strong oscillatory activity at the frequency of asterixis whereas both control groups showed physiological 10 Hz and 20 Hz components of the sensorimotor mu-rhythm. Discussion The pathological corticomuscular coherence in HE-patients with mini-asterixis demonstrates the cortical loop of mini-asterixis in hepatic encephalopathy. Mini-asterixis reflects most likely a pathologically decelerated and augmented synchronized rhythmical motor cortical output possibly due to functional alterations in the basal-ganglia-thalamo-cortical loops. Pathological synchronization of neuronal activity may turn out to be a promising pathophysiological concept for other clinical deficits of HE. References 1. Timmermann L, Gross J, Kircheis G, Haussinger D, Schnitzler A. Cortical origin of mini-asterixis in hepatic encephalopathy, Neurology 2002, 58(2):295-8

Back to Main

Acknowledgment Supported by the Deutsche Forschungsgemeinschaft (SFB 575, C4)

Go to Main Abstract page

© 2002 Elsevier Science (USA). All rights reserved.

Back to Main

NeuroImage Human Brain Mapping 2002 Meeting

Order to appear: 748

EEG-Correlated fMRI of Human Generalized Spike-Wave Activity: Afraim Salek-Haddadi , Louis Lemieux , Martin Merschhemke , Karl Friston , John Duncan , David R Fish Department of Clinical and Experimental Epilepsy, Institute of Neurology, University College London, Queen Square, London UK; MRI Unit, National Society for Epilepsy, Chalfont St. Peter, Buckinghamshire, UK. Wellcome Department of Imaging Neuroscience, Institute of Neurology, University College London, Queen Square, London UK Subject: Neurology Abstract Introduction Generalized epileptic disorders are defined by bilateral cerebral involvement at seizure onset and share a strikingly stereotyped EEG feature, the 3Hz Generalized Spike-Wave Discharge (GSWD). A large body of work in several animal models supports the ‘corticoreticular hypothesis’, attributing essential roles to both thalamus and cortex in GSWD generation, but there is little to establishing the relevance of basic work to humans. The advent of simultaneous and continuous EEG-Correlated fMRI1 provides an unprecedented opportunity to identify and study the neural correlates of EEG phenomena with high spatio-temporal resolution. Methods We studied a patient with intractable idiopathic generalised epilepsy using a 35-minute continuous whole-brain fMRI time-series during which 10-channels of scalp EEG were recorded simultaneously. This was enabled by an MR-compatible set-up with post-processing techniques to removing pulse (cardiobalistogram)2 and imaging1 artefact from the EEG. Four prolonged runs of 3Hz GSWD (absence seizures) were captured. Two approaches to integrating the EEG data were compared using SPM99 and found to yield almost identical results. Seizure onsets and offsets were visually identified and seizure-related BOLD changes modelled through convolution of a boxcar regressor with a canonical Haemodynamic Response Function (HRF). Secondly, Fourier analysis was used to derive a running estimate of power spectral density at 3Hz which was convolved with a HRF to provide a regressor for the SPM analyses. Results There were two distinct and highly significant patterns of GSWD-related BOLD change, time-locked to the GSWD. Activations were seen exclusively within the thalami bilaterally (Fig. 1) whilst profound deactivations were evident outside (Fig. 2), symmetrically and over large areas of cortical grey matter with a frontal emphasis. Furthermore, all changes were consistent across individual seizures. Discussion Current density source reconstruction supports two principal centres of gravity, frontal and occipital, underlying GSWD3. Though PET and Doppler studies of cerebral blood flow and glucose metabolism during GSWD are

Back to Main

Back to Main

Back to Main

NeuroImage Human Brain Mapping 2002 Meeting

Order to appear: 749

Neural correlates of recovery from stroke in individual patients: a cross sectional fMRI study N S Ward

, M M Brown , A J Thompson , R S J Frackowiak

Wellcome Department of Imaging Neuroscience, Institute of Neurology, University College, London. Division of Neurology, Institute of Neurology, University College, London Subject: Neurology Abstract Introduction Most functional imaging studies in stroke patients performing a motor task have demonstrated activation in a number of areas not usually involved in simple motor tasks in normal subjects (1). It is not clear whether these changes are related to the recovery process, primarily because patients with poor recovery are rarely studied. We report preliminary findings in eight patients in whom recovery ranged from poor to good, and have correlated the changes in activation patterns during a motor task with degree of recovery. Methods Eight right-handed patients (age 37-71 years, mean 57) were recruited 3 to 60 months after first stroke affecting the non-dominant hemisphere (5 subcortical, 3 subcortical with cortical extension). The control group consisted of twenty five normal right handed volunteers (age 26-80 years, mean 47.6). Subjects were studied using fMRI during a dynamic isometric left hand grip task, performed at 25% and 50% of subjects maximum rate. Target forces were determined as a proportion of each subject's maximum grip force with the affected/left hand. Target force and rate were visually cued. Subjects were pre-trained prior to scanning. Analysis All images were processed and analysed using SPM99. Events (hand grips) were modelled as delta functions convolved with a canonical haemodynamic response function. For each subject, parameter estimates of event-related activity at each voxel were generated using the general linear model. Statistical parametric maps of the t-statistic were generated from linear contrasts between different conditions. Individual patients were compared to pooled data across all control subjects, in order to take account of both within and between subject variance, using a two sample t-test. We looked for a correlation between activation pattern (grip versus rest) and degree of recovery (as measured by hand grip) within the patient group (using a fixed effects model). All results are corrected for whole brain multiple comparisons (p<0.05).

Back to Main

Results No patients exhibited mirror movements. Individual activation patterns varied between patients, but included recruitment of bilateral and medial cortical areas over and above that seen in the control group in six patients. In the two patients with good recovery, we could not demonstrate any differences between patient and control group. Recovery of function was inversely correlated with activations in bilateral sensorimotor cortex, dorsal premotor cortex, supplementary motor area, anterior cingulate cortex, insula cortex, dorsal prefrontal cortex, inferior and superior parietal cortex, cerebellar hemispheres and vermis, right putamen and thalamus. Discussion This preliminary analysis suggests that the activation patterns observed during the performance of a motor task in patients after stroke are related to degree of recovery at the time of the study. Performance of a task in which the degree of effort was controlled across the group was associated with recruitment of more widespread cortical areas in those with poor recovery, whilst normal activation patterns were seen only in those patients with good recovery. Recruitment of widespread cortical areas may represent a stage along the road to recovery, but in itself does not ensure full recovery. References 1. Weiller et al., Annals of Neurology 1993; 33: 181-189.

Go to Main Abstract page

© 2002 Elsevier Science (USA). All rights reserved.

Back to Main

NeuroImage Human Brain Mapping 2002 Meeting

Order to appear: 750

Voxel-Based Morphometry Reveals Progressive Grey Matter Degeneration in Temporal Lobe Epilepsy Simon Keller , Udo Wieshmann , Neil Roberts The Magnetic Resonance and Image Analysis research Centre (MARIARC), University of Liverpool, UK The Walton Centre for Neurology and Neurosurgery, Liverpool, UK Subject: Neurology Abstract Although grey matter abnormalities, particularly of the hippocampus, are frequently reported in patients with TLE, the extent to which these abnormalities are the cause or consequence of repeated temporal lobe seizures is not known. We sought to investigate the relationship between global brain structure and seizure duration (SD) in patients with left and right TLE using voxel-based morphometry (VBM). VBM has previously been applied in order to characterize grey matter abnormalities in patients with temporal lobe epilepsy (TLE) [1], juvenile myoclonic epilepsy [2], and affective aggression and TLE [3]. Methods In the course of pre-surgical evaluation for temporal lobectomy, 49 patients with TLE were interpreted as having left-sided seizure onset (LSSO) and 40 patients were interpreted as having right-sided seizure onset (RSSO) on the basis of surface electroencephalogram (EEG), and invasive Foramen Ovale (FO) recordings if EEG was nonlocalising. There were no significant differences in SD (t=0.997, p<0.325), age of onset (t=-0.406, p<0.687) and age (t=0.703, p<0.96) between patients with LSSO and RSSO (see Table 1). 3D T1-weighted MR scans obtained for all patients were stereotactically normalized and segmented using default parameters in SPM99 (Wellcome Department of Cognitive Neurology, www.fil.ion.ucl.ac.uk). Grey matter images were smoothed with an isotropic Gaussian kernel with FWHM of 10mm. Analyses between grey matter concentration (GMC) and SD were performed on a voxel-by-voxel basis in a simple regression model. Results are thresholded at p<0.001. Results SD was negatively correlated (GMC reduction) with GMC of voxels in left medial temporal lobe in LSSO patients, including hippocampus, entorhinal cortex, amygdala and parahippocampal gyrus. There were also negative correlations between SD and GMC in voxel clusters in bilateral medial prefrontal cortex and right cerebellum in LSSO patients. In patients with RSSO, a single cluster of voxels was negatively correlated with SD in right hippocampus (see Figure 1). There were no positive correlations (GMC increase) between GMC and SD in either group of patients. Regions correlated with SD were not related to age or age of onset of patients. Discussion Results are consistent with evidence indicating progressive neuronal atrophy of the epileptiform hippocampus in patients with TLE [4,5]. Progressive grey matter reduction in medial prefrontal cortex and right cerebellum may

Back to Main

be due to excitotoxic discharges from the pathological hippocampus, as these structures have been shown to be reciprocally connected [6,7]. These results suggest that early and effective medical and surgical minimization of recurrent seizures may inhibit subsequent (extra) hippocampal damage, providing improved psychological prognosis. Furthermore, the findings suggest the need for side-specific seizure management and surgery. References [1] Keller, S. et al., 2002. Neuroimage, In Press. [2] Woermann, F. et al. 1999. Brain, 122, 2101-7. [3] Woermann, F. et al. 2000. J Neurol Neurosurg Psychiatry, 68, 162-9. [4] Salmenpera, T. et al. 1998. Lancet, 351, 35. [5] Theodore, W. et al. 1999. Neurology, 52, 132-6. [6] Passingham R. 1993. Oxford university press: New York. [7] Oganesian E. et al. 1980 Fiziol Zh SSSR Im I M Sechenova, 66, 1632-9.

Go to Main Abstract page

© 2002 Elsevier Science (USA). All rights reserved.

Back to Main

NeuroImage Human Brain Mapping 2002 Meeting

Order to appear: 751

Entorhinal Cortex Volumes in Alzheimer's Disease and Control Populations: Correlations With Biologic and Cognitive Measures Francois Lalonde , Michael Myslobodsky , Karen Putnam , Trey Sunderland Geriatric Psychiatry Branch, NIMH, NIH Psychobiology Research Unit, Tel-Aviv University Subject: Neurology Abstract Introduction The entorhinal cortex (EC) is one of the first structures affected by neuronal degenerative changes early in the progression of Alzheimer's disease (AD). We previously demonstrated that, as a group, patients deemed to be "at-risk" for AD tended to have greater EC volume asymmetry [1]. These observations are extended to show the presence of molecular and neuropsychological concomitants of left and right EC atrophy. Subjects and Methods Of 38 individuals included in the initial study [1], -amyloid peptide (A ) CSF values were obtained for 5 women and 2 men diagnosed as probable Alzheimer's (mean MMSE score of 21.6± 6.7) as well as for 7 female and 5 male control subjects (CON) (mean MMSE scores of 29.0 ± 1.1). With the exception of one AD patient, all subjects were right handed. The CON group had a mean age of 64.0 years (± 9.2) and mean education of 16.5 years (± 3.5). The AD group was older (mean = 74.6 ± 9.0, F=9.9, p<.01) and less educated (mean = 14.3 ± 3.5, F=4.8, p<.05). All subjects had normal MRI and no history of neurological or psychiatric disorders. High-resolution T1-weighted 124-slice sagittal brain volumes were acquired using a 3D SPGR sequence on a 1.5T GE Horizon scanner (TR/TE/flip 24/3/30°) with slice thickness and FOV set to 1.5 and 240mm, respectively. The brain volumes were then aligned in all three planes and resliced coronally in the plane orthogonal to the Commisural-Obex reference plane [2]. EC anterior and posterior boundaries were determined by the mutual topographic relationships between the hippocampus, limen insulae, the anterior commissure, lateral pulvinar, lateral pallidum, putamen, optic tract and the lateral geniculate. EC volumes were calculated by multiplying the sum of the EC lengths by the slice thickness. The volumes were then normalized to hemicranial volume represented by the cerebral module, i.e. its mean length, breadth, and height. A concentrations were determined using a sandwich ELISA technique.

Back to Main

Neuropsychological test scores were taken from a battery of tests administered to all patients at admission. Results and Discussion Right EC volumes were highly correlated with levels of A , (CON group, r=.66, p< .05; AD group, r=.80, p< .05; CON and AD groups combined, r=.75, p< .001). Correlations between A values and 20 neuropsychological measures were calculated separately for each group to avoid spurious correlations due to the low AD scores. For the CON group, A values were significantly correlated with category (r=.81, p< .005) and letter fluencies (r=.65, p< .05), and visual memory span (r=.78, p< .005). Likewise, AD patients showed a strong but not significant correlation with visual memory span (r=.77 p=.07). By contrast, none of the neuropsychological measures were significantly correlated with right EC volumes. Although based on a small number of observations, the CON group data suggest an association between levels of A and neuroanatomical, as well as neuropsychological markers that may precede any association between between neuroanatomical and neuropsychological markers. Further longitudinal study of larger numbers of older controls is needed. References [1] Lalonde et al. Proc. of the ISMRM, 8(1), 291, 2000. [2] Tamraz, J.C. & Comair, Y.G., Atlas of Regional Anatomy of the Brain Using MRI, 2000.

