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1. Investigating the cognitive architecture of verbal fluency: evidence from an interference design on 487 controls

Author

Flore Dorchies, Camille Muchembled, Corinne Adamkiewicz, Olivier Godefroy, and Martine Roussel

Subjects
verbal fluency, dual tasks, linguistic processes, executive processes, switching, time course, Psychology, BF1-990
Abstract

IntroductionNumerous studies have explored the linguistic and executive processes underlying verbal fluency using association designs, which provide limited evidence. To assess the validity of our model, we aimed to refine the cognitive architecture of verbal fluency using an interference design.MethodsA total of 487 healthy participants performed letter and semantic fluency tests under the single condition and dual conditions while concurrently performing a secondary task that interferes with speed, semantics, phonology, or flexibility. We examined the effect of such interference on fluency indices including correct responses, clustering, switching, and time course.Results(1) All secondary tasks decreased fluency (p

Published
2024
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2. Prevalence of Amyloid Cerebral Deposits and Cognitive Outcome After Stroke: The IDEA3 Study

Author

Olivier Godefroy, Mélanie Barbay, Jeanne Martin, Trevor Shields, Chantal Lamy, Audrey Courselle-Arnoux, Sandrine Canaple, Claire Leclercq, Martine Roussel, Marc-Etienne Meyer, Etienne Marchal, and Frank A. Wollenweber

Subjects
Specialties of internal medicine, RC581-951, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571
Abstract

Introduction: The contribution of associated Alzheimer disease to poststroke cognitive impairment has been suggested on clinical grounds. However, the few published studies using amyloid PET have provided a widely ranging prevalence and a questionable relationship with cognitive status.The main objective of the study was to determine the prevalence of amyloid PET positivity among poststroke patients with at least one impaired cognitive score. The secondary objectives were to determine the association between clinical, cognitive, and imaging characteristics at baseline with amyloid status. Methods: The IDEA3 cohort included 91 stroke patients (cerebral infarct: 89%; hemorrhage: 11%). They were assessed at 808 ± 589 days poststroke with a cognitive battery, MRI, and florbetapir PET. Clinical, cognitive, and imaging characteristics at baseline were compared according to amyloid status. Results: Amyloid PET was positive for 14 patients, corresponding to a prevalence of 15.4% (95%CI: 7.97-22.8). Amyloid-positive patients were older (p = 0.0001), did not differ according to the cause of stroke, except for a tendency towards a higher frequency of cerebral amyloid angiopathy in the hemorrhagic subgroup (p = 0.06). Their cognitive performance was lower on both the cognitive screening test (p = 0.023) and battery (p = 0.02), without a specific profile. Discussion: This study supports the mild prevalence of amyloid burden and shows that it contributes to poststroke cognitive impairment.

Published
2024
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3. Poststroke action slowing: Motor and attentional impairments and their imaging determinants. Evidence from lesion-symptom mapping, disconnection and fMRI activation studies

Author

Elisa Ouin, Martine Roussel, Ardalan Aarabi, Audrey Courselle-Arnoux, Sophie Tasseel-Ponche, Michel Thiebaut de Schotten, and Olivier Godefroy

Subjects
Specialties of internal medicine, RC581-951, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571
Abstract

Introduction: Although action slowing is the main cognitive impairment in stroke survivors, its mechanisms and determinants are still poorly understood.The objectives of the present study were to determine the mechanisms of post-stroke action slowing using validated simple tests and identify its imaging determinants using mLSM. Methods: Action speed in the GRECogVASC cohort was assessed using finger tapping and SRT tests performed with both hands and analyzed using previously validated indices. Imaging determinants were identified using validated mLSM analyses and disconnection analysis and compared to those of an fMRI activation meta-analytic database. Results: Both the tapping time and SRT were 10.7% slower for the 394 patients (p = 0.0001) than for the 786 controls, without a group × test interaction (p = 0.2). The intra-individual distribution curve was characterized by a rightward shift with an unaltered attentional peak. The mLSM analyses showed tapping to be associated with lesions in the frontostriatal tract (p = 0.0007). The SRT was associated with lesions in the frontostriatal tract (p = 0.04) and the orbital part of F3 (p = 0.0001). The SRT-tapping index was associated with lesions in the orbital part of F3 (p = 0.0001). All lesions were located in the right hemisphere only and were responsible for the disconnection of several structures involved in motor preparation, initiation, and speed. A comparison with fMRI activation meta-analytic data highlighted mostly the same regions, including the orbital part of F3, the ventral and dorsal parts of F1, and the premotor and cingulate regions in the right hemisphere. Discussion: Our results confirm the marked impairment of action speed in stroke and show that the primary mechanism is motor slowing and that it is related to lesions in the right frontostriatal tract. A deficit in sustained alertness accounted for action slowing in the subgroup with lesions in the right orbital part of F3. Our SRT and mLSM results were in accordance with the fMRI activation data. Thus, stroke induces slowing in the broad network associated with SRT tasks by disrupting the frontostriatal tract and, to a lesser extent, other sites involved in attention.

Published
2024
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4. Poststroke apathy: Major role of cognitive, depressive and neurological disorders over imaging determinants

Author

Mickael Aubignat, Martine Roussel, Ardalan Aarabi, Chantal Lamy, Sophie Tasseel-Ponche, and Olivier Godefroy

Subjects
Specialties of internal medicine, RC581-951, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571
Abstract

Apathy occurs in approximately one third of people after stroke. Despite its frequency and functional consequences, the determinants of apathy have only been partially defined. The major difficulty lies in disentangling the reduction in activity due to apathy itself from those secondary to comorbidities, such as depression, sensorimotor deficits, and cognitive impairment. Here, we aimed to examine the prevalence of apathy, identify confounding sources of hypoactivity, and define its neuroimaging determinants using multivariate voxel lesion symptom-mapping (mVLSM) analyses. We assessed apathy in a subgroup (n ¼ 325, mean age: 63.8 ± 10.5 years, 91.1% ischemic stroke) of the GRECogVASC cohort using the validated Behavioral Dysexecutive Syndrome Inventory, interpreted using GREFEX criteria, as well as confounding factors (depression, anxiety, severity of the neurological deficit, and gait disorders). mVLSM analysis was used to define neuroimagingdeterminants andwas repeated after controlling for confounding factors. Apathy was present for 120 patients (36.9%, 95% CI: 31.7-42.2). Stepwise linear regression identified three factors associated with apathy: depressive symptoms (R2 = .3, p < .0001), cognitive impairment (R2 = .015, p < .02), and neurological deficit (R2 = .110, p < .0001). Accordingly, only 9 (7.5%) patients had apathy without a confounding factor, i.e., isolated apathy. In conventional VLSM analysis, apathy was associated with a large number of subcortical lesions that were no longer considered after controlling for confounding factors. Strategic site analysis identified five regions associated with isolated apathy: the F3 orbitalis pars, left amygdala, left thalamus, left pallidum, and mesencephalon. mVLSM analysis identified four strategic sites associated with apathy: the right corticospinal tract (R2 = .11; p < .0001), left frontostriatal tract (R2 0 .11; p < .0001), left thalamus (R2 = .04; p < .0001), and left amygdala (R2 = .01; p < .013). These regions remained significant after controlling for confounding factors but explained a lower amount of variance.

Published
2024
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5. NETWORK-BASED LESION IMPACT SCORE IS AN INDEPENDENT PREDICTOR OF POST-STROKE COGNITIVE IMPAIRMENT

Author

J. Matthijs Biesbroek, Nick A Weaver, Hugo P Aben, Hugo J Kuijf, Jill Abrigo, Hee-Joon Bae, Mélanie Barbay, Jonathan G Best, Régis Bordet, Francesca M. Chappell, Christopher P.L.H. Chen, Thibaut Dondaine, Ruben S. van der Giessen, Olivier Godefroy, Jules Verne, Bibek Gyanwali, Olivia K.L. Hamilton, Saima Hilal, Irene M.C. Huenges Wajer, Yeonwook Kang, L. Jaap Kappelle, Beom Joon Kim, Sebastian Köhler, Paul L.M. de Kort, Peter J. Koudstaal, Gregory Kuchcinski, Bonnie Y.K. Lam, Byung-Chul Lee, Keon-Joo Lee, Jae-Sung Lim, Renaud Lopes, Stephen D.J. Makin, Anne-Marie Mendyk, Vincent C.T. Mok, Mi Sun Oh, Robert J. van Oostenbrugge, Martine Roussel, Lin Shi, Julie Staals, Maria del C. Valdés-Hernández, Narayanaswamy Venketasubramanian, Frans R.J. Verhey, Joanna M. Wardlaw, David J. Werring, Xu Xin, Kyung-Ho Yu, Martine J.E. van Zandvoort, Lei Zhao, and Geert Jan Biessels

Subjects
Specialties of internal medicine, RC581-951, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571
Published
2024
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7. Age-related differences in structural and resting-state functional brain network organization across the adult lifespan: A cross-sectional study

Author

Maedeh Khalilian, Monica N. Toba, Martine Roussel, Sophie Tasseel-Ponche, Olivier Godefroy, and Ardalan Aarabi

Subjects
Brain structural connectivity, Brain functional connectivity, Rich-club organization, Structure–function coupling, Vulnerability analysis, Aging, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571
Abstract

We investigated age-related trends in the topology and hierarchical organization of brain structural and functional networks using diffusion-weighted imaging and resting-state fMRI data from a large cohort of healthy aging adults. At the cross-modal level, we explored age-related patterns in the RC involvement of different functional subsystems using a high-resolution functional parcellation. We further assessed age-related differences in the structure–function coupling as well as the network vulnerability to damage to rich club connectivity.Regardless of age, the structural and functional brain networks exhibited a rich club organization and small-world topology. In older individuals, we observed reduced integration and segregation within the frontal-occipital regions and the cerebellum along the brain's medial axis. Additionally, functional brain networks displayed decreased integration and increased segregation in the prefrontal, centrotemporal, and occipital regions, and the cerebellum. In older subjects, structural networks also exhibited decreased within-network and increased between-network RC connectivity. Furthermore, both within-network and between-network RC connectivity decreased in functional networks with age. An age-related decline in structure–function coupling was observed within sensory-motor, cognitive, and subcortical networks. The structural network exhibited greater vulnerability to damage to RC connectivity within the language-auditory, visual, and subcortical networks. Similarly, for functional networks, increased vulnerability was observed with damage to RC connectivity in the cerebellum, language-auditory, and sensory-motor networks. Overall, the network vulnerability decreased significantly in subjects older than 70 in both networks. Our findings underscore significant age-related differences in both brain functional and structural RC connectivity, with distinct patterns observed across the adult lifespan.

Published
2024
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11. Dual-task versus single-task gait rehabilitation after stroke: the protocol of the cognitive-motor synergy multicenter, randomized, controlled superiority trial (SYNCOMOT)

Author

Sophie Tasseel-Ponche, Martine Roussel, Monica N. Toba, Thibaud Sader, Vincent Barbier, Arnaud Delafontaine, Jonathan Meynier, Carl Picard, Jean-Marc Constans, Alexis Schnitzler, Olivier Godefroy, and Alain Pierre Yelnik

Subjects
Stroke, Rehabilitation, Multitask, Gait, Cognitive-motor interference, Protocol, Medicine (General), R5-920
Abstract

Abstract Background Gait disorders and cognitive impairments are prime causes of disability and institutionalization after stroke. We hypothesized that relative to single-task gait rehabilitation (ST GR), cognitive-motor dual-task (DT) GR initiated at the subacute stage would be associated with greater improvements in ST and DT gait, balance, and cognitive performance, personal autonomy, disability, and quality of life in the short, medium and long terms after stroke. Methods This multicenter (n=12), two-arm, parallel-group, randomized (1:1), controlled clinical study is a superiority trial. With p

Published
2023
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12. Network impact score is an independent predictor of post-stroke cognitive impairment: A multicenter cohort study in 2341 patients with acute ischemic stroke

Author

J. Matthijs Biesbroek, Nick A. Weaver, Hugo P. Aben, Hugo J. Kuijf, Jill Abrigo, Hee-Joon Bae, Mélanie Barbay, Jonathan G. Best, Régis Bordet, Francesca M. Chappell, Christopher P.L.H. Chen, Thibaut Dondaine, Ruben S. van der Giessen, Olivier Godefroy, Bibek Gyanwali, Olivia K.L. Hamilton, Saima Hilal, Irene M.C. Huenges Wajer, Yeonwook Kang, L. Jaap Kappelle, Beom Joon Kim, Sebastian Köhler, Paul L.M. de Kort, Peter J. Koudstaal, Gregory Kuchcinski, Bonnie Y.K. Lam, Byung-Chul Lee, Keon-Joo Lee, Jae-Sung Lim, Renaud Lopes, Stephen D.J. Makin, Anne-Marie Mendyk, Vincent C.T. Mok, Mi Sun Oh, Robert J. van Oostenbrugge, Martine Roussel, Lin Shi, Julie Staals, Maria del C. Valdés-Hernández, Narayanaswamy Venketasubramanian, Frans R.J. Verhey, Joanna M. Wardlaw, David J. Werring, Xu Xin, Kyung-Ho Yu, Martine J.E. van Zandvoort, Lei Zhao, and Geert Jan Biessels

Subjects
Post-stroke cognitive impairment, Brain connectomics, Ischaemic stroke, Dementia, Diffusion-weighted imaging, Computer applications to medicine. Medical informatics, R858-859.7, Neurology. Diseases of the nervous system, RC346-429
Abstract

Background: Post-stroke cognitive impairment (PSCI) is a common consequence of stroke. Accurate prediction of PSCI risk is challenging. The recently developed network impact score, which integrates information on infarct location and size with brain network topology, may improve PSCI risk prediction. Aims: To determine if the network impact score is an independent predictor of PSCI, and of cognitive recovery or decline. Methods: We pooled data from patients with acute ischemic stroke from 12 cohorts through the Meta VCI Map consortium. PSCI was defined as impairment in ≥ 1 cognitive domain on neuropsychological examination, or abnormal Montreal Cognitive Assessment. Cognitive recovery was defined as conversion from PSCI 24 months) and cognitive recovery or decline using logistic regression. Models were adjusted for age, sex, education, prior stroke, infarct volume, and study site. Results: We included 2341 patients with 4657 cognitive assessments. PSCI was present in 398/844 patients (47%) 24 months. Cognitive recovery occurred in 64/181 (35%) patients and cognitive decline in 26/287 (9%). The network impact score predicted PSCI in the univariable (OR 1.50, 95%CI 1.34–1.68) and multivariable (OR 1.27, 95%CI 1.10–1.46) GEE model, with similar ORs in the logistic regression models for specified post-stroke intervals. The network impact score was not associated with cognitive recovery or decline. Conclusions: The network impact score is an independent predictor of PSCI. As such, the network impact score may contribute to a more precise and individualized cognitive prognostication in patients with ischemic stroke. Future studies should address if multimodal prediction models, combining the network impact score with demographics, clinical characteristics and other advanced brain imaging biomarkers, will provide accurate individualized prediction of PSCI. A tool for calculating the network impact score is freely available at https://metavcimap.org/features/software-tools/lsm-viewer/.

Published
2022
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13. Cerebral fat embolism: An unusual case report and literature review

Author

Alexandre Perron, Sandrine Canaple, Audrey Ullmer, Hervé Deramond, Martine Roussel, and Olivier Godefroy

Subjects
Cerebral fat embolism, Microhemorrhage, Susceptibility-weighted imaging, Surgery, RD1-811, Neurology. Diseases of the nervous system, RC346-429
Abstract

Background: Fat embolism syndrome (FES) is a rare syndrome induced by embolization of lipid droplets in the bloodstream, commonly seen after long-bone fractures or orthopedic surgery. Case presentation: We report an unusual case of cognitive impairment following a motor scooter accident for which repeated brain MRI, performed on the tenth day after trauma, showed decreased hyperintense lesions on T2-FLAIR and DWI and numerous scattered small foci of low signal in the regions in T2*-weighted (T2*WI) gradient-echo and SWI images. Conclusion: We report a case of mental deterioration after a lucid interval that illustrates the usefulness of repeating brain MRI, especially the SWI sequence, to show the classic “starfield pattern” but also a possible dynamic and extensive appearance of hypointense punctate foci suggestive of the diagnosis. We recommend actively searching for an uncommon distal bone fracture if the initial body CT scan is negative and the diagnosis of CFE is suspected.

Published
2021
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14. The Behavioral and Cognitive Executive Disorders of Stroke: The GREFEX Study.

Author

Martine Roussel, Olivier Martinaud, Hilde Hénon, Martine Vercelletto, Claire Bindschadler, Pierre-Alain Joseph, Philippe Robert, Pierre Labauge, Olivier Godefroy, and GREFEX Study Group

Subjects
Medicine, Science
Abstract

BACKGROUND:Many studies have highlighted the high prevalence of executive disorders in stroke. However, major uncertainties remain due to use of variable and non-validated methods. The objectives of this study were: 1) to characterize the executive disorder profile in stroke using a standardized battery, validated diagnosis criteria of executive disorders and validated framework for the interpretation of neuropsychological data and 2) examine the sensitivity of the harmonization standards protocol proposed by the National Institute of Neurological Disorders and Stroke and Canadian Stroke Network (NINDS-CSN) for the diagnosis of Vascular Cognitive Impairment. METHODS:237 patients (infarct: 57; cerebral hemorrhage: 54; ruptured aneurysm of the anterior communicating artery (ACoA): 80; cerebral venous thrombosis (CVT): 46) were examined by using the GREFEX battery. The patients' test results were interpreted with a validated framework derived from normative data from 780 controls. RESULTS:Dysexecutive syndrome was observed in 88 (55.7%; 95%CI: 48-63.4) out of the 156 patients with full cognitive and behavioral data: 40 (45.5%) had combined behavioral and cognitive syndromes, 29 (33%) had a behavioral disorder alone and 19 (21.6%) had a cognitive syndrome alone. The dysexecutive profile was characterized by prominent impairments of initiation and generation in the cognitive domain and by hypoactivity with disinterest and anticipation loss in the behavioral domain. Cognitive impairment was more frequent (p = 0.014) in hemorrhage and behavioral disorders were more frequent (p = 0.004) in infarct and hemorrhage. The harmonization standards protocol underestimated (p = 0.007) executive disorders in CVT or ACoA. CONCLUSIONS:This profile of executive disorders implies that the assessment should include both cognitive tests and a validated inventory for behavioral dysexecutive syndrome. Initial assessment may be performed with a short cognitive battery, such as the harmonization standards protocol. However, administration of a full cognitive battery is required in selected patients.

Published
2016
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15. Functional architecture of executive processes: Evidence from verbal fluency and lesion mapping in stroke patients

Author

Olivier Godefroy, Ardalan Aarabi, Flore Dorchies, Mélanie Barbay, Daniela Andriuta, Momar Diouf, Michel Thiebaut de Schotten, Rania Kassir, Sophie Tasseel-Ponche, Martine Roussel, Sandrine Canaple, Chantal Lamy, Claire Leclercq, Audrey Courselle-Arnoux, Sandrine Despretz-Wannepain, Pascal Despretz, Hassan Berrissoul, Carl Picard, Gwénolé Loas, Hervé Deramond, Hervé Taillia, Anne-Emmanuelle Ardisson, Claudine Nédélec-Ciceri, Camille Bonnin, Catherine Thomas-Anterion, Francoise Vincent-Grangette, Jérome Varvat, Véronique Quaglino, Hélène Beaunieux, Christine Moroni, Audrey Martens-Chazelles, Stéphanie Batier-Monperrus, Cécile Monteleone, Véronique Costantino, and Eric Theunssens

Subjects
Neuropsychology and Physiological Psychology, Cognitive Neuroscience, Experimental and Cognitive Psychology
Published
2023
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16. Poststroke apathy: Major role of cognitive, depressive and neurological disorders over imaging determinants

Author

Mickael Aubignat, Martine Roussel, Ardalan Aarabi, Chantal Lamy, Daniela Andriuta, Sophie Tasseel-Ponche, Malek Makki, Olivier Godefroy, Mélanie Barbay, Sandrine Canaple, Claire Leclercq, Audrey Arnoux, Sandrine Despretz-Wannepain, Pascal Despretz, Hassan Berrissoul, Carl Picard, Momar Diouf, Gwénolé Loas, Hervé Deramond, Hervé Taillia, Anne-Emmanuelle Ardisson, Claudine Nédélec-Ciceri, Camille Bonnin, Catherine Thomas-Anterion, Francoise Vincent-Grangette, Jérome Varvat, Véronique Quaglino, Hélène Beaunieux, Christine Moroni, Audrey Martens-Chazelles, Stéphanie Batier-Monperrus, Cécile Monteleone, Véronique Costantino, Eric Theunssens, Université de Picardie Jules Verne (UPJV), Laboratoire de Neurosciences Fonctionnelles et Pathologies - UR UPJV 4559 (LNFP), CHU Amiens-Picardie, GRECogVASC study group, Service de neurologie [Amiens], Centre de Recherche en Psychologie : Cognition, Psychisme et Organisations - UR UPJV 7273 (CRP-CPO), Psychologie : Interactions, Temps, Emotions, Cognition (PSITEC) - ULR 4072 (PSITEC), and Université de Lille

Subjects
Stroke, Neuropsychology and Physiological Psychology, Depression, Cognitive Neuroscience, Voxel lesion symptom-mapping, Apathy, Mild cognitive impairment, Dementia, Experimental and Cognitive Psychology, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract

International audience; Apathy occurs in approximately one third of people after stroke. Despite its frequency and functional consequences, the determinants of apathy have only been partially defined. The major difficulty lies in disentangling the reduction in activity due to apathy itself from those secondary to comorbidities, such as depression, sensorimotor deficits, and cognitive impairment. Here, we aimed to examine the prevalence of apathy, identify confounding sources of hypoactivity, and define its neuroimaging determinants using multivariate voxel lesion symptom-mapping (mVLSM) analyses. We assessed apathy in a subgroup (n = 325, mean age: 63.8 ± 10.5 years, 91.1% ischemic stroke) of the GRECogVