Stéphane Lehéricy

L'Institut du Cerveau et de la Moelle Épinière, Lutetia Parisorum, Île-de-France, France

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Publications (309)1385.16 Total impact

  • Médecine du Sommeil 03/2015; DOI:10.1016/j.msom.2015.01.147
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    ABSTRACT: Gilles de la Tourette syndrome is a neurodevelopmental disorder characterized by the presence of motor and vocal tics. We hypothesized that patients with this syndrome would present an aberrant pattern of cortical formation, which could potentially reflect global alterations of brain development. Using 3 Tesla structural neuroimaging, we compared sulcal depth, opening, and length and thickness of sulcal gray matter in 52 adult patients and 52 matched controls. Cortical sulci were automatically reconstructed and identified over the whole brain, using BrainVisa software. We focused on frontal, parietal, and temporal cortical regions, in which abnormal structure and functional activity were identified in previous neuroimaging studies. Partial correlation analysis with age, sex, and treatment as covariables of noninterest was performed amongst relevant clinical and neuroimaging variables in patients. Patients with Gilles de la Tourette syndrome showed lower depth and reduced thickness of gray matter in the pre- and post-central as well as superior, inferior, and internal frontal sulci. In patients with associated obsessive-compulsive disorder, additional structural changes were found in temporal, insular, and olfactory sulci. Crucially, severity of tics and of obsessive-compulsive disorder measured by Yale Global Tic severity scale and Yale-Brown Obsessive-Compulsive scale, respectively, correlated with structural sulcal changes in sensorimotor, temporal, dorsolateral prefrontal, and middle cingulate cortical areas. Patients with Gilles de la Tourette syndrome displayed an abnormal structural pattern of cortical sulci, which correlated with severity of clinical symptoms. Our results provide further evidence of abnormal brain development in GTS. © 2015 International Parkinson and Movement Disorder Society. © 2015 International Parkinson and Movement Disorder Society.
    Movement Disorders 03/2015; DOI:10.1002/mds.26207 · 5.63 Impact Factor
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    ABSTRACT: Combinatorial syntax has been shown to be underpinned by cortical key regions such as Broca's area and temporal cortices, and by subcortical structures such as the striatum. The cortical regions are connected via several cortico-to-cortical tracts impacting syntactic processing (e.g., the arcuate) but it remains unclear whether and how the striatum can be integrated into this cortex-centered syntax network. Here, we used a systematic stepwise approach to investigate the existence and syntactic function of an additional deep Broca-striatum pathway. We first asked 15 healthy controls and 12 patients with frontal/striatal lesions to perform three syntax tests. The results obtained were subjected to voxel-based lesion-symptom mapping (VLSM) to provide an anatomo-functional approximation of the pathway. The significant VLSM clusters were then overlapped with the probability maps of four cortico-cortical language tracts generated for 12 healthy participants (arcuate, extreme capsule fiber system, uncinate, aslant), including a probabilistic Broca-striatum tract. Finally, we carried out quantitative analyses of the relationship between the lesion load along the tracts and syntactic processing, by calculating tract-lesion overlap for each patient and analyzing the correlation with syntactic data. Our findings revealed a Broca-striatum tract linking BA45 with the left caudate head and overlapping with VLSM voxel clusters relating to complex syntax. The lesion load values for this tract were correlated with complex syntax scores, whereas no such correlation was observed for the other tracts. These results extend current syntax-network models, by adding a deep "Broca-caudate pathway," and are consistent with functional accounts of frontostriatal circuits. Hum Brain Mapp, 2015. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.
    Human Brain Mapping 02/2015; DOI:10.1002/hbm.22769 · 6.92 Impact Factor
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    ABSTRACT: To validate semiautomated spinal cord segmentation in healthy subjects and patients with neurodegenerative diseases and trauma. Forty-nine healthy subjects, as well as 29 patients with amyotrophic lateral sclerosis, 19 with spinal muscular atrophy, and 14 with spinal cord injuries were studied. Cord area was measured from T2 -weighted 3D turbo spin echo images (cord levels from C2 to T9) using the semiautomated segmentation method of Losseff et al (Brain [1996] 119(Pt 3):701-708), compared with manual segmentation. Reproducibility was evaluated using the inter- and intraobserver coefficient of variation (CoV). Accuracy was assessed using the Dice similarity coefficient (DSC). Robustness to initialization was assessed by simulating modifications to the contours drawn manually prior to segmentation. Mean interobserver CoV was 4.00% for manual segmentation (1.90% for Losseff's method) in the cervical region and 5.62% (respectively 2.19%) in the thoracic region. Mean intraobserver CoV was 2.34% for manual segmentation (1.08% for Losseff's method) in the cervical region and 2.35% (respectively 1.34%) in the thoracic region. DSC was high (0.96) in both cervical and thoracic regions. DSC remained higher than 0.8 even when modifying initial contours by 50%. The semiautomated segmentation method showed high reproducibility and accuracy in measuring spinal cord area. J. Magn. Reson. Imaging 2014. © 2014 Wiley Periodicals, Inc.