Go to Main Abstract page

© 2002 Elsevier Science (USA). All rights reserved.

Back to Main NeuroImage Human Brain Mapping 2002 Meeting

Order to appear: 752

fMRI demonstrates rapid switching of brain function Graeme D Jackson, Anthony B Waites, David F Abbott, Ari Syngeniotis, Gavin C A Fabinyi, Michael M Saling Brain Research Institute, Austin and Repatriation Medical Centre, Melbourne, Australia Subject: Neurology Abstract Introduction Functional language recovery has previously been reported in two patients presenting with aphasia after stroke [1], where by day three, activation occurred in the right inferior frontal gyrus, suggesting a rapid transfer of function from left to right. To determine when cognitive transfer occurs, fMRI imaging before and after injury to language critical areas is needed. We present a patient who demonstrates rapid language transfer as measured by fMRI both before and after reorganisation. Methods The patient had intractable epilepsy from infancy due to focal cortical dysplasia (FCD) in the left middle frontal gyrus (MFG). At age 14, episodes of intense anxiety began which were interpreted as partial seizures. Surgical resection of the FCD was carried out with Neuropsychological testing throughout cortical stimulation and resection. Pathology confirmed FCD with balloon cells. fMRI was performed with a 3 Tesla GE Signa LX whole body scanner, acquiring whole brain (22 slice) GR-EPI volumes (TR/TE/a=3600/40ms/400, 24cm FOV, voxels=1.87x1.87x5mm3). States investigated were a noun-verb generation (NVG) task (silent generation of a verb every 4 seconds when presented with a priming noun) and an orthographic lexical retrieval (OLR) task (silent generation of words beginning with a presented letter, one each 18 seconds, with strict rules governing acceptable words), both contrasted against a baseline fixation task. Regional activation maps were generated using SPM99, thresholded at p<0.001 (uncorrected). Activated pixels in the anterior medial, left, and right, and posterior left and right regions were counted. Laterality indices for the anterior and posterior regions were calculated separately. Results Prior to surgery, both OLR and NVG showed activation in left MFG at the lesion margins. During surgery, cortical stimulation and resection of the lesion while the patient was awake and neuropsychological testing showed no deficits in language or working memory. Postoperative fMRI, 14 days after surgery, showed no activation in the left MFG, but marked activation in the homologous contralateral MFG. There was also strong anterior cingulate activation. After 12 months, the focus of activation had returned to the left (Fig.1, 2) Discussion This patient demonstrated rapid brain switching which preserved high-level function throughout cortical stimulation and resection while awake. FMRI shows that she uses very different areas of the brain to achieve this function following resection. This almost instantaneous change must reflect pre-existing connections taking over functions (brain switching), presumably due to removal of inhibitory influences from the original neural areas. Longitudinal measurements show a slow reorganisation, taking place over more than a year, with return of functions to the original side. This slower process is more typical brain plasticity. This may involve neuronal, synaptic and connectivity changes. This reorganisation differed according to task and was associated with an objective improvement in her performance on the COWAT test and her ability to sustain reading comprehension. References 1. Thulborn et al 1999 Stroke 30(4) 749-54

Back to Main

Go to Main Abstract page

© 2002 Elsevier Science (USA). All rights reserved.

Back to Main

NeuroImage Human Brain Mapping 2002 Meeting

Order to appear: 753

Spontaneous Slow and Fast Wave Activity in Brain Tumor Patients Localized by Magnetoencephalography M. Moeller

, H. Kober

, O. Ganslandt

, A. Begerow , J. Vieth , R. Fahlbusch

Department of Neurosurgery, University of Erlangen, Germany Biomagnetism Group, University of Erlangen, Germany Subject: Neurology Abstract Introduction In this study we investigated the abnormal neuronal brain activity in patients with structural brain lesions by spontaneous magnetoencephalography (MEG) measurements. We therefore quantified the abnormal slow and fast wave activity of the tumor affected hemisphere and compared it with the contralateral unaffected hemisphere in brain tumor patients. Additionally the values were compared with the slow and fast wave activity of normal healthy subjects. Methods We investigated 83 patients with brain tumors and 18 healthy subjects. Spontaneous magnetic brain activity was measured in a magnetically shielded room by a 2x37 channel MEG system (Bti, San Diego, USA). A data set of 600 seconds was collected simultaneously over both hemispheres. Co-registered electrocardiogram signal was removed automatically from the raw data set. After notch filtering at 50 Hz the processed data were digitally filtered at 2-6 Hz and 12,5-30 Hz for the analysis of slow and fast wave activity. We calculated the equivalent current dipoles by using the single dipole model and analyzed the dipoles by the Dipole Density Plot. Results were visualized by isocontour lines and inserted into individual 3D-MR images (Siemens AG, Erlangen, Germany). Therefore the subject`s head surface was digitally scanned with an electromagnetic digitizer and fitted to the reconstructed MRI headshape using a contour fit program. Results Comparing the maximal dipole density of abnormal brain activity of the tumor affected hemisphere with that of subjects in the mean we found higher slow and fast wave activity in the tumor affected than in the hemispheres of subjects. Slow wave activity was significantly higher in all patients except of those suffering from an oligodendroglioma compared to subjects. Fast wave activity was only in tendency higher in the affected hemispheres of patients compared to those of healthy subjects. Significantly higher

Back to Main

fast wave activity values could only be found in the group of patients with glioblastoma. The comparison of the brain activity of the affected with that of the contralateral hemisphere brought ambiguous results. Most patients showed higher slow and fast wave activity over the affected hemisphere. Significantly higher activity in the affected compared to the healthy hemisphere was found in patients with glioblastoma (slow wave) and astrocytoma and meningeoma (fast wave). In 13 patients we found higher slow and fast wave activity in the contralateral hemisphere. Conclusion MEG is able to quantify abnormal neuronal activity in brain tumor patients. Brain tumor patients showed significantly higher slow and in tendency higher fast wave activity compared to the hemispheres of subjects. The increased abnormal slow and fast wave brain activity in the tumor affected hemispheres mirrors the impact of an adjacent tumor on the function of normal brain cells. Increased abnormal slow and fast wave activity seems to be an indicator of the functional impairment of neurons caused by irritation of local tumor pressure of an extended tumor, by tumor infiltration or by biochemical changes caused by tumor metabolites or edema which might also irritate the contralateral hemisphere.

Go to Main Abstract page

© 2002 Elsevier Science (USA). All rights reserved.

Back to Main

NeuroImage Human Brain Mapping 2002 Meeting

Order to appear: 754

Dynamically Spreading Wave of Gray Matter Loss Visualized in Alzheimer’s Disease using Cortical Pattern Matching and a Brain Atlas Encoding Atrophic Rates Paul M. Thompson , Kiralee M. Hayashi , Greig de Zubicaray , Andrew L. Janke , Stephen E. Rose , Stephanie Dittmer , James Semple , David Herman , Michael S. Hong , Michael S. Mega , David M. Doddrell , Arthur W. Toga Laboratory of Neuro Imaging, Brain Mapping Division, and UCLA Alzheimer Disease Center, Department of Neurology, UCLA School of Medicine Centre for Magnetic Resonance, University of Queensland, Brisbane 4072, Australia McConnell Brain Imaging Center, Montreal Neurological Institute, McGill University, Canada GlaxoSmithKline Pharmaceuticals plc, Cambridge, UK Subject: Neurology Abstract We report the mapping of a dynamically spreading wave of gray matter loss in the brains of Alzheimer’s patients, scanned repeatedly with MRI. The loss pattern spread from temporal cortices into frontal and cingulate brain regions as the disease progressed. Deficit patterns were resolved with a novel 4D cortical pattern matching strategy which computes correspondences between cortical gyri across subjects and across time. This procedure separates geometric (shape) and tissue density changes over time, controlling for cortical pattern variation. Systematic features were reinforced in the average maps, and compared with tensor-based measures of atrophic rates encoded in a statistical brain atlas [1],[2]. Methods A population-based brain atlas containing 6840 anatomical surface models was created from 3D MRI (SPGR) scans of 43 AD patients (age: 68.7+/-1.7 yrs.; 24 females/19 males; MMSE score: 20.0+/-0.8) and 34 controls matched for age, education, gender and handedness (all right-handed). After affine alignment of individual data, gyral pattern and shape variations were encoded using high-dimensional elastic deformation mappings [3] driving each subject’s cortical anatomy into a group average configuration. Dynamic maps of atrophic rates, with millions of degrees of freedom, were generated for 17 AD patients and 14 matched controls scanned longitudinally (interscan interval: 2.6±0.3 yrs.; final age: 71.3±1.8 yrs.). To create maps of change, parametric surface models of cortical, hippocampal, ventricular, and callosal systems drove an elastic warping field reconfiguring the earlier scan’s anatomy onto the later one. Local volume loss was quantified. Changes in cortical gray matter density were mapped by computing warping fields that matched cortical patterns across hemispheres, across time, and across subjects. Annualized 4D maps of tissue loss rates within each subject [4] were elastically

Back to Main

realigned for averaging across diagnostic groups, and covaried for age, sex, hemisphere, and MMSE score. Statistics of local loss rates were visualized using color-coded maps; significance was assessed using a covariant partial differential equation [5] to induce a grid on the population average cortex whose deformation gradient matched the smoothness tensor of the residuals. Permutation was applied to features in its parameter space. Results A dynamically spreading wave of cortical gray matter loss (up to 4-5%/year locally) was detected in the AD patients, beginning in temporal cortices. Primary sensorimotor cortices were comparatively spared as the loss pattern shifted into frontal cortices, and intensified in the cingulate and paralimbic belts. Corpus callosum curvature increases were significant in controls (p<0.05), higher in AD (p<0.05), and were strongly correlated with hippocampal loss rates in both groups (pooled p<0.002 left, p<0.000004 right; r=0.54,0.73). In AD, greatest dynamic change rates were found in the inferior ventricular horns (L:+14.7+/-5.8%/yr.; R:+16.3+/-3.5%/yr.), with significant expansion rates bilaterally even in controls (L:+3.7+/-1.2%/yr.; R:+1.7+/-1.2%; p<0.001,p<0.01). Conclusion These dynamic maps show promise in charting the dynamic progress of Alzheimer’s disease, and reveal a changing pattern of deficits. We will use them in future to detect where deficit patterns are modified by drug treatment and known risk genotypes. References [1]. Janke et al. Proc. ISMRM 580(2000); [2]-[5]: Thompson et al., Nature 404(6774):190-193(2000); Nature Neuroscience 4(12):1253-8(2001); PNAS 98(20):11650-11655(2001); HBM 9(2):81-92(2000).

Go to Main Abstract page

© 2002 Elsevier Science (USA). All rights reserved.

Back to Main

NeuroImage Human Brain Mapping 2002 Meeting

Order to appear: 755

Brain Mapping of Alzheimer's Disease, a Combination Study of X-CT, MRI, and PET Taiju Matsuzawa, H Matsui, T Yamaguchi, H Miyazawa, M Ueda, R Kawashima, K Yanai, H Fukuda, K Yamaguchi, M Ito, M Ito Subject: Neurology Abstract Background:It has long been believed that the focus of Alzheimer's disease (AD) lies in cerebral cortex. However, with the utilization of X-CT and MRI with many patients and normal volunteers including 627 male and 638 female subjects a total of 1,265 Japanese, we have observed that cerebral cortex is morphologically intact during the onset of AD. The study of quantitative functional images of glucose utilization from positron emission tomography (PET) had revealed that the impairments of cerebral cortex are functional. Objective:The purpose of this study is to clarify the focus and brain mapping of AD during the onset and progression. Methods:Morphological changes of limbic system were measured through the particular method of MRI (Matsuzawa's Tomography:the MR imaging visualized the triple structure [i.e. the brain stem, the limbic system, and the cortex] on the same plane); and dysfunction of cerebral cortex was measured through PET with glucose metabolism rate. Results and conclusion:the focus of AD lies in bilateral limbic system. What is taking place during the course of AD is destructive experiment-like phenomenon on hippocampus and amygdala of major nuclei in limbic system. The destruction progresses from hippocampus and stretches into amygdala and nucleus accumbens bilaterally and symmetrically through both sides of limbic system. Functional impairments of all associtaion cortices, hypothalamus, and nucleus basalis of Meynert are secondary events, which induce varied symptoms.

Go to Main Abstract page

© 2002 Elsevier Science (USA). All rights reserved.

