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1. Parkinson Disease Propagation Using MRI Biomarkers and Partial Least Squares Path Modeling

Author: Marie Vidailhet, Cecile Gallea, Claire Ewenczyk, Rahul Gaurav, Lydia Yahia-Cherif, Romain Valabregue, Isabelle Arnulf, Stéphane Lehéricy, Sara Fernandez-Vidal, Nadya Pyatigorskaya, and Fatma Gargouri
Subjects: Male, 0301 basic medicine, REM Sleep Behavior Disorder, Severity of Illness Index, REM sleep behavior disorder, 03 medical and health sciences, 0302 clinical medicine, Goodness of fit, medicine, Humans, Partial least squares path modeling, Least-Squares Analysis, medicine.diagnostic_test, business.industry, Neurodegeneration, Brain, Parkinson Disease, Magnetic resonance imaging, Models, Theoretical, medicine.disease, Magnetic Resonance Imaging, Diffusion Tensor Imaging, 030104 developmental biology, Disease Progression, Female, Neurology (clinical), Brainstem, business, Neuroscience, Biomarkers, 030217 neurology & neurosurgery, Braak staging, Diffusion MRI
Abstract: ObjectivesThe classic Braak neuropathologic staging model in Parkinson disease (PD) suggests that brain lesions progress from the medulla oblongata to the cortex. An alternative model in which neurodegeneration first occurs in the cortex has also been proposed. These 2 models may correspond to different patient phenotypes. To test these 2 models and to investigate whether they were influenced by the presence of REM sleep behavior disorder (RBD), we used multimodal MRI and partial least squares path modeling (PLS-PM) assuming that patients with RBD followed distinct neurodegeneration pattern.MethodsFifty-four patients with PD (34 with RBD) and 25 healthy volunteers were scanned with T1-weighted, diffusion tensor, and neuromelanin-sensitive imaging. Volume, signal, and mean, axial, and radial diffusivities were calculated in brainstem, basal forebrain, and cortical regions. PLS-PM, estimating a network of causal relationships between blocks of variables, was used to build and test an analytical model based on Braak staging. The overall quality of the model was assessed with goodness of fit coefficient (Gof).ResultsPLS-PM was run on patients with PD with RBD and without RBD separately. In PD with RBD, a brainstem-to-cortex model had significant Gof (0.71,p= 0.01), whereas a cortex-to-brainstem model did not. In contrast, in patients with PD without RBD, the brainstem-to-cortex model was not significant (Gof = 0.64,p= 0.27), and the cortex-to-brainstem model was highly significant (Gof = 0.72,p= 0.008).ConclusionsWith the PLS-PM imaging–based model, the neurodegeneration pattern of patients with PD with RBD was consistent with the Braak brainstem-to-cortex model, whereas that of patients without RBD followed the cortex-to-brainstem model.
Published: 2020
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2. Multimodal Magnetic Resonance Imaging Quantification of Brain Changes in Progressive Supranuclear Palsy

Author: Stéphane Lehéricy, Marie Vidailhet, Lydia Yahia-Cherif, Romain Valabregue, Nadya Pyatigorskaya, Fatma Gargouri, Isabelle Arnulf, Benoît Magnin, Cyril Poupon, Eric Bardinet, Bertrand Degos, Rahul Gaurav, Emmanuel Roze, Claire Ewenczyk, and Cecile Gallea
Subjects: Male, 0301 basic medicine, Pathology, medicine.medical_specialty, Basal Ganglia, 03 medical and health sciences, 0302 clinical medicine, Parkinsonian Disorders, Neuromelanin, Mesencephalon, Basal ganglia, Fractional anisotropy, Humans, Medicine, Aged, Pedunculopontine nucleus, business.industry, Putamen, Brain, Parkinson Disease, Middle Aged, Multiple System Atrophy, eye diseases, Pons, Diffusion Magnetic Resonance Imaging, 030104 developmental biology, Dentate nucleus, Globus pallidus, nervous system, Neurology, Female, Supranuclear Palsy, Progressive, Neurology (clinical), business, 030217 neurology & neurosurgery
Abstract: Background Progressive supranuclear palsy (PSP) is a neurodegenerative clinically heterogeneous disorder, formal diagnosis being based on postmortem histological brain examination. Objective We aimed to perform a precise in vivo staging of neurodegeneration in PSP using quantitative multimodal MRI. The ability of MRI biomarkers to differentiate PSP from PD was also evaluated. Methods Eleven PSP patients were compared to 26 age-matched healthy controls and 51 PD patients. Images were acquired at 3 Tesla (three-dimensional T1 -weighted, diffusion tensor, and neuromelanin-sensitive images) and 7 Tesla (three-dimensional-T2 * images). Regions of interest included the cortical areas, hippocampus, amygdala, basal ganglia, basal forebrain, brainstem nuclei, dentate nucleus, and cerebellum. Volumes, mean diffusivity, and fractional anisotropy were measured. In each region, a threshold value for group categorization was calculated, and four grades of change (0-3) were determined. Results PSP patients showed extensive volume decreases and diffusion changes in the midbrain, SN, STN, globus pallidus, basal forebrain, locus coeruleus, pedunculopontine nucleus, and dentate nucleus, in close agreement with the degrees of impairment in histological analyses. The predictive factors for the separation of PSP and healthy controls were, in descending order, the neuromelanin-based SN volume; midbrain fractional anisotropy; volumes of the midbrain, globus pallidus, and putamen; and fractional anisotropy in the locus coeruleus. The best predictors for separating PSP from PD were the neuromelanin-based volume in the SN, fractional anisotropy in the pons, volumes of the midbrain and globus pallidus, and fractional anisotropy in the basal forebrain. Conclusions These results suggest that it is possible to evaluate brain neurodegeneration in PSP noninvasively, even in small brainstem nuclei, in close agreement with previously published histological data. © 2019 International Parkinson and Movement Disorder Society.
Published: 2019
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3. Visual Sensory Processing is Altered in Myoclonus Dystonia

Author: Bertrand Degos, Luc Defebvre, Cécile Delorme, Christine Tranchant, Yulia Worbe, Pierre Krystkoviak, Marie Vidailhet, David Grabli, Eavan McGovern, Clément Tarrano, Jean-Christophe Corvol, Pierre Pouget, Stéphane Thobois, Jean‐Michel Pedespan, Romain Valabregue, Emmanuel Roze, Vanessa Brochard, Nicolas Wattiez, Jean-Luc Houeto, Adrian Degardin, Institut de génétique et biologie moléculaire et cellulaire (IGBMC), Université Louis Pasteur - Strasbourg I-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), and Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Adult, Male, Myoclonus, 0301 basic medicine, medicine.medical_specialty, Visual sensory, Sensory processing, Movement, medicine.medical_treatment, Sensory system, Audiology, 03 medical and health sciences, 0302 clinical medicine, medicine, Humans, Discrimination threshold, Dystonia, Movement Disorders, business.industry, Left primary visual cortex, Middle Aged, medicine.disease, nervous system diseases, 030104 developmental biology, Visual cortex, medicine.anatomical_structure, Neurology, Dystonic Disorders, Visual Perception, Female, Neurology (clinical), medicine.symptom, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, 030217 neurology & neurosurgery
Abstract: BACKGROUND: Abnormal sensory processing, including temporal discrimination threshold, has been described in various dystonic syndromes. OBJECTIVE: To investigate visual sensory processing in DYT-SGCE and identify its structural correlates. METHODS: DYT-SGCE patients without DBS (DYT-SGCE-non-DBS) and with DBS (DYT-SGCE-DBS) were compared to healthy volunteers in three tasks: a temporal discrimination threshold, a movement orientation discrimination, and movement speed discrimination. Response times attributed to accumulation of sensory visual information were computationally modelized, with mu parameter indicating sensory mean growth rate. We also identified the structural correlates of behavioral performance for temporal discrimination threshold. RESULTS: Twenty-four DYT-SGCE-non-DBS, 13 DYT-SGCE-DBS, and 25 healthy volunteers were included in the study. In DYT-SGCE-DBS, the discrimination threshold was higher in the temporal discrimination threshold (P = 0.024), with no difference among the groups in other tasks. The sensory mean growth rate (mu) was lower in DYT-SGCE in all three tasks (P < 0.01), reflecting a slower rate of sensory accumulation for the visual information in these patients independent of DBS. Structural imaging analysis showed a thicker left primary visual cortex (P = 0.001) in DYT-SGCE-non-DBS compared to healthy volunteers, which also correlated with lower mu in temporal discrimination threshold (P = 0.029). In DYT-SGCE-non-DBS, myoclonus severity also correlated with a lower mu in the temporal discrimination threshold task (P = 0.048) and with thicker V1 on the left (P = 0.022). CONCLUSION: In DYT-SGCE, we showed an alteration of the visual sensory processing in the temporal discrimination threshold that correlated with myoclonus severity and structural changes in the primary visual cortex. (c) 2019 International Parkinson and Movement Disorder Society.
Published: 2019
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4. Acute Diffusivity Biomarkers for Prediction of Motor and Language Outcome in Mild-to-Severe Stroke Patients

Author: Romain Valabregue, Christine Pires, Mélika Amor-Sahli, Serena Magno, Charlotte Rosso, Stéphane Lehéricy, Anne Leger, Eric A. Moulton, and Yves Samson
Subjects: Male, medicine.medical_specialty, Motor Disorders, Pyramidal Tracts, computer.software_genre, 050105 experimental psychology, White matter, 03 medical and health sciences, 0302 clinical medicine, Physical medicine and rehabilitation, Voxel, Aphasia, medicine, Humans, Arcuate fasciculus, 0501 psychology and cognitive sciences, Stroke, Aged, Advanced and Specialized Nursing, medicine.diagnostic_test, business.industry, 05 social sciences, Magnetic resonance imaging, Recovery of Function, Middle Aged, medicine.disease, Diffusion Tensor Imaging, medicine.anatomical_structure, Corticospinal tract, Female, Neurology (clinical), medicine.symptom, Cardiology and Cardiovascular Medicine, business, computer, 030217 neurology & neurosurgery, Diffusion MRI
Abstract: Background and Purpose— Early severity of stroke symptoms—especially in mild-to-severe stroke patients—are imperfect predictors of long-term motor and aphasia outcome. Motor function and language processing heavily rely on the preservation of important white matter fasciculi in the brain. Axial diffusivity (AD) from the diffusion tensor imaging model has repeatedly shown to accurately reflect acute axonal damage and is thus optimal to probe the integrity of important white matter bundles and their relationship with long-term outcome. Our aim was to investigate the independent prognostic value of the AD of white matter tracts in the motor and language network evaluated at 24 hours poststroke for motor and aphasia outcome at 3 months poststroke. Methods— Seventeen (motor cohort) and 28 (aphasia cohort) thrombolyzed patients with initial mild-to-severe stroke underwent a diffusion tensor imaging sequence at 24 hours poststroke. Motor and language outcome were evaluated at 3 months poststroke with a composite motor score and the aphasia handicap scale. We first used stepwise regression to determine which classic (age, initial motor or aphasia severity, and lesion volume) and imaging (ratio of affected/unaffected AD of motor and language fasciculi) factors were related to outcome. Second, to determine the specificity of our a priori choices of fasciculi, we performed voxel-based analyses to determine if the same, additional, or altogether new regions were associated with long-term outcome. Results— The ratio of AD in the corticospinal tract was the sole predictor of long-term motor outcome, and the ratio of AD in the arcuate fasciculus—along with age and initial aphasia severity—was an independent predictor of 3-month aphasia outcome. White matter regions overlapping with these fasciculi naturally emerged in the corresponding voxel-based analyses. Conclusions— AD of the corticospinal tract and arcuate fasciculus are effective biomarkers of long-term motor and aphasia outcome, respectively.
Published: 2019
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5. Medial prefrontal disengagement during self-focus in formerly depressed patients prone to rumination

Author: Frédéric Limosin, Philippe Fossati, Philip Gorwood, Nicolas Hoertel, Romain Valabregue, Jean-Yves Rotge, Cédric Lemogne, Caroline Dubertret, Christophe Guerin-Langlois, Ayna Baladi Nejad, Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Université Paris Descartes - Faculté de Médecine (UPD5 Médecine), Université Paris Descartes - Paris 5 (UPD5), and Université Paris Diderot - Paris 7 (UPD7)
Subjects: Adult, Male, [SDV]Life Sciences [q-bio], media_common.quotation_subject, Prefrontal Cortex, Neuropsychological Tests, Young Adult, 03 medical and health sciences, 0302 clinical medicine, medicine, Humans, Personality, Disengagement theory, Prefrontal cortex, Anterior cingulate cortex, Depression (differential diagnoses), media_common, Psychiatric Status Rating Scales, Brain Mapping, Depressive Disorder, Major, Depression, business.industry, Cognition, Middle Aged, medicine.disease, Magnetic Resonance Imaging, 030227 psychiatry, Psychiatry and Mental health, Clinical Psychology, Rumination, Cognitive, medicine.anatomical_structure, Rumination, Major depressive disorder, Female, medicine.symptom, business, 030217 neurology & neurosurgery, Clinical psychology
Abstract: Background Medial prefrontal cortex (MPFC) activity during self-referential processing has been associated with rumination and found aberrant in depression. We investigated whether this aberrant activity reflects a trait marker that persists in remitted patients. Methods Twenty-five patients fully remitted from major depression for at least 6 months, and 29 matched healthy controls were scanned with fMRI while presented with personality trait words in two conditions: Self condition asked whether the trait described themselves; General condition asked whether the trait was generally desirable. Contrasts-of-interest were examined in a factorial model and rumination correlates were examined in 2-sample t-tests with Ruminative Response Style score as covariate. All findings were reported at a conservative p Results Self-referential processing increased anterior cortical midline activity to a similar extent in both groups. Dorsal anterior cingulate cortex (MNI(x,y,z) = -12,20,26) and dorsal MPFC (MNI(x,y,z) = -6,46,40) activity during self-referential processing was positively associated with rumination in healthy control subjects and negatively associated with rumination in remitted patients. Limitations A longitudinal design tracking the relationship between rumination and MPFC activity would have aided the interpretation of our findings as to whether high ruminators are exhibiting an adaptive process to maintain remission or whether it represents a maladaptive process considering that high ruminators have an increased vulnerability for relapse. Conclusions The association between increased anterior cortical midline activity during self-referential processing and rumination differentiated healthy controls from formerly depressed patients. Self-referential neural processing during remission from depression may depend on the cognitive tendencies to ruminate.
Published: 2019
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6. Cystathionine as a marker for 1p/19q codeleted gliomas by in vivo magnetic resonance spectroscopy

Author: Małgorzata Marjańska, Marc Sanson, Lucien Tchara, Anna Luisa Di Stefano, Romain Valabregue, Stéphane Lehéricy, Francesca Branzoli, Clément Pontoizeau, Chris Ottolenghi, Dinesh K. Deelchand, and Aurélie Kamoun
Subjects: Adult, Male, In vivo magnetic resonance spectroscopy, Cancer Research, Magnetic Resonance Spectroscopy, Brain tumor, 1p/19q Codeletion, Young Adult, 03 medical and health sciences, Cystathionine, 0302 clinical medicine, In vivo, Glioma, Biomarkers, Tumor, Tumor Cells, Cultured, medicine, Humans, Neoplasm Invasiveness, Prospective Studies, Phosphoglycerate dehydrogenase, Phosphoglycerate Dehydrogenase, Aged, Cell Proliferation, biology, Brain Neoplasms, Chemistry, Middle Aged, Prognosis, medicine.disease, Cystathionine beta synthase, Survival Rate, Real-time polymerase chain reaction, Oncology, Chromosomes, Human, Pair 1, 030220 oncology & carcinogenesis, Basic and Translational Investigations, biology.protein, Cancer research, Female, Neurology (clinical), Chromosome Deletion, Chromosomes, Human, Pair 19, 030217 neurology & neurosurgery, Follow-Up Studies
Abstract: Background Codeletion of chromosome arms 1p and 19q (1p/19q codeletion) highly benefits diagnosis and prognosis in gliomas. In this study, we investigated the effect of 1p/19q codeletion on cancer cell metabolism and evaluated possible metabolic targets for tailored therapies. Methods We combined in vivo 1H (proton) magnetic resonance spectroscopy (MRS) measurements in human gliomas with the analysis of a series of standard amino acids by liquid chromatography-mass spectroscopy (LC-MS) in human glioma biopsies. Sixty-five subjects with low-grade glioma were included in the study: 31 underwent the MRI/MRS examination, 47 brain tumor tissue samples were analyzed with LC-MS, and 33 samples were analyzed for gene expression with quantitative PCR. Additionally, we performed metabolic tracer experiments in cell models with 1p deletion. Results We report the first in vivo detection of cystathionine by MRS in 1p/19q codeleted gliomas. Selective accumulation of cystathionine was observed in codeleted gliomas in vivo, in brain tissue samples, as well as in cells harboring heterozygous deletions for serine- and cystathionine-pathway genes located on 1p: phosphoglycerate dehydrogenase (PHGDH) and cystathionine gamma-lyase (CTH). Quantitative PCR analyses showed 40-50% lower expression of both PHGDH and CTH in 1p/19q codeleted gliomas compared with their non-codeleted counterparts. Conclusions Our results provide strong evidence of a selective vulnerability of codeleted gliomas to serine and glutathione depletion and point to cystathionine as a possible noninvasive marker of treatment response.
Published: 2019
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7. The spatiotemporal changes in dopamine, neuromelanin and iron characterizing Parkinson's disease

Author: Mathieu Santin, Nicolas Villain, I. Arnulf, Stéphane Lehéricy, Smaranda Leu-Semenescu, Emma Biondetti, Miquel Vila, Jean-Christophe Corvol, Marie-Odile Habert, Pauline Dodet, Graziella Mangone, M. Vidailhet, Rahul Gaurav, Lydia Yahia-Cherif, Romain Valabregue, Matthew Hutchison, Nadya Pyatigorskaya, Institut du Cerveau = Paris Brain Institute (ICM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Università degli studi 'G. d'Annunzio' Chieti-Pescara [Chieti-Pescara] (Ud'A), Center for NeuroImaging Research-Human MRI Neuroimaging core facility for clinical research [ICM Paris] (CENIR), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Centre d'investigation clinique Biothérapie [CHU Pitié-Salpêtrière] (CIC-BTi), Centre d'investigation clinique pluridisciplinaire [CHU Pitié Salpêtrière] (CIC-P 1421), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de Neurologie [CHU Pitié-Salpêtrière], IFR70-CHU Pitié-Salpêtrière [AP-HP], Service de Neuroradiologie [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Laboratoire d'Imagerie Biomédicale (LIB), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Service de Médecine nucléaire [CHU Pitié-Salpétrière], Service de Pathologies du sommeil [CHU Pitié-Salpêtrière], Universitat Autònoma de Barcelona (UAB), Vall d’Hebron Research Institute (VHIR), Centro de Investigacion Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Instituto de Salud Carlos III [Madrid] (ISC), Institució Catalana de Recerca i Estudis Avançats (ICREA), HAL-SU, Gestionnaire, Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Center for NeuroImaging Research - CENIR, Sorbonne Université (SU), Centre d’Investigation Clinique en Biothérapies [CHU Pitié-Salpêtrière] (CIC-BT), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de médecine nucléaire [CHU Pitié-Salpétrière], Service des Pathologies du sommeil [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Institut Català de la Salut, [Biondetti E, Gaurav R] Sorbonne Université, Institut du Cerveau - Paris Brain Institute - ICM, INSERM, CNRS, Paris, France. ICM, Centre de NeuroImagerie de Recherche - CENIR, Paris, France. ICM, Team 'Movement Investigations and Therapeutics' (MOV'IT), Paris, France. [Santin MD, Valabrègue R] Sorbonne Université, Institut du Cerveau - Paris Brain Institute - ICM, INSERM, CNRS, Paris, France. ICM, Centre de NeuroImagerie de Recherche - CENIR, Paris, France. [Mangone G] Sorbonne Université, Institut du Cerveau - Paris Brain Institute - ICM, INSERM, CNRS, Paris, France. Assistance Publique Hôpitaux de Paris, Hôpital Pitié-Salpêtrière, Department of Neurology, Centre d'Investigation Clinique Neurosciences, Paris, France. Assistance Publique Hôpitaux de Paris, Hôpital Pitié-Salpêtrière, Department of Neurology, Paris, France. [Pyatigorskaya N] Sorbonne Université, Institut du Cerveau - Paris Brain Institute - ICM, INSERM, CNRS, Paris, France. ICM, Team 'Movement Investigations and Therapeutics' (MOV'IT), Paris, France. Assistance Publique Hôpitaux de Paris, Hôpital Pitié-Salpêtrière, Department of Neuroradiology, Paris, France. [Vila M] Grup de Recerca en Malalties Neurodegeneratives, Vall d'Hebron Institut de Recerca (VHIR), Barcelona, Spain. Center for Networked Biomedical Research on Neurodegenerative Diseases (CIBERNED). Departament de Bioquímica i Biologia Molecular, Universitat Autònoma de Barcelona, Bellaterra, Spain. Catalan Institution for Research and Advanced Studies (ICREA), 08010 Barcelona, Spain, and Vall d'Hebron Barcelona Hospital Campus
Subjects: Male, Parkinson's disease, Time Factors, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, aminoácidos, péptidos y proteínas::aminoácidos::aminoácidos cíclicos::aminoácidos aromáticos::tirosina::melaninas [COMPUESTOS QUÍMICOS Y DROGAS], Striatum, Imaging, 030218 nuclear medicine & medical imaging, Cohort Studies, 0302 clinical medicine, iron, enfermedades del sistema nervioso::enfermedades del sistema nervioso central::enfermedades cerebrales::enfermedades de los ganglios basales::trastornos parkinsonianos::enfermedad de Parkinson [ENFERMEDADES], Medicine, Longitudinal Studies, Prospective Studies, dopamine transporter, biology, AcademicSubjects/SCI01870, Dopaminergic, imaging, Middle Aged, Organic Chemicals::Amines::Biogenic Amines::Biogenic Monoamines::Dopamine [CHEMICALS AND DRUGS], Magnetic Resonance Imaging, Substantia Nigra, Dopamine transporter, Neurones dopaminèrgiques, Nervous System Diseases::Central Nervous System Diseases::Brain Diseases::Basal Ganglia Diseases::Parkinsonian Disorders::Parkinson Disease [DISEASES], Female, neuromelanin, dopamine, Amino Acids, Peptides, and Proteins::Amino Acids::Amino Acids, Cyclic::Amino Acids, Aromatic::Tyrosine::Melanins [CHEMICALS AND DRUGS], medicine.drug, Iron, Substantia nigra, Neuromelanin, 03 medical and health sciences, Dopamine, parkinson disease, Parkinson, Malaltia de - Imatgeria per ressonància magnètica, Humans, Other subheadings::Other subheadings::/diagnostic imaging [Other subheadings], Aged, Melanins, business.industry, Pars compacta, pars compacta, [SDV.NEU.NB] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Otros calificadores::Otros calificadores::/diagnóstico por imagen [Otros calificadores], Original Articles, medicine.disease, Corpus Striatum, compuestos orgánicos::aminas::aminas biógenas::monoaminas biógenas::dopamina [COMPUESTOS QUÍMICOS Y DROGAS], nervous system, biology.protein, Parkinson’s disease, AcademicSubjects/MED00310, Neurology (clinical), business, Neuroscience, 030217 neurology & neurosurgery
Abstract: In Parkinson’s disease, there is a progressive reduction in striatal dopaminergic function, and loss of neuromelanin-containing dopaminergic neurons and increased iron deposition in the substantia nigra. We tested the hypothesis of a relationship between impairment of the dopaminergic system and changes in the iron metabolism. Based on imaging data of patients with prodromal and early clinical Parkinson’s disease, we assessed the spatiotemporal ordering of such changes and relationships in the sensorimotor, associative and limbic territories of the nigrostriatal system. Patients with Parkinson’s disease (disease duration < 4 years) or idiopathic REM sleep behaviour disorder (a prodromal form of Parkinson’s disease) and healthy controls underwent longitudinal examination (baseline and 2-year follow-up). Neuromelanin and iron sensitive MRI and dopamine transporter single-photon emission tomography were performed to assess nigrostriatal levels of neuromelanin, iron, and dopamine. For all three functional territories of the nigrostriatal system, in the clinically most and least affected hemispheres separately, the following was performed: cross-sectional and longitudinal intergroup difference analysis of striatal dopamine and iron, and nigral neuromelanin and iron; in Parkinson’s disease patients, exponential fitting analysis to assess the duration of the prodromal phase and the temporal ordering of changes in dopamine, neuromelanin or iron relative to controls; and voxel-wise correlation analysis to investigate concomitant spatial changes in dopamine-iron, dopamine-neuromelanin and neuromelanin-iron in the substantia nigra pars compacta. The temporal ordering of dopaminergic changes followed the known spatial pattern of progression involving first the sensorimotor, then the associative and limbic striatal and nigral regions. Striatal dopaminergic denervation occurred first followed by abnormal iron metabolism and finally neuromelanin changes in the substantia nigra pars compacta, which followed the same spatial and temporal gradient observed in the striatum but shifted in time. In conclusion, dopaminergic striatal dysfunction and cell loss in the substantia nigra pars compacta are interrelated with increased nigral iron content., Using multi-modal imaging (MRI and SPECT) in patients with prodromal and early clinical Parkinson’s disease, Biondetti et al. reveal dopaminergic changes, abnormal iron metabolism and neuromelanin changes first in the sensorimotor, then the associative and finally the limbic regions of the nigrostriatal system.
Published: 2021
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8. Longitudinal Changes in Neuromelanin MRI Signal in Parkinson's Disease: A Progression Marker

Author: Lydia Yahia-Cherif, Romain Valabregue, Jesse M. Cedarbaum, Marie Vidailhet, Rahul Gaurav, Jean-Christophe Corvol, Stéphane Lehéricy, Claire Ewenczyk, Emma Biondetti, R. Matthew Hutchison, Nadya Pyatigorskaya, Graziella Mangone, Gestionnaire, Hal Sorbonne Université, Institut du Cerveau = Paris Brain Institute (ICM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Center for NeuroImaging Research-Human MRI Neuroimaging core facility for clinical research [ICM Paris] (CENIR), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Service de Neuroradiologie [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Biogen Inc. [Cambridge, MA, USA], Service de Neurologie [CHU Pitié-Salpêtrière], IFR70-CHU Pitié-Salpêtrière [AP-HP], Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Centre de Neuro-Imagerie de Recherche (CENIR), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Service de neurologie 1 [CHU Pitié-Salpétrière], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), and Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)
Subjects: Male, 0301 basic medicine, medicine.medical_specialty, Movement disorders, Parkinson's disease, [SDV]Life Sciences [q-bio], Urology, Substantia nigra, Regular Issue Articles, 03 medical and health sciences, 0302 clinical medicine, Neuromelanin, medicine, Humans, Prospective Studies, Research Articles, parkinsonism, Melanins, neuroimaging, Pars compacta, business.industry, Parkinsonism, Parkinson Disease, medicine.disease, Magnetic Resonance Imaging, 3. Good health, Substantia Nigra, [SDV] Life Sciences [q-bio], 030104 developmental biology, Neurology, Case-Control Studies, neurodegenerative disorders, Cohort, biomarker, Biomarker (medicine), Female, Neurology (clinical), medicine.symptom, business, Biomarkers, 030217 neurology & neurosurgery, Research Article
Abstract: International audience; BackgroundDevelopment of reliable and accurate imaging biomarkers of dopaminergic cell neurodegeneration is necessary to facilitate therapeutic drug trials in Parkinson's disease (PD). Neuromelanin‐sensitive MRI techniques have been effective in detecting neurodegeneration in the substantia nigra pars compacta (SNpc). The objective of the current study was to investigate longitudinal neuromelanin signal changes in the SNpc in PD patients.MethodsIn this prospective, longitudinal, observational case–control study, we included 140 PD patients and 64 healthy volunteers divided into 2 cohorts. Cohort I included 99 early PD patients (disease duration, 1.5 ± 1.0 years) and 41 healthy volunteers analyzed at baseline (V1), where 79 PD patients and 32 healthy volunteers were rescanned after 2.0 ± 0.2 years of follow‐up (V2). Cohort II included 41 progressing PD patients (disease duration, 9.3 ± 3.7 years) and 23 healthy volunteers at V1, where 30 PD patients were rescanned after 2.4 ± 0.5 years of follow‐up. Subjects were scanned at 3 T MRI using 3‐dimensional T1‐weighted and neuromelanin‐sensitive imaging. Regions of interest were delineated manually to calculate SN volumes, volumes corrected by total intracranial volume, signal‐to‐noise ratio, and contrast‐to‐noise ratio.ResultsResults showed (1) significant reduction in volume and volume corrected by total intracranial volume between visits, greater in progressing PD than nonsignificant changes in healthy volunteers; (2) no significant effects of visit for signal intensity (signal‐to‐noise ratio); (3) significant interaction in volume between group and visit; (4) greater volume corrected by total intracranial volume at baseline in female patients and greater decrease in volume and increase in the contrast‐to‐noise ratio in progressing female PD patients compared with male patients; and (5) correlations between neuromelanin SN changes and disease severity and duration.ConclusionsWe observed a progressive and measurable decrease in neuromelanin‐based SN signal and volume in PD, which might allow a direct noninvasive assessment of progression of SN loss and could represent a target biomarker for disease‐modifying treatments. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society
Published: 2021
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9. Dissociation in reactive and proactive inhibitory control in Myoclonus dystonia

Author: Vanessa Brochard, Cyril Atkinson-Clement, Yulia Worbe, David Grabli, Stéphane Thobois, Jean‐Michel Pedespan, Nicolas Wattiez, Christine Tranchant, Romain Valabregue, Pierre Krystkoviak, Emmanuel Roze, Bertrand Degos, Clément Tarrano, Emmanuelle Apartis, Charlotte Rosso, Cécile Delorme, Camille-Albane Porte, Luc Defebvre, Jean-Luc Houeto, Marie Vidailhet, Eavan McGovern, Jean-Christophe Corvol, Pierre Pouget, Adrian Degardin, Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Hôpital Côte de Nacre [CHU Caen], CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Université de Caen Normandie (UNICAEN), Normandie Université (NU), Centre d'investigation clinique Neurosciences [CHU Pitié Salpêtrière] (CIC Neurosciences), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Neurophysiologie Respiratoire Expérimentale et Clinique (UMRS 1158), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), St Vincent's University Hospital, Institut des sciences cognitives Marc Jeannerod - Centre de neuroscience cognitive - UMR5229 (CNC), Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, Hospices Civils de Lyon (HCL), Hôpital neurologique et neurochirurgical Pierre Wertheimer [CHU - HCL], Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Fédération de Médecine Translationnelle de Strasbourg (FMTS), Université de Strasbourg (UNISTRA), Hôpital Avicenne [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpitaux Paris Seine-Saint-Denis [Bobigny], CHU de Bordeaux Pellegrin [Bordeaux], CHU Amiens-Picardie, CIC - Poitiers, Université de Poitiers-Centre hospitalier universitaire de Poitiers (CHU Poitiers)-Direction Générale de l'Organisation des Soins (DGOS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier de Tourcoing, Troubles cognitifs dégénératifs et vasculaires - U 1171 (TCDV), Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Recherche de l'Institut du Cerveau et de la Moelle épinière (CRICM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), CHU Saint-Antoine [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Neurophysiologie Respiratoire Expérimentale et Clinique, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut du Cerveau = Paris Brain Institute (ICM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Université de Caen Normandie - UFR Santé (UNICAEN Santé), Normandie Université (NU)-Normandie Université (NU), Centre d'investigation clinique pluridisciplinaire [CHU Pitié Salpêtrière] (CIC-P 1421), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Service de neurologie [Poitiers], Centre hospitalier universitaire de Poitiers (CHU Poitiers), CHU Lille, Service de Neurologie [CHU Saint-Antoine], Atkinson-Clement, Cyril, Service de pédiatrie, CHU Pellegrin, Département de neurologie[Lille], Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service de neurologie et pathologie du mouvement, Hôpital Roger Salengro [Lille]-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Equipe NEMESIS - Centre de Recherches de l'Institut du Cerveau et de la Moelle épinière (NEMESIS-CRICM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Institut des sciences cognitives Marc Jeannerod - Centre de neuroscience cognitive - UMR5229 (ISC-MJ), and ANR-18-CE37-0008,CADETS,Cognition et développement cérébral chez adolescents avec Syndrome de Gilles de la Tourette(2018)
Subjects: Male, Myoclonus, 0301 basic medicine, Deep Brain Stimulation, medicine.medical_treatment, lcsh:Medicine, Stop signal, Synaptic Transmission, Comorbidities, [SCCO]Cognitive science, 0302 clinical medicine, lcsh:Science, ComputingMilieux_MISCELLANEOUS, Dystonia, Multidisciplinary, Inhibition, Psychological, Dystonic Disorders, Proactive Inhibition, Neurological manifestations, Facilitation, Female, medicine.symptom, Adult, medicine.medical_specialty, Deep brain stimulation, Dissociative Disorders, Globus Pallidus, Inhibitory postsynaptic potential, Article, Young Adult, 03 medical and health sciences, Internal medicine, Reaction Time, medicine, Humans, Movement disorders, Reactive inhibition, business.industry, [SCCO.NEUR]Cognitive science/Neuroscience, lcsh:R, Reactive Inhibition, [SCCO] Cognitive science, medicine.disease, nervous system diseases, 030104 developmental biology, Endocrinology, nervous system, lcsh:Q, business, Neurological disorders, 030217 neurology & neurosurgery
Abstract: Myoclonus-dystonia (MD) is a syndrome characterized by myoclonus of subcortical origin and dystonia, frequently associated with psychiatric comorbidities. The motor and psychiatric phenotypes of this syndrome likely result from cortico-striato-thamalo-cerebellar-cortical pathway dysfunction. We hypothesized that reactive and proactive inhibitory control may be altered in these patients. Using the Stop Signal Task, we assessed reactive and proactive inhibitory control in MD patients with (n = 12) and without (n = 21) deep brain stimulation of the globus pallidus interna and compared their performance to matched healthy controls (n = 24). Reactive inhibition was considered as the ability to stop an already initiated action and measured using the stop signal reaction time. Proactive inhibition was assessed through the influence of several consecutive GO or STOP trials on decreased response time or inhibitory process facilitation. The proactive inhibition was solely impaired in unoperated MD patients. Patients with deep brain stimulation showed impairment in reactive inhibition, independent of presence of obsessive–compulsive disorders. This impairment in reactive inhibitory control correlated with intrinsic severity of myoclonus (i.e. pre-operative score). The results point to a dissociation in reactive and proactive inhibitory control in MD patients with and without deep brain stimulation of the globus pallidus interna.
Published: 2020
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10. The supplementary motor area modulates interhemispheric interactions during movement preparation

Author: Elodie Hainque, Cecilia Bonnet, Vanessa Brochard, Emmanuel Roze, Constance Flamand-Roze, Oriane Trouillard, Jean-Charles Lamy, Cecile Gallea, Stéphane Lehéricy, Isabelle Dusart, Romain Valabregue, Cécile Hubsch, Benoît Béranger, Traian Popa, Jean-Louis Golmard, Pierre Bitoun, Marie Vidailhet, Bertrand Degos, Norbert Brüggemann, Quentin Welniarz, Sabine Meunier, and Aurélie Méneret
Subjects: Adult, Male, Adolescent, Movement, medicine.medical_treatment, Intention, Mirror movements, Functional Laterality, 050105 experimental psychology, Hand movements, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Healthy volunteers, Coordinated movement, medicine, Humans, 0501 psychology and cognitive sciences, Radiology, Nuclear Medicine and imaging, Research Articles, Movement Disorders, Radiological and Ultrasound Technology, Supplementary motor area, Movement (music), business.industry, 05 social sciences, Motor Cortex, Middle Aged, Evoked Potentials, Motor, SMA, Magnetic Resonance Imaging, Transcranial Magnetic Stimulation, Healthy Volunteers, Transcranial magnetic stimulation, medicine.anatomical_structure, Neurology, Female, Neurology (clinical), Anatomy, business, Neuroscience, Psychomotor Performance, 030217 neurology & neurosurgery
Abstract: The execution of coordinated hand movements requires complex interactions between premotor and primary motor areas in the two hemispheres. The supplementary motor area (SMA) is involved in movement preparation and bimanual coordination. How the SMA controls bimanual coordination remains unclear, although there is evidence suggesting that the SMA could modulate interhemispheric interactions. With a delayed‐response task, we investigated interhemispheric interactions underlying normal movement preparation and the role of the SMA in these interactions during the delay period of unimanual or bimanual hand movements. We used functional MRI and transcranial magnetic stimulation in 22 healthy volunteers (HVs), and then in two models of SMA dysfunction: (a) in the same group of HVs after transient disruption of the right SMA proper by continuous transcranial magnetic theta‐burst stimulation; (b) in a group of 22 patients with congenital mirror movements (CMM), whose inability to produce asymmetric hand movements is associated with SMA dysfunction. In HVs, interhemispheric connectivity during the delay period was modulated according to whether or not hand coordination was required for the forthcoming movement. In HVs following SMA disruption and in CMM patients, interhemispheric connectivity was modified during the delay period and the interhemispheric inhibition was decreased. Using two models of SMA dysfunction, we showed that the SMA modulates interhemispheric interactions during movement preparation. This unveils a new role for the SMA and highlights its importance in coordinated movement preparation.
Published: 2019
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11. Simultaneous proton density, T

Author: Lisa, Leroi, Vincent, Gras, Nicolas, Boulant, Mathilde, Ripart, Emilie, Poirion, Mathieu D, Santin, Romain, Valabregue, Franck, Mauconduit, Lucie, Hertz-Pannier, Denis, Le Bihan, Ludovic, de Rochefort, and Alexandre, Vignaud
Subjects: Adult, Male, Young Adult, Imaging, Three-Dimensional, Phantoms, Imaging, Image Processing, Computer-Assisted, Brain, Humans, Reproducibility of Results, Female, Protons, Magnetic Resonance Imaging, Algorithms
Abstract: Performing simultaneous quantitative MRI at ultrahigh field is challenging, as BEleven optimized contrasts were acquired with an unbalanced SSFP sequence by varying flip-angle amplitude and RF phase-cycling increment, at a 1.0 × 1.0 × 3.0 mmWhole-brain 3D maps of effective flip angle, proton density, and relaxation times were estimated. Parallel transmission improved the robustness of the results at 7 T. Results were in accordance with literature and with measurements from standard methods.These preliminary results show robust proton density, flip angle, T
Published: 2020

12. Multimodal magnetic resonance imaging investigation of basal forebrain damage and cognitive deficits in Parkinson's disease

Author: M. Vidailhet, Claire Ewenczyk, Stéphane Lehéricy, Marie Sarazin, Fatma Gargouri, Nadya Pyatigorskaya, Lydia Yahia-Cherif, Romain Valabregue, Cecile Gallea, Marie Mongin, Gestionnaire, Hal Sorbonne Université, Sorbonne Université (SU), Sorbonne Université - Faculté de Médecine (SU FM), Center for NeuroImaging Research-Human MRI Neuroimaging core facility for clinical research [ICM Paris] (CENIR), Institut du Cerveau = Paris Brain Institute (ICM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Service de Neurologie [CHU Pitié-Salpêtrière], IFR70-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de Neuroradiologie [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Centre Hospitalier Sainte Anne [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Imagerie Moléculaire in Vivo (IMIV - U1023 - ERL9218), Service Hospitalier Frédéric Joliot (SHFJ), Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre de Neuro-Imagerie de Recherche (CENIR), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Service de neurologie 1 [CHU Pitié-Salpétrière], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)
Subjects: Male, cognition, 0301 basic medicine, Parkinson's disease, Basal Forebrain, [SDV.IB.IMA]Life Sciences [q-bio]/Bioengineering/Imaging, resting state fMRI, Neuropsychological Tests, Multimodal Imaging, diffusion MRI, Executive Function, 03 medical and health sciences, 0302 clinical medicine, cholinergic, Cortex (anatomy), Neural Pathways, medicine, Humans, Cognitive Dysfunction, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Prefrontal cortex, Research Articles, Aged, Brain Mapping, Basal forebrain, Resting state fMRI, business.industry, functional connectivity, Fornix, Parkinson Disease, Middle Aged, medicine.disease, Executive functions, Magnetic Resonance Imaging, acetylcholine, Olfactory bulb, [SDV.IB.IMA] Life Sciences [q-bio]/Bioengineering/Imaging, 030104 developmental biology, medicine.anatomical_structure, nervous system, Neurology, Female, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Neurology (clinical), business, Neuroscience, 030217 neurology & neurosurgery, Research Article
Abstract: Background Cognitive deficits in Parkinson's disease (PD) may result from damage in the cortex as well as in the dopaminergic, noradrenergic, and cholinergic inputs to the cortex. Cholinergic inputs to the cortex mainly originate from the basal forebrain and are clustered in several regions, called Ch1 to Ch4, that project to the hippocampus (Ch1‐2), the olfactory bulb (Ch3), and the cortex and amygdala (Ch4). Objective We investigated changes in basal forebrain and their role in cognitive deficits in PD. Methods We studied 52 nondemented patients with PD (Hoehn & Yahr 1‐2) and 25 age‐matched healthy controls using diffusion and resting state functional MRI. Results PD patients had a loss of structural integrity within the Ch1‐2 and Ch3‐4 nuclei of the basal forebrain as well as in the fornix. Tractography showed that the probability of anatomical connection was decreased in PD between Ch3‐4 and the associative prefrontal cortex, occipital cortex, and peri‐insular regions. There was a reduction in functional connectivity between Ch1‐2 and the bilateral hippocampi and parahippocampal gyri, the left middle and superior temporal gyri, and the left fusiform gyrus and between Ch3‐4 and the right inferior frontal gyrus and the right and left thalamus. In Ch1‐2, loss of structural integrity and connectivity correlated with scores at the memory tests, whereas changes in Ch3‐4 correlated with scores of global cognition and executive functions. Conclusion This study highlights the association between deficits of different cholinergic nuclei of the basal forebrain and the extent of cognitive impairments in nondemented PD patients. © 2018 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.
Published: 2018
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13. Comparison of spatial normalization strategies of diffusion MRI data for studying motor outcome in subacute-chronic and acute stroke

Author: Claire Kemlin, Charlotte Rosso, Belen Diaz, Stéphane Lehéricy, Sara Leder, Yves Samson, Eric A. Moulton, and Romain Valabregue
Subjects: Male, Normalization (statistics), medicine.medical_specialty, Cognitive Neuroscience, Pyramidal Tracts, 030218 nuclear medicine & medical imaging, Lesion, White matter, Correlation, 03 medical and health sciences, Nerve Fibers, 0302 clinical medicine, Physical medicine and rehabilitation, Fractional anisotropy, medicine, Humans, Aged, Aged, 80 and over, Movement Disorders, business.industry, Middle Aged, Stroke, Diffusion Magnetic Resonance Imaging, medicine.anatomical_structure, Neurology, Acute Disease, Chronic Disease, Corticospinal tract, Spatial normalization, Female, medicine.symptom, business, 030217 neurology & neurosurgery, Diffusion MRI
Abstract: A common means of studying motor recovery in stroke patients is to extract Diffusion Tensor Imaging (DTI) parameters from the corticospinal tract (CST) and correlate them with clinical outcome scores. To that purpose, conducting group-level analyses through spatial normalization has become a popular approach. However, the reliability of such analyses depends on the accuracy of the particular registration strategy employed. To date, most studies have employed scalar-based registration using either high-resolution T1 images or Fractional Anisotropy (FA) maps to warp diffusion data to a common space. However, more powerful registration algorithms exist for aligning major white matter structures, such as Fiber Orientation Distribution (FOD)-based registration. Regardless of the strategy chosen, automatic normalization algorithms are prone to distortions caused by stroke lesions. While lesion masking is a common means to lessen such distortions, the extent of its effect on tract-related DTI parameters and their correlation with motor outcome has yet to be determined. Here, we aimed to address these concerns by first investigating the effect of common T1 and FA-based registration as well as novel FOD-based registration algorithms with and without lesion masking on lesion load and DTI parameter extraction of the CST in datasets typically acquired for subacute-chronic and acute stroke patients. Second, we studied how differences in these procedures influenced correlation strength between CST damage (through DTI parameters) and motor outcome. Our results showed that, for high-quality subacute-chronic stroke data, FOD-based registration captured significantly higher lesion loads and significantly larger FA asymmetries in the CST. This was also associated with significantly stronger correlations in motor outcome with respect to T1 or FA-based registration methods. For acute data acquired in a clinical setting, there were few observed differences, suggesting that commonly employed FA-based registration is appropriate for group-level analyses.
Published: 2018
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14. Elucidating the Structural and Functional Correlates of Upper-Limb Poststroke Motor Impairment

Author: Vanessa Brochard, Yves Samson, Claire Kemlin, Charlotte Rosso, Mickael A. Obadia, Sara Leder, Jean-Charles Lamy, Marion Houot, Elena Meseguer, Romain Valabregue, Marion Yger, Jean-Christophe Corvol, and Eric A. Moulton
Subjects: Adult, Male, medicine.medical_specialty, medicine.medical_treatment, Pyramidal Tracts, 030204 cardiovascular system & hematology, Corpus callosum, Brain Ischemia, Corpus Callosum, Upper Extremity, 03 medical and health sciences, 0302 clinical medicine, Physical medicine and rehabilitation, medicine, Humans, Stroke, Neurorehabilitation, Aged, Aged, 80 and over, Advanced and Specialized Nursing, Hand Strength, business.industry, Functional Neuroimaging, Motor Cortex, Middle Aged, Evoked Potentials, Motor, medicine.disease, Magnetic Resonance Imaging, Transcranial Magnetic Stimulation, Transcranial magnetic stimulation, Diffusion Tensor Imaging, medicine.anatomical_structure, Laterality, Upper limb, Female, Neurology (clinical), Primary motor cortex, Cardiology and Cardiovascular Medicine, business, 030217 neurology & neurosurgery, Motor cortex
Abstract: Background and Purpose— Many studies have attempted to bring to light the neural correlates of poststroke motor impairment, but few have used multimodal approach to explain it. The aim of this study was to elucidate neural structural and functional correlates of upper limb motor impairment by combining electrophysiological, anatomic, and functional neuroimaging data. Methods— Forty ischemic stroke patients (median [min–max] age: 63 [33–82] years, time poststroke: 3.5 [1.1–58] months) with unilateral upper limb weakness were included. The upper limb motor impairment was defined by a motor composite score. Simple linear analysis followed by multiple linear regression analysis were performed to identify which variables (corticospinal excitability, laterality indices within the primary motor cortex or corticospinal [CST], and corpus callosum tracts integrity) were the best explaining factors of upper limb motor impairment. Results— There was a significant correlation between the resting motor threshold ratio and CST damage ( r = −0.50 [95% CI, −0.70 to −0.22]; P r = −0.73 [95% CI, −0.85 to −0.54]; P P Conclusions— The implementation of quantitative neurophysiological measurements such as the resting motor threshold as a surrogate marker of impairment could be considered in neurorehabilitation trials.
Published: 2019
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15. Deep brain activation patterns involved in virtual gait without and with a doorway: An fMRI study

Author: Carine Karachi, Brian Lau, Mélanie Pélégrini-Issac, Romain Valabregue, Jason Sellers, Cecile Gallea, Pierre Leboucher, Marie-Laure Welter, Véronique Marchal, Eric Bertasi, Eric Bardinet, Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Laboratoire d'Imagerie Biomédicale (LIB), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Centre de Neuro-Imagerie de Recherche (CENIR), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Plateforme PRISME [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Service de neurophysiologie [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Service de Neurochirurgie [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Research was funded by the 'Investissements d’Avenir' (investing in the future) program ANR-10-IAIHU-06. This work was supported by a grant from the 'Régie Autonome des Transports Parisiens' (RATP) and the grant ANR 'Technologie de la Santé' [N˚ ANR-GUI-AAP-05 ECOTECH]. The contribution of JS was supported by an ATIP-Avenir grant to BL from the Mairie de Paris., Institut du Cerveau = Paris Brain Institute (ICM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Center for NeuroImaging Research-Human MRI Neuroimaging core facility for clinical research [ICM Paris] (CENIR), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], and Bodescot, Myriam
Subjects: Male, Cerebellum, Physiology, Red nucleus, [SDV.IB.IMA]Life Sciences [q-bio]/Bioengineering/Imaging, Deep Brain Stimulation, medicine.medical_treatment, Walking, Basal Ganglia, Diagnostic Radiology, 0302 clinical medicine, Gait (human), Thalamus, Functional Magnetic Resonance Imaging, Basal ganglia, Medicine and Health Sciences, Image Processing, Computer-Assisted, Gait, Cerebral Cortex, Brain Mapping, Multidisciplinary, Radiology and Imaging, 05 social sciences, Brain, Magnetic Resonance Imaging, medicine.anatomical_structure, Medicine, Female, Brainstem, Anatomy, Gait Analysis, Psychology, Locomotion, Research Article, Adult, Deep brain stimulation, Imaging Techniques, Science, Neuroimaging, Research and Analysis Methods, 050105 experimental psychology, Young Adult, 03 medical and health sciences, Diagnostic Medicine, medicine, Humans, 0501 psychology and cognitive sciences, Biological Locomotion, [SCCO.NEUR]Cognitive science/Neuroscience, [SCCO.NEUR] Cognitive science/Neuroscience, Biology and Life Sciences, Spinal cord, [SDV.IB.IMA] Life Sciences [q-bio]/Bioengineering/Imaging, Caudate Nucleus, Neuroscience, human activities, 030217 neurology & neurosurgery
Abstract: International audience; The human gait program involves many brain areas such as motor cortices, cerebellum, basal ganglia, brainstem, and spinal cord. The mesencephalic locomotor region (MLR), which contains the pedunculopontine (PPN) and cuneiform (CN) nuclei, is thought to be one of the key supraspinal gait generators. In daily life activities, gait primarily occurs in complex conditions, such as through narrow spaces, or while changing direction or performing motor or cognitive tasks. Here, we aim to explore the activity of these subcortical brain areas while walking through narrow spaces, using functional MRI in healthy volunteers and designing a virtual reality task mimicking walking down a hallway, without and with an open doorway to walk through. As a control, we used a virtual moving walkway in the same environment. Twenty healthy volunteers were scanned. Fifteen subjects were selected for second level analysis based on their ability to activate motor cortices. Using the contrast Gait versus Walkway, we found activated clusters in motor cortices, cerebellum, red nucleus, thalamus, and the left MLR including the CN and PPN. Using the contrast Gait with Doorway versus Walkway with Doorway, we found activated clusters in motor cortices, left putamen, left internal pallidum, left substantia nigra, right subthalamic area, and bilateral MLR involving the CN and PPN. Our results suggest that unobstructed gait involves a motor network including the PPN whereas gait through a narrow space requires the additional participation of basal ganglia and bilateral MLR, which may encode environmental cues to adapt locomotion.
Published: 2019
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16. Multivariate prediction of functional outcome using lesion topography characterized by acute diffusion tensor imaging

Author: Charlotte Rosso, Stéphane Lehéricy, Eric A. Moulton, Romain Valabregue, Yves Samson, Institut du Cerveau = Paris Brain Institute (ICM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Center for NeuroImaging Research-Human MRI Neuroimaging core facility for clinical research [ICM Paris] (CENIR), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Service de Neuroradiologie [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service d'Urgences Cérébro-Vasculaires [CHU Pitié-Salpêtrière], Gestionnaire, Hal Sorbonne Université, Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Centre de Neuro-Imagerie de Recherche (CENIR), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), and Service des Urgences Cérébro-Vasculaires [CHU Pitié-Salpétriêre]
Subjects: Male, Support Vector Machine, [SDV.IB.IMA]Life Sciences [q-bio]/Bioengineering/Imaging, lcsh:RC346-429, Brain Ischemia, 0302 clinical medicine, Acute stroke, Diagnosis, Computer-Assisted, Stroke, Thrombectomy, Aged, 80 and over, 05 social sciences, Radial diffusivity, Regular Article, Middle Aged, Functional outcome, Prognosis, Outcome (probability), medicine.anatomical_structure, Diffusion tensor imaging, Neurology, lcsh:R858-859.7, Female, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Radiology, medicine.symptom, medicine.medical_specialty, Cognitive Neuroscience, lcsh:Computer applications to medicine. Medical informatics, 050105 experimental psychology, White matter, Lesion, 03 medical and health sciences, Fractional anisotropy, medicine, Humans, 0501 psychology and cognitive sciences, Radiology, Nuclear Medicine and imaging, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], lcsh:Neurology. Diseases of the nervous system, Aged, business.industry, medicine.disease, [SDV.IB.IMA] Life Sciences [q-bio]/Bioengineering/Imaging, Multivariate Analysis, Multivariate prediction, Neurology (clinical), business, Prediction, 030217 neurology & neurosurgery, Diffusion MRI
Abstract: The relationship between stroke topography and functional outcome has largely been studied with binary manual lesion segmentations. However, stroke topography may be better characterized by continuous variables capable of reflecting the severity of ischemia, which may be more pertinent for long-term outcome. Diffusion Tensor Imaging (DTI) constitutes a powerful means of quantifying the degree of acute ischemia and its potential relation to functional outcome. Our aim was to investigate whether using more clinically pertinent imaging parameters with powerful machine learning techniques could improve prediction models and thus provide valuable insight on critical brain areas important for long-term outcome. Eighty-seven thrombolyzed patients underwent a DTI sequence at 24 h post-stroke. Functional outcome was evaluated at 3 months post-stroke with the modified Rankin Score and was dichotomized into good (mRS ≤ 2) and poor (mRS > 2) outcome. We used support vector machines (SVM) to classify patients into good vs. poor outcome and evaluate the accuracy of different models built with fractional anisotropy, mean diffusivity, axial diffusivity, radial diffusivity asymmetry maps, and lesion segmentations in combination with lesion volume, age, recanalization status, and thrombectomy treatment. SVM classifiers built with axial diffusivity maps yielded the best accuracy of all imaging parameters (median [IQR] accuracy = 82.8 [79.3–86.2]%), compared to that of lesion segmentations (76.7 [73.3–82.8]%) when predicting 3-month functional outcome. The analysis revealed a strong contribution of clinical variables, notably – in descending order – lesion volume, thrombectomy treatment, and recanalization status, in addition to the deep white matter at the crossroads of major white matter tracts, represented by brain regions where model weights were highest. Axial diffusivity is a more appropriate imaging marker to characterize stroke topography for predicting long-term outcome than binary lesion segmentations. Keywords: Acute stroke, Prediction, Prognosis, Functional outcome, Diffusion tensor imaging
Published: 2019
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17. Early alteration of the locus coeruleus in phenotypic variants of Alzheimer’s disease

Author: Michel Bottlaender, Stéphane Lehéricy, Marie Sarazin, Pierre Macé, Fabien Caillé, Philippe Gervais, Julien Lagarde, Romain Valabregue, Adeline Michel, Pauline Olivieri, Université Sorbonne Paris Cité (USPC), Imagerie Moléculaire in Vivo (IMIV - U1023 - ERL9218), Service Hospitalier Frédéric Joliot (SHFJ), Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Centre Hospitalier Sainte Anne [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut du Cerveau = Paris Brain Institute (ICM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Center for NeuroImaging Research-Human MRI Neuroimaging core facility for clinical research [ICM Paris] (CENIR), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Unité de recherche en NeuroImagerie Applicative Clinique et Translationnelle (UNIACT), Service NEUROSPIN (NEUROSPIN), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Centre de Neuro-Imagerie de Recherche (CENIR), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), and Gestionnaire, Hal Sorbonne Université
Subjects: 0301 basic medicine, Male, Amyloid, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Logopenic aphasia, Neurosciences. Biological psychiatry. Neuropsychiatry, Disease, Brief Communication, 03 medical and health sciences, 0302 clinical medicine, Alzheimer Disease, medicine, Humans, RC346-429, Aged, business.industry, General Neuroscience, Prodromal Stage, [SDV.NEU.NB] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Middle Aged, medicine.disease, Phenotype, Pathophysiology, 030104 developmental biology, Locus coeruleus, Female, Locus Coeruleus, Neurology (clinical), Tauopathy, Neurology. Diseases of the nervous system, business, Brief Communications, Neuroscience, 030217 neurology & neurosurgery, RC321-571
Abstract: International audience; Neuropathological studies showed early locus coeruleus (LC) neuronal loss associated with tauopathy in Alzheimer's Disease (AD). We used the LC signal intensity (LC-I) on 3T MRI to assess the LC integrity in AD (n = 37) and controls (n = 17). The LC-I was decreased in AD regardless of typical (amnesic) and atypical presentation (logopenic aphasia/visuo-spatial deficit), from the prodromal stage, and independently of the amyloid load measured by PiB-PET. The LC-I was correlated with memory performance of typical AD. This supports the pathophysiological model in which the LC plays a critical role in AD and may thus be a potential therapeutic target.
Published: 2019
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18. Comparative Study of MRI Biomarkers in the Substantia Nigra to Discriminate Idiopathic Parkinson Disease

Author: Claire Ewenczyk, Marie Mongin, M. Vidailhet, Benoît Magnin, Lydia Yahia-Cherif, Romain Valabregue, Cyril Poupon, Nadya Pyatigorskaya, Dario Arnaldi, and Stéphane Lehéricy
Subjects: Male, Substantia nigra, Neuroimaging, Sensitivity and Specificity, 030218 nuclear medicine & medical imaging, 03 medical and health sciences, 0302 clinical medicine, Computer-Assisted, Neuromelanin, Fractional anisotropy, Image Interpretation, Computer-Assisted, Medicine, Humans, Radiology, Nuclear Medicine and imaging, Aged, Female, Magnetic Resonance Imaging, Melanins, Middle Aged, Parkinson Disease, Substantia Nigra, Image Interpretation, business.industry, Adult Brain, Radial diffusivity, Individual level, Mr imaging, Hyperintensity, nervous system, Neurology (clinical), Nuclear medicine, business, 030217 neurology & neurosurgery, Diffusion MRI
Abstract: BACKGROUND AND PURPOSE: Several new MR imaging techniques have shown promising results in patients with Parkinson disease; however, the comparative diagnostic values of these measures at the individual level remain unclear. Our aim was to compare the diagnostic value of MR imaging biomarkers of substantia nigra damage for distinguishing patients with Parkinson disease from healthy volunteers. MATERIALS AND METHODS: Thirty-six patients and 20 healthy volunteers were prospectively included. The MR imaging protocol at 3T included 3D T2-weighted and T1-weighted neuromelanin-sensitive images, diffusion tensor images, and R2* mapping. T2* high-resolution images were also acquired at 7T to evaluate the dorsal nigral hyperintensity sign. Quantitative analysis was performed using ROIs in the substantia nigra drawn manually around the area of high signal intensity on neuromelanin-sensitive images and T2-weighted images. Visual analysis of the substantia nigra neuromelanin-sensitive signal intensity and the dorsolateral nigral hyperintensity on T2* images was performed. RESULTS: There was a significant decrease in the neuromelanin-sensitive volume and signal intensity in patients with Parkinson disease. There was also a significant decrease in fractional anisotropy and an increase in mean, axial, and radial diffusivity in the neuromelanin-sensitive substantia nigra at 3T and a decrease in substantia nigra volume on T2* images. The combination of substantia nigra volume, signal intensity, and fractional anisotropy in the neuromelanin-sensitive substantia nigra allowed excellent diagnostic accuracy (0.93). Visual assessment of both substantia nigra dorsolateral hyperintensity and neuromelanin-sensitive images had good diagnostic accuracy (0.91 and 0.86, respectively). CONCLUSIONS: The combination of neuromelanin signal and volume changes with fractional anisotropy measurements in the substantia nigra showed excellent diagnostic accuracy. Moreover, the high diagnostic accuracy of visual assessment of substantia nigra changes using dorsolateral hyperintensity analysis or neuromelanin-sensitive signal changes indicates that these techniques are promising for clinical practice.
Published: 2018