    Journal of Magnetic Resonance Imaging 02/2015; 41(2). DOI:10.1002/jmri.24571 · 2.79 Impact Factor
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    ABSTRACT: To study the effect of donepezil on the rate of hippocampal atrophy in prodromal Alzheimer's disease (AD). A double-blind, randomized, placebo-controlled parallel group design using donepezil (10 mg/day) in subjects with suspected prodromal AD. Subjects underwent two brain magnetic resonance imaging scans (baseline and final visit). The primary efficacy outcome was the annualized percentage change (APC) of total hippocampal volume (left + right) measured by an automated segmentation method. Two-hundred and sixteen only subjects were randomized across 28 French expert clinical sites. In the per protocol population (placebo = 92 and donepezil = 82), the donepezil group exhibited a significant reduced rate of hippocampal atrophy (APC = -1.89%) compared with the placebo group (APC = -3.47%), P < .001. There was no significant difference in neuropsychological performance between treatment groups. A 45% reduction of rate of hippocampal atrophy was observed in prodromal AD following 1 year of treatment with donepezil compared with placebo. Copyright © 2014 The Alzheimer's Association. Published by Elsevier Inc. All rights reserved.
    Alzheimer's & dementia: the journal of the Alzheimer's Association 01/2015; DOI:10.1016/j.jalz.2014.10.003 · 17.47 Impact Factor
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    ABSTRACT: To design a fast and accurate semi-automated segmentation method for spinal cord 3T MR images and to construct a template of the cervical spinal cord. A semi-automated double threshold-based method (DTbM) was proposed enabling both cross-sectional and volumetric measures from 3D T2-weighted turbo spin echo MR scans of the spinal cord at 3T. Eighty-two healthy subjects, 10 patients with amyotrophic lateral sclerosis, 10 with spinal muscular atrophy and 10 with spinal cord injuries were studied. DTbM was compared with active surface method (ASM), threshold-based method (TbM) and manual outlining (ground truth). Accuracy of segmentations was scored visually by a radiologist in cervical and thoracic cord regions. Accuracy was also quantified at the cervical and thoracic levels as well as at C2 vertebral level. To construct a cervical template from healthy subjects' images (n=59), a standardization pipeline was designed leading to well-centered straight spinal cord images and accurate probability tissue map. Visual scoring showed better performance for DTbM than for ASM. Mean Dice similarity coefficient (DSC) was 95.71% for DTbM and 90.78% for ASM at the cervical level and 94.27% for DTbM and 89.93% for ASM at the thoracic level. Finally, at C2 vertebral level, mean DSC was 97.98% for DTbM compared with 98.02% for TbM and 96.76% for ASM. DTbM showed similar accuracy compared with TbM, but with the advantage of limited manual interaction. A semi-automated segmentation method with limited manual intervention was introduced and validated on 3T images, enabling the construction of a cervical spinal cord template.