Back to Main

NeuroImage Human Brain Mapping 2002 Meeting

Order to appear: 756

Transcranial Doppler and Near Infrared Spectroscopy can evaluate the hemodynamic effect of carotid artery occlusion Fabrizio Vernieri , Francesco Tibuzzi , Patrizio Pasqualetti , Nicola Rosato , Francesco Passarelli , Paolo Maria Rossini , Mauro Silvestrini AFaR, Dept. of Neuroscience, Ospedale Fatebenefratelli, Isola Tiberina, Rome, Italy Neurology, Campus Biomedico, Rome, Italy Neurology, University of Ancona, Italy Subject: Neurology Abstract The hemodynamic effect of an occlusion of the internal carotid artery (ICA) on the distal circulation has been categorized into three stages. When collateral vessels (stage 0) are not adequate, reflex autoregulatory vasodilatation of arterioles (stage I) can maintain normal cerebral blood flow (CBF). Transcranial Doppler (TCD) follow-up studies demonstrated the importance of collaterals and of cerebral vasomotor reactivity (VMR) on the outcome of patients with ICA occlusion. When the autoregulatory mechanism fails to occur and CBF begins to fall, the brain can increase the amount of oxygen it extracts from the blood (oxygen extraction fraction [OEF]) to maintain normal cerebral oxygen metabolism. This stage II of hemodynamic compromise has been termed “misery perfusion” and an increased OEF is considered an independent risk factors for stroke; nowadays, the measurement of stage II is possible only with positron emission tomography (PET). Near infrared spectroscopy (NIRS) is a non-invasive technique that, providing a real time assessment of fluctuations in cerebral hemoglobin, has been used to estimate the cerebral blood volume and to measure the cerebral VMR. Moreover, NIRS technology, allowing the absolute measurement of absorption and scattering coefficients of oxy-and deoxyhemoglobin, can determine the oxygen concentration in-situ in the blood stream in a simple and noninvasive way. In order to evaluate all the three stages of cerebral hemodynamic status, 23 subjects with ICA occlusion (11 symptomatic in the vascular territory of the middle cerebral artery (MCA) ipsilateral to the carotid artery occlusion and 12 asymptomatic) underwent a simultaneous examination by means of TCD and NIRS at rest condition and during cerebral VMR test. Cerebral VMR to hypercapnia was obtained by means of CO2 inhalation reactivity test and measured by TCD and NIRS. The main result of this study is that it exists a difference between asymptomatic and symptomatic patients (6.94 vs 3.83; p=0.027) in terms of hemoglobin saturation (oxygen %) increase measured by NIRS. The opportunity to perform NIRS and TCD together allows us to have a complete information about the cerebral hemodynamic status in patients with occlusive disease in a simple, noninvasive and reliable way. Further studies on a larger number of patients are needed to demonstrate that oxygen % obtained by NIRS, measuring the stage II of hemodynamic effect of carotid occlusive disease, can be identified as a

Back to Main

prognostic risk factor for stroke.

Go to Main Abstract page

© 2002 Elsevier Science (USA). All rights reserved.

Back to Main

NeuroImage Human Brain Mapping 2002 Meeting

Order to appear: 757

fcMRI of the hippocampus using the 'seed voxel' method: observations in normal subjects Karel Deblaere, Pieter Vandemaele, Ann Tieleman, Eric Achten Department of Neuroradiology, Ghent University Hospital, Ghent, Belgium Subject: Neurology Abstract Introduction functional connectivity MRI (fcMRI) has the ability to demonstrate covariance in signal intensity in functionally related cortical and subcortical brain structures during resting state echo planar imaging[14]. These synchronous changes in signal intensity are thought to be related to low frequency synchronous blood flow changes and suggest neuronal connections between the regions identified with this technique. Stein et al [4] demonstrated functional connectivity in the hippocampal structures using a seed voxel to determine the signal intensity time course to correlate with. The number of voxels correlating with the seed voxel varied with the the seed voxel chosen . The aim of this study was to assess the within-subject variabilty in the resulting cross correlation maps depending on the position of the seed voxel along the long axis of the hippocampus in order to determine an optimal placement of this seed voxel. Materials and Methods Resting state EPI data (12 4mm slices, in plane resolution = 3x3 mm, TR=2 s, TE= 76 ms, flip angle=90 °) were acquired in 3 healthy subjects. The slice position was in the coronal plane, orthogonal to the long axis of the hippocampus. Using the same position an anatomical T1 image was acquired for optimal visual seed voxel selection. Image processing was performed using the AFNI software package (Robert Cox, Medical College of Wisconsin). The EPI data were spatially smoothed using a Gaussian filter (FWHM =8mm). A three-point Hamming filter was applied for temporal smoothing of the signal. Seed voxel were placed in the center of the right/left hippocampus in the 4 contiguous slices posterior to the amygdala. Signal time courses were calculated for each of these seed voxels . Correlation coefficients between every single seed voxel and every other voxel in the scanned volume were calculated. The number of correlating voxels above a correlation threshold of at least 0.55 (depending on cluster size) in ipsi- and contralateral hippocampus were counted for each seed voxel position. Results As already indicated by Stein et al [4] significant more correlating voxels were found in the ipsilateral

Back to Main

hippocampus when the seed voxel was placed in the right hippocampus when compared to the left hippocampus. There were also less correlating voxels in the hippocampus contralateral of the hippocampus in which the seed voxel was placed. Observation of the cluster data suggests that the number of both ipsi- and contralateral cross-correlating voxels decreases when the seed voxel was placed in more posterior part (body and tail) of the hippocampus. Conclusions Further study need to be performed on more subjects, but our data suggest that an adequate choice of the seed voxel is necessary to obtain reliable fcMRI maps of the hippocampal structures. Our data suggest optimal placement of the seed voxel in the head of the hippocampus. References 1.B. Biswal et al. Magn Res Med (1995) 34:537-541 2.D. Cordes et al. AJNR (2000) 21:1636-1644 3.M.J. Lowe et al. Neuroimage(1998) 7:119-132 4.T. Stein et al. AJNR (2000) 21:1397-1401

Go to Main Abstract page

© 2002 Elsevier Science (USA). All rights reserved.

Back to Main

NeuroImage Human Brain Mapping 2002 Meeting

Order to appear: 758

An FMRI study of the Stroop effect in patients with Multiple Sclerosis A. Parry , J. Palace , P.M Matthews FMRIB Centre, The John Radcliffe Hospital, Headington, Oxford, OX3 9DU Department of Neurology, The Radcliffe Infirmary, Woodstock Road, Oxford, OX2 6HE Subject: Neurology Abstract Background Cognitive impairment in multiple sclerosis (MS) may arise secondary to axonal injury and subsequent dysfunction in neural networks normally recruited during performance of specific cognitive tasks. The clinical consequences of this however may initially be limited if parallel neural pathways become "unmasked" to maintain performance standards. Aims A combined quantitative approach using FMRI and structural MRI measures of disease burden was used to determine; (i) whether patients with MS recruit different brain regions to healthy controls during performance of the Counting Stroop task (Bush 1998) (ii) the relationship between disease burden (lesion load and normalised brain parenchymal volume [NBPV]) and the pattern of FMRI activation in MS patients Methods Eleven MS patients, eleven age/sex-matched healthy controls. All righthanded. Counting Stroop 9 minute block design -[REST (30secs)-8x(AB)-REST (30secs)]. A="neutral" animal words e.g., cat, dog, mouse, bird B="interference" number words e.g., one, two, three, four Stimuli presented every 1.5 seconds Report via button press the number of words on the screen (1-4), regardless of word meaning. The Stroop effect (mean reaction time during the interference task-mean reaction time during the neutral task) and the number of errors were recorded. Imaging/analysis FMRI; EPI sequence, 3 Tesla Image analysis; FMRIB Software Library (www.fmrib.ox.ac.uk/fsl) Group analysis; random effects model, Z>2.0, cluster threshold p<0.05.

Back to Main

Contrast of interest; interference-neutral Between-group analysis; (1) patients-controls (2) controls-patients. Region of interest approach using clusters identified in the group analyses to determine the mean signal intensity for each subject/region. Manual definition of MS lesions on proton density images NPBV calculated using SIENAX (www.fmrib.ox.ac.uk/fsl) on T1-weighted images. Results Behaviour No significant effect of subject group on either the magnitude of the Stroop effect (patients, median 82ms [11-153]; controls, median 119ms [56-275]) or number of errors during the interference task (patients, median 7 [2-20]; controls, median 5 [1-12], Wilks' Lambda F 1.35, p=0.28). FMRI between-group analysis patients-controls; left superior frontal gyrus (-15.3, 34.3, 40.1, p=<0.001) controls-patients; opercula surface of the right inferior frontal gyrus (29.8, 20.0, 9.29). Bilateral superior parietal lobe (-42.3, -26.3, 66.6), and (46.8, -27.1, 63.0). For each patient, an FMRI abnormality index (AI) was calculated (mean signal intensity in left superior frontal gyrus/mean signal intensity in right inferior frontal gyrus), i.e., high AI= greater difference between the patient and the control group result. There was a significant correlation between AI and both NBPV (r= -0.71, p = 0.02) and lesion load (r = 0.72, p = 0.02). Conclusion There was a marked laterality difference in frontal regions activated by MS patients and controls. The right inferior prefrontal region activated in controls (and not patients) is commonly involved in tasks involving inhibition of a pre-potent response. Diffuse brain disease from MS may lead to dysfunctioning of the neural networks normally used during the Stroop task with subsequent recruitment of additional brain regions to maintain normal task performance. This hypothesis is supported by the significant correlations observed between AI and measures of disease burden.

Go to Main Abstract page

© 2002 Elsevier Science (USA). All rights reserved.

Back to Main

NeuroImage Human Brain Mapping 2002 Meeting

Order to appear: 759

Comparing isolated and simultaneous movements for presurgical evaluation purposes Alexander Geissler , Rupert Lanzenberger , Markus Barth , Josef Bruck , Andreas Gartus , Roland Beisteiner Department of Neurology, General Hospital and University of Vienna, Austria Department of Radiology, General Hospital and University of Vienna, Austria Subject: Neurology Abstract Presurgical FMRI measurements for localization of eloquent cortex may be long and unpleasant for patients when more than one motor function needs to be tested. Thus a decrease in medical examination time without decrease of localization quality is desirable. From data on motor somatotopy1,2, it is known, that motor localization of a given effector may vary with the type of movement or co-movements performed. We therefore analysed the quality of two motor localization tasks (hand movements and chin movements) when performed either in a time saving simultaneous or a conventional isolated fashion. FMRI data were acquired from 4 healthy normal subjects (aged 21 to 31), with one of them measured two times with different slice positions (B3, B4). A 3 T BRUKER Medspec scanner was used with a phase corrected blipped GE, isolated shot EPI sequence (TE/TR = 55.5/4000ms, 128x128matrix, 230x230 FOV, 25 axial slices, slice thickness 3mm, sinc-pulse-excitation). Individual plaster helmets were applied for optimised head fixation3. 3 paradigms (opening and closing of the dominant hand / upward-downward movements of the chin / simultaneous hand and chin movements) were applied. One run alternated 4 rest and 3 movement periods with 20 s duration each. A minimum of 5 runs per paradigm was recorded. Data were realigned with a 3D-sinc interpolation using AIR 3.0 and fMRI risk maps4 were generated by performing a correlation analysis with a box car reference function. The critical correlation threshold was chosen as the highest leaving pixels of 100% reliability (= active in all runs). For every paradigm the brain slice containing the largest number of most reliably activated pixels was defined as maximum activation focus. For independent control a standard SPM99 analysis with 4 mm FWHM data smoothing was performed. With risk maps (table 1), for all subjects maximum activation was found in the same slice at nearly identical location with isolated and simultaneous movements except for the left hand movement of subject SV, who was our only left-handed subject. SPM99 yielded 2 incongruent results (B3, SV) which might be due to the artificial data smoothing. The number of pixels and activated slices varied considerably between isolated and simultaneous movements and between subjects. We suppose that this variability reflects differences in motion execution (force, speed, etc.). In conclusion, our data indicate that maximum activation foci for critical primary motor areas stay constant, independent of isolated or

Back to Main

simultaneous movement of 2 different effectors. This argues in favour of the applicability of time saving simultaneous motor mapping paradigms in presurgical evaluation of primary motor cortex.

References 1.) Sanes J, Donoghue J. Annu. Rev. Neurosci 2000;23 :393-415. 2.) Beisteiner R, Windischberger C, Lanzenberger R, et al. NeuroImage 2001;13:1016-1026. 3.) Edward V, Windischberger C, Cunnington R, et al. Human Brain Mapping 2000;11(3):207-213. 4.) Beisteiner R, Lanzenberger R, Novak K, et al. Neuroscience Letters 2000;290:13-16.

Go to Main Abstract page

© 2002 Elsevier Science (USA). All rights reserved.