19. Hippocampal-thalamic wiring in medial temporal lobe epilepsy: Enhanced connectivity per hippocampal voxel

Author: Lionel Thivard, Vera Dinkelacker, Romain Valabregue, Sophie Dupont, Stéphane Lehéricy, Michel Baulac, Séverine Samson, Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre de Neuro-Imagerie de Recherche (CENIR), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Equipe NEMESIS - Centre de Recherches de l'Institut du Cerveau et de la Moelle épinière (NEMESIS-CRICM), Centre de Recherche de l'Institut du Cerveau et de la Moelle épinière (CRICM), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), Service de Neuroradiologie [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Service de Neurologie [CHU Pitié-Salpêtrière], IFR70-CHU Pitié-Salpêtrière [AP-HP], Cortex et Epilepsie [Paris], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), Colliot, Olivier, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Center for NeuroImaging Research-Human MRI Neuroimaging core facility for clinical research [ICM Paris] (CENIR), Institut du Cerveau = Paris Brain Institute (ICM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Service de neurologie 1 [CHU Pitié-Salpétrière], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)
Subjects: Male, MESH: Functional Neuroimaging, MESH: Hippocampus, [SDV.IB.IMA]Life Sciences [q-bio]/Bioengineering/Imaging, MESH: Organ Size, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, [INFO.INFO-IM] Computer Science [cs]/Medical Imaging, Hippocampus, MESH: Cognition, Hippocampal formation, Functional Laterality, MESH: Magnetic Resonance Imaging, Executive Function, Cognition, [INFO.INFO-CV] Computer Science [cs]/Computer Vision and Pattern Recognition [cs.CV], 0302 clinical medicine, Thalamus, MESH: Executive Function, Neural Pathways, Brain segmentation, MESH: Thalamus, 0303 health sciences, MESH: Middle Aged, medicine.diagnostic_test, Organ Size, Middle Aged, Magnetic Resonance Imaging, MESH: Recognition (Psychology), MESH: Case-Control Studies, Diffusion Tensor Imaging, [INFO.INFO-TI] Computer Science [cs]/Image Processing [eess.IV], Neurology, MESH: Young Adult, [INFO.INFO-TI]Computer Science [cs]/Image Processing [eess.IV], MESH: Epilepsy, Temporal Lobe, Female, Psychology, [SPI.SIGNAL]Engineering Sciences [physics]/Signal and Image processing, MESH: Diffusion Tensor Imaging, Tractography, Adult, Adolescent, Temporal lobe, Young Adult, 03 medical and health sciences, [INFO.INFO-IM]Computer Science [cs]/Medical Imaging, medicine, Humans, MESH: Functional Laterality, [SPI.SIGNAL] Engineering Sciences [physics]/Signal and Image processing, 030304 developmental biology, MESH: Adolescent, Hippocampal sclerosis, Sclerosis, MESH: Humans, Functional Neuroimaging, MESH: Neural Pathways, [SDV.NEU.NB] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, [INFO.INFO-CV]Computer Science [cs]/Computer Vision and Pattern Recognition [cs.CV], Recognition, Psychology, MESH: Adult, medicine.disease, MESH: Male, MESH: Cognition Disorders, [SDV.IB.IMA] Life Sciences [q-bio]/Bioengineering/Imaging, Epilepsy, Temporal Lobe, nervous system, Case-Control Studies, Neurology (clinical), MESH: Sclerosis, Cognition Disorders, Functional magnetic resonance imaging, MESH: Female, Neuroscience, 030217 neurology & neurosurgery
Abstract: International audience; Medial temporal lobe epilepsy (TLE) with hippocampal sclerosis is often accompanied by widespread changes in ipsilateral and contralateral white matter connectivity. Recent studies have proposed that patients may show pathologically enhanced wiring of the limbic circuits. To better address this issue, we specifically probed connection patterns between hippocampus and thalamus and examined their impact on cognitive function. A group of 44 patients with TLE (22 with right and 22 with left hippocampal sclerosis) and 24 healthy control participants were examined with high-resolution T1 imaging, memory functional magnetic resonance imaging (fMRI) and probabilistic diffusion tractography. Thirty-four patients had further extensive neuropsychological testing. After whole brain segmentation with FreeSurfer, tractography streamline samples were drawn with hippocampus as the seed and thalamus as the target region. Two tractography strategies were applied: The first targeted the anatomic thalamic volume segmented in FreeSurfer and the second a functional region of interest in the mediodorsal thalamus derived from the activation during delayed recognition memory. We found a pronounced enhancement of connectivity between the sclerotic hippocampus and the ipsilateral thalamus both in the right and left TLE as compared to healthy control participants. This finding held for both the anatomically and the functionally defined thalamic target. Although differences were apparent in the number of absolute fibers, they were most pronounced when correcting for hippocampal volume. In terms of cognitive function, the number of hippocampal-thalamic connections was negatively correlated with performance in a variety of executive tasks, notably in the Trail Making Test, thus suggesting that the pathologic wiring did not compensate cognitive curtailing. We suggest that TLE is accompanied by an abnormal and dysfunctional enhancement of connectivity between the hippocampus and the thalamus, which is maximal on the side of the sclerosis. This pathologic pattern of limbic wiring might reflect structural remodeling along common pathways of seizure propagation.
Published: 2015
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20. Autosomal dominant cerebellar ataxias: Imaging biomarkers with high effect sizes

Author: Isaac M. Adanyeguh, Vincent Perlbarg, Pierre-Gilles Henry, Daisy Rinaldi, Elodie Petit, Romain Valabregue, Alexis Brice, Alexandra Durr, Fanny Mochel, Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), iCONICS, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre de Neuro-Imagerie de Recherche (CENIR), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de Génétique Cytogénétique et Embryologie [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Groupe de Recherche Clinique Neurométabolique [Paris], and Université Pierre et Marie Curie - Paris 6 (UPMC)
Subjects: Adult, Male, Imaging biomarkers, Adolescent, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Fixel analysis, Neuroimaging, lcsh:Computer applications to medicine. Medical informatics, lcsh:RC346-429, Young Adult, Image Processing, Computer-Assisted, Humans, Spinocerebellar Ataxias, lcsh:Neurology. Diseases of the nervous system, Aged, Brain, Middle Aged, Magnetic Resonance Imaging, Diffusion imaging, Diffusion Tensor Imaging, Apparent fiber density, Disease Progression, lcsh:R858-859.7, Female, Spinocerebellar ataxia, Biomarkers
Abstract: Objective: As gene-based therapies may soon arise for patients with spinocerebellar ataxia (SCA), there is a critical need to identify biomarkers of disease progression with effect sizes greater than clinical scores, enabling trials with smaller sample sizes. Methods: We enrolled a unique cohort of patients with SCA1 (n = 15), SCA2 (n = 12), SCA3 (n = 20) and SCA7 (n = 10) and 24 healthy controls of similar age, sex and body mass index. We collected longitudinal clinical and imaging data at baseline and follow-up (mean interval of 24 months). We performed both manual and automated volumetric analyses. Diffusion tensor imaging (DTI) and a novel tractography method, called fixel-based analysis (FBA), were assessed at follow-up. Effect sizes were calculated for clinical scores and imaging parameters. Results: Clinical scores worsened as atrophy increased over time (p 1.2) compared to clinical scores (
Published: 2018
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21. Alterations of the nigrostriatal pathway in a 6-OHDA rat model of Parkinson's disease evaluated with multimodal MRI

Author: Justine Lambert, Vincent Perlbarg, Anne-Laure Privat, Alexandra Petiet, Mehdi Felfli, Benjamin Butler, Stéphane Lehéricy, and Romain Valabregue
Subjects: Male, 0301 basic medicine, Pathology, Parkinson's disease, Nigrostriatal pathway, lcsh:Medicine, Striatum, Multimodal Imaging, Biochemistry, Diagnostic Radiology, Rats, Sprague-Dawley, 0302 clinical medicine, Animal Cells, Functional Magnetic Resonance Imaging, Medicine and Health Sciences, lcsh:Science, Neurons, Brain Mapping, Movement Disorders, Multidisciplinary, Radiology and Imaging, Neurodegeneration, Brain, Parkinson Disease, Neurochemistry, Neurodegenerative Diseases, Magnetic Resonance Imaging, Substantia Nigra, Globus pallidus, medicine.anatomical_structure, Neurology, Anatomy, Neurochemicals, Cellular Types, Research Article, medicine.drug, medicine.medical_specialty, Histology, Tyrosine 3-Monooxygenase, Imaging Techniques, Neuroimaging, Substantia nigra, Research and Analysis Methods, Sensitivity and Specificity, 03 medical and health sciences, Diagnostic Medicine, Dopamine, medicine, Animals, Oxidopamine, Pars compacta, business.industry, lcsh:R, Biology and Life Sciences, Cell Biology, medicine.disease, Corpus Striatum, Rats, Neostriatum, Disease Models, Animal, 030104 developmental biology, nervous system, Case-Control Studies, Cellular Neuroscience, Anisotropy, lcsh:Q, business, Dopaminergics, Biomarkers, 030217 neurology & neurosurgery, Neuroscience
Abstract: Parkinson’s disease is characterized by neurodegeneration of the dopaminergic neurons in the substantia nigra pars compacta. The 6-hydroxydopamine (6-OHDA) rat model has been used to study neurodegeneration in the nigro-striatal dopaminergic system. The goal of this study was to evaluate the reliability of diffusion MRI and resting-state functional MRI biomarkers in monitoring neurodegeneration in the 6-OHDA rat model assessed by quantitative histology. We performed a unilateral injection of 6-OHDA in the striatum of Sprague Dawley rats to produce retrograde degeneration of the dopamine neurons in the substantia nigra pars compacta. We carried out a longitudinal study with a multi-modal approach combining structural and functional MRI together with quantitative histological validation to follow the effects of the lesion. Functional and structural connectivity were assessed in the brain of 6-OHDA rats and sham rats (NaCl injection) at 3 and 6 weeks post-lesioning using resting-state functional MRI and diffusion-weighted. Our results showed (i) increased functional connectivity in ipsi- and contra-lesioned regions of the cortico-basal ganglia network pathway including the motor cortex, the globus pallidus, and the striatum regions at 3 weeks; (ii) increased fractional anisotropy (FA) in the ipsi- and contralateral striatum of the 6-OHDA group at 3 weeks, and increased axial diffusivity (AD) and mean diffusivity in the ipsilateral striatum at 6 weeks; (iii) a trend for increased FA in both substantia nigra of the 6-OHDA group at 3 weeks. Optical density measurements of tyrosine-hydroxylase (TH) staining of the striatum showed good correlations with the FA and AD measurements in the striatum. No correlations were found between the number of TH-stained dopaminergic neurons and MRI measurements in the substantia nigra. This study suggested that (i) FA and AD were reliable biomarkers to evaluate neurodegeneration in the cortico-basal ganglia network of the 6-OHDA model, (ii) diffusion MRI and resting-state functional MRI (rsfMRI) were not sensitive enough to detect changes in the substantia nigra in this model.
Published: 2018

22. Triheptanoin improves brain energy metabolism in patients with Huntington disease

Author: Alexandra Dürr, Pierre-Gilles Henry, Isaac M. Adanyeguh, Romain Valabregue, Daisy Rinaldi, Fanny Mochel, and Samantha Caillet
Subjects: Adult, Male, Brain activation, medicine.medical_specialty, Magnetic Resonance Spectroscopy, Energy metabolism, Stimulation, Disease, Biology, Article, Phosphocreatine, Young Adult, chemistry.chemical_compound, Inorganic phosphate, Internal medicine, medicine, Humans, In patient, Triglycerides, Brain, Middle Aged, Triheptanoin, Huntington Disease, Endocrinology, chemistry, Female, Neurology (clinical), Energy Metabolism
Abstract: Objective: Based on our previous work in Huntington disease (HD) showing improved energy metabolism in muscle by providing substrates to the Krebs cycle, we wished to obtain a proof-of-concept of the therapeutic benefit of triheptanoin using a functional biomarker of brain energy metabolism validated in HD. Methods: We performed an open-label study using 31 P brain magnetic resonance spectroscopy (MRS) to measure the levels of phosphocreatine (PCr) and inorganic phosphate (Pi) before (rest), during (activation), and after (recovery) a visual stimulus. We performed 31 P brain MRS in 10 patients at an early stage of HD and 13 controls. Patients with HD were then treated for 1 month with triheptanoin after which they returned for follow-up including 31 P brain MRS scan. Results: At baseline, we confirmed an increase in Pi/PCr ratio during brain activation in controls—reflecting increased adenosine triphosphate synthesis—followed by a return to baseline levels during recovery ( p = 0.013). In patients with HD, we validated the existence of an abnormal brain energy profile as previously reported. After 1 month, this profile remained abnormal in patients with HD who did not receive treatment. Conversely, the MRS profile was improved in patients with HD treated with triheptanoin for 1 month with the restoration of an increased Pi/PCr ratio during visual stimulation ( p = 0.005). Conclusion: This study suggests that triheptanoin is able to correct the bioenergetic profile in the brain of patients with HD at an early stage of the disease. Classification of evidence: This study provides Class III evidence that, for patients with HD, treatment with triheptanoin for 1 month restores an increased MRS Pi/PCr ratio during visual stimulation.
Published: 2015
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23. Highly specific determination of IDH status using edited in vivo magnetic resonance spectroscopy

Author: Laurent Capelle, Chiara Villa, Dinesh K. Deelchand, Francesca Branzoli, Bertrand Baussart, Małgorzata Marjańska, Franck Bielle, Anna Luisa Di Stefano, Chris Ottolenghi, Stéphane Lehéricy, Romain Valabregue, and Marc Sanson
Subjects: In vivo magnetic resonance spectroscopy, Oncology, Adult, Male, Cancer Research, medicine.medical_specialty, Magnetic Resonance Spectroscopy, Volume of interest, 03 medical and health sciences, symbols.namesake, Young Adult, 0302 clinical medicine, Internal medicine, Glioma, Suspected diagnosis, medicine, Biomarkers, Tumor, Mutational status, Humans, Prospective Studies, Precision Medicine, Sanger sequencing, business.industry, Brain Neoplasms, Editorials, Middle Aged, medicine.disease, Prognosis, Isocitrate Dehydrogenase, Idh mutation, Isocitrate dehydrogenase, 030220 oncology & carcinogenesis, Basic and Translational Investigations, Mutation, symbols, Female, Neurology (clinical), business, 030217 neurology & neurosurgery, Biomarkers, Follow-Up Studies
Abstract: Background Mutations in the isocitrate dehydrogenase (IDH) enzyme affect 40% of gliomas and represent a major diagnostic and prognostic marker. The goals of this study were to evaluate the performance of noninvasive magnetic resonance spectroscopy (MRS) methods to determine the IDH status of patients with brain gliomas through detection of the oncometabolite 2-hydroxyglutarate (2HG) and to compare performance of these methods with DNA sequencing and tissue 2HG analysis. Methods Twenty-four subjects with suspected diagnosis of low-grade glioma were included prospectively in the study. For all subjects, MRS data were acquired at 3T using 2 MRS methods, edited MRS using Mescher-Garwood point-resolved spectroscopy (MEGA-PRESS) sequence and a PRESS sequence optimized for 2HG detection, using a volume of interest larger than 6 mL. IDH mutational status was determined by a combination of automated immunohistochemical analysis and Sanger sequencing. Levels of 2HG in tissue samples measured by gas chromatography-mass spectrometry were compared with those estimated by MRS. Results Edited MRS provided 100% specificity and 100% sensitivity in the detection of 2HG. The 2HG levels estimated by this technique were in line with those derived from tissue samples. Optimized PRESS provided lower performance, in agreement with previous findings. Conclusions Our results suggest that edited MRS is one of the most reliable tools to predict IDH mutation noninvasively, showing high sensitivity and specificity for 2HG detection. Integrating edited MRS in clinical practice may be highly beneficial for noninvasive diagnosis of glioma, prognostic assessment, and treatment planning.
Published: 2017

24. Magnetic Resonance Imaging Biomarkers to Assess Substantia Nigra Damage in Idiopathic Rapid Eye Movement Sleep Behavior Disorder

Author: Dario Arnaldi, Stéphane Lehéricy, Lydia Yahia-Cherif, Romain Valabregue, Marie Vidailhet, Isabelle Arnulf, Smaranda Leu-Semenescu, Rahul Gaurav, and Nadya Pyatigorskaya
Subjects: Male, Movement disorders, Parkinson's disease, REM sleep behavior disorder, Prodromal Symptoms, brain imaging, 030218 nuclear medicine & medical imaging, 03 medical and health sciences, 0302 clinical medicine, Neuroimaging, Physiology (medical), Fractional anisotropy, medicine, Humans, Aged, Melanins, neuroimaging, medicine.diagnostic_test, business.industry, Dopaminergic Neurons, Parkinsonism, Parkinson Disease, Magnetic resonance imaging, sleep and neurodegenerative disorders, medicine.disease, Magnetic Resonance Imaging, Diffusion Tensor Imaging, ROC Curve, substantia nigra, Case-Control Studies, Parkinson’s disease, Anisotropy, movement disorders, Female, Neurology (clinical), neuromelanin, medicine.symptom, Nuclear medicine, business, Biomarkers, 030217 neurology & neurosurgery, Diffusion MRI
Abstract: Objectives Idiopathic rapid eye movement sleep behavior disorder (iRBD) is considered to be a prodromal stage of Parkinson's disease (PD). At PD onset, 40 to 70% of the dopaminergic neurons in the substantia nigra (SN) are already lost. Thus, milder SN damage is expected in participants with iRBD. We aimed to quantify SN damage in participants with iRBD using multimodal magnetic resonance imaging (MRI) and to determine biomarker efficacy in preclinical Parkinsonism. Methods Nineteen participants with iRBD and 18 controls underwent 3-Tesla MRI, including diffusion tensor imaging, neuromelanin (NM)-sensitive imaging, and T2* mapping. Regions of interest in the SN area were drawn in NM-sensitive and T2-weighted images. The volume and normalized signal intensity in NM-sensitive images, R2*, and diffusion tensor measures were quantified in the SN. Additionally, two raters performed visual analysis of the SN using the NM-sensitive images. Results Participants with iRBD showed a reduction in the NM-sensitive volume and signal intensity and a decrease in fractional anisotropy (FA) versus controls, but showed no differences in axial, radial, or mean diffusivity or in R2*. For NM-sensitive volume and signal intensity, the receiver operating characteristic analysis discriminated between participants with iRBD and controls with a diagnostic accuracy of 0.86 and 0.79, respectively, whereas the accuracy was 0.77 for FA. The three biomarkers had a combined accuracy of 0.92. The fraction of participants correctly characterized by visual assessment was 0.81. Conclusions NM-sensitive imaging and FA allowed for the detection of SN damage in participants with iRBD with good diagnostic accuracy. These measures may represent valuable biomarkers for prodromal Parkinsonism.
Published: 2017
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25. Why do patients with neurodegenerative frontal syndrome fail to answer: ‘In what way are an orange and a banana alike?’

Author: Emmanuelle Volle, Bruno Dubois, Romain Valabregue, Isabelle Le Ber, Béatrice Garcin, Julien Lagarde, Jean-Christophe Corvol, Marie Vidailhet, and Richard Levy
Subjects: Adult, Male, Elementary cognitive task, Concept Formation, Neuropsychological Tests, Cognitive neuroscience, behavioral disciplines and activities, Alzheimer Disease, medicine, Humans, Prospective Studies, Gray Matter, Prefrontal cortex, Anterior cingulate cortex, Brain Diseases, Neurodegenerative Diseases, Cognition, Middle Aged, medicine.disease, Executive functions, Magnetic Resonance Imaging, Frontal Lobe, medicine.anatomical_structure, Frontal lobe, Frontotemporal Dementia, Female, Neurology (clinical), Psychology, Neuroscience, Psychomotor Performance, Frontotemporal dementia, Cognitive psychology
Abstract: Concept formation is the ability to create an abstract link between dissimilar objects or thoughts and is crucial for abstract and creative thinking. This process is related to the integrity of the prefrontal cortex, given the altered performances reported in patients with frontal damage, particularly those suffering from the behavioural variant of frontotemporal dementia. However, the cognitive mechanisms and neural bases of verbal concept formation are not clearly understood. The present study was aimed at addressing the following unresolved issues regarding concept formation in the field of neurology and cognitive neuroscience: (i) Are alterations in concept formation specific to frontotemporal dementia or are they also present in other cortical neurodegenerative disorders such as Alzheimer's disease? (ii) Is impaired performance in concept formation due to cortical lesions specific to frontotemporal dementia or to a cortico-subcortical frontal syndrome? and (iii) What are the cognitive mechanisms and neural bases underlying concept formation? To address these questions, we designed the Verbal Concept Formation Task, an experimental paradigm based on the similarities test. Patients presenting with severe frontal dysfunction (frontotemporal dementia, n = 18, and the Richardson form of progressive supranuclear palsy, n = 21) or with medial temporal pathology (amnestic mild cognitive impairment or Alzheimer's disease, n = 14) and healthy participants (n = 18) were given the Verbal Concept Formation Task and a large battery of neuropsychological tests. In addition, all participants underwent 3D T1-weighted MRI to analyse grey matter volume using voxel-based morphometry. Frontal patients were significantly impaired on the Verbal Concept Formation Task as compared to non-frontal participants (P = 0.00001). Global performance score was positively correlated with scores in cognitive tasks assessing executive functions and with grey matter volume in several areas, mostly in the frontal-basal-ganglion network. Two types of errors were observed in frontal patients. The most frequent was discriminating instead of grouping items ('linking deficit'). Patients also linked items on a concrete instead of an abstract basis ('abstraction deficit'). Linking and abstraction deficits were related to partially different areas: the linking deficit to the dorsal anterior cingulate cortex, right middle frontal gyrus and both inferior parietal lobules and the abstraction deficit to the head of the caudate nuclei and the left superior frontal gyrus. These data suggest that verbal concept formation requires the integrity of the prefrontal-basal-ganglion functional network. In addition, it can be divided into two distinct cognitive processes, which are underlain by two partially different neural networks.
Published: 2014
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26. Structural connectivity differences in left and right temporal lobe epilepsy

Author: Vera Dinkelacker, Séverine Samson, Michel Baulac, Daniela Sammler, Lionel Thivard, Stéphane Lehéricy, Xavier Leclerc, Romain Valabregue, Sophie Dupont, Olivier Colliot, Pierre Besson, Services de neuroradiologie [Lille], Hôpital Roger Salengro [Lille]-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Algorithms, models and methods for images and signals of the human brain (ARAMIS), Inria Paris-Rocquencourt, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre de Recherche de l'Institut du Cerveau et de la Moelle épinière (CRICM), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de Neurologie [CHU Pitié-Salpêtrière], IFR70-CHU Pitié-Salpêtrière [AP-HP], Cortex et Epilepsie [Paris], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), Max Planck Institute for Human Cognitive and Brain Sciences [Leipzig] (IMPNSC), Max-Planck-Gesellschaft, Service environnement du Grand Port Maritime de Rouen, 34 boulevard de Boisguilbert, F-76022 Rouen Cedex 3, France, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre National de la Recherche Scientifique (CNRS), Service de neurologie 1 [CHU Pitié-Salpétrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Colliot, Olivier, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)
Subjects: Adult, Male, Cognitive Neuroscience, Hippocampus, Functional Laterality, 050105 experimental psychology, Temporal lobe, 03 medical and health sciences, Epilepsy, 0302 clinical medicine, Cortex (anatomy), Fractional anisotropy, Connectome, medicine, Humans, 0501 psychology and cognitive sciences, [SPI.SIGNAL] Engineering Sciences [physics]/Signal and Image processing, Temporal cortex, Hippocampal sclerosis, Sclerosis, 05 social sciences, Middle Aged, medicine.disease, Magnetic Resonance Imaging, medicine.anatomical_structure, Epilepsy, Temporal Lobe, Neurology, Female, Nerve Net, Psychology, [SPI.SIGNAL]Engineering Sciences [physics]/Signal and Image processing, Neuroscience, 030217 neurology & neurosurgery, Diffusion MRI
Abstract: International audience; 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.
Published: 2014
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27. Broca's Area Damage is Necessary but not Sufficient to Induce After-effects of cathodal tDCS on the Unaffected Hemisphere in Post-stroke Aphasia

Author: Jean-Christophe Corvol, V. Perlbarg, Céline Arbizu, B. Alshawan, Chiara Zavanone, A. Leger, Romain Valabregue, Stéphane Lehéricy, S. Ferrieux, Charlotte Rosso, Yves Samson, Sabine Meunier, and P. Vargas
Subjects: Adult, Male, medicine.medical_specialty, Biophysics, Audiology, Transcranial Direct Current Stimulation, Lateralization of brain function, tDCS, lcsh:RC321-571, Lesion, White matter, Aphasia, medicine, Arcuate fasciculus, Humans, Single-Blind Method, Broca's area, Stroke, lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry, Aged, Language, Aphasia, Broca, Brain Mapping, Diffusion tensor, Cross-Over Studies, Resting state fMRI, General Neuroscience, Middle Aged, medicine.disease, Magnetic Resonance Imaging, Resting state functional magnetic resonance imaging, Broca Area, medicine.anatomical_structure, Treatment Outcome, Female, Neurology (clinical), medicine.symptom, Psychology, Photic Stimulation, Cognitive psychology
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 matter pathways. Results tDCS had different effects on picture naming accuracy in BA+ and BA− patients (TYPE × GROUP 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.
Published: 2014

28. Aphasia Severity in Chronic Stroke Patients

Author: Romain Valabregue, Patricia Vargas, Stéphane Lehéricy, Anne Leger, François Henry-Amar, Charlotte Rosso, Céline Arbizu, and Yves Samson
Subjects: Adult, Male, medicine.medical_specialty, computer.software_genre, Severity of Illness Index, behavioral disciplines and activities, White matter, Lesion, Young Adult, Physical medicine and rehabilitation, Voxel, Aphasia, Fractional anisotropy, medicine, Humans, Stroke, Aged, Aged, 80 and over, Brain, General Medicine, Middle Aged, medicine.disease, White Matter, Diffusion Tensor Imaging, medicine.anatomical_structure, nervous system, Chronic Disease, Female, Disconnection, medicine.symptom, Psychology, Neuroscience, computer, Diffusion MRI
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 ( R2 = 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.
Published: 2014
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29. Differentiating between axonal damage and demyelination in healthy aging by combining diffusion-tensor imaging and diffusion-weighted spectroscopy in the human corpus callosum at 7 T

Author: Emily T. Wood, Francesca Branzoli, Ece Ercan, Mathijs Buijs, Romain Valabregue, Itamar Ronen, Andrew G. Webb, Centre de Neuro-Imagerie de Recherche (CENIR), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre National de la Recherche Scientifique (CNRS), C. J. Gorter Center for High Field MRI, Leiden University Medical Center (LUMC), Neuroimmunology Branch, Center for NeuroImaging Research-Human MRI Neuroimaging core facility for clinical research [ICM Paris] (CENIR), Institut du Cerveau = Paris Brain Institute (ICM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Universiteit Leiden-Universiteit Leiden, and HAL-UPMC, Gestionnaire
Subjects: Adult, Male, Aging, Magnetic Resonance Spectroscopy, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Thermal diffusivity, Corpus callosum, Corpus Callosum, 030218 nuclear medicine & medical imaging, White matter, Young Adult, 03 medical and health sciences, Myelin, 0302 clinical medicine, Nuclear magnetic resonance, Fractional anisotropy, medicine, Humans, Diffusion (business), Spectroscopy, Diffusion-weighted MRS, Aged, Chemistry, General Neuroscience, [SDV.NEU.NB] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Middle Aged, Axons, Intracellular metabolites, Diffusion Magnetic Resonance Imaging, Diffusion Tensor Imaging, medicine.anatomical_structure, Healthy aging, DTI, Anisotropy, Female, Neurology (clinical), Geriatrics and Gerontology, Neuroscience, 030217 neurology & neurosurgery, Demyelinating Diseases, Developmental Biology, Diffusion MRI
Abstract: International audience; Diffusion-tensor imaging and single voxel diffusion-weighted magnetic resonance spectroscopy were used at 7T to explore in vivo age-related microstructural changes in the corpus callosum. Sixteen healthy elderly (age range 60–71 years) and 13 healthy younger controls (age range 23–32 years) were included in the study. In healthy elderly, we found lower water fractional anisotropy and higher water mean diffusivity and radial diffusivity in the corpus callosum, indicating the onset of demyelination processes with healthy aging. These changes were not associated with a concomitant significant difference in the cytosolic diffusivity of the intra-axonal metabolite N-acetylaspartate (p = 0.12), the latter representing a pure measure of intra-axonal integrity. It was concluded that the possible intra-axonal changes associated with normal aging processes are below the detection level of diffusion-weighted magnetic resonance spectroscopy in our experiment (e.g., smaller than 10%) in the age range investigated. Lower axial diffusivity of total creatine was observed in the elderly group (p = 0.058), possibly linked to a dysfunction in the energy metabolism associated with a deficit in myelin synthesis.
Published: 2016
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30. Pedunculopontine network dysfunction in Parkinson's disease with postural control and sleep disorders

Author: Cecile, Gallea, Claire, Ewenczyk, Bertrand, Degos, Marie-Laure, Welter, David, Grabli, Smaranda, Leu-Semenescu, Romain, Valabregue, Pierre, Berroir, Lydia, Yahia-Cherif, Eric, Bertasi, Sara, Fernandez-Vidal, Eric, Bardinet, Emmanuel, Roze, Habib, Benali, Cyril, Poupon, Chantal, François, Isabelle, Arnulf, Stéphane, Lehéricy, and Marie, Vidailhet
Subjects: Male, Sleep Wake Disorders, Functional Neuroimaging, Motor Cortex, Brain, Parkinson Disease, REM Sleep Behavior Disorder, Middle Aged, Gyrus Cinguli, Magnetic Resonance Imaging, Case-Control Studies, Neural Pathways, Pedunculopontine Tegmental Nucleus, Humans, Female, Postural Balance, Aged
Abstract: The objective of this study was to investigate pedunculopontine nucleus network dysfunctions that mediate impaired postural control and sleep disorder in Parkinson's disease.We examined (1) Parkinson's disease patients with impaired postural control and rapid eye movement sleep behavior disorder (further abbreviated as sleep disorder), (2) Parkinson's disease patients with sleep disorder only, (3) Parkinson's disease patients with neither impaired postural control nor sleep disorder, and (4) healthy volunteers. We assessed postural control with clinical scores and biomechanical recordings during gait initiation. Participants had video polysomnography, daytime sleepiness self-evaluation, and resting-state functional MRIs.Patients with impaired postural control and sleep disorder had longer duration of anticipatory postural adjustments during gait initiation and decreased functional connectivity between the pedunculopontine nucleus and the supplementary motor area in the locomotor network that correlated negatively with the duration of anticipatory postural adjustments. Both groups of patients with sleep disorder had decreased functional connectivity between the pedunculopontine nucleus and the anterior cingulate cortex in the arousal network that correlated with daytime sleepiness. The degree of dysfunction in the arousal network was related to the degree of connectivity in the locomotor network in all patients with sleep disorder, but not in patients without sleep disorder or healthy volunteers.These results shed light on the functional neuroanatomy of pedunculopontine nucleus networks supporting the clinical manifestation and the interdependence between sleep and postural control impairments in Parkinson's disease. © 2016 International Parkinson and Movement Disorder Society.
Published: 2016

31. Optimizing full-brain coverage in human brain MRI through population distributions of brain size

Author: Romain Valabregue, Stephen M. Smith, Jan K. Buitelaar, Maarten Mennes, Christian F. Beckmann, and Mark Jenkinson
Subjects: Adult, Male, Adolescent, Computer science, Cognitive Neuroscience, Other Research Donders Center for Medical Neuroscience [Radboudumc 0], Neuroimaging, Young Adult, medicine, Humans, Child, Image resolution, Simulation, Voxel size, Aged, Demography, Aged, 80 and over, Neurodevelopmental disorders Donders Center for Medical Neuroscience [Radboudumc 7], medicine.diagnostic_test, business.industry, Orientation (computer vision), 220 Statistical Imaging Neuroscience, Brain, Magnetic resonance imaging, Pattern recognition, Human brain, Middle Aged, Magnetic Resonance Imaging, medicine.anatomical_structure, Diffusion Magnetic Resonance Imaging, Neurology, Repetition Time, Child, Preschool, Brain size, Female, Artificial intelligence, business, Diffusion MRI
Abstract: Contains fulltext : 135996.pdf (Publisher’s version ) (Closed access) When defining an MRI protocol, brain researchers need to set multiple interdependent parameters that define repetition time (TR), voxel size, field-of-view (FOV), etc. Typically, researchers aim to image the full brain, making the expected FOV an important parameter to consider. Especially in 2D-EPI sequences, non-wasteful FOV settings are important to achieve the best temporal and spatial resolution. In practice, however, imperfect FOV size estimation often results in partial brain coverage for a significant number of participants per study, or, alternatively, an unnecessarily large voxel-size or number of slices to guarantee full brain coverage. To provide normative FOV guidelines we estimated population distributions of brain size in the x-, y-, and z-direction using data from 14,781 individuals. Our results indicated that 11mm in the z-direction differentiate between obtaining full brain coverage for 90% vs. 99.9% of participants. Importantly, we observed that rotating the FOV to optimally cover the brain, and thus minimize the number of slices needed, effectively reduces the required inferior-superior FOV size by ~5%. For a typical adult imaging study, 99.9% of the population can be imaged with full brain coverage when using an inferior-superior FOV of 142mm, assuming optimal slice orientation and minimal within-scan head motion. By providing population distributions for brain size in the x-, y-, and z-direction we improve the potential for obtaining full brain coverage, especially in 2D-EPI sequences used in most functional and diffusion MRI studies. We further enable optimization of related imaging parameters including the number of slices, TR and total acquisition time.
Published: 2016

32. Glial and axonal changes in systemic lupus erythematosus measured with diffusion of intracellular metabolites

Author: Mark A. van Buchem, Tom W J Huizinga, Francesca Branzoli, César Magro-Checa, Emily T. Wood, Itamar Ronen, Andrew G. Webb, Gerda M Steup-Beekman, Ece Ercan, and Romain Valabregue
Subjects: Adult, Male, Pathology, medicine.medical_specialty, Magnetic Resonance Spectroscopy, Phosphocreatine, Central nervous system, Corpus callosum, Creatine, 030218 nuclear medicine & medical imaging, Choline, Corpus Callosum, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, immune system diseases, Medicine, Humans, neuropsychiatry, skin and connective tissue diseases, Aspartic Acid, medicine.diagnostic_test, business.industry, Lupus Vasculitis, Central Nervous System, astrocytes, biomarkers, Magnetic resonance imaging, Original Articles, Middle Aged, Axons, medicine.anatomical_structure, Diffusion Tensor Imaging, gliosis, chemistry, Gliosis, inflammation, Case-Control Studies, Female, Neurology (clinical), medicine.symptom, business, Neuroglia, 030217 neurology & neurosurgery, Diffusion MRI
Abstract: Systemic lupus erythematosus is an inflammatory autoimmune disease with multi-organ involvement. Central nervous system involvement in systemic lupus erythematosus is common and results in several neurological and psychiatric symptoms that are poorly linked to standard magnetic resonance imaging outcome. Magnetic resonance imaging methods sensitive to tissue microstructural changes, such as diffusion tensor imaging and magnetization transfer imaging, show some correlation with neuropsychiatric systemic lupus erythematosus (NPSLE) symptoms. Histological examination of NPSLE brains reveals presence of cerebral oedema, loss of neurons and myelinated axons, microglial proliferation and reactive astrocytosis, microinfacrts and diffuse ischaemic changes, all of which can affect both diffusion tensor imaging and magnetization transfer imaging in a non-specific manner. Here we investigated the underlying cell-type specific microstructural alterations in the brain of patients with systemic lupus erythematosus with and without a history of central nervous system involvement. We did so combining diffusion tensor imaging with diffusion-weighted magnetic resonance spectroscopy, a powerful tool capable of characterizing cell-specific cytomorphological changes based on diffusion of intracellular metabolites. We used a 7 T magnetic resonance imaging scanner to acquire T1-weighted images, diffusion tensor imaging datasets, and single volume diffusion-weighted magnetic resonance spectroscopy data from the anterior body of the corpus callosum of 13 patients with systemic lupus erythematosus with past NPSLE, 16 patients with systemic lupus erythematosus without past NPSLE, and 19 healthy control subjects. Group comparisons were made between patients with systemic lupus erythematosus with/without past NPSLE and healthy controls on diffusion tensor imaging metrics and on diffusion coefficients of three brain metabolites: the exclusively neuronal/axonal N-acetylaspartate, and the predominantly glial creatine + phosphocreatine and choline compounds. In patients with systemic lupus erythematosus with past NPSLE, significantly higher diffusion tensor imaging mean and radial diffusivities were accompanied by a significantly higher intracellular diffusion of total creatine (0.202 ± 0.032 μm2/ms, P = 0.018) and total choline (0.142 ± 0.031 μm2/ms, P = 0.044) compared to healthy controls (0.171 ± 0.024 μm2/ms, 0.124 ± 0.018 μm2/ms, respectively). Total N-acetylaspartate, total creatine and total choline diffusion values from all patients with systemic lupus erythematosus correlated positively with systemic lupus erythematosus disease activity index score (P = 0.033, P = 0.040, P = 0.008, respectively). Our results indicate that intracellular alterations, and in particular changes in glia, as evidenced by increase in the average diffusivities of total choline and total creatine, correlate with systemic lupus erythematosus activity. The higher diffusivity of total creatine and total choline in patients with NPSLE, as well as the positive correlation of these diffusivities with the systemic lupus erythematosus disease activity index are in line with cytomorphological changes in reactive glia, suggesting that the diffusivities of choline compounds and of total creatine are potentially unique markers for glial reactivity in response to inflammation.
Published: 2016
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33. Medulla oblongata damage and cardiac autonomic dysfunction in Parkinson disease

Author: Claire Ewenczyk, Stéphane Lehéricy, Isabelle Arnulf, Marie Mongin, Eden Debellemaniere, Lydia Yahia-Cherif, Romain Valabregue, Marie Vidailhet, Cyril Poupon, and Nadya Pyatigorskaya
Subjects: 0301 basic medicine, Adult, Male, Adolescent, Heart Diseases, Physical examination, Disease, 03 medical and health sciences, Young Adult, 0302 clinical medicine, Heart Rate, Heart rate, medicine, Heart rate variability, Humans, Wakefulness, Balance (ability), Aged, Medulla Oblongata, medicine.diagnostic_test, Parkinson Disease, Middle Aged, Sleep in non-human animals, 030104 developmental biology, Diffusion Tensor Imaging, Autonomic Nervous System Diseases, Anesthesia, Medulla oblongata, Female, Neurology (clinical), Psychology, Sleep, 030217 neurology & neurosurgery, Diffusion MRI
Abstract: Objective: To characterize medulla oblongata damage using diffusion tensor imaging (DTI) in Parkinson disease (PD) and correlate it with dysfunction of the cardiac sympathetic/vagal balance. Methods: Fifty-two patients with PD and 24 healthy controls were included in the study. All participants underwent clinical examination and 3T MRI using 3D T1-weighted imaging and DTI. DTI metrics were calculated within manually drawn regions of interest. Heart rate variability was evaluated using spectral analysis of the R–R cardiac interval during REM and slow-wave sleep based on continuous overnight electrocardiographic monitoring. Respiratory frequency was measured in 30-second contiguous epochs of REM and slow-wave sleep. The relationships between imaging and cardiac variables were calculated using partial correlations followed by the multiple comparisons permutation approach. Results: The changes in heart rate and respiratory frequency variability from slow-wave sleep to REM sleep in healthy controls were no longer detectable in patients with PD. There were significant increases in the mean ( p = 0.006), axial ( p = 0.006), and radial diffusivities ( p = 0.005) in the medulla oblongata of patients with PD. In PD, diffusion changes were specifically correlated with a lower heart rate and respiratory frequency variability during REM sleep. Conclusions: This study provides evidence that medulla oblongata damage underlies cardiac sympathetic/vagal balance and respiratory dysfunction in patients with PD.
Published: 2016

34. Tissue at risk in the deep middle cerebral artery territory is critical to stroke outcome

Author: Didier Dormont, Romain Valabregue, Olivier Colliot, Stéphane Lehéricy, Sophie Crozier, Yves Samson, Charlotte Rosso, Equipe NEMESIS - Centre de Recherches de l'Institut du Cerveau et de la Moelle épinière (NEMESIS-CRICM), Centre de Recherche de l'Institut du Cerveau et de la Moelle épinière (CRICM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service de Neuroradiologie [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)
Subjects: Male, medicine.medical_specialty, Time Factors, Neurology, medicine.medical_treatment, Infarction, DWI, Magnetic resonance angiography, 030218 nuclear medicine & medical imaging, 03 medical and health sciences, 0302 clinical medicine, medicine.artery, [INFO.INFO-IM]Computer Science [cs]/Medical Imaging, medicine, Humans, Radiology, Nuclear Medicine and imaging, Stroke, Aged, Outcome, Neuroradiology, medicine.diagnostic_test, business.industry, Brain, Infarction, Middle Cerebral Artery, Recanalization, Thrombolysis, Middle Aged, medicine.disease, Magnetic Resonance Imaging, 3. Good health, Middle cerebral artery, Female, Neurology (clinical), Neurosurgery, Radiology, Cardiology and Cardiovascular Medicine, business, Magnetic Resonance Angiography, 030217 neurology & neurosurgery, MRI
Abstract: International audience; INTRODUCTION: The clinical efficacy of thrombolysis in stroke patients is explained by the increased rate of recanalization, which limits infarct growth. However, the efficacy could also be explained by the protection of specific sites of the brain. Here, we investigate where is this outcome-related tissue at risk using voxel-based analysis. METHODS: We included 68 acute stroke patients with middle cerebral artery (MCA) occlusion on the admission MRI performed within 6 h of symptoms onset (H6) and 16 controls. MCA recanalization was assessed using the magnetic resonance angiography performed at day 1 (D1). Apparent diffusion coefficient (ADC) changes were analyzed using a voxel-based method between patients vs. controls group at admission (H6) in non-recanalized vs. recanalized and in 3-month poor vs. good outcome patients at D1. RESULTS: Complete or partial MCA recanalization was observed in 52 of 68 patients. Good outcome at 3 months occurred in 40 patients (59%). In non-recanalized patients, ADC was decreased in the deep MCA and watershed arterial territory (the lenticular nucleus, internal capsule, and the overlying periventricular white matter). This decrease was not observed in recanalized patients at D1 or patients at H6. Fiber tracking suggested that the area is crossed by the cortico-spinal, cerebellar, and intra-hemispheric association tracts. Finally, this area almost co-localized with the area associated with poor outcome. CONCLUSIONS: A clinically relevant area of tissue at risk may occur in patients with MCA infarcts at the level of deep white matter fiber tracts. These findings suggest that neuroprotection research should be refocused on white matter.
Published: 2011
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35. Specialization for written words over objects in the visual cortex

Author: Evelyn Eger, Romain Valabregue, Marcin Szwed, Laurent D. Cohen, Andreas Kleinschmidt, Stanislas Dehaene, Alexis Amadon, Unité de neurosciences intégratives et computationnelles (UNIC), Centre National de la Recherche Scientifique (CNRS), Neuroimagerie cognitive - Psychologie cognitive expérimentale (UNICOG-U992), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Collège de France - Chaire Psychologie cognitive expérimentale, Collège de France (CdF (institution)), Neuroimagerie cognitive (LCogn), Université Paris-Sud - Paris 11 (UP11)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Equipe NEMESIS - Centre de Recherches de l'Institut du Cerveau et de la Moelle épinière (NEMESIS-CRICM), Centre de Recherche de l'Institut du Cerveau et de la Moelle épinière (CRICM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Laboratoire d'Imagerie et de Spectroscopie (LRMN), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Institut de Recherches sur les lois Fondamentales de l'Univers (IRFU), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, Département d'Astrophysique, de physique des Particules, de physique Nucléaire et de l'Instrumentation Associée (DAPNIA), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris Saclay (COmUE)-Institut National de la Santé et de la Recherche Médicale (INSERM), Chaire Psychologie cognitive expérimentale, Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), and Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)
Subjects: Adult, Male, Adolescent, genetic structures, Writing, Cognitive Neuroscience, Letter recognition, perceptual learning, Visual word form recognition, visual word form recognition, object recognition, 050105 experimental psychology, Young Adult, 03 medical and health sciences, Gaze-contingency paradigm, 0302 clinical medicine, Form perception, Visual memory, Image Interpretation, Computer-Assisted, Biased Competition Theory, [INFO.INFO-IM]Computer Science [cs]/Medical Imaging, Humans, 0501 psychology and cognitive sciences, Visual word form area, letter recognition, 10. No inequality, Vision for perception and vision for action, Visual Cortex, High-level vision, Visual search, Brain Mapping, 05 social sciences, Object recognition, Magnetic Resonance Imaging, Perceptual learning, high-level vision, Pattern Recognition, Visual, Reading, Neurology, Female, Psychology, N2pc, 030217 neurology & neurosurgery, Cognitive psychology
Abstract: International audience; The Visual Word Form Area (VWFA) is part of the left ventral visual stream that underlies the invariant identification of visual words. It remains debated whether this region is truly selective for words relative to common objects; why this particular part of the visual system is reproducibly engaged in reading; and whether reading expertise also relies on perceptual learning within earlier visual areas. In this fMRI study we matched written words and line-drawings of objects in luminance, contour length and number of features. We then compared them to control images made by scrambling procedures that kept local features intact. Greater responses to written words than to objects were found not only in the VWFA, but also in areas V1/V2 and V3v/V4. Furthermore, by contrasting stimuli reduced either to line junctions (vertices) or to line midsegments, we showed that the VWFA partially overlaps with regions of ventral visual cortex particularly sensitive to the presence of line junctions that are useful for object recognition. Our results indicate that preferential processing of written words can be observed at multiple levels of the visual system. It is possible that responses in early visual areas might be due to some remaining differences between words and controls not eliminated in the present stimuli. However, our results concur with recent comparisons of literates and illiterates and suggest that these early visual activations reflect the effects of perceptual learning under pressure for fast, parallel processing that is more prominent in reading than other visual cognitive processes.
Published: 2011
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36. Get Aroused and Be Stronger: Emotional Facilitation of Physical Effort in the Human Brain

Author: Bruno Dubois, Marie-Laure Cléry-Melin, Philippe Fossati, Romain Valabregue, Gilles Lafargue, Liane Schmidt, Mathias Pessiglione, Centre de Recherche de l'Institut du Cerveau et de la Moelle épinière (CRICM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Neurosciences Fonctionnelles et Pathologies (LNFP), Université de Lille, Droit et Santé-Centre National de la Recherche Scientifique (CNRS), Equipe NEMESIS - Centre de Recherches de l'Institut du Cerveau et de la Moelle épinière (NEMESIS-CRICM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Emotion, CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Université Pierre et Marie Curie - Paris 6 (UPMC), Center for NeuroImaging Research-Human MRI Neuroimaging core facility for clinical research [ICM Paris] (CENIR), Institut du Cerveau = Paris Brain Institute (ICM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), Université Pierre et Marie Curie - Paris 6 (UPMC)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre National de la Recherche Scientifique (CNRS), Centre de Neuro-Imagerie de Recherche (CENIR), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], and Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)
Subjects: Adult, Male, Time Factors, Ventrolateral prefrontal cortex, Emotions, Prefrontal Cortex, Neuropsychological Tests, 050105 experimental psychology, Developmental psychology, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Functional neuroimaging, Task Performance and Analysis, Sensation, [INFO.INFO-IM]Computer Science [cs]/Medical Imaging, medicine, Humans, 0501 psychology and cognitive sciences, Brain Mapping, Motivation, Hand Strength, General Neuroscience, 05 social sciences, Brain, Brain pathway, Galvanic Skin Response, Articles, Human brain, Hand, Magnetic Resonance Imaging, medicine.anatomical_structure, Linear Models, Facilitation, Female, Psychology, Emotional arousal, Photic Stimulation, Psychomotor Performance, 030217 neurology & neurosurgery, Motor cortex, Cognitive psychology
Abstract: International audience; Effort magnitude is commonly thought to reflect motivation, but little is known about the influence of emotional factors. Here, we manipulated the emotional state of subjects, via the presentation of pictures, before they exerted physical effort to win money. After highly arousing pictures, subjects produced more force and reported lower effort sensation, regardless of monetary incentives. Functional neuroimaging revealed that emotional arousal, as indexed by postscan ratings, specifically correlated with bilateral activity in the ventrolateral prefrontal cortex. We suggest that this region, by driving the motor cortex, constitutes a brain pathway that allows emotional arousal to facilitate physical effort.
Published: 2009
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37. Orthostatic tremor: a cerebellar pathology?

Author: L. Marais, Sara Fernandez-Vidal, Traian Popa, Daniel García-Lorenzo, Cecile Gallea, Emmanuel Roze, Romain Valabregue, Emmanuelle Apartis, Eric Bardinet, Sabine Meunier, Marie Vidailhet, Bertrand Degos, André-Pierre Legrand, Stéphane Lehéricy, and Cécile Hubsch
Subjects: 0301 basic medicine, Adult, Male, Cerebellum, medicine.medical_specialty, medicine.medical_treatment, Electromyography, Grey matter, Dizziness, Efferent Pathways, 03 medical and health sciences, 0302 clinical medicine, Physical medicine and rehabilitation, Cerebellar Diseases, Tremor, Medicine, Humans, Aged, Supplementary motor area, medicine.diagnostic_test, business.industry, Functional Neuroimaging, Motor Cortex, Middle Aged, Magnetic Resonance Imaging, Transcranial Magnetic Stimulation, nervous system diseases, Transcranial magnetic stimulation, 030104 developmental biology, medicine.anatomical_structure, Treatment Outcome, nervous system, Frontal lobe, Anesthesia, Cerebellar vermis, Female, Neurology (clinical), Nerve Net, business, 030217 neurology & neurosurgery, Motor cortex
Abstract: SEE MUTHURAMAN ET AL DOI101093/AWW164 FOR A SCIENTIFIC COMMENTARY ON THIS ARTICLE: Primary orthostatic tremor is characterized by high frequency tremor affecting the legs and trunk during the standing position. Cerebellar defects were suggested in orthostatic tremor without direct evidence. We aimed to characterize the anatomo-functional defects of the cerebellar motor pathways in orthostatic tremor. We used multimodal neuroimaging to compare 17 patients with orthostatic tremor and 17 age- and gender-matched healthy volunteers. Nine of the patients with orthostatic tremor underwent repetitive transcranial stimulation applied over the cerebellum during five consecutive days. We quantified the duration of standing position and tremor severity through electromyographic recordings. Compared to healthy volunteers, grey matter volume in patients with orthostatic tremor was (i) increased in the cerebellar vermis and correlated positively with the duration of the standing position; and (ii) increased in the supplementary motor area and decreased in the lateral cerebellum, which both correlated with the disease duration. Functional connectivity between the lateral cerebellum and the supplementary motor area was abnormally increased in patients with orthostatic tremor, and correlated positively with tremor severity. After repetitive transcranial stimulation, tremor severity and functional connectivity between the lateral cerebellum and the supplementary motor area were reduced. We provide an explanation for orthostatic tremor pathophysiology, and demonstrate the functional relevance of cerebello-thalamo-cortical connections in tremor related to cerebellar defects.
Published: 2016

38. Triheptanoin dramatically reduces paroxysmal motor disorder in patients with GLUT1 deficiency

Author: Laurent Servais, Bénédicte Héron, Sandrine Vuillaumier, Elsa Kaphan, Domitille Gras, Emmanuel Roze, Raphael Schiffmann, Romain Valabregue, Elodie Hainque, Samantha Caillet, Chris Ottolenghi, Isaac M. Adanyeguh, Agathe Roubertie, Fanny Mochel, Jean-Yves Hogrel, Daisy Rinaldi, Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de neuropédiatrie [Debré], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Robert Debré, CHU Trousseau [APHP], Institut des Neurosciences de Montpellier (INM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Neuro-Oncologie [Hôpital de la Timone - APHM], Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Center for NeuroImaging Research-Human MRI Neuroimaging core facility for clinical research [ICM Paris] (CENIR), Institut du Cerveau = Paris Brain Institute (ICM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Biochimie Hormonale et Génétique, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Baylor Research Institute, Baylor College of Medecine, Université Paris Descartes - Paris 5 (UPD5), Laboratoire de Biochimie Métabolique, CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut de Myologie, Université Pierre et Marie Curie - Paris 6 (UPMC)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Association française contre les myopathies (AFM-Téléthon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute ( ICM ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ) -CHU Pitié-Salpêtrière [APHP], Service de génétique [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Pitié-Salpêtrière [APHP], Service d'Explorations Fonctionnelles Neurologie [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Robert Debré, Service de diabétologie [CHU Pitié-Salpétrière], Service de Neuropédiatrie [CHU Trousseau], Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Trousseau [APHP], Institut des Neurosciences de Montpellier - Déficits sensoriels et moteurs ( INM ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université de Montpellier ( UM ), Aix Marseille Université ( AMU ) -Assistance Publique - Hôpitaux de Marseille ( APHM ) - Hôpital de la Timone [CHU - APHM] ( TIMONE ), Centre de Neuro-Imagerie de Recherche ( CENIR ), Assistance publique - Hôpitaux de Paris (AP-HP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Université Paris Descartes - Paris 5 ( UPD5 ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Assistance publique - Hôpitaux de Paris (AP-HP)-Association française contre les myopathies ( AFM-Téléthon ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [APHP]-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Pitié-Salpêtrière [APHP], CHU Pitié-Salpêtrière [APHP]-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Robert Debré, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Trousseau [APHP], Institut des Neurosciences de Montpellier - Déficits sensoriels et moteurs (INM), Centre de Neuro-Imagerie de Recherche (CENIR), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Université Pierre et Marie Curie - Paris 6 (UPMC)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Association française contre les myopathies (AFM-Téléthon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service de Génétique Cytogénétique et Embryologie [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de Neuroradiologie [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Association française contre les myopathies (AFM-Téléthon)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Pierre et Marie Curie - Paris 6 (UPMC), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de Diabétologie [CHU Pitié-Salpétrière], and Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)
Subjects: Male, 0301 basic medicine, Motor disorder, Magnetic Resonance Spectroscopy, Movement disorders, Phosphocreatine, Pilot Projects, chemistry.chemical_compound, 0302 clinical medicine, Young adult, Child, Glucose Transporter Type 1, Movement Disorders, Middle Aged, 3. Good health, Triheptanoin, Psychiatry and Mental health, METABOLIC DISEASE, Cardiology, Female, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Occipital Lobe, medicine.symptom, Adult, medicine.medical_specialty, Adolescent, Phosphates, Young Adult, 03 medical and health sciences, Chorea, Internal medicine, medicine, Humans, Triglycerides, business.industry, Functional Neuroimaging, Therapeutic effect, medicine.disease, Surgery, 030104 developmental biology, chemistry, [ SDV.NEU ] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Neurology (clinical), Energy Metabolism, business, Occipital lobe, 030217 neurology & neurosurgery
Abstract: Objective:On the basis of our previous work with triheptanoin, which provides key substrates to the Krebs cycle in the brain, we wished to assess its therapeutic effect in patients with glucose transporter type 1 deficiency syndrome (GLUT1-DS) who objected to or did not tolerate ketogenic diets. Methods:We performed an open-label pilot study with three phases of 2 months each (baseline, treatment and withdrawal) in eight patients with GLUT1-DS (7–47 years old) with non-epileptic paroxysmal manifestations. We used a comprehensive patient diary to record motor and non-motor paroxysmal events. Functional31P-NMR spectroscopy was performed to quantify phosphocreatine (PCr) and inorganic phosphate (Pi) within the occipital cortex during (activation) and after (recovery) a visual stimulus. Results:Patients with GLUT1-DS experienced a mean of 30.8 (±27.7) paroxysmal manifestations (52% motor events) at baseline that dropped to 2.8 (±2.9, 76% motor events) during the treatment phase (p=0.028). After withdrawal, paroxysmal manifestations recurred with a mean of 24.2 (±21.9, 52% motor events; p=0.043). Furthermore, brain energy metabolism normalised with triheptanoin, that is, increased Pi/PCr ratio during brain activation compared to the recovery phase (p=0.021), and deteriorated when triheptanoin was withdrawn. Conclusions:Treatment with triheptanoin resulted in a 90% clinical improvement in non-epileptic paroxysmal manifestations and a normalised brain bioenergetics profile in patients with GLUT1-DS. Trial registration number:NCT02014883.
Published: 2016
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39. The Brain Network of Naming: A Lesson from Primary Progressive Aphasia

Author: Sophie Ferrieux, Romain Valabregue, Bruno Dubois, Claire Boutet, Marie Nogues, Richard Levy, Didier Dormont, Marc Teichmann, Raffaella Migliaccio, Stéphane Lehéricy, Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Center for NeuroImaging Research-Human MRI Neuroimaging core facility for clinical research [ICM Paris] (CENIR), Institut du Cerveau = Paris Brain Institute (ICM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Service de Neuroradiologie [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Laboratoire d'imagerie fonctionnelle [CHU Pitié-Salpétriêre] (LIF), Université Pierre et Marie Curie - Paris 6 (UPMC)-CHU Pitié-Salpêtrière [AP-HP], Service de Neurologie [CHU Saint-Antoine], CHU Saint-Antoine [AP-HP], HAL UPMC, Gestionnaire, Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre National de la Recherche Scientifique (CNRS), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre de Neuro-Imagerie de Recherche (CENIR), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de neuroradiologie diagnostique et fonctionnelle [CHU Pitié-Salpêtrière], Laboratoire d'imagerie fonctionnelle [Paris] (LIF), Université Pierre et Marie Curie - Paris 6 (UPMC), Département de neurologie, APHP St Antoine, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-CHU Pitié-Salpêtrière [AP-HP], and Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)
Subjects: Male, Central Nervous System, Word processing, Social Sciences, lcsh:Medicine, Pathology and Laboratory Medicine, Nervous System, Brain mapping, Diagnostic Radiology, Primary progressive aphasia, Cognition, 0302 clinical medicine, Overlap zone, Medicine and Health Sciences, Psychology, Gray Matter, lcsh:Science, Language, Brain Mapping, Multidisciplinary, Radiology and Imaging, 05 social sciences, Organ Size, Conceptual semantics, Middle Aged, Magnetic Resonance Imaging, Temporal Lobe, Semantics, Female, Anatomy, Comprehension, Research Article, Cognitive psychology, Imaging Techniques, Brain Morphometry, Neuroimaging, Phonology, Research and Analysis Methods, 050105 experimental psychology, Temporal lobe, 03 medical and health sciences, Signs and Symptoms, Diagnostic Medicine, Terminology as Topic, medicine, Humans, Speech, 0501 psychology and cognitive sciences, Aged, Analysis of Variance, Morphometry, [SCCO.NEUR]Cognitive science/Neuroscience, [SCCO.NEUR] Cognitive science/Neuroscience, lcsh:R, Cognitive Psychology, Biology and Life Sciences, Linguistics, medicine.disease, Aphasia, Primary Progressive, Cognitive Science, lcsh:Q, Atrophy, Nerve Net, Conceptual Semantics, Voxel-Based Morphometry, 030217 neurology & neurosurgery, Neuroscience
Abstract: International audience; ObjectiveWord finding depends on the processing of semantic and lexical information, and it involves an intermediate level for mapping semantic-to-lexical information which also subserves lexical-to-semantic mapping during word comprehension. However, the brain regions implementing these components are still controversial and have not been clarified via a comprehensive lesion model encompassing the whole range of language-related cortices. Primary progressive aphasia (PPA), for which anomia is thought to be the most common sign, provides such a model, but the exploration of cortical areas impacting naming in its three main variants and the underlying processing mechanisms is still lacking.MethodsWe addressed this double issue, related to language structure and PPA, with thirty patients (11 semantic, 12 logopenic, 7 agrammatic variant) using a picture-naming task and voxel-based morphometry for anatomo-functional correlation. First, we analyzed correlations for each of the three variants to identify the regions impacting naming in PPA and to disentangle the core regions of word finding. We then combined the three variants and correlation analyses for naming (semantic-to-lexical mapping) and single-word comprehension (lexical-to-semantic mapping), predicting an overlap zone corresponding to a bidirectional lexical-semantic hub.Results and ConclusionsOur results showed that superior portions of the left temporal pole and left posterior temporal cortices impact semantic and lexical naming mechanisms in semantic and logopenic PPA, respectively. In agrammatic PPA naming deficits were rare, and did not correlate with any cortical region. Combined analyses revealed a cortical overlap zone in superior/middle mid-temporal cortices, distinct from the two former regions, impacting bidirectional binding of lexical and semantic information. Altogether, our findings indicate that lexical/semantic word processing depends on an anterior-posterior axis within lateral-temporal cortices, including an anatomically intermediate hub dedicated to lexical-semantic integration. Within this axis our data reveal the underpinnings of anomia in the PPA variants, which is of relevance for both diagnosis and future therapy strategies.
Published: 2016
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40. Lateral Temporal Lobe: An Early Imaging Marker of the Presymptomatic GRN Disease?

Author: Paola, Caroppo, Marie-Odile, Habert, Stanley, Durrleman, Aurélie, Funkiewiez, Vincent, Perlbarg, Valérie, Hahn, Hugo, Bertin, Malo, Gaubert, Alexandre, Routier, Didier, Hannequin, Vincent, Deramecourt, Florence, Pasquier, Sophie, Rivaud-Pechoux, Martine, Vercelletto, Geoffrey, Edouart, Romain, Valabregue, Pascal, Lejeune, Mira, Didic, Jean-Christophe, Corvol, Habib, Benali, Stephane, Lehericy, Bruno, Dubois, Olivier, Colliot, Alexis, Brice, Isabelle, Le Ber, Arthur, Tenenhaus, Centre de Recherche de l'Institut du Cerveau et de la Moelle épinière (CRICM), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), Laboratoire d'Imagerie Biomédicale (LIB), Algorithms, models and methods for images and signals of the human brain (ARAMIS), Inria Paris-Rocquencourt, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Neurosciences précliniques, Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire d'Imagerie Fonctionnelle (LIF), Université Pierre et Marie Curie - Paris 6 (UPMC)-IFR14-IFR49-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de la Mémoire et de la Maladie d'Alzheimer [Paris] (IM2A), Université Pierre et Marie Curie - Paris 6 (UPMC), Transferts, écoulements, fluides, énergétique (TREFLE), Université Sciences et Technologies - Bordeaux 1-École Nationale Supérieure de Chimie et de Physique de Bordeaux (ENSCPB)-Centre National de la Recherche Scientifique (CNRS), Institut de Mécanique et d'Ingénierie de Bordeaux (I2M), Institut National de la Recherche Agronomique (INRA)-Université de Bordeaux (UB)-École Nationale Supérieure d'Arts et Métiers (ENSAM), Arts et Métiers Sciences et Technologies, HESAM Université (HESAM)-HESAM Université (HESAM)-Arts et Métiers Sciences et Technologies, HESAM Université (HESAM)-HESAM Université (HESAM)-Institut Polytechnique de Bordeaux-Centre National de la Recherche Scientifique (CNRS), Laboratoire d'océanographie de Villefranche (LOV), Observatoire océanologique de Villefranche-sur-mer (OOVM), Centre National de la Recherche Scientifique (CNRS)-Institut national des sciences de l'Univers (INSU - CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut national des sciences de l'Univers (INSU - CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS), Génétique du cancer et des maladies neuropsychiatriques (GMFC), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Troubles cognitifs dégénératifs et vasculaires - U 1171 (TCDV), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Neurologie et thérapeutique expérimentale, Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR70-Université Pierre et Marie Curie - Paris 6 (UPMC), Service de neurologie [Nantes], Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Hôpital Guillaume-et-René-Laennec [Saint-Herblain], Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Laboratoire d'Imagerie Biomédicale [Paris] (LIB), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Institut de la Mémoire et de la Maladie d'Alzheimer [CHU Pitié-Salpétriêre] (IM2A), Université Pierre et Marie Curie - Paris 6 (UPMC)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université Sciences et Technologies - Bordeaux 1 (UB)-École Nationale Supérieure de Chimie et de Physique de Bordeaux (ENSCPB)-Centre National de la Recherche Scientifique (CNRS), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Arts et Métiers Sciences et Technologies, HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Institut Polytechnique de Bordeaux-Centre National de la Recherche Scientifique (CNRS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Troubles cognitifs dégénératifs et vasculaires - U 1171 - EA 1046 (TCDV), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Université Pierre et Marie Curie - Paris 6 (UPMC)-IFR70-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CHU Lille, CNRS, Inserm, Université de Lille, Lille Neurosciences & Cognition (LilNCog) - U 1172, Troubles cognitifs dégénératifs et vasculaires - U1171, Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer (JPArc) - U1172, Troubles cognitifs dégénératifs et vasculaires - U 1171 [TCDV], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-CHU Pitié-Salpêtrière [AP-HP], École Nationale Supérieure d'Arts et Métiers (ENSAM), HESAM Université (HESAM)-HESAM Université (HESAM)-Institut Polytechnique de Bordeaux-Centre National de la Recherche Scientifique (CNRS)-Université de Bordeaux (UB)-Institut National de la Recherche Agronomique (INRA), Colliot, Olivier, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-CHU Pitié-Salpêtrière [APHP]-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-CHU Pitié-Salpêtrière [APHP], HESAM Université (HESAM)-HESAM Université (HESAM)-Institut Polytechnique de Bordeaux-Institut National de la Recherche Agronomique (INRA)-Centre National de la Recherche Scientifique (CNRS)-Université de Bordeaux (UB), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut national des sciences de l'Univers (INSU - CNRS)-Observatoire océanologique de Villefranche-sur-mer (OOVM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Troubles cognitifs dégénératifs et vasculaires (U1171), Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-INSERM, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-CHU Pitié-Salpêtrière [APHP], and CHU Pitié-Salpêtrière [APHP]
Subjects: Adult, Male, longitudinal, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, frontotemporal dementia, Cortical thickness, Progranulins, Fluorodeoxyglucose F18, preclinical study, progranulin, Humans, Longitudinal Studies, frontotemporal lobar degeneration, GRN, PET, dementia, presymptomatic, [SPI.SIGNAL] Engineering Sciences [physics]/Signal and Image processing, [SDV.NEU.NB] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Organ Size, Magnetic Resonance Imaging, Temporal Lobe, Frontal Lobe, Positron-Emission Tomography, Asymptomatic Diseases, Mutation, Disease Progression, Intercellular Signaling Peptides and Proteins, Female, Radiopharmaceuticals, [SPI.SIGNAL]Engineering Sciences [physics]/Signal and Image processing, Research Article
Abstract: International audience; The preclinical stage of frontotemporal lobar degeneration (FTLD) is not well characterized. We conducted a brain metabolism (FDG-PET) and structural (cortical thickness) study to detect early changes in asymptomatic GRN mutation carriers (aGRN+) that were evaluated longitudinally over a 20-month period. At baseline, a left lateral temporal lobe hypometabolism was present in aGRN+ without any structural changes. Importantly, this is the first longitudinal study and, across time, the metabolism more rapidly decreased in aGRN+ in lateral temporal and frontal regions. The main structural change observed in the longitudinal study was a reduction of cortical thickness in the left lateral temporal lobe in carriers. A limit of this study is the relatively small sample (n = 16); nevertheless, it provides important results. First, it evidences that the pathological processes develop a long time before clinical onset, and that early neuroimaging changes might be detected approximately 20 years before the clinical onset of disease. Second, it suggests that metabolic changes are detectable before structural modifications and cognitive deficits. Third, both the baseline and longitudinal studies provide converging results implicating lateral temporal lobe as early involved in GRN disease. Finally, our study demonstrates that structural and metabolic changes could represent possible biomarkers to monitor the progression of disease in the presymptomatic stage toward clinical onset.
Published: 2015
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41. Hyperglycaemia, Insulin Therapy and Critical Penumbral Regions for Prognosis in Acute Stroke: Further Insights from the INSULINFARCT Trial

Author: Christine Pires, Stéphane Lehéricy, Yves Samson, Sophie Crozier, Didier Dormont, Jean-Christophe Corvol, Sandrine Deltour, Mélika Amor-Sahli, Flore Baronnet, Romain Valabregue, Anne Leger, Charlotte Rosso, Centre de Neuro-Imagerie de Recherche (CENIR), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service des Urgences Cérébro-Vasculaires [CHU Pitié-Salpétriêre], CHU Pitié-Salpêtrière [AP-HP], CIC AP-HP (pitie-Salpetriere)/inserm, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Neuroradiologie [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Sorbonne Université-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre National de la Recherche Scientifique (CNRS), Service des Urgences Cérébro-Vasculaires [Paris], Sorbonne Université-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut d'astrophysique spatiale (IAS), Université Paris-Sud - Paris 11 (UP11)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS), Algorithms, models and methods for images and signals of the human brain (ARAMIS), Inria Paris-Rocquencourt, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Sorbonne Université-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Center for NeuroImaging Research-Human MRI Neuroimaging core facility for clinical research [ICM Paris] (CENIR), Institut du Cerveau = Paris Brain Institute (ICM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Male, medicine.medical_specialty, [SDV.IB.IMA]Life Sciences [q-bio]/Bioengineering/Imaging, medicine.medical_treatment, Science, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Infarction, Brain damage, White matter, Internal medicine, [INFO.INFO-IM]Computer Science [cs]/Medical Imaging, Humans, Insulin, Medicine, Effective diffusion coefficient, Stroke, Aged, Aged, 80 and over, Multidisciplinary, medicine.diagnostic_test, business.industry, Penumbra, Magnetic resonance imaging, Middle Aged, Prognosis, medicine.disease, Magnetic Resonance Imaging, 3. Good health, Surgery, medicine.anatomical_structure, Hyperglycemia, Cardiology, Female, medicine.symptom, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Research Article
Abstract: BackgroundRecently, the concept of 'clinically relevant penumbra' was defined as an area saved by arterial recanalization and correlated with stroke outcome. This clinically relevant penumbra was located in the subcortical structures, especially the periventricular white matter. Our aims were to confirm this hypothesis, to investigate the impact of admission hyperglycemia and of insulin treatment on the severity of ischemic damages in this area and to study the respective contributions of infarct volume and ischemic damage severity of the clinically relevant penumbra on 3-month outcome.MethodsWe included 99 patients from the INSULINFARCT trial. Voxel-Based Analysis was carried on the Apparent Diffusion Coefficient (ADC) maps obtained at day one to localize the regions, which were more damaged in patients i) with poor clinical outcomes at three months and ii) without arterial recanalization. We determined the intersection of the detected areas, which represents the clinically relevant penumbra and investigated whether hyperglycemic status and insulin regimen affected the severity of ischemic damages in this area. We performed logistic regression to examine the contribution of infarct volume or early ADC decrease in this strategic area on 3-month outcome.FindingsLower ADC values were found in the corona radiata in patients with poor prognosis (p< 0.0001) and in those without arterial recanalization (p< 0.0001). The tracking analysis showed that lesions in this area interrupted many important pathways. ADC values in this area were lower in hyperglycemic than in normoglycemic patients (average decrease of 41.6 ± 20.8 x10(-6) mm2/s) and unaffected by the insulin regimen (p: 0.10). ADC values in the clinically relevant penumbra, but not infarct volumes, were significant predictors of 3-month outcome.ConclusionThese results confirm that the deep hemispheric white matter is part of the clinically relevant penumbra and show that hyperglycaemia exacerbates the apparition of irreversible ischemic damage within 24 hours in this area. However, early intensive insulin therapy fails to protect this area from infarction.Trial registrationClinicalTrials.gov NCT00472381.
Published: 2015
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42. The brain signature of paracetamol in healthy volunteers: a double-blind randomized trial

Author: Bruno Pereira, Romain Valabregue, Nicolas Macian, Gisèle Pickering, Louis Boyer, Claude Dubray, Stéphane Lehéricy, Adrian Kastler, Betty Jean, Centre de Pharmacologie Clinique, Laboratoire de Pharmacologie Médicale, Université d'Auvergne - Clermont-Ferrand I (UdA), Service d’Imagerie Médicale et Radiologie Interventionnelle [CHU Clermont-Ferrand], CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand, Centre d'Investigation Clinique [CHU Clermont-Ferrand] (CIC 1405), Institut National de la Santé et de la Recherche Médicale (INSERM)-Direction de la recherche clinique et de l’innovation [CHU Clermont-Ferrand] (DRCI), Délégation à la Recherche Clinique et à l'Innovation, CHU Clermont-Ferrand, Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Image Science for Interventional Techniques (ISIT), Université d'Auvergne - Clermont-Ferrand I (UdA)-Clermont Université-Centre National de la Recherche Scientifique (CNRS), HAL-UPMC, Gestionnaire, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Male, Analgesics.non-narcotic, paracetamol, Pharmaceutical Science, law.invention, Double blind, Neuroimaging, Randomized controlled trial, law, Drug Discovery, Healthy volunteers, medicine, Humans, pain, nociception, Original Research, Acetaminophen, Drug Design, Development and Therapy, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, business.industry, digestive, oral, and skin physiology, fMRI, Brain, Analgesics, Non-Narcotic, Crossover study, 3. Good health, Anesthesia, pharmacology, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, medicine.drug
Abstract: Gisèle Pickering,1–3 Adrian Kastler,4 Nicolas Macian,1,2 Bruno Pereira,5 Romain Valabrègue,6 Stéphane Lehericy,6 Louis Boyer,4,7 Claude Dubray,1–3 Betty Jean4 1CHU Clermont-Ferrand, Centre de Pharmacologie Clinique, 2Centre d’Investigation Clinique – Inserm 1405, 3Clermont Université, Laboratoire de Pharmacologie, Faculté de médecine, 4CHU Gabriel Montpied, Clermont-Ferrand, Service d’Imagerie Ostéo-articulaire thoracique et neurologique, 5CHU Clermont-Ferrand, Délégation Recherche Clinique et à l’Innovation, Clermont-Ferrand, France; 6Institut du Cerveau et de la Moelle epiniere – ICM, Centre de NeuroImagerie de Recherche CENIR, Inserm U1127, CNRS UMR 7225, Sorbonne Universités, UPMC University Paris, Paris, France, Department of Neuroradiology, Groupe Hospitalier Pitié-Salpêtrière, Paris, France; 7UMR CNRS UdA 6284, Clemont-Ferrand, France Background: Paracetamol’s (APAP) mechanism of action suggests the implication of supraspinal structures but no neuroimaging study has been performed in humans.Methods and results: This randomized, double-blind, crossover, placebo-controlled trial in 17 healthy volunteers (NCT01562704) aimed to evaluate how APAP modulates pain-evoked functional magnetic resonance imaging signals. We used behavioral measures and functional magnetic resonance imaging to investigate the response to experimental thermal stimuli with APAP or placebo administration. Region-of-interest analysis revealed that activity in response to noxious stimulation diminished with APAP compared to placebo in prefrontal cortices, insula, thalami, anterior cingulate cortex, and periaqueductal gray matter.Conclusion: These findings suggest an inhibitory effect of APAP on spinothalamic tracts leading to a decreased activation of higher structures, and a top-down influence on descending inhibition. Further binding and connectivity studies are needed to evaluate how APAP modulates pain, especially in the context of repeated administration to patients with pain. Keywords: paracetamol, nociception, fMRI, pharmacology, pain&nbsp
Published: 2015
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43. Intrinsic signature of essential tremor in the cerebello-frontal network

Author: Stéphane Lehéricy, L. Marais, André-Pierre Legrand, Cécile Hubsch, Daniel García-Lorenzo, Sabine Meunier, Cecile Gallea, Eric Bardinet, Emmanuel Roze, Romain Valabregue, Bertrand Degos, Marie Vidailhet, Sara Fernandez-Vidal, and Traian Popa
Subjects: Adult, Male, Cerebellum, Essential Tremor, Rest, Models, Neurological, Severity of Illness Index, Cortex (anatomy), Neural Pathways, medicine, Image Processing, Computer-Assisted, Humans, Aged, Essential tremor, Supplementary motor area, Original Articles, Anatomy, Middle Aged, medicine.disease, Magnetic Resonance Imaging, Frontal Lobe, Oxygen, medicine.anatomical_structure, Dentate nucleus, Cerebellar cortex, Female, Neurology (clinical), Primary motor cortex, Psychology, Neuroscience, Motor cortex
Abstract: See Raethjen and Muthuraman (doi:[10.1093/brain/awv238][1]) for a scientific commentary on this article. Essential tremor is a movement disorder characterized by tremor during voluntary movements, mainly affecting the upper limbs. The cerebellum and its connections to the cortex are known to be involved in essential tremor, but no task-free intrinsic signatures of tremor related to structural cerebellar defects have so far been found in the cortical motor network. Here we used voxel-based morphometry, tractography and resting-state functional MRI at 3 T to compare structural and functional features in 19 patients with essential tremor and homogeneous symptoms in the upper limbs, and 19 age- and gender-matched healthy volunteers. Both structural and functional abnormalities were found in the patients' cerebellum and supplementary motor area. Relative to the healthy controls, the essential tremor patients' cerebellum exhibited less grey matter in lobule VIII and less effective connectivity between each cerebellar cortex and the ipsilateral dentate nucleus. The patient's supplementary motor area exhibited (i) more grey matter; (ii) a lower amplitude of low-frequency fluctuation of the blood oxygenation level-dependent signal; (iii) less effective connectivity between each supplementary motor area and the ipsilateral primary motor hand area, and (iv) a higher probability of connection between supplementary motor area fibres and the spinal cord. Structural and functional changes in the supplementary motor area, but not in the cerebellum, correlated with clinical severity. In addition, changes in the cerebellum and supplementary motor area were interrelated, as shown by a correlation between the lower amplitude of low-frequency fluctuation in the supplementary motor area and grey matter loss in the cerebellum. The structural and functional changes observed in the supplementary motor area might thus be a direct consequence of cerebellar defects: the supplementary motor area would attempt to reduce tremor in the motor output by reducing its communication with M1 hand areas and by directly modulating motor output via its corticospinal projections. * Abbreviation : ALFF : amplitude of low-frequency fluctuation CDTC : cerebello-dentato-thalamo-cortical MI : primary motor cortex SMA : supplementary motor area VBM : voxel-based morphometry [1]: /lookup/doi/10.1093/brain/awv238
Published: 2015

44. High nigral iron deposition in LRRK2 and Parkin mutation carriers using R2* relaxometry

Author: Nadya, Pyatigorskaya, Michael, Sharman, Jean-Christophe, Corvol, Romain, Valabregue, Lydia, Yahia-Cherif, Fabrice, Poupon, Florence, Cormier-Dequaire, Hartwig, Siebner, Stephan, Klebe, Marie, Vidailhet, Alexis, Brice, and Stephane, Lehéricy
Subjects: Adult, Male, Heterozygote, Iron, Ubiquitin-Protein Ligases, Parkinson Disease, Middle Aged, Protein Serine-Threonine Kinases, Globus Pallidus, Leucine-Rich Repeat Serine-Threonine Protein Kinase-2, Magnetic Resonance Imaging, Neostriatum, Substantia Nigra, Thalamus, Mutation, Humans, Female, Aged
Abstract: The goal of this work was to investigate iron deposition in the basal ganglia and thalamus in symptomatic and asymptomatic leucine-rich repeat kinase 2 (LRRK2) and Parkin-associated Parkinson's disease (PD), using R2* relaxometry rate.Twenty subjects with genetic PD (four symptomatic and two asymptomatic Parkin subjects, nine symptomatic and five asymptomatic LRRK2 subjects) were compared with 20 patients with idiopathic PD (IPD) and 20 healthy subjects. Images were obtained at 3 teslas, using multi-echo T2 and T2* sequences. R2 and R2* values were calculated in the substantia nigra (SN), the striatum, the globus pallidus, and the thalamus.The R2* values in the SN were increased in IPD and mutation-carrying patients as compared with controls and in mutation-carrying patients as compared with IPD. Asymptomatic mutation carriers showed higher R2* values than controls and did not differ from IPD patients. No changes were seen in the other structures or in R2 values.These results are consistent with increased iron load in LRRK2- and Parkin-mutation carriers. The increased R2* in asymptomatic PD-mutation carriers suggests that iron deposition occurs early during the preclinical phase of the disease. R2* measurements may be used as markers for investigating nigrostriatal damage in preclinical mutation-carrying patients.
Published: 2015

45. Altered structural connectivity of cortico-striato-pallido-thalamic networks in Gilles de la Tourette syndrome

Author: Andreas Hartmann, Stéphane Lehéricy, Alan Tucholka, Romain Valabregue, Jean-François Mangin, Sophie Lecomte, Linda Marrakchi-Kacem, Pamela Guevara, Marie Vidailhet, Fabrice Poupon, Yulia Worbe, and Cyril Poupon
Subjects: Adult, Male, Gilles de la Tourette syndrome, Tic disorder, Tics, Thalamus, Globus Pallidus, structural connectivity and tractography, Tourette syndrome, Basal Ganglia, White matter, Young Adult, Basal ganglia, medicine, Image Processing, Computer-Assisted, Humans, Paracentral lobule, Cerebral Cortex, cortico-basal ganglia networks, Original Articles, medicine.disease, Magnetic Resonance Imaging, Neostriatum, medicine.anatomical_structure, nervous system, Cerebral cortex, Anisotropy, Female, Neurology (clinical), Nerve Net, Psychology, Neuroscience, Tourette Syndrome
Abstract: See Jackson (doi:10.1093/brain/awu338) for a scientific commentary on this article. The neural substrate of Gilles de la Tourette syndrome is unknown. Worbe et al. use probabilistic tractography to demonstrate widespread structural abnormalities in cortico-striato-pallido-thalamic white matter pathways—likely arising from abnormal brain development—in patients with this syndrome., 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.
Published: 2014

46. Connectivity between Right Inferior Frontal Gyrus and Supplementary Motor Area Predicts After-Effects of Right Frontal Cathodal tDCS on Picture Naming Speed

Author: Chiara Zavanone, Yohan Attal, P. Vargas, Yves Samson, Christine Delmaire, Romain Valabregue, Sabine Meunier, Stéphane Lehéricy, Charlotte Rosso, Damian M. Herz, Laurent D. Cohen, Frédéric Humbert, Céline Arbizu, Axel Thielscher, Arnaud Messé, Hartwig R. Siebner, S. Ferrieux, Center for NeuroImaging Research-Human MRI Neuroimaging core facility for clinical research [ICM Paris] (CENIR), Institut du Cerveau = Paris Brain Institute (ICM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut de la Mémoire et de la Maladie d'Alzheimer [CHU Pitié-Salpétriêre] (IM2A), Université Pierre et Marie Curie - Paris 6 (UPMC)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Universidad Nacional de San Antonio Abad del Cusco (UNSAAC), Algorithms, models and methods for images and signals of the human brain (ARAMIS), Inria Paris-Rocquencourt, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Laboratoire d'Imagerie Fonctionnelle (LIF), Université Pierre et Marie Curie - Paris 6 (UPMC)-IFR14-IFR49-Institut National de la Santé et de la Recherche Médicale (INSERM), Services de neuroradiologie [Lille], Hôpital Roger Salengro [Lille]-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Danish Research Centre for Magnetic Resonance (DRCMR), Hvidovre Hospital, Equipe NEMESIS - Centre de Recherches de l'Institut du Cerveau et de la Moelle épinière (NEMESIS-CRICM), Centre de Recherche de l'Institut du Cerveau et de la Moelle épinière (CRICM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre de Neuro-Imagerie de Recherche (CENIR), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-CHU Pitié-Salpêtrière [AP-HP], Institut de la Mémoire et de la Maladie d'Alzheimer [Paris] (IM2A), Université Pierre et Marie Curie - Paris 6 (UPMC), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-CHU Pitié-Salpêtrière [AP-HP], Service de Neuroradiologie [CHU Pitié-Salpêtrière], Colliot, Olivier, Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-CHU Pitié-Salpêtrière [AP-HP], and Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)
Subjects: Male, [SDV.IB.IMA]Life Sciences [q-bio]/Bioengineering/Imaging, medicine.medical_treatment, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Functional magnetic resonance imaging, [INFO.INFO-IM] Computer Science [cs]/Medical Imaging, MESH: Frontal Lobe, Brain mapping, tDCS, [INFO.INFO-CV] Computer Science [cs]/Computer Vision and Pattern Recognition [cs.CV], Neural Pathways, Image Processing, Computer-Assisted, MESH: Brain Mapping, Language, MESH: Aged, Brain Mapping, MESH: Middle Aged, Cross-Over Studies, medicine.diagnostic_test, Transcranial direct-current stimulation, Supplementary motor area, General Neuroscience, Motor Cortex, MESH: Electric Stimulation, Middle Aged, SMA, MESH: Image Processing, Computer-Assisted, Frontal Lobe, medicine.anatomical_structure, Diffusion tensor imaging, [INFO.INFO-TI] Computer Science [cs]/Image Processing [eess.IV], Frontal lobe, MESH: Young Adult, MESH: Language, [INFO.INFO-TI]Computer Science [cs]/Image Processing [eess.IV], Female, Psychology, [SPI.SIGNAL]Engineering Sciences [physics]/Signal and Image processing, MESH: Diffusion Tensor Imaging, Motor cortex, Adult, Biophysics, MESH: Motor Cortex, MESH: Cross-Over Studies, lcsh:RC321-571, Young Adult, medicine, [INFO.INFO-IM]Computer Science [cs]/Medical Imaging, Humans, Electrodes, lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry, [SPI.SIGNAL] Engineering Sciences [physics]/Signal and Image processing, Aged, MESH: Humans, MESH: Neural Pathways, [SDV.NEU.NB] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, [INFO.INFO-CV]Computer Science [cs]/Computer Vision and Pattern Recognition [cs.CV], MESH: Adult, MESH: Electrodes, MESH: Male, Electric Stimulation, [SDV.IB.IMA] Life Sciences [q-bio]/Bioengineering/Imaging, Neurology (clinical), Neuroscience, MESH: Female, Diffusion MRI
Abstract: Background: Cathodal transcranial direct current stimulation (tDCS) of the right frontal cortex improves language abilities in post-stroke aphasic patients. Yet little is known about the effects of right frontal cathodal tDCS on normal language function. Objective/hypothesis: To explore the cathodal tDCS effects of the right-hemispheric homologue of Broca's area on picture naming in healthy individuals. We hypothesized that cathodal tDCS improves picture naming and that this effect is determined by the anatomical and functional connectivity of the targeted region. Methods: Cathodal and sham tDCS were applied to the right inferior frontal gyrus in 24 healthy subjects before a picture-naming task. All participants were studied with magnetic resonance imaging at pre-interventional baseline. Probabilistic tractography and dynamic causal modeling of functional brain activity during a word repetition task were applied to characterize anatomical and functional connectivity. Results: Subjects named pictures faster after cathodal relative to sham tDCS. The accelerating effect of tDCS was explained by a reduced frequency of very slow responses. tDCS-induced acceleration of picture naming correlated with larger volumes of the tract connecting the right Broca's area and the supplementary motor area (SMA) and greater functional coupling from the right SMA to the right Broca's area. Conclusions: The results support the notion that the after-effects of tDCS on brain function are at least in part determined by the anatomical and functional connectivity of the targeted region.
Published: 2014

47. Fronto-tectal white matter connectivity mediates facilitatory effects of non-invasive neurostimulation on visual detection

Author: Lorena Chanes, Romain Valabregue, Raffaella Migliaccio, Romain Quentin, Antoni Valero-Cabré, Centre de recherche en neurosciences de Lyon - Lyon Neuroscience Research Center (CRNL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut du Cerveau = Paris Brain Institute (ICM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Center for NeuroImaging Research-Human MRI Neuroimaging core facility for clinical research [ICM Paris] (CENIR), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Quentin, Romain, Centre de NeuroImagerie de Recherche, Université Pierre et Marie Curie, and Universitat Oberta de Catalunya (UOC)
Subjects: Male, Visual perception, camp ocular frontal, genetic structures, Imagen por resonancia magnética, medicine.medical_treatment, projeccions cortico-tectals, Frontal Eye Field, Brain mapping, Nerve Fibers, Myelinated, [SCCO]Cognitive science, imagen de tensor de difusión, estimulación magnética transcraneal, Neural Pathways, transcranial magnetic stimulation, Image Processing, Computer-Assisted, Visuo-Spatial Attention, Attention, Prefrontal cortex, Cortico-tectal projections, neuroanatomía, Brain Mapping, Brain, diffusion tensor imaging, neuroanatomia, Transcranial Magnetic Stimulation, medicine.anatomical_structure, Diffusion Tensor Imaging, Neurology, proyecciones cortico-tectales, Visual Perception, imatge de tensor de difusió, Female, Psychology, Adult, Adolescent, neuroanatomy, Cognitive Neuroscience, Article, campo ocular frontal, White matter, Young Adult, frontal eye field, Magnetic resonance imaging, medicine, Humans, Neurostimulation, estimulació magnètica transcranial, Superior colliculus, cortico-tectal projections, visuo-spatial attention, atención visoespacial, atenció visoespacial, [SCCO] Cognitive science, Transcranial magnetic stimulation, Neuroanatomy, Imatgeria per ressonància magnètica, Neuroscience, Photic Stimulation
Abstract: International audience; The causal ability of pre-target FEF activity to modulate visual detection for perithreshold stimuli has been recently demonstrated in humans by means of non-invasive neurostimulation. Yet in spite of the network-distributed effects of these type of techniques, the white matter (WM) tracts and distant visual nodes contributing to such behavioral impact remain unknown. We hereby used individual data from a group of healthy human subjects, who received time-locked pulses of active or sham Transcranial Magnetic Stimulation (TMS) to the right Frontal Eye Field (FEF) region, and experienced increases in visual detection sensitivity. We then studied the extent to which interindividual differences in visual modulation might be dependent on the WM patterns linking the targeted area to other regions relevant for visuo-attentional behaviors. We report a statistically significant correlation between the probability of connection in a right fronto-tectal pathway (FEF-Superior Colliculus) and the modulation of visual sensitivity during a detection task. Our findings support the potential contribution of this pathway and the superior colliculus in the mediation of visual performance from frontal regions in humans. Furthermore, we also show the ability of a TMS/DTI correlational approach to contribute to the disambiguation of the specific long-range pathways driving network-wide neurostimulatory effects on behavior, anticipating their future role in guiding a more efficient use of focal neurostimulation.
Published: 2013
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48. The clinical and anatomical heterogeneity of environmental dependency phenomena

Author: Olivier Colliot, Isabelle Le Ber, Richard Levy, Romain Valabregue, Julien Lagarde, Jean-Christophe Corvol, Marie Vidailhet, CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre de Recherche de l'Institut du Cerveau et de la Moelle épinière (CRICM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Algorithms, models and methods for images and signals of the human brain (ARAMIS), Inria Paris-Rocquencourt, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Neuro-anatomie fonctionnelle du comportement et de ses troubles, Université Pierre et Marie Curie - Paris 6 (UPMC)-IFR70-Institut National de la Santé et de la Recherche Médicale (INSERM), Fédération de neurologie 4, Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Fédération des Maladies du Système Nerveux, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], and Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Male, medicine.medical_specialty, media_common.quotation_subject, Grey matter, Audiology, Environment, Neuropsychological Tests, behavioral disciplines and activities, 050105 experimental psychology, 03 medical and health sciences, 0302 clinical medicine, [INFO.INFO-TS]Computer Science [cs]/Signal and Image Processing, medicine, Humans, 0501 psychology and cognitive sciences, Utilization behavior, media_common, Aged, Behavior, Mental Disorders, 05 social sciences, Neuropsychology, Brain, medicine.disease, Executive functions, Magnetic Resonance Imaging, Frontal Lobe, medicine.anatomical_structure, Neurology, Frontal lobe, Frontotemporal Dementia, Female, Neurology (clinical), Supranuclear Palsy, Progressive, Psychology, Imitation, Neuroscience, [SPI.SIGNAL]Engineering Sciences [physics]/Signal and Image processing, 030217 neurology & neurosurgery, psychological phenomena and processes, Frontotemporal dementia, Stroop effect
Abstract: International audience; Following damage to the frontal lobes, the observation of patients presenting with environmental dependency syndrome (EDS), particularly with its two main components-grasping and imitation behavior, provides a unique opportunity to gain new insights into the neural bases of human autonomy and free-will. In the present study, thirty-nine patients with frontal lobe dysfunction [21 with progressive supranuclear palsy (PSP), and 18 with the behavioral variant of frontotemporal dementia, (bvFTD)] were tested for environmental dependency phenomena and underwent neuropsychological evaluation and T1-weighted 3D brain MRI. We correlated scores obtained by assessing grasping, imitation and utilization behaviors with both neuropsychological executive test performance and grey matter density on MRI using Voxel-Based Morphometry (VBM). This study confirms the high frequency of two environmental dependency phenomena- grasping and imitation- in patients with frontal lobe syndrome (34/39 patients) and the rarity of utilization behavior (2/39). The grasping score was significantly and positively correlated with those obtained in all executive tests except the Stroop test, while the imitation score was not. In the VBM study, while the grasping score was correlated with grey matter density in the right superior frontal gyrus and both inferior temporal gyri, the imitation score was correlated with changes in the right insula, left medial frontal gyrus and left precuneus. Environmental dependency is associated with the dysfunction of a frontoparietal network. Within this large network, grasping and imitation behaviors can be dissociated from both neuropsychological and anatomical standpoints, underlining the clinical and anatomical heterogeneity of environmental dependency phenomena.
Published: 2013
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49. Assessment of corticospinal tract (CST) damage in acute stroke patients: Comparison of tract-specific analysis versus segmentation of a CST template

Author: Frédéric Humbert, Charlotte Rosso, P. Vargas, Stéphane Lehéricy, Marie Gaudron, Yves Samson, Eric Bertasi, Romain Valabregue, Centre de Recherche de l'Institut du Cerveau et de la Moelle épinière (CRICM), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), Equipe NEMESIS - Centre de Recherches de l'Institut du Cerveau et de la Moelle épinière (NEMESIS-CRICM), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Adult, Carotid Artery Diseases, Male, Pathology, medicine.medical_specialty, Statistics as Topic, Pyramidal Tracts, Motor Activity, Sensitivity and Specificity, 030218 nuclear medicine & medical imaging, Diagnosis, Differential, Correlation, 03 medical and health sciences, Imaging, Three-Dimensional, 0302 clinical medicine, Reference Values, Image Interpretation, Computer-Assisted, Fractional anisotropy, medicine, Humans, Radiology, Nuclear Medicine and imaging, Segmentation, Dominance, Cerebral, Stroke, Aged, Acute stroke, Neurologic Examination, Brain Mapping, business.industry, Cerebral Infarction, Middle Aged, Image Enhancement, medicine.disease, Magnetic Resonance Imaging, Oxygen, Diffusion Tensor Imaging, Corticospinal tract, Female, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Nuclear medicine, business, 030217 neurology & neurosurgery, Tractography, Diffusion MRI
Abstract: Purpose: To compare two techniques to assess corticospinal tract (CST) damage in stroke patients: tract-specific analysis by probabilistic tractography and segmentation using a CST template. Materials and Methods: We extracted fractional anisotropy (FA) values, the FA ratio, and mean diffusivity (MD) in 18 stroke patients and 21 healthy volunteers matched for age and sex. We compared the two methods in order to determine their ability to detect 1) differences between diffusion tensor imaging (DTI) parameters of healthy volunteers and stroke patients, 2) the correlation between DTI parameters and clinical scores, and 3) the correlation between DTI parameters and blood oxygen level-dependent (BOLD) signals in a fist-closure task. Results: FA values were higher with the tractography approach than with the segmentation method, but differences between the ipsilesional CST and the homologous region in healthy subjects were detected using both methods. In patients, clinical scores were significantly correlated with FA values and FA ratios with both methods. The BOLD signal was positively correlated with FA values for CST with the segmentation but not with the tractography approach. Conclusion: CST damage in stroke patients can be assessed by either probabilistic tractography or segmentation of a CST template. Although each method has advantages and limitations, both are sensitive enough to detect differences among stroke patients and identify specific correlations with clinical scores. J. Magn. Reson. Imaging 2013;37:836–845. © 2012 Wiley Periodicals, Inc.
Published: 2013
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50. Visuospatial deficits in posterior cortical atrophy: structural and functional correlates

Author: Paolo Bartolomeo, Romain Valabregue, Marie Sarazin, Bruno Dubois, Marie-Odile Habert, Dalila Samri, Katia Andrade, Aurélie Kas, Centre de Recherche de l'Institut du Cerveau et de la Moelle épinière (CRICM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Equipe NEMESIS - Centre de Recherches de l'Institut du Cerveau et de la Moelle épinière (NEMESIS-CRICM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Laboratoire d'Imagerie Fonctionnelle (LIF), Université Pierre et Marie Curie - Paris 6 (UPMC)-IFR14-IFR49-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), Service de médecine nucléaire [CHU Pitié-Salpétrière], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), Fédération de neurologie 4, Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], and Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)
Subjects: Male, Bisection, Grey matter, Functional Laterality, Perceptual Disorders, 03 medical and health sciences, 0302 clinical medicine, Atrophy, Neuroimaging, medicine, [INFO.INFO-IM]Computer Science [cs]/Medical Imaging, Humans, Middle frontal gyrus, Aged, 030304 developmental biology, Cerebral Cortex, Tomography, Emission-Computed, Single-Photon, Brain Mapping, Nerve Fibers, Unmyelinated, 0303 health sciences, Functional Neuroimaging, Posterior cortical atrophy, Voxel-based morphometry, Anatomy, Middle Aged, medicine.disease, Magnetic Resonance Imaging, Psychiatry and Mental health, medicine.anatomical_structure, Cerebral blood flow, Female, Surgery, Neurology (clinical), Psychology, Neuroscience, Psychomotor Performance, 030217 neurology & neurosurgery
Abstract: International audience; OBJECTIVE: To determine the neural substrates of biased spatial orienting in posterior cortical atrophy (PCA) by using a combined structural and functional neuroimaging approach. BACKGROUND: Patients with spatial neglect typically bisect horizontal long lines towards their brain lesions but the precise neural substrates of this spatial bias remain controversial and poorly explored in neurodegenerative disorders such as PCA. METHODS: 15 patients with PCA underwent brain MRI and single photon emission computed tomography (SPECT) and were required to bisect five 20 cm long lines, each centred on an A4 horizontal sheet. Direct correlations between average deviations on the bisection task and both (1) the degree of grey matter density, as estimated by voxel based morphometry and (2) regional cerebral blood flow, as assessed by SPECT, were performed. RESULTS: Seven patients (47%) had pathological bias on the bisection task, deviating consistently towards the non-neglected side for each of the five lines. Rightward bias (sign of left-sided neglect) was more frequent and severe than leftward bias (sign of right-sided neglect). Correlation analyses showed that rightward deviations correlated with atrophy and hypoperfusion exclusively in the right hemisphere, involving a large scale fronto-parietal network; cortical atrophy was prominent in the parieto-temporal cortex but extended to the frontal region; hypoperfusion was substantial both in the middle frontal gyrus and in the postcentral region. No correlations emerged from leftward deviations. CONCLUSION: The results indicate that rightward bias (sign of left-sided neglect) in PCA depends on dysfunction of a large fronto-parietal network in the right hemisphere, related to both cortical atrophy and decreased cerebral perfusion.
Published: 2012
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