    PLoS ONE 01/2015; 10(3):e0122224. DOI:10.1371/journal.pone.0122224 · 3.53 Impact Factor
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    ABSTRACT: Gilles de la Tourette syndrome is a childhood-onset syndrome characterized by the presence and persistence of motor and vocal tics. A dysfunction of cortico-striato-pallido-thalamo-cortical networks in this syndrome has been supported by convergent data from neuro-pathological, electrophysiological as well as structural and functional neuroimaging studies. Here, we addressed the question of structural integration of cortico-striato-pallido-thalamo-cortical networks in Gilles de la Tourette syndrome. We specifically tested the hypothesis that deviant brain development in Gilles de la Tourette syndrome could affect structural connectivity within the input and output basal ganglia structures and thalamus. To this aim, we acquired data on 49 adult patients and 28 gender and age-matched control subjects on a 3 T magnetic resonance imaging scanner. We used and further implemented streamline probabilistic tractography algorithms that allowed us to quantify the structural integration of cortico-striato-pallido-thalamo-cortical networks. To further investigate the microstructure of white matter in patients with Gilles de la Tourette syndrome, we also evaluated fractional anisotropy and radial diffusivity in these pathways, which are both sensitive to axonal package and to myelin ensheathment. In patients with Gilles de la Tourette syndrome compared to control subjects, we found white matter abnormalities in neuronal pathways connecting the cerebral cortex, the basal ganglia and the thalamus. Specifically, striatum and thalamus had abnormally enhanced structural connectivity with primary motor and sensory cortices, as well as paracentral lobule, supplementary motor area and parietal cortices. This enhanced connectivity of motor cortex positively correlated with severity of tics measured by the Yale Global Tics Severity Scale and was not influenced by current medication status, age or gender of patients. Independently of the severity of tics, lateral and medial orbito-frontal cortex, inferior frontal, temporo-parietal junction, medial temporal and frontal pole also had enhanced structural connectivity with the striatum and thalamus in patients with Gilles de la Tourette syndrome. In addition, the cortico-striatal pathways were characterized by elevated fractional anisotropy and diminished radial diffusivity, suggesting microstructural axonal abnormalities of white matter in Gilles de la Tourette syndrome. These changes were more prominent in females with Gilles de la Tourette syndrome compared to males and were not related to the current medication status. Taken together, our data showed widespread structural abnormalities in cortico-striato-pallido-thalamic white matter pathways in patients with Gilles de la Tourette, which likely result from abnormal brain development in this syndrome.
    Brain 11/2014; DOI:10.1093/brain/awu311 · 10.23 Impact Factor
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    ABSTRACT: A hallmark of Parkinson's disease (PD) is the progressive neurodegeneration of dopaminergic neurons in the substantia nigra pars compacta (SNc). Dopaminergic denervation is commonly imaged using radiotracer imaging in target structures such as the striatum. Until recently, imaging made only a modest contribution to detecting neurodegenerative changes in the substantia nigra (SN) directly. Histologically, the SN is subdivided into the ventral pars reticulata and the dorsal pars compacta, which is composed of dopaminergic neurons. In humans, dopaminergic neurons, which are known to accumulate neuromelanin, form clusters of cells (nigrosomes) that penetrate deep into the SN pars reticulata (SNr). The SNr contains higher levels of iron than the SNc in normal subjects. Neuromelanin and T2*-weighted imaging therefore better detect the SNc and the SNr, respectively. The development of ultra-high field 7 Tesla (7T) magnetic resonance imaging (MRI) provided the increase in spatial resolution and in contrast that was needed to detect changes in SN morphology. 7T MRI allows visualization of nigrosome-1 as a hyperintense signal area on T2*-weighted images in the SNc of healthy subjects and its absence in PD patients, probably because of the loss of melanized neurons and the increase of iron deposition. This review is designed to provide a better understanding of the correspondence between the outlines and subdivisions of the SN detected using different MRI contrasts and the histological organization of the SN. The recent findings obtained at 7T will then be presented in relation to histological knowledge. © 2014 International Parkinson and Movement Disorder Society
    Movement Disorders 11/2014; 29(13). DOI:10.1002/mds.26043 · 5.63 Impact Factor
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    ABSTRACT: This study investigates a fast distribution-matching, data-driven algorithm for 3D multimodal MRI brain glioma tumor and edema segmentation in different modalities. From a very simple user input, we learn non-parametric model distributions which characterize the normal regions in the current data. Then, we state our segmentation problems as the optimization of several cost functions of the same form, each containing two terms: (i) a distribution matching prior, which evaluates a global similarity between distributions, and (ii) a smoothness prior to avoid the occurrence of small, isolated regions in the solution. Obtained following recent bound-relaxation results, the optima of the cost functions yield the complement of the tumor region or edema region in nearly real-time. Based on global rather than pixel wise information, the proposed algorithm does not require an external learning from a large, manually-segmented training set, as is the case of the existing methods. Therefore, the ensuing results are independent of the choice of a training set. Quantitative evaluations over the publicly available training and testing data set from the MICCAI multimodal brain tumor segmentation challenge (BraTS 2012) demonstrated that our algorithm yields a highly competitive performance for complete edema and tumor segmentation, among nine existing competing methods, with an interesting computing execution time (less than 0.5s per image).