Back to Main

NeuroImage Human Brain Mapping 2002 Meeting

Order to appear: 760

Saccadic eye movement deficits following surgical resection of frontal lobe tumors: an fMRI study Dan Milea , Sophie Rivaud-Péchoux , Stéphane Lehéricy ¶, Elie Lobel , Hugues Duffau , Hugues Capelle , Jean-Francois Mangin¶, Claude Marsault , Alain Berthoz , Charles Pierrot-Deseilligny LPPA, Collège de France, Paris, France Departments of Neurology and INSERM 289, Pitié-Salpêtrière, Paris, France Department of Neuroradiology, Pitié-Salpêtrière, Paris, France Department of Neurosurgery, Pitié-Salpêtrière, Paris, France ¶Service Hospitalier Fréderic Joliot, CEA, Orsay, France Subject: Neurology Abstract Introduction Frontal lobe surgery for tumoral resection may result in a deficit in the control of eye movement (1,2). We prospectively studied the occurrence and characteristics of saccade deficits in 7 patients, using electrooculographic recordings (prior and after surgery) and correlated these findings with surgical, anatomical and functional MRI data. Material and methods Subjects: Seven patients undergoing surgical resection of frontal lobe low grade gliomas were studied prior and within 1 year after surgery, using ocular movements assessment and functional MRI. Electro-oculographic data : Latency and gain of visually-guided saccades as well as the percentage of errors in the antisaccade paradigm were measured prior and after surgery. Imaging: The MR protocol was carried out with a GE 1.5 T MR unit with BOLD fMRI. The pre and postoperative examinations included functional axial gradient echo EPI and anatomical 3D fast SPGR images. The post-operative MR examination also included FLAIR images. Tasks: The tasks consisted in self-paced horizontal saccadic eye movements. Analysis: Data were motion corrected, temporally filtered and analyzed using SPM 99 software (WDCN, London). Activated pixels were overlaid on axial anatomical images and 3D reconstructions. Pre and post-operative MR examinations were analyzed blinded to the clinical outcome of the patients. Volume calculation and anatomical localization of the tumors and the surgical resections were performed using a dedicated software (Anatomist). Results Visually guided saccades were altered in one patient, in which latency and gain of contralateral saccades were significantly increased, compared to preoperative recordings. This deficit was related to the surgical

Back to Main

resection of the frontal eye field area, as this area was resected in this patient only. Antisaccade deficits (percentage of errors) were found in 4 patients. In these patients the resection involved the superior frontal gyrus, affecting the supplementary eye field. In the same patients, the anterior cingular area, the callosal fibers and the internal capsule were lesioned, whereas these areas were spared in the 3 remaining patients. There was no difference in the volume of surgical resection between patients with and without antisaccade deficits. Conclusion Long-lasting saccadic eye movement deficits may occur following resection of frontal lobe tumors. Antisaccade deficit was observed after removal of a more medial region, including the anterior cingular area, the corpus callosum and the internal capsule, probably damaging the prefrontal efferent tracts, whereas resection of a similar tumoral volume, but more laterally, had no effect on saccadic eye movements. Frontal eye field resection resulted in controlateral visually-guided saccade deficit. (1) Pierrot-Deseilligny C. Eur Neurol 1994;34:121-34. (2) Rivaud S. Exp Brain Res 1994;102:110-20. Acknoledgements: This research was supported by the Fondation pour la Recherche Médicale and IFR 49.

Go to Main Abstract page

© 2002 Elsevier Science (USA). All rights reserved.

Back to Main

NeuroImage Human Brain Mapping 2002 Meeting

Order to appear: 761

PERILESIONAL ACTIVATION ASSOCIATED WITH POSTISCHEMIC MOTOR RECOVERY: A COMBINED FUNCTIONAL DIFFUSIONWEIGHTED AND BOLD MRI STUDY. Vicente González , Ferdinand Binkofski , Klaus-Martin Stephan , Hans-Jörg Wittsack , Cornelia Stöckel , Rüdiger J. Seitz , Hans-Joachim Freund Dept. of Neurology, Heinrich-Heine-University Düsseldorf, Germany Institute of Diagnostic Radiology, Heinrich-Heine-University Düsseldorf, Germany Subject: Neurology Abstract Introduction: Diffusion-weighted MR imaging (DWI) identifies ischemic tissue shortly after stroke onset (1). Although acute DWI lesions are highly correlated with the chronic infarct volume (2) there is also evidence that DWI abnormalities can be larger (3), as they are potentially reversible for a limited time period (4). In order to elucidate the functional viability of the DWI damaged tissue in patients with ischemic infarctions in the territory of the middle cerebral artery (MCA), we compared the relationship of the DWI lesion with the perilesional BOLD foci related to finger movements and object manipulation. Patients and methods: FMRI investigations were performed in 19 patients (46-78 ys) with their first-ever circumscribed ischemic lesion in the pericentral area but early clinical recovery. The latency between the BOLD study and the initial DWI measurement was 6 days on average. Two different tasks were employed: a sequential finger-thumb opposition task (substituted by repetitive closing and opening of the fist in three patients unable to perform individual finger movements) and tactile exploration of different objects. Each active condition lasted for 20 s and was followed by 20 s baseline (rest). FMRI measurements were performed on a 1.5-T clinical MR scanner (Siemens Vision) utilizing standard echo-planar sequences (TR=4 s, TE=66 ms, =90°). Voxel size was 3 x 3 x 4 mm. 30 consecutive slices oriented parallel to the AC-PC line, covering the whole brain, were acquired. After realignment and smoothing with radius of 4 mm, individual data analysis was performed. Using a standard box-car reference function categorical task-condition - rest comparisons were calculated and statistical analysis of signal changes (t-test) was performed using a significance level of Z > 3.12 (p<0.001 uncorrected) and K threshold = 10 for spatial extent (SPM 99). The activation pixels were projected onto axial diffusion-weighted images, which were

Back to Main

matched with the MPI-Tool. 20 axial diffusion-weighted slices (thickness 5 mm, interslice gap 1.5 mm) were acquired with b values of 0 and 1000 s/mm² and diffusion gradients in the 3 orthogonal directions in space. Results: BOLD activations were found along the outer rim of the DWI lesions in all patients. Peripheral DWI damaged areas were recruited during task performance with the affected hand (Figure). In patients with larger lesions the activation volume was also increased and extended into the most hyperintense zone. Additionally, we found network-mediated recruitment of ipsilesional and contralesional motor cortical areas at a global scale, which are determined by the lesion location, lesion volume and motor task.

Discussion: The postischemic recruitment of the neural tissue in the outer rim of the DWI lesions indicates that their peripheral fraction is functionally recovered at early subacute stage. This may be due to direct reversal of the DWI injury and resolution of vasogenic and cytotoxic edema. References: 1. Warach S et al. 1996, J Cereb Blood Flow Metab 16:53-59. 2. Lövblad KO et al. 1997, Ann Neurol 42:164-70. 3. Barber PA et al. 1998, Neurology 51:418-26 4. Sorensen AG et al. 1996, Radiology 2:39140.

Go to Main Abstract page

© 2002 Elsevier Science (USA). All rights reserved.

Back to Main

NeuroImage Human Brain Mapping 2002 Meeting

Order to appear: 762

Maturation of white matter tracts during adolescence: a longitudinal MRI study Kate Watkins , Tomas Paus , Jean-Francois Mangin , Alex Zijdenbos , Louis Collins , Jason Lerch , Keith Worsley , Jonathan Blumenthal , Jay Giedd , Judith Rapoport Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada Child Psychiatry Branch, National Institute of Mental Health, Bethesda, MD, USA Service Hospitalier Frederic Joliot, Orsay, France Subject: Neurology Abstract The development of behaviours and cognition during childhood and adolescence is associated with patterns of maturation in the brain, particularly changes in white matter due to increased myelination or axon diameter or both. A previous analysis of MRI scans obtained in a large group of children demonstrates age-related increases in white matter in two pathways, namely the putative corticospinal tract and the frontotemporal pathway (arcuate fasciculus) presumably connecting the anterior and posterior speech regions[1]. In the present study, we sought to replicate these cross-sectional findings using a longitudinal design and to test whether previously unreported age-related changes in white matter tracts may be revealed using this more powerful within-subject design. T1-weighted MRI scans of the brain were obtained in 35 children and adolescents (age range 10.3 - 21.7 years) at two time points separated by at least 15 months (range 15 - 78 months). These images were nonuniformity corrected and nonlinearly transformed[2] to match a template in standardized stereotaxic space. The images were then classified by means of an automated algorithm (INSECT) into maps of grey matter, white matter and cerebro-spinal fluid[3]. The binary maps of white matter were extracted and smoothed using a 10mm full-width at half-maximum Gaussian kernel to create images representing the relative amounts of white matter throughout the brain. These maps were entered into a within-subject statistical analysis whereby the relationship with time between the two scans and the amount of white matter was calculated at each voxel. Significant relationships with t>5.0 are reported. White matter tracts can be identified by reference to diffusion tensor imaging, highlighting putative fascicle trajectories[4]. Time-related increases in white matter were seen bilaterally (but more predominantly on the left) in the corticospinal tracts and in the arcuate fasciculus. The increase in the left arcuate fasciculus continued within this hemisphere to include the white matter of the superior longitudinal fasciculus, presumably linking posterior temporal and inferior frontal cortices. In the left superior frontal lobe, increases were seen in several small tracts possibly linking superior and middle frontal cortices with more posterior and

Back to Main

inferior brain regions. Bilateral increases were also seen in the tracts linking occipital and temporal cortices. These findings replicate those of the previous cross-sectional study of a larger sample[1] and, thereby, emphasize the greater power of a longitudinal design, i.e., using repeated measures in a smaller sample. The longitudinal analysis also revealed novel findings: bilateral increases in occipito-temporal pathways and left hemisphere increases in dorsal premotor and prefrontal white matter. With the exception of the occipito-temporal white matter increases, the changes seen were more predominant in the left hemisphere and, therefore, are likely to reflect the development of behaviours supported by this hemisphere, such as lateralized motor and language functions. [1] Paus T et al. (1999) Science 283: 1908-1911. [2] Collins DL et al. (1995) Hum Brain Mapp 3: 190. [3] Zijdenbos A et al. (1996) Proc 4th Inter Conf on Visualization in Biomedical Computing, KH Hohne & R Kikinis (Eds.), Springer, Berlin: 439-448. [4] Poupon C et al. (2000) NeuroImage 12:184-195.

Go to Main Abstract page

© 2002 Elsevier Science (USA). All rights reserved.

Back to Main

NeuroImage Human Brain Mapping 2002 Meeting

Order to appear: 763

Functional mapping using synthetic aperture magnetometry for presurgical evaluation of refractory epilepsy Amami Kato , Masaaki Taniguchi , Masayuki Hirata , Hirotomo Ninomiya , Youichi Saitoh , Stephan E Robinson , Taizo Kihara , Norio Hirabuki¶, Hironobu Nakamura¶, Toshiki Yoshimine Department of Neurosurgery, Osaka University Medical School Neurosurgery, Hanwa Memorial Hospital CTF Systems Aloka Co. ¶Department of Radiology, Osaka University Medical School || Subject: Neurology Abstract Synthetic aperture magnetometry (SAM) is a high-resolution spatial filtering based on the algorithm of Frost's adaptive beamformer. It is completely different from the conventional dipole analysis solving inverse problem. It enables to measure the time course of the currentodensity in the small portion of the brain with an enhanced sensitivity (currentodensitogram). With this technique, the tomographic mapping of the power changes during task performance can be obtained (SAM statistical method). In the present study we analyzed the power changes in various frequency bands during sensorimotor and language tasks focusing event-related synchronization (ERS) or desynchronization (ERD). For the sensorimotor functional mapping, subjects repeated self-pacing grasping of the right or left hand 100 times. The acquired data were synchronized by a trigger from an optical switch attached to the index finger; this detected the very initial movement. Data were stored digitally from 1.5 sec prior to and 0.5 sec after trigger-onset with sampling rate of 625 Hz. The ERD of beta band demonstrated consistent localization at the contralateral hand area, whereas the ERD of alpha and low-gamma bands demonstrated considerable inter-subject variability. In the patient with a glioma around the central sulcus, hand movement of non-affected side demonstrated ERD of the beta band predominantly on the contralateral hand area, whereas hand movement of affected side demonstrated ERD exclusively on the ipsilateral hemisphere. For the language functional mapping, subjects were instructed to read without phonation one hundred of 3-character hiragana semantic words presented serially on the LCD monitor for 3 seconds with an interval of 3 seconds. The ERD and ERS of alpha to high frequency gamma bands were evaluated as spatial and temporal clusters after presentation of the stimulus. The clusters of ERD or ERS were localized over the both hemispheres including classical language-

Back to Main

related cortices in the dominant hemisphere. The ERS clusters were predominantly localized in sequence, at the occipital area in the early stage after stimulus, then the parieto-temporal area and finally at the frontal area. Whereas the ERD clusters tended to be localized multifocally in parallel. By comparing with the result of amythal test, the ERD of beta to low gamma bands at the dorsolateral frontal area were suggested important in determining the dominant hemisphere. The results indicated that SAM statistical method well demonstrated the changes of rhythmic brain activity in sensorimotor and language related areas. This analysis would be useful for functional mapping in the presurgical planning because of the simplicity of the task required. key words: magnetoencephalography, synthetic aperture magnetometry, brain rhythm, neurosurgery, sensorimotor, language

Go to Main Abstract page

© 2002 Elsevier Science (USA). All rights reserved.

Back to Main

NeuroImage Human Brain Mapping 2002 Meeting

Order to appear: 764

Cerebellar control of oculomotion in patients with neuronal calcium channel mutations: high resolution magnetic resonance imaging, genotype-phenotype correlation, and functional-anatomical correlation. Sarah Ying , Jeffry Alger , Michelle Lee , Alain Pitiot , Joanna Jen , Robert Baloh , Susan Perlman , Daniel Geschwind , Marco Iacoboni , John Mazziotta ¶, Arthur Toga UCLA Department of Neurology, Los Angeles, California, USA UCLA Department of Radiological Sciences, Los Angeles, California, USA INRIA Projet Epidaure, Sophia Antipolis, France UCLA Department of Psychiatry and Behavioral Sciences, Los Angeles, California, USA ¶UCLA Department of Medical and Molecular Pharmacology, Los Angeles, California, USA Subject: Neurology Abstract Introduction: Our goal was to study abnormalities of brain morphology in patients sharing abnormal visual-vestibular oculomotion and a mutation in the CACNA1A gene on chromosome 19p. CACNA1A encodes for Ca(V)2.1, the pore-forming -1-A subunit of the human neuronal P/Q-type voltagedependent calcium channel. This pilot study was designed to evaluate genotype-phenotype correlation in patients as well as functional-anatomical correlation. Although the different CACNA1A mutations -trinucleotide repeat expansion in spinocerebellar ataxia type 6 (SCA6), or missense or nonsense mutations in episodic ataxia type 2 (EA2) -- would predict markedly different protein products, clinical manifestations are known to demonstrate prominent overlap. On the other hand, although normal distribution of this channel encompasses the entire central nervous system, clinical abnormalities heavily favor the midline cerebellum, with early development of dysarthria, gait ataxia, gaze-evoked and downbeat nystagmus, and disruption of the visual pursuit system and visual-vestibular interaction. Thus we also sought to establish whether anatomic phenotype more closely reflects genotype or clinical phenotype. Methods: Eight patients were compared to age- and gender-matched controls, as well as to unaffected family members when possible. An average of eight T1-weighted magnetic resonance images with 0.59 to 1.05 mm3 isotropic voxels were obtained. The orientation of each acquisition underwent slight stochastic variation. Automatic registration and three-dimensional signal interpolation produced higher resolution tomographic images with a voxel size of 0.5 mm3. Through semi-automated segmentation and tissue classification, we were able to obtain volumetric data that were both precise and reliable for all

Back to Main

regions except the inferior frontal and temporal lobes. Results: Comparison of volumetric phenotype revealed significant differences in affected individuals versus normal controls, particularly in the cerebellar vermis and hemispheres. However, there was no evidence of differential involvement between the various CACNA1A mutations; nor was there selective atrophy of cerebellar areas controlling pursuit and visual-vestibular interaction. Conclusion: In this small sample, morphometry was more highly correlated with presence than mechanism of mutation. This suggests that SCA6 and EA2 represent a spectrum of disease in which specific functional abnormalities are not macropathologically localizable.

Go to Main Abstract page

© 2002 Elsevier Science (USA). All rights reserved.

Back to Main

NeuroImage Human Brain Mapping 2002 Meeting

Order to appear: 765

Brain MRI Volumetry in Non-demented Elderly Individuals Woo Suk Tae , Seung Bong Hong , Jeanyung Chey , Eun Kyung Lee Neuroimaging Laboratory, Department of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea Department of Psychology, Seoul National University, Seoul, Korea Subject: Neurology Abstract Purpose: To investigate the structural change of non-demented elderly individuals with low cognitive performance (LCP), volumes of cerebrum, frontal lobe, temporal lobe, and hippocampus, and midsagittal area of corpus callosum were measured in people with LCP and age matched subjects with normal cognitive performance (NCP). Methods: Fifteen NCP subjects (72.2 77.81 year-old, 4 males, 11 females) and fifteen LCP subjects (72.1 37.83 year-old, 6 males, 9 females) underwent 1.6 mm thickness whole brain SPGR MRI. Volumes of cerebrum, frontal lobe, temporal lobe and hippocampus were measured with semi-automated VOI method. The mid-sagittal image was obtained with image reconstruction. According to the Witelson¡¯s criteria, the area of corpus callosum was divided into 7 sub-regions (a1 to a7 from anterior to posterior). In each sub-region, the pixel number was counted according to ROI definition. The difference of each measurement between NCP and LCP subjects were tested by ANCOVA (adjusted by age and cerebral volume). Results: The cerebral volume was not different between groups (NCP: 945.3 62.4 cm3, LCP: 906.9 72.5 cm3, p=0.131). Left frontal lobe(p=0.020), left temporal lobe(p=0.029), left hippocampus(p=0.034) and the rostrum(p=0.007) of corpus callosum were significantly smaller in LCP group than in NCP group. Conclusions: People with LCP seem to have structural abnormality (atrophy) in left frontal lobe (probably caudal/orbital prefrontal lobe), left hippocampus and left temporal lobe. This finding indicates that LCP is related to the atrophy of brain structures in left hemisphere

Go to Main Abstract page

© 2002 Elsevier Science (USA). All rights reserved.

Back to Main

Back to Main

NeuroImage Human Brain Mapping 2002 Meeting

Order to appear: 766

Fast functional whole brain mapping with high resolution using a 3T system in a clinical setting Anders Wennerberg , Danielle van Westen , Johan Olsrud , Sara Brockstedt , Jimmy Lätt , JanAnders Ahnlide , Ingmar Rosén , Karsten Wicklow , Freddy Ståhlberg , Elna-Marie Larsson Huddinge University Hospital, Karolinska Institutet, Sweden Lund University Hospital,Sweden Siemens AG, Erlangen, Germany Subject: Neurology Abstract Introduction: A major advantage with a 3T MRI system is the potential to acquire high resolution isotropic whole brain functional (fMRI) images. The purpose of this study was to cover cerebrum and cerebellum with an isotropic spatial resolution (27µl) and a temporal resolution (3 sec) for preoperative evaluation of intracranial tumours. Materials and methods: Written informed consent was obtained from all subjects. At present 2 tumor patients and 2 volunteers have been included. The study was performed on a 3T MR head scanner (Siemens Magnetom Allegra). Whole brain, single shot EPI, T2* weighted images were acquired (TR=3000 msec, TE=30 msec, FA=90°, FOV 192 mm, slice thickness=3 mm, interslice gap=0.3 mm, number of slices=40, matrix=64x64, timeframes=80). Motion correction was performed using a 3D k-space image registration software provided by the manufacturer. Statistical analysis was applied in two sessions. The first session was at the MRI console using the software supplied by the manufacturer for a preliminary analysis of the functional data. The second session included postprocessing with a standard suite of statistical methods. The suite of stimulation paradigms consisted of sensory and motor stimulation, language paradigms and visual stimulation. All stimulation paradigms followed a block design BABABAB (B=baseline task, A=activation task). Results: Whole brain coverage allows visualization of brain activation in the cerebral hemispheres as well as in the cerebellum. In fig. 1-3 below, fMRI response is shown in motor cortex (fig 1), SMA (fig 2) and medial in cerebellum (fig 3), superimposed on the T2* weighted functional EPI images. 3 slices out of a

Back to Main

set of 40 slices with isotropic resolution (3x3x3 mm) are shown. In all subjects motor and sensory stimulation resulted in activation in the motor cortex and in the cerebellar hemispheres. Language paradigms activated sites corresponding to Broca's and Wernicke's areas. The signal change in the cerebrum was 6-8% and in the cerebellum 2-4%. Discussion: Functional brain mapping designed to cover the whole brain ensures mapping of eloquent cortex in patients with brain tumors. Functional mapping in combination with morphological images and MRangiography obtained in the same session provides the neurosurgeons with complete information necessary for presurgical planning. The stimulation paradigms were validated on volunteers and proved to be useful in patients with brain tumors. In general, paradigms are constructed to activate a specific area in the brain, however, no paradigm activates a single spot in the brain. Whole brain coverage allows for combination of the results from several paradigms thus increasing reliability of activation. Conclusion: Succesful implementation of fMRI in clinical routine requires proximity of the 3T MRI suite to neuroradiologists and neurosurgeons as well as whole brain coverage and standardized paradigms.

Back to Main

Go to Main Abstract page

© 2002 Elsevier Science (USA). All rights reserved.

Back to Main

NeuroImage Human Brain Mapping 2002 Meeting

Order to appear: 767

Applicability of DTI-based fiber tracing for neurosurgical planning Dorothee P. Auer , Benno Pütz , Christoff Gössl , Ludwig M. Auer Max-Planck-Institute of Psychiatry, Munich, Germany Institute of Applied Sciences in Medicine, ISM-Austria, Salzburg, Austria Subject: Neurology Abstract Diffusion tensor (DT) imaging provides information about the alignment and direction of myelinated white matter tracts. DT-derived parameters may be used to calculate fractional anisotropy (FA) or colorcoded direction maps which highlight myelinated fiber tracts [1]. Direct fiber tracing may be achieved by various tracking algorithms [2-6]). Preliminary results have been obtained in patients with Wallerian degeneration [7] and brain tumor [6]. Depicting the course of functionally important white matter tracts in patients with brain tumors may however be particularly useful for improved surgical planning and neuronavigation. The aim of the present study was to evaluate the applicability and usefulness of a recently developed fiber tracing technique [6] for neurosurgical planning. Methods: 34 brain tumor patients, referred for preoperative MRI, and 40 controls were studied at 1.5 T (Signa Echospeed, GEMS). A diffusion-weighted SE-EPI sequence with 6 non-collinear gradient orientations and 4 b-factors was used. 24 slices were acquired with a resolution of 1.875x1.875x3mm3 (1mm gap) achieving subtotal brain coverage. Fiber tracing was performed using a linear state-space model as previously described [6] from manually defined start regions. Moreover, 26 patients and 6 controls underwent fMRI using single-shot GE-EPI sequences while performing various motor, language or visual tasks. Results and Discussion: The pyramidal tract could be traced in all controls and all healthy hemispheres in tumor patients from the mesencephalic ROI as determined with known anatomical landmarks (pons, crura cerebri, internal capsule, centrum semiovale and subcortical precentral gyrus) and fMRI results. Detectability at the pontine and subcortical level showed some variability and criticially depended on the chosen anisotropy threshold. Tracing results were improved when using the data acquired with b={0, 880}s/mm2 which led to improved contrast in respective FA maps. Displacement of the pyramidal tract was found in frontal and parietal tumors. In most cases, the traced fiber course could be followed up to precentral gyrus (hand area) and was thus qualitatively confirmed by the fMRI results. However, spatial coregistration of fMRI and fiber tracing is required to quantitatively assess the colocalization or deviation at the motor gray white matter junction. The possibility to delineate other white matter tracts from any selected region of interest is another, particularly interesting application for neurosurgical planning.

Back to Main

Analysis of the connectivity of possible approach routes was performed by tracking all fibers contained in the peritumoral white matter. Conclusion: This study shows the feasibility to visualize the pyramidal tract and other major white matter bundles in relation to cerebral gliomas using diffusion tensor imaging and a novel tracking algorithms. This technique provides important functional topographical information for planning and simulation of neurosurgical interventions which may usefully complement presurgical cortical mapping by standard fMRI. Further development is needed to fuse tracking results with fMRI maps and deformable brain and tumor volumes for next generation neuronavigation. References [1] Nakada Neuroscience Research. 22:389, 1995, [2] Conturo, PNAS 96:10422, 1999, [3] Mori, AnnNeurol 45:265, 1999, [4] Poupon, NeuroImage 12:184, 2000, [5] Basser, MRM 44:625, 2000, [6] Gössl, NeuroImage, in press, [7] Wieshmann, NeuroImage. 10:225, 1999

Go to Main Abstract page

© 2002 Elsevier Science (USA). All rights reserved.

Back to Main

NeuroImage Human Brain Mapping 2002 Meeting

Order to appear: 768

Localized hippocampal grey matter density loss in Williams syndrome Andreas Meyer-Lindenberg , Shruti Japee , Philip Kohn , Carolyn B. Mervis , Colleen A. Morris , Karen Faith Berman Unit on Integrative Neuroimaging, CBDB, NIMH Department of Psychological and Brain Sciences, University of Louisville Department of Pediatrics, University of Nevada School of Medicine Subject: Neurology Abstract Williams syndrome, caused by a microdeletion on chromosome 7q11.23, usually results in mild to moderate mental retardation and a distinctive behavioral phenotype involving relative strengths in auditory rote memory and language, and an extreme weakness in visuospatial construction(1). In this study, we wished to canvas the entire brain for significant morphological alterations without being constrained by conventional anatomical landmarks. To achieve this, we employed the method of voxelbased morphometry. To validate these results and to obtain absolute volume measurements, we used template-based volumetry. To avoid a confound of general intellectual impairment, we chose a subgroup of 10 participants with genetically confirmed Williams syndrome, but normal-range IQ, who were compared to matched controls. Methods: Axially acquired T1-weighted structural MRIs (0.94*0.94*1.2mm) were skull-stripped, segmented, normalized to a standard template, smoothed and processed using established methodology for voxel-based morphometry (2) in a random-effects statistical model. Template-based volumetry was performed for each hemisphere and tissue compartment separately. Results: Williams syndrome brains were found to be significantly smaller with proportional reductions in ventricular volume. Compared to normal controls, the brain in Williams syndrome showed a significant reduction of grey matter density in the left hippocampus ( p<0.001, corrected, voxel level). A trend was also observed in the right hippocampus p=0.084, corrected, voxel-level, p<0.0001, uncorrected). Discussion: Using voxel-based morphometric methods, we demonstrate a localized hippocampal structural abnormality in the grey matter compartment of the brains of Williams syndrome participants. A prominent locus in the Williams syndrome deletion is a gene coding for LIM Kinase 1. This enzyme is highly expressed in the brain (3), and murine models of kinase deficiency show impaired hippocampal maturation (4). This suggests that our studies reveal a genetic-morphological correlation in Williams syndrome. This intriguing preliminary result should be validated by other (for example region-of-interest based) analytic methods, in different cohorts of patients and controls, and using patient-specific templates. In addition to these, we are currently using functional neuroimaging methods to explore if, and

Back to Main

how, this structural abnormality is reflected in the cognitive and behavioral abnormalities characterizing Williams syndrome. 1. Morris & Mervis, Annu Rev Genomics Hum Genet 1, 461 2. Good et al. Neuroimage 14, 685 3. Frangiskakis et al. Cell 86, 594 4. Grant et al. Science 258, 1903

Figure: Significant reductions in hippocampal grey matter density (p<0.001, corrected, voxel level, random effects model) in Williams syndrome compared to normal controls.

Go to Main Abstract page

© 2002 Elsevier Science (USA). All rights reserved.

Back to Main

NeuroImage Human Brain Mapping 2002 Meeting

Order to appear: 769

Comparison of fMRI activation and cerebral atrophy P. Vannini , P. Julin , T. Jonsson , M. Kristoffersen-Wiberg , L-O. Wahlund , O. Almkvist Dept. of NEUROTEC, Div of Geriatric Medicine, Karolinska Institutet Center for Surgical Sciences (CFSS), Div of Diagnostic Radiology, Karolinska Institutet, Stockholm, Sweden Subject: Neurology Abstract Functional MRI (fMRI) has proved a useful tool to examine age-related changes in functional activation. Although many studies have looked at age-related changes in cerebral hemodynamics [1, 2], few studies have looked at the effect of cerebral atrophy on the fMRI signal. For healthy young and elderly subjects, we studied patterns of brain activation associated with two finger-tapping tasks and measures of total relative brain volume. Material and Methods Subjects In total, 12 young and 7 elderly healthy subjects (Mean age 25.4 and 64.9, respectively) participated in the study. Informed written consent was obtained from all subjects. Due to technical problems, two young subjects had to be excluded from analysis in each condition. Paradigm Two different fingers-to-thumb opposition tasks were used, the first task was a fixed pattern (FIX) and the second task was a non-repetitive, selective generation pattern (SELF). Periods of hand relaxation (REST) alternating with the two tasks served as a control. Within a set, there was an alternation of experimental conditions over time and the general model was: rest (40s), first activation (32s), rest (48s), second activation (40s) and rest (56s). Data Acquisition and Analysis BOLD images were acquired with a Siemens Magnetom Vision 1.5T. Functional image analysis was performed off-line using AFNI software. A ROI (4x4mm) near the central sulcus, including M1/S1 and another ROI including SMA were identified as target regions. The sum of activation seen in these target areas was considered. Pixels with activation above a significant threshold (p<0.01) were used to identify the spatial extent of activation. Total relative brain volume (brain volume/brain volume + cerebrospinal fluid (CSF) volume) was calculated from an EPI sequence covering the whole brain. The operator was blinded to subject’s age. Extra-cranial tissues were removed interactively. Using automated histogram analysis, the signal intensity of the 3D image sets were normalised and segmented into brain and CSF using a global threshold. Results Activation was seen in target regions (M1/S1 and SMA) for all subjects. For young compared to elderly

Back to Main

subjects, there was a significantly greater number of activated pixels of target regions both in FIX (Mean±SD: 11.3±4.5 vs. 6.4±1.8; p=0.02) as well as in SELF (Mean±SD: 11.8±4.4 vs. 7.4±2.2; p=0.03). In addition, young compared to elderly subjects had a significantly larger total relative brain volume, i.e., relatively more brain tissue and less CSF (Mean±SD: 0.85±0.04 vs. 0.93±0.03; p=0.02). Conclusions The results showed that elderly subjects both have smaller activated areas in fMRI and a smaller total relative brain volume. Further studies, analysing the effects of regional atrophy as well as hemodynamics, are needed to better understand age-related changes in functional activation. 1.D´Esposito, M., et al., The effect of normal aging on the coupling of neural activity to the bold hemodynamic response. Neuroimage, 1999. 10: p. 6-14. 2.Buckner, R.L., et al., Functional Brain imaging of young, nondemented and demented older adults. Journal of Cognitive Neuroscience, 2000. 12(suppl. 2): p. 24-34.

Go to Main Abstract page

© 2002 Elsevier Science (USA). All rights reserved.

Back to Main

NeuroImage Human Brain Mapping 2002 Meeting

Order to appear: 770

Quantitative Spatial Comparison of Magnetic Source Imaging with Intraoperative Cortical Mapping in Patients with Brain Tumors Timothy Roberts , Hagen Schiffbauer

, Paul Ferrari , Mitch Berger

University of California, San Francisco University of Tuebingen Subject: Neurology Abstract Purpose: To quantitatively compare the localization of sensorimotor and language cortex as estimated by magnetoencephalography (MEG) and magnetic source imaging with intraoperative electrophysiological cortical stimulation mapping in patients with brain tumors. Materials & Methods: Forty-three non-consecutive patients underwent preoperative somatosensory magnetic source imaging (MSI). Forty-seven patients underwent MSI for determination of hemispheric dominance and estimation of putative language areas. A dual 37-channel biomagnetometer (Magnes II, 4D Neuroimaging, San Diego, CA) was used to acquire the magnetoencephalograms (MEG). For somatosensory mapping, patients received painless tactile somatosensory stimulation of the lip, hand digits and toe, during MEG recording. The early somatosensory evoked field (30-70ms) was modeled using a single equivalent current dipole approach to estimate the spatial coordinates of somatosensory cortex localization. For language mapping, patients were presented binaurally with simple vowel stimuli, with no task demands. The late field (post 150ms) was analyzed to determine hemispheric dominance, and a source was modeled at the peak evoked field in the latency range 150-500ms, subject to an instantaneous single equivalent current dipole model/data correlation of r>0.97. High resolution MRI volume datasets with fiducials were separately acquired. MEG and MRI were co-registered to form the final MSI. Patients underwent image-guided tumor resection including electrophysiological cortical mapping of somatosensory and/or motor, or essential language. Cortical mapping sites, as preserved on neuronavigation system screen snapshots, and the corresponding MEG source localizations were identified in the MSI volume dataset using the MRVision software package. Point to point (3-D) distances between the cortical stimulation sites and the corresponding MEG source localization were determined; since intraoperative mapping involves cortical surface stimulation, 2D point-to-point distances were additionally measured between intra-operative sites and projections of the MEG sources onto the cortical surface.

Back to Main

Results: In a subgroup of 37 patients we compared an intraoperative motor response to a somatosensory cortex localization based on the MSI. The 2-D and 3-D distances between the two corresponding points were 19.0 +/- 1.3 mm and 22.8 +/- 1.6 mm. In a second subgroup of 28 patients we compared intraoperative cortical mapping of somatosensory response stimulation with MSI-based somatosensory localizations. The 2-D and 3-D distances between the two corresponding points were 12.5 +/- 1.4 mm and 20.5 +/- 1.5 mm. For the patients undergoing MSI for determination of hemispheric dominance for language, the mean distance between the defined late-field MEG source and cortical sites of speech arrest intraoperatively was 23.4 +/- 3.9mm. Conclusions: Preoperative MSI with the above paradigms and intraoperative electrophysiological mapping show a favorable degree of correlation, particularly for mapping of sensorimotor cortex. Inter-modality source estimation distances are smaller for somatosensory-somatosensory than somatosensory-motor comparisons. However, the observed 6-7mm increase in site separation obtained when comparing somatosensory-motor sites is predictable and systematic (in the anterior-posterior direction). Projection of MSI source localizations to the cortical surface for comparison with cortical stimulation mapping reduces the discrepancy between the modalities to the magnitude of the uncertainty of each individual method. Thus, MSI can be considered a valuable and accurate planning adjunct in the treatment of patients with intra-axial brain tumors.

Go to Main Abstract page

© 2002 Elsevier Science (USA). All rights reserved.

Back to Main

NeuroImage Human Brain Mapping 2002 Meeting

Order to appear: 771

Interictal Magnetoencephalography (MEG) in Partial Epilepsy: Is it Useful? Intrasubject Spatial Comparison with Ictal Onset Source and Functional Mapping Estimates of the Epileptogenic Zone Tim Roberts, Lily Tang, Mary Mantle University of California, San Francisco Subject: Neurology Abstract To evaluate the accuracy of interictal magnetoencephalography (MEG) in localizing the primary epileptogenic focus, intrasubject comparisons of interictal spike localization estimates with ictal seizure onset sources were made. In subjects with focal sensorimotor seizure presentation, MEG-derived somatosensory mapping source localizations were estimated and were compared with interictal spike cluster localizations. MATERIALS & METHODS 13 patients underwent magnetoencephalography (MEG) using a dual 37-channel biomagnetometer (Magnes II, 4D-Neuroimaging, San Diego, CA), with resolvable interictal epileptiform activity. Furthermore, five patients also had ictal events, the onsets of which were captured on simultaneous MEG/EEG recordings. Eight patients presented with focal sensorimotor epilepsy (i.e. seizures involving motion or sensation of hand and/or face). Somatosensory magnetic source imaging (MSI) functional mapping using tactile stimulation was thus performed, as appropriate. An equivalent current dipole (ECD) was used to estimate the location of the current source. For modeling of interictal spike, seizure onset and somatosensory functional sources, a model/data correlation of r>0.97 was required. Magnetic source images were constructed by registering MEG source coordinates to anatomic MRI. Correlation of the spatial coordinates of ictal and somatosensory mapping localizations with interictal spike clusters were assessed, in terms of the standard deviation (SD) of the multiple interictal source localizations obtained. Distances between ictal onset sources and the centroid of a cluster of interictal sources are thus additionally represented in effective Z-scores (where a Z-score of 1 implies that the distance between the ictal source and the centroid of the interictal sources is equal to one SD of the interictal source localizations), in the x- (anterior-posterior), y- (medio-lateral) and z- (superior-inferior) axis. RESULTS MEG interictal activity in each of the 13 subjects occurred in the same anatomic region as the ictal and somatosensory source localizations, respectively. The mean distance between the ictal foci and interictal spike clusters was 1.1±0.6cm. The effective Z-scores for the five ictal foci ranged from 0.1 to 3.6, with

Back to Main

the average being 1.6±0.7, 0.7±0.1, and 1.8±0.5 in the x-, y-, and z- axis, respectively. Somatosensory mapping also consistently colocalized with interictal spikes with a mean distance of 1.6±1.1 cm. The average Z-scores were 1.2±0.5 cm, 0.9±0.5, and 2.1±0.5, in the x-, y-, and z- axes. No systematic directional bias was observed. The interictal source localizations were tightly clustered. The mean volume of an ellipsoid defined by one SD of the interictal dipole clusters (in each axis) was 0.96cm3. MEG localizations are concordant with structural abnormalities detected on surface coil MRI in the majority of cases. In 3 cases where routine MRI were normal, lateralizing MEG interictal activity was detected. Four subjects underwent surgical resection of the epileptogenic tissue, and became either seizure-free or had significant reduction in seizure activity post-surgery. In those cases, intraoperative findings were concordant with interictal MEG localizations. CONCLUSION Interictal MEG spike localizations were concordant with ictal onset sources, where available and with somatosensory mapping localization, where appropriate, as estimates of epileptogenic foci. These findings support the interpretation of interictal MEG as a spatially accurate, useful and effective noninvasive method for estimating the primary seizure focus.

Go to Main Abstract page

© 2002 Elsevier Science (USA). All rights reserved.

Back to Main

NeuroImage Human Brain Mapping 2002 Meeting

Order to appear: 772

Determination of Hemispheric Dominance for Language using the Late Evoked Neuromagnetic Field in Response to Vowel vs. Consonant-vowel (CV) Stimuli, in Passive vs. Attending States Tim Roberts , Nicole Gage , Paul Ferrari , Hagen Schiffbauer

, Mitch Berger

University of California, San Francisco University of Tuebingen Subject: Neurology Abstract Purpose: To evaluate late field magnetoencephalography (MEG) for assessment of hemispheric dominance for language. In particular, to assess the influence of stimulus complexity (simple vowel vs. consonant-vowel (CV) tokens) and the additional role of a linguistic discrimination task on measures of lateralized late-field activity. Methods: 47 patients were enrolled. 45 proceeded to intra-operative awake speech mapping; the remaining 2 were confirmed by Wada testing as right hemisphere dominant. Bilateral MEG recordings were made during passive auditory stimulation with simple vowel sounds (/a/ and /u/) at male and female pitches. Similar recordings were made during presentation of CV tokens (/ba/, /pa/, /bae/, /pae/). The two stimuli sets were then re-presented to the patients, who were instructed to perform a linguistically relevant discrimination (e.g. /a/ from /u/, irrespective of pitch). The late field was defined as commencing at the first field minimum following the 100ms auditory evoked field (AEF) component and was truncated after 250ms. For each sample within this 250ms latency window a current dipole source model was applied separately for signals recorded from each hemisphere. Rigid criteria, including model-data correlation of r>0.97 were applied; if exceeded, the data sample was enumerated. A lateralization index (LI) was calculated for each stimulus from the number of such qualifying samples in each hemisphere. LIs in the range ?0.2 to +0.2 were interpreted as unresolvable. LIs were not calculated if AEF evoked response amplitude was weak (<20fT), or if the number of qualifying time samples was fewer than 25 (10%, floor effect). Results: Of 47 patients, unambiguous hemispheric dominance could be defined from the MEG LIs in 23 cases, using passive presentation of simple vowels. In the remaining 24, evoked response amplitudes were insufficient, or substantial bilateral activity was present. For patients who subsequently had confirmed left hemispheric essential language sites (n=25), 9 had unambiguous MEG LIs. In all 9 cases MEG predicted left hemispheric dominance. In the remaining 16 cases, no prediction was possible from MEG. In no case did MEG based on simple vowel presentation and passive listening predict (incorrectly)

Back to Main

right hemispheric dominance. The two cases with right hemispheric dominance indicated by Wada testing showed rightward MEG LIs. With CVs, and with the addition of task demands to either stimulus set, both sensitivity and specificity of the late field MEG analysis deteriorated (passive CVs: 6/25 correctly identified left hemispheric, 1/25 incorrect right hemispheric and 18/25 indeterminate). Conclusion: MEG based LIs derived from the late (post-auditory) components of the neuromagnetic field evoked by simple vowel stimuli can be used for predicting hemispheric dominance for language. Where predictions are possible, given stringent analysis criteria, accuracy is high with respect to intra-operative speech mapping and Wada testing. Despite low sensitivity, this method offers an appealing screening alternative to Wada testing or awake intraoperative mapping. Using single equivalent dipole modeling appears to constrain the choice of linguistic stimuli to extremely simple conditions; we suspect confounding activity from multiple brain areas contaminates this simple measure in more complex stimulus paradigms.

Go to Main Abstract page

© 2002 Elsevier Science (USA). All rights reserved.

Back to Main

NeuroImage Human Brain Mapping 2002 Meeting

Order to appear: 773

Increased Cerebellar Metabolism in Alzheimer’s disease. James Patterson

, Kerrie Tainter , David Lilien , Michael Glabus

Louisiana State University Health Sciences Center - Department of Psychiatry, Biomedical Research Foundation PET Imaging Center Louisiana State University Health Sciences Center - Department of Radiology Unit on Integrative Neuroimaging, Clinical Brain Disorders Branch, National Institute of Mental Health, NIH Subject: Neurology Abstract Background: The cerebral metabolic abnormalities of senile dementia, Alzheimer’s type (SDAT) are well known, and include a characteristic pattern of parietal and temporal hypometabolism, the severity of which generally parallels the clinical course. Very few studies have ever examined cerebellar changes in SDAT. Indeed, the cerebellum is still in use as a “standard” region used to scale cerebral cortical perfusion in some semi-quantitative studies utilizing single photon emission tomography (SPECT) with perfusion tracers. Methods: We retrospectively reviewed positron emission tomography (PET) studies with 18-F-fluorodeoxyglucose (FDG) in 21 patients referred for diagnostic scans with various stages of cognitive decline, and compared them statistically to 15 normal control subjects. Statistical Parametric Mapping (SPM) was used to evaluate scan data. Group analysis was performed as well as correlation with an index of clinical severity based on image evaluations by an experienced PET physician utilizing standard clinical criteria for SDAT. All scans were corrected for global intensity differences using a scale factor based on occipital metabolism. This was based on previously documented findings of more severely demented patients having widespread parietal, temporal, and even frontal metabolism reductions, which can lead to artificially induced regions of apparent increased activity (in unaffected regions) after proportional scaling correction with a scale factor based on global intensity. However, occipital cortex was consistently normal by both visual inspection and SPM evaluation. Age was entered as a nuisance covariate. As we had an a priori hypothesis of increased metabolism in the cerebellum (based on the author’s previous publication [Patterson JC, 2001 Am J Geriatric Psychiatry 9:1], as well as visual inspection of the scans by a trained nuclear medicine physician), an uncorrected significance threshold of T=3.37 was used with an extent threshold of 100 voxels. Results: We found significant decreased metabolism in parietal and temporal lobes (based on correction for whole brain), consistent with previous published results. We also found significant increased cerebellar metabolism in patients with Alzheimer’s disease. In the group analysis, this was maximal in the left cerebellum at [-18 –56 –42] (Z=4.65). Moreover, this functional cerebellar abnormality was also

Back to Main

present in early stages, and increased inversely with cerebral cortical metabolic decreases. Interestingly, the region that correlated with the radiological rating of severity was not the left cerebellum, but the cerebellar vermis [0 –62 –34], (Z=4.3). Conclusion: Alzheimer’s disease in our patients is associated with decreases in metabolism in the parietal and temporal lobes, consistent with published results. We also found increased metabolism in the cerebellum, which varied inversely with cerebral hypometabolism, indicating that this structure may play a role in the pathophysiology of Alzheimer’s. This is consistent with the multitude of studies in the functional imaging literature that report the cerebellum’s involvement in cognitive processes, as well as the strong neuroanatomical connections the cerebellum has with the parietal lobe. This pilot data will be expanded to further characterize the changes present in Alzheimer’s, and to investigate the possible role of the cerebellum in SDAT and other dementias.

Go to Main Abstract page

© 2002 Elsevier Science (USA). All rights reserved.

Back to Main

NeuroImage Human Brain Mapping 2002 Meeting

Order to appear: 774

The conduction time between hippocampi on both sides analyzed by synthetic aperture magnetometry (SAM) Hirotomo Ninomiya, Amami Kato, Katsumi Imai*, Masayuki Hirata, Masaaki Taniguchi, Takahito Baba, Shunichiro Hirano, Toshiki Yoshimine Osaka University Medical School, Departments of Neurosurgery and *Pediatrics Subject: Neurology Abstract Introduction: There are a few reports to measure the cortico-cortico conduction time. Still less, there is few reports to measure the conduction time between hippocampi on both sides with a human being. We aimed to analyze this conduction time by magnetoencephalography (MEG) with a spatial filter. Methods: MEG was measured with a sampling rate of 625 Hz from the medial temporal lobe epilepsy patient. Ictal MEG was analyzed by SAM. SAM is a spatial filtering method for MEG using an adaptive beamformer and shows high performance to obtain the regional electrical activity of selected brain region as if virtual sensors are inserted. The serial currentodensity at the region in the MRI corresponding to the hippocampi on both sides was calculated by SAM. Time delay of peak phase of each ictal spikes were acquired. The currentodensity were also acquired. Results: MEG and SAM currentodensitography (CDG) showed repeated 14 spikes before the ictal oscillation with high frequency. This interval was 9.7 sec and consisted of 5700 samples. On the affected side, the average of the currentodensity was 2.59E-10 A-m and standard deviation was 9.24E-08 and variance was 8.54E-15 during this 9.7 sec. On the contralateral side, the average, standard deviation and variance were 3.45E-10, 7.29E-08 and 5.31E-15 respectively. The minimal time delay showed 0 msec and the maximal one was 24 msec. The average time delay was 8.9 msec. The peak currentodensity showed from a minimum of 92.2 nA-m to a maximum of 393 nA-m and the average was 279 nA-m on the affected side. The time delay of the contra lateral side was from 83.0 nA-m to 282 nA-m and the average was 194 nA-m on the contralateral side. Discussion: SAM isn't a solution of an inverse problem such as equivalent current dipole analysis. The spatially selective beamformer modification of the SAM method eliminates background noise from other brain regions and allows the elucidation of meaningful signals from selected target regions . And it requires no bias in selecting spikes showing a dipole pattern. Consequently, SAM enables to display active multiple sources simultaneously with high temporal resolution. The cortico-cortico conduction time has been reported to be 2.8-22.5 m/sec with a rhesus monkey. The Interval between both hippocampi was 6 cm. So, it could takes 2.7-21 msec to propagate the epileptic discharge of the affected side to the contra lateral side. A phase delay of 8.9 msec of our result would be agreed reasonably with this past report. Conclusions: In this study, we applied the spatial filter to the ictal MEG. It took 8.9 msec to conduct the epileptic discharges from the affected hippocampal region to the contralateral region. SAM is the useful filtering

Back to Main

technic to analyze the magnetic field consisted of multiple epileptic sources.

Go to Main Abstract page

© 2002 Elsevier Science (USA). All rights reserved.

Back to Main

NeuroImage Human Brain Mapping 2002 Meeting

Order to appear: 775

Cortical Thickness in Alzheimer's disease Jason Lerch , Jens Pruessner Hampel

, Alex Zijdenbos , Stefan Teipel , Katharina Buerger , Harald

McConnell Brain Imaging Centre, Montreal Neurological Institute, McGill University, Montreal, Canada Dementia Research Section and Memory Clinic, Ludwigs-Maximilian University, Munich, Germany Subject: Neurology Abstract Previous studies - mostly relying on manual measurements - have repeatedly demonstrated specific atrophy in Alzheimer's disease (AD) compared to normal controls [1]. The object of this study was to examine the uselfulness of a fully automated cortical thickness measure to investigate changes occurring in AD. METHODS 42 T1 scans (25 AD and 17 controls) from the Klinikum der Innenstadt, Ludwig-MaximiliansUniversitaet, Munich, Germany, were registered to Talairach space [2] and corrected for non-uniformity artefacts[3]. The MR image was classified into white matter, grey matter, and CSF[4], followed by an extraction of inner and outer surfaces using deformable models[5], which provides the advantage of colocalising vertices across brains, allowing for population statistics. Cortical thickness was measured at each vertex using Laplace's equation[6] (reimplemented locally). For a more detailed description of the methodology see [7]. Statistical analysis was performed at each vertex, employing clinical diagnosis, or Mini-Mental-State-Exam (MMSE) scores. RESULTS In the main group analysis, significant differences in cortical thickness occurred in the medial temporal lobes, the orbito-frontal cortex, the posterior cortex, and the posterior cingulate. In the temporal lobes, effects were strongest in the left entorhinal cortex and left parahippocampal gyrus (F values 20 to 40). The frontal lobes demonstrated an effect bilaterally in the orbito-frontal areas(F 20 to 37). In the posterior cortex significant effects existed bilaterally in the superior and inferior (F 8 to 15) parietal lobules. AD subjects also showed decreased cortical thickness in the associative visual areas bilaterally (F 17 to 20) and the posterior cingulates (F 27 to 40). Regression against MMSE scores showed additional significant results in both the ventral and dorsal visual pathways along with a left-hemisphere dominant effect in the major language areas. Noticeable here were Broca's (F 33 left, 12 right) and

Back to Main

Wernicke's area (F 28 left, 4 right). DISCUSSION The results confirm previous findings of specific atrophy in AD, especially in the limbic system and its cortical connections. It was intriguing to find a precise anatomical outline of the entorhinal cortex as a result of the statistical analysis, since it is discussed as being affected early and profoundly in the course of AD. Moreover, the effects in the language areas seen only in the MMSE regression point to the importance of language function in determining MMSE scores. REFERENCES [1] Double KL, Halliday GM, Kril JJ, et. al. Neurobiol. Aging 17:513-521 [2] Collins DL, Neelin P, Peters TM, Evans AC. J. Comp. Assisted Tomography 18:192-205, 1994. [3] Sled JG, Zijdenbos AP, Evans AC. IEEE TMI, 17:87-97, 1998 [4] Zijdenbos AP, Forghani R, Evans AC. MICCAI 439-448, 1998. [5] MacDonald D, Kabani N, Avid D, Evans AC. NeuroImage 12:340-356, 2002. [6] Jones SE, Buchbinder BR, Aharon I. Hum. Brain Mapping, 11:12-32, 2000. [7] Lerch J, Evans AC, Pruessner J, et. al. HBM 2002 abstract.

Go to Main Abstract page

© 2002 Elsevier Science (USA). All rights reserved.

Back to Main

NeuroImage Human Brain Mapping 2002 Meeting

Order to appear: 776

Metabolic changes following Subthalamotomy for Advanced Parkinson?s Disease: Comparison of Early and Long-term Results Anna Barnes , Philip Su , Maja Trost , Yilong Ma , Ham-Min Tseng , Ruoh-fang Yen , David Eidelberg Center for Neuroscience Research, North Shore University Hospital, Manhasset, New York and New York University School of Medicine, New York, New York Department of Neurology, National Taiwan University Hospital, Taipei, Taiwan Subject: Neurology Abstract Introduction. In a previous FDG PET study of unilateral subthalamotomy (Su et al 2001), we found a reduction of glucose utilization in the ipsilateral midbrain, SN, GPi, thalamus and pons at 3 months postoperatively. Additionally, we demonstrated the relationship between clinical improvement at this time point and the suppression of a Parkinsons disease (PD) - related metabolic covariance pattern (PDRP) (Moeller et al 1999). In this study we determined whether these functional changes persisted at 12 months following surgery and whether they correlated with clinical improvement. Methods. We studied 5 advanced PD patients with FDG PET before, and at 3 and 12 months following unilateral STN ablation. At each imaging time point the patients were evaluated off-medication with the Unified Parkinsons Disease Rating Scale (UPDRS)- Motor examination. All images were processed and analyzed using SPM99 with an hypothesis testing threshold of p< 0.01(voxel height). Differences in regional glucose utilization between 3 and 12 months post-surgery were highlighted by exclusive masking of the 3 month SPM(t) with the SPM(t) obtained at 12 months. Additionally, we quantified the expression of the previously identified PD related metabolic covariance pattern PDRP in each hemisphere (operated, un-operated) at the three imaging time points on an individual case basis. Results. Clinical improvement (P<0.05) in UPDRS ratings for bradykinesia, rigidity, tremor, and gait were present at 3 months. With the exception of tremor, these improvements persisted at 12 months. SPM analysis indicated that the metabolic reduction in the ipsilateral putamen/GPi that was observed at 3 months remained reduced at 12 months. However, the ipsilateral reduction in ventral thalamic metabolism that was present at 3 months studies was no longer significant on long term follow-up. PDRP activity in the operated hemisphere was significantly reduced at both 3 and 12 months (P<0.03). By contrast no change in PDRP activity was evident in the un-operated hemisphere at either time point. Conclusions.

Back to Main

The sustained benefit of unilateral subthalamotomy is associated with long term reductions in pallidal and brain stem glucose utilization. Post-operative recurrence of tremor is consistent with an elevation in ventral thalamic metabolism between 3 and 12 months suggesting differential effects on pathways mediating this symptom. Similarly, sustained reduction in PDRP activity is consistent with long term alleviation of akinetic-rigid manifestations. By contrast tremor recurrence is likely to be associated with changes in a separate, independent brain network (Antonini et al 1998).

Go to Main Abstract page

© 2002 Elsevier Science (USA). All rights reserved.

Back to Main NeuroImage Human Brain Mapping 2002 Meeting

Order to appear: 777

Motor Activity Differences Between Imagined Finger Movements in Normal Controls and Patients With Focal Hand Dystonia AJ Blood , J Choi , AW Flaherty , G Bonmassar , F Hochberg , SA Greenberg , BR Rosen , AB Young , BG Jenkins Departments of Neurology and Radiology, Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard University, MA Department of Neurology, Brigham and Womens Hospital, Harvard University, MA Subject: Neurology Abstract Introduction: Previous functional imaging studies have indicated that some forms of dystonia are associated with abnormal levels of activity in motor regions of the brain during performance of motor tasks 1,2. However, it is unknown if movement itself is necessary to trigger abnormal brain activity in these patients, or if abnormal activity arises prior to movement. To test this hypothesis, we used fMRI in focal hand dystonia patients and healthy controls to compare brain activity during movement (finger tapping) and motor imagery (imagined finger tapping). Methods: Whole brain fMRI scans were collected using a Siemens 3.0 T scanner, in four focal hand dystonia patients and three control subjects while they tapped (FT), or imagined tapping (IFT) their fingers on the keys of a buttonbox. The FT and IFT conditions consisted of alternating (real or imaginary) right 5th and left 2nd finger keypresses with right 2nd and left 5th finger keypresses. Tapping was performed at a rate of 2 Hz continuously for three, 1min blocks (alternating with 30 seconds of rest) and was cued aurally. Data were analyzed by contrasting BOLD signals in FT and rest, or IFT and rest conditions. Regions of interest identified in the FT/rest contrast were used to calculate percent BOLD signal change from baseline (rest) in selected regions for FT and IFT conditions. Results and Discussion: In both dystonia patients and control subjects, FT versus rest contrasts identified activity in motor regions, including SMA, primary motor (M1) cortex, premotor cortex, thalamus, putamen, and cerebellum (p<0.01). While there were small activity differences in these regions between dystonia and control subjects, only SMA and cerebellum differences were significant (p<0.05). In contrast, during IFT, activity in all motor regions tested was significantly greater in dystonia patients than in controls (p<0.05). In fact, motor region activity during IFT in dystonia patients closely resembled activity observed during FT (Fig. 1). Ongoing analysis of motion sensor measurements will verify whether any small movements occurred during IFT. These findings suggest that movement itself is not necessary to evoke abnormal brain motor activity in dystonia patients. References: 1. Pujol J, Roset-Llobet J, Roseines-Cubells D, Deus J, Narberhaus B et al. (2000) Neuroimage 12(3):257-67. 2. Ceballos-Baumann AO, Brooks DJ (1998) Adv in Neurol 78:135-152.

Back to Main

Go to Main Abstract page

© 2002 Elsevier Science (USA). All rights reserved.

Back to Main NeuroImage Human Brain Mapping 2002 Meeting

Order to appear: 778

Age-related changes in T1 relaxation times across the surface of the cortex David H. Salat Fischl

, Anders M. Dale , Andre J.W. van der Kouwe , Richard J. Clarke , Florent Segonne , Suzanne Corkin , Bruce

MGH/MIT/HMS Athinoula A. Martinos Center for Biomedical Imaging, Charlestown MA MIT Department of Brain and Cognitive Sciences, Cambridge MA Subject: Neurology Abstract Introduction The brain undergoes substantial morphological and neurochemical changes with advancing age. Although gross atrophy is typically apparent in magnetic resonance (MR) scans of older adults, conventional MR is unable to detect more subtle changes in tissue composition. Quantitative MR imaging (qMRI) techniques can be used to estimate MR tissue signal parameters, such as signal relaxation times. Prior studies have used qMRI to detect brain changes below the resolution of conventional MRI in clinical syndromes such as sickle cell disease [1]. Thus, changes in qMRI measures may be useful for detecting more subtle tissue changes, and could be useful in clinical applications, such as the diagnosis of preclinical dementia. Past qMRI studies have measured only age-related T1 changes in a limited number of cortical regions [2]. We examined how T1 relaxation times change with normal aging using accurate reconstructions of the brain from MR scans [3, 4], allowing visualization of change across the complete cortical surface. Methods We obtained scans from younger (YP; n = 8; mean age = 24.3, 18-35; 5M/3F) and older participants (OP; n = 6; mean age = 73.5, 68-80; 3M/3F). YP were recruited from the MIT/MGH community. OP were recruited through the Harvard Cooperative on Aging. Participants were excluded if they had a history of neurological, psychiatric, or medical illness that could contribute to dementia. Multiple high-resolution FLASH scans with different flip angles were collected for the calculation of T1 relaxation times (Siemens 1.5T Sonata, resolution 1x1x1 mm, TR = 20ms, TE = 3.2ms, FA = 3o, 5o, 15o, 30o in most participants). The optimal gray/white and pial surface placement as well as the MR tissue parameters (T1 and proton density) were then estimated using a maximum likelihood approach. First a rough estimate of the per-class tissue parameters (white matter/gray matter/CSF) was used to find the optimal surface placement, then the parameters were re-estimated, and the surfaces were re-positioned. This procedure was iterated until convergence. Maps were averaged across participants, using a spherical morph to align cortical folding [5]. Results Preliminary results suggested that OP had significantly smaller relaxation times bilaterally that were most pronounced in inferior frontal (near Brodmann area [BA] 47) and anterior temporal cortex (near BA 21/22), and the entire cingulate gyrus (near BA 23/24). In contrast, there were mean increases in portions of primary somatosensory (near BA 1) and visual cortex (near BA 17/18; although these differences did not reach statistical significance). Differences were estimated at ~75 to 90 msec in statistically significant regions. Discussion Aging is accompanied by T1 relaxation changes in inferior frontal, anterior temporal, and cingulate cortices. These regional differences have only slight overlap with reported age-related morphological changes, such as cortical thinning measured with structural imaging techniques [6]. Future studies will examine the biological mechanisms of these changes and their significance with normal aging. 1. Steen RG et al. J Magn Reson Imaging. 1998; 8:535-43. 2. Cho S et al. Magn Reson Imaging. 1997;15(10):1133-43. 3. Dale AM et al. Neuroimage. 1999;9(2):179-94. 5. Fischl B et al. Neuroimage. 1999;9(2):195-207. 6. Fischl B, et al. Hum Brain Mapp. 1999;8(4):272-84. 7. Salat DH et al. OHBM Abstracts, 2001.

Back to Main

Go to Main Abstract page

© 2002 Elsevier Science (USA). All rights reserved.

Back to Main

NeuroImage Human Brain Mapping 2002 Meeting

Order to appear: 779

Superior Temporal Gyrus Volume Differences in Early Onset Schizophrenia Janelle Taylor , Rebecca Blanton , Jennifer Levitt , Rochelle Caplan , Daniel Nobel , Arthur Toga LONI,Dept. of Neurology,Division of brain mapping, UCLA School of Medicine Division of Child Psychiatry, UCLA Subject: Neurology Abstract STG Volume Differences in Early Onset Schizophrenia Janelle Taylor, Rebecca Blanton, Jennifer Levitt*, Rochelle Caplan*, Daniel Nobel, Arthur Toga Laboratory of Neuro Imaging, Dept. of Neurology, Division of Brain Mapping, UCLA School of Medicine, Los Angeles, CA, USA *Division of Child Psychiatry, UCLA, Los Angeles, CA, USA Introduction Early onset schizophrenia is a rare developmental disorder occurring in approximately 1 in every 10,000 children before age 12 . The disorder has similar symptomotology as adult onset schizophrenia; auditory hallucinations, poor affect, and developmental deficits in speech, language and cognition. Early onset schizophrenia is also characterized by decreased total cerebral and gray matter volume and increased ventricular volume . The STG (Superior Temporal Gyrus) has been implicated in language pathogenesis related schizophrenic symptoms. The goal of this preliminary study was to assess volumetric differences of the STG and HG between groups with early onset schizophrenia and normals. Methods Subjects included ten children screened with K-SADS and met DSM IV criteria for early onset schizophrenia (mean age 11.1 years, mean Full Scale IQ 91.1) and ten normal children (mean age 11.3 years and mean full scale IQ 121.5). Controls were screened for neurological, psychiatric, or language disorders by K-SADS interviews with the parent and child. Subjects completed T1-weighted MRI scans using a 1.5 Tesla GE Signa Scanner. A sagittal SPGR series was collected using an imaging acquisition matrix of 256x256x124 and a slice thickness of 1.2 mm were used for all scans. One rater blind to diagnosis, age, and gender manually traced the STG and HG. The STG was divided into anterior and posterior regions and traced primarily in the coronal viewing plane. The intrarater reliability was determined using the coefficient of variation. One case was traced unilaterally six times.

Back to Main

The reliability values for the right anterior and posterior STG, and right HG were 2.5%, 3.2%, and 9.02% respectively. A second rater traced six cases, unilaterally using the developed protocol. The interater reliability was calculated using a simple correlation analysis. The interater reliability values for the right anterior and posterior STG and right HG were 83%, 88% and 96% respectively. Total volumes were calculated bilaterally for the anterior and posterior STG and HG. An Analysis of Varience (ANOVA) was done using bilateral anterior and posterior STG and HG volumes as the dependent variables and diagnosis as the independent variable. Results Right posterior STG volumes were significantly smaller in subjects with early-onset schizophrenia, compared to normals (p< .05). There were no significant differences between the groups in the volume of bilateral anterior STG, left posterior STG bilateral, HG, and total brain volume. Conclusions Our preliminary results suggest a decrease in right posterior STG volume in early onset schizophrenics. These results are consistent with other studies that found decreased volume in the right STG. The STG is a multimodal region, posessing both auditory and language functions. Therefore, the smaller volume size may contribute to the symptomotology of early-onset schizophrenia. Future studies and larger sample size are needed to clarify abnormalities in these regions.

Go to Main Abstract page

© 2002 Elsevier Science (USA). All rights reserved.

Back to Main

NeuroImage Human Brain Mapping 2002 Meeting

Order to appear: 780

Therapeutic Modulation of Motor Sequence Learning Networks in Parkinson’s Disease Maren Carbon , Masafumi Fukuda , Maria-Felice Ghilardi , Vijay Dhawan , David Eidelberg North Shore-Long Island Jewish Research Institue Coloumbia University, NY Subject: Neurology Abstract OBJECTIVE: To determine the relationship between changes in motor sequence learning performance in Parkinson’s disease (PD) during different therapeutic interventions and the modulation of learningrelated brain networks. BACKGROUND: In a previous H215O PET study (Nakamura et al. 2001) we used principal component analysis (PCA) to identify a brain network associated with sequence learning performance in normal subjects. We found that this network also correlated with learning in unmedicated PD patients. In this study we examined how learning performance and network activity are modulated by antiparkinsonian treatment. METHODS: 18 normal control subjects (age 43.0 ± 15.8 years) and 14 PD patients were scanned with H2O15 PET (age 55.5 ± 10.3 years) while performing two kinematically controlled tasks: 1. Motor execution (MCCW): paced reaching movements toward 8 radially displayed targets that were presented in a predictable counterclockwise order. 2. Motor learning (MSEQ): the targets were presented in a repeating pattern. Subjects were explicitly required to synchronize target acquisition with a tone, thus encouraging sequence learning and anticipation of the correct target. Performance during PET recording was quantified as a global learning index (GL) defined as the total number of correct anticipatory movements in each trial block. Seven of the PD patients were treated with pallidal deep brain stimulation (DBS) and the other seven patients received levodopa infusion; motor ratings improved by approximately 30% in both treatment groups. All patients were scanned while performing both tasks in the ON and OFF conditions. MSEQ-MCCW difference scans were analyzed using voxel-based PCA to quantify the activity of the normal learning-related network in the ON and OFF conditions. RESULTS: 1.) Consistent with our earlier study, voxel-based PCA of MSEQ-MCCW scan pairs revealed the presence of a significant brain network (9.2% VAF) which correlated with the GL index (R2=0.6, p<0.001). This pattern was characterized by activation in the following areas: bilaterally in the caudate, dorsolateral prefrontal cortex (BA 46/10), inferior prefrontal cortex (BA 47 right, BA 11 left), premotor cortex (BA 6), precuneus (BA 7), occipital association cortices (BA 18/19), and in the right anterior cingulate area (BA 32). 2.) In the PD patients scanned at baseline (OFF) the activity of this network correlated with GL (R2= 0.31, p= 0.04). 3.) With treatment ON-OFF changes in network expression

Back to Main

correlated significantly with improved learning performance (R2 =0.51; p=0.001). CONCLUSIONS: 1.) A reproducible pattern of brain activation is present in normal subjects scanned while performing the MSEQ learning task. Voxel-based PCA confirms the topography of the pattern identified previously using region of interest (ROI) approaches. 2.) As demonstrated previously (Nakamura et al. 2001), the activity of this pattern correlates with learning performance in PD patients scanned off medication. 3.) Modulation of this brain network by treatment suggests its potential application as a functional imaging marker for the study of cognitive manifestations of parkinsonism.

Go to Main Abstract page

© 2002 Elsevier Science (USA). All rights reserved.