    Computerized Medical Imaging and Graphics 10/2014; 40. DOI:10.1016/j.compmedimag.2014.10.009 · 1.50 Impact Factor
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    ABSTRACT: Les lésions pseudo-tumorales constituent une entité diagnostique rare mais importante à identifier en neuroradiologie. Ces lésions peuvent survenir au cours des pathologies inflammatoires (maladies systémiques, vascularites, démyélinisantes), infectieuses, et vasculaires. Par ailleurs, chez un patient ayant une tumeur traitée, la pseudo-progression et la radionécrose constituent également un diagnostic différentiel non tumoral important à individualiser de l’évolution tumorale. Le diagnostic de pseudotumeur ou d’évolution pseudo-tumorale peut être difficile à réaliser en imagerie. Toutefois, certaines caractéristiques IRM en séquence conventionnelle et en diffusion, perfusion et spectroscopie permettent d’évoquer le caractère pseudo-tumoral d’une lésion. La présence d’éventuelles lésions intracrâniennes associées peut orienter vers une maladie systémique ou infectieuse. Une lésion en hyposignal T2 oriente vers une granulomatose ou une histiocytose, surtout si une atteinte méningée ou hypothalamo-hypophysaire est associée. Les lésions non tumorales ne sont généralement pas hyperperfusées. Enfin, en l’absence de diagnostic étiologique de certitude, l’évolution spontanée ou sous traitement de ces lésions est un élément diagnostique fondamental.
    10/2014; DOI:10.1016/j.jradio.2014.08.002
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    ABSTRACT: BACKGROUND: An international Delphi panel has defined a harmonized protocol (HarP) for the manual segmentation of the hippocampus on MR. The aim of this study is to study the concurrent validity of the HarP toward local protocols, and its major sources of variance. METHODS: Fourteen tracers segmented 10 Alzheimer's Disease Neuroimaging Initiative (ADNI) cases scanned at 1.5 T and 3T following local protocols, qualified for segmentation based on the HarP through a standard web-platform and resegmented following the HarP. The five most accurate tracers followed the HarP to segment 15 ADNI cases acquired at three time points on both 1.5 T and 3T. RESULTS: The agreement among tracers was relatively low with the local protocols (absolute left/right ICC 0.44/0.43) and much higher with the HarP (absolute left/right ICC 0.88/0.89). On the larger set of 15 cases, the HarP agreement within (left/right ICC range: 0.94/0.95 to 0.99/0.99) and among tracers (left/right ICC range: 0.89/0.90) was very high. The volume variance due to different tracers was 0.9% of the total, comparing favorably to variance due to scanner manufacturer (1.2), atrophy rates (3.5), hemispheric asymmetry (3.7), field strength (4.4), and significantly smaller than the variance due to atrophy (33.5%, P < .001), and physiological variability (49.2%, P < .001). CONCLUSIONS: The HarP has high measurement stability compared with local segmentation protocols, and good reproducibility within and among human tracers. Hippocampi segmented with the HarP can be used as a reference for the qualification of human tracers and automated segmentation algorithms.
    Alzheimer's and Dementia 09/2014; DOI:10.1016/j.jalz.2014.05.1756 · 17.47 Impact Factor
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    ABSTRACT: Pseudotumoral lesions are uncommon but important to identity lesions. They can occur during inflammatory diseases (systemic diseases, vasculitis, demyelinating diseases), infectious, and vascular diseases. Also, in a patient with a treated tumor, pseudo-progression and radionecrosis must be differentiated from the tumoral development. Diagnosis can be difficult on an MRI scan, but some MRI aspects in conventional sequences, diffusion, perfusion and spectroscopy can suggest the pseudotumoral origin of a lesion. Imaging must be interpreted according to the context, the clinic and the biology. The presence of associated intracranial lesions can orientate towards a systemic or infectious disease. A T2 hyposignal lesion suggests granulomatosis or histiocytosis, especially if a meningeal or hypothalamic–pituitary involvement is associated. Non-tumoral lesions are generally not hyperperfused. In the absence of a definitive diagnosis, the evolution of these lesions, whether under treatment or spontaneous, is fundamental.
    09/2014; 95(10). DOI:10.1016/j.diii.2014.08.004
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    ABSTRACT: Severe cognitive impairment involving multiple cognitive domains can occur early during the course of multiple sclerosis (MS). We investigated resting state functional connectivity changes in large-scale brain networks and related structural damage underlying cognitive dysfunction in patients with early MS. Patients with relapsing MS (3-5 years disease duration) were prospectively assigned to two groups based on a standardized neuropsychological evaluation: (1) cognitively impaired group (CI group, n = 15), with abnormal performances in at least 3 tests; (2) cognitively preserved group (CP group, n = 20) with normal performances in all tests. Patients and age-matched healthy controls underwent a multimodal 3T magnetic resonance imaging (MRI) including anatomical T1 and T2 images, diffusion imaging and resting state functional MRI. Structural MRI analysis revealed that CI patients had a higher white matter lesion load compared to CP and a more severe atrophy in gray matter regions highly connected to networks involved in cognition. Functional connectivity measured by integration was increased in CP patients versus controls in attentional networks (ATT), while integration was decreased in CI patients compared to CP both in the default mode network (DMN) and ATT. An anatomofunctional study within the DMN revealed that functional connectivity was mostly altered between the medial prefrontal cortex (MPFC) and the posterior cingulate cortex (PCC) in CI patients compared to CP and controls. In a multilinear regression model, functional correlation between MPFC and PCC was best predicted by PCC atrophy. Disconnection in the DMN and ATT networks may deprive the brain of compensatory mechanisms required to face widespread structural damage. Hum Brain Mapp, 2014. © 2014 Wiley Periodicals, Inc.
    Human Brain Mapping 09/2014; 35(9). DOI:10.1002/hbm.22505 · 6.92 Impact Factor
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    ABSTRACT: Background The inter-individual variability of behavioral effects after tDCS applied to the unaffected right hemisphere in stroke may be related to factors such as the lesion location. Objective /Hypothesis: We investigated the effect of left Broca’s area (BA) damage on picture naming in aphasic patients after cathodal tDCS applied over the right BA. Methods We conducted a study using pre-interventional diffusion and resting state functional MRI (rsfMRI) and two cross-over tDCS sessions (TYPE: sham and cathodal) over the right homologous BA in aphasic stroke patients with ischemic lesions involving the left BA (BA+) or other left brain areas (BA-). Picture naming accuracy was assessed after each session. Inter-hemispheric (IH) functional balance was investigated via rsfMRI connectivity maps using the right BA as a seed. Probabilistic tractography was used to study the integrity of language white smatter pathways. Results tDCS had different effects on picture naming accuracy in BA+ and BA- patients (TYPExGROUP interaction, F(1,19): 4.6, p:0.04). All BA- patients except one did not respond to tDCS and demonstrated normal IH balance between the right and left BA when compared to healthy subjects. BA+ patients were improved by tDCS in 36% and had decreased level of functional IH balance. Improvement in picture naming after cathodal tDCS was associated with the integrity of the arcuate fasciculus in BA+ patients. Conclusions Behavioral effects of cathodal tDCS on the unaffected right hemisphere differ depending on whether BA and the arcuate fasciculus are damaged. Therefore, IH imbalance could be a direct consequence of anatomical lesions.
    Brain Stimulation 09/2014; 7(5). DOI:10.1016/j.brs.2014.06.004 · 5.43 Impact Factor
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    ABSTRACT: Background. The contribution of lesion size and location in poststroke aphasia is debated, especially the extent to which aphasia severity is affected by damage to specific white matter areas. Objective. To identify specific white matter areas critical for poststroke aphasia global severity and to determine whether injury to these areas had more impact on aphasia severity than the infarct volume. Methods. Twenty-three chronic poststroke aphasic patients were assessed with the Aphasia Rapid Test (ART) and the Boston Diagnosis Aphasia Examination (BDAE) global severity scales and underwent diffusion tensor and structural imaging. Voxel-based diffusion tensor imaging regression analysis was used to determine in which areas fractional anisotropy (FA) abnormalities were correlated with ART and BDAE severity scales. The relationships between aphasia severity, FA values, and infarct volumes were investigated using global and partial correlations. Results. We found a critical area associated with aphasia severity overlapping with the arcuate and the inferior fronto-occipital fasciculi, resulting in a combined disconnection of the dorsal and ventral pathways. ART scores were inversely correlated with FA values in this region, with greater severity present with lower FA values (correlation coefficient = -0.833, P < .0001). The proportion of variance explained by the FA value was higher than the proportion of variance explained by the infarct volume (R(2) = 68% vs 27%, P = .01). The impact of infarct volume on aphasia severity disappeared when damage to this critical white matter area was taken into account (P = .38). Conclusion. The assessment of the integrity of this region may potentially have a clinical impact in neurorehabilitation and acute decision making.
    Neurorehabilitation and neural repair 08/2014; DOI:10.1177/1545968314543926 · 4.62 Impact Factor
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    A Jon Stoessl, Stephane Lehericy, Antonio P Strafella
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    ABSTRACT: Recent advances in structural and functional imaging have greatly improved our ability to assess normal functions of the basal ganglia, diagnose parkinsonian syndromes, understand the pathophysiology of parkinsonism and other movement disorders, and detect and monitor disease progression. Radionuclide imaging is the best way to detect and monitor dopamine deficiency, and will probably continue to be the best biomarker for assessment of the effects of disease-modifying therapies. However, advances in magnetic resonance enable the separation of patients with Parkinson's disease from healthy controls, and show great promise for differentiation between Parkinson's disease and other akinetic-rigid syndromes. Radionuclide imaging is useful to show the dopaminergic basis for both motor and behavioural complications of Parkinson's disease and its treatment, and alterations in non-dopaminergic systems. Both PET and MRI can be used to study patterns of functional connectivity in the brain, which is disrupted in Parkinson's disease and in association with its complications, and in other basal-ganglia disorders such as dystonia, in which an anatomical substrate is not otherwise apparent. Functional imaging is increasingly used to assess underlying pathological processes such as neuroinflammation and abnormal protein deposition. This imaging is another promising approach to assess the effects of treatments designed to slow disease progression.
    The Lancet 06/2014; 384(9942). DOI:10.1016/S0140-6736(14)60041-6 · 39.21 Impact Factor
  • Clinical Neurophysiology; 06/2014
  • Clinical Neurophysiology; 06/2014
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    ABSTRACT: Our knowledge on temporal lobe epilepsy (TLE) with hippocampal sclerosis has evolved towards the view that this syndrome affects widespread brain networks. Diffusion weighted imaging studies have shown alterations of large white matter tracts, most notably in left temporal lobe epilepsy, but the degree of altered connections between cortical and subcortical structures remains to be clarified. We performed a whole brain connectome analysis in 39 patients with refractory temporal lobe epilepsy and unilateral hippocampal sclerosis (20 right and 19 left) and 28 healthy subjects. We performed whole-brain probabilistic fiber tracking using MRtrix and segmented 164 cortical and subcortical structures with Freesurfer. Individual structural connectivity graphs based on these 164 nodes were computed by mapping the mean fractional anisotropy (FA) onto each tract. Connectomes were then compared using two complementary methods: permutation tests for pair-wise connections and Network Based Statistics to probe for differences in large network components. Comparison of pair-wise connections revealed a marked reduction of connectivity between left TLE patients and controls, which was strongly lateralized to the ipsilateral temporal lobe. Specifically, infero-lateral cortex and temporal pole were strongly affected, and so was the perisylvian cortex. In contrast, for right TLE, focal connectivity loss was much less pronounced and restricted to bilateral limbic structures and right temporal cortex. Analysis of large network components revealed furthermore that both left and right hippocampal sclerosis affected diffuse global and interhemispheric connectivity. Thus, left temporal lobe epilepsy was associated with a much more pronounced pattern of reduced FA, that included major landmarks of perisylvian language circuitry. These distinct patterns of connectivity associated with unilateral hippocampal sclerosis show how a focal pathology influences global network architecture, and how left or right-sided lesions may have differential and specific impacts on cerebral connectivity.
    NeuroImage 05/2014; 100. DOI:10.1016/j.neuroimage.2014.04.071 · 6.13 Impact Factor
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    ABSTRACT: To evaluate multimodal MRI of the spinal cord in predicting disease progression and one-year clinical status in amyotrophic lateral sclerosis (ALS) patients. After a first MRI (MRI1), 29 ALS patients were clinically followed during 12 months; 14/29 patients underwent a second MRI (MRI2) at 11±3 months. Cross-sectional area (CSA) that has been shown to be a marker of lower motor neuron degeneration was measured in cervical and upper thoracic spinal cord from T2-weighted images. Fractional anisotropy (FA), axial/radial/mean diffusivities (λ⊥, λ//, MD) and magnetization transfer ratio (MTR) were measured within the lateral corticospinal tract in the cervical region. Imaging metrics were compared with clinical scales: Revised ALS Functional Rating Scale (ALSFRS-R) and manual muscle testing (MMT) score. At MRI1, CSA correlated significantly (P<0.05) with MMT and arm ALSFRS-R scores. FA correlated significantly with leg ALFSRS-R scores. One year after MRI1, CSA predicted (P<0.01) arm ALSFSR-R subscore and FA predicted (P<0.01) leg ALSFRS-R subscore. From MRI1 to MRI2, significant changes (P<0.01) were detected for CSA and MTR. CSA rate of change (i.e. atrophy) highly correlated (P<0.01) with arm ALSFRS-R and arm MMT subscores rate of change. Atrophy and DTI metrics predicted ALS disease progression. Cord atrophy was a better biomarker of disease progression than diffusion and MTR. Our study suggests that multimodal MRI could provide surrogate markers of ALS that may help monitoring the effect of disease-modifying drugs.
    PLoS ONE 04/2014; 9(4):e95516. DOI:10.1371/journal.pone.0095516 · 3.53 Impact Factor

Publication Stats

11k Citations
1,385.16 Total Impact Points


  • 2011–2015
    • L'Institut du Cerveau et de la Moelle Épinière
      Lutetia Parisorum, Île-de-France, France
  • 2006–2015
    • Pierre and Marie Curie University - Paris 6
      • Centre de Recherche de l'Institut du Cerveau et de la Moelle Epinière
      Lutetia Parisorum, Île-de-France, France
    • Centre Hospitalier Universitaire de Grenoble
      Grenoble, Rhône-Alpes, France
    • Seattle BioMed
      Seattle, Washington, United States
    • Boston University
      Boston, Massachusetts, United States
  • 1994–2015
    • Hôpital La Pitié Salpêtrière (Groupe Hospitalier "La Pitié Salpêtrière - Charles Foix")
      • • Service de Médecine Nucléaire
      • • Service de Neurochirurgie
      Lutetia Parisorum, Île-de-France, France
  • 2014
    • Université Paris-Sorbonne - Paris IV
      Lutetia Parisorum, Île-de-France, France
  • 2007–2014
    • CENIR - Centre de Neuroimagerie de Recherche
      Lutetia Parisorum, Île-de-France, France
  • 1989–2014
    • French Institute of Health and Medical Research
      Lutetia Parisorum, Île-de-France, France
  • 2011–2013
    • Université Paris-Sud 11
      Orsay, Île-de-France, France
  • 2008–2013
    • Polytech Paris-UPMC
      Lutetia Parisorum, Île-de-France, France
  • 2000–2013
    • French National Centre for Scientific Research
      Lutetia Parisorum, Île-de-France, France
    • Centro de Estudios y Experimentación de Obras Públicas
      Madrid, Madrid, Spain
  • 2008–2011
    • Unité Inserm U1077
      Caen, Lower Normandy, France
  • 2006–2011
    • UPMC
      Pittsburgh, Pennsylvania, United States
  • 2010
    • City of Stockholm
      Tukholma, Stockholm, Sweden
  • 2007–2010
    • Collège de France
      Lutetia Parisorum, Île-de-France, France
  • 2009
    • Université de Montréal
      Montréal, Quebec, Canada
    • Assistance Publique – Hôpitaux de Paris
      Lutetia Parisorum, Île-de-France, France
    • Centre Hospitalier Régional Universitaire de Lille
      • Division of Neurology
      Lille, Nord-Pas-de-Calais, France
  • 2004–2009
    • Centre Hospitalier Universitaire Rouen
      Rouen, Upper Normandy, France
    • Université de Bretagne Occidentale
      Brest, Brittany, France
  • 2004–2008
    • Hôpitaux Universitaires La Pitié salpêtrière - Charles Foix
      Lutetia Parisorum, Île-de-France, France
  • 2004–2006
    • Center for Magnetic Resonance Research Minnesota, USA
      Minneapolis, Minnesota, United States
  • 2005
    • University of Minnesota Duluth
      Duluth, Minnesota, United States
  • 2000–2004
    • Atomic Energy and Alternative Energies Commission
      Fontenay, Île-de-France, France
  • 2001
    • Cea Leti
      Grenoble, Rhône-Alpes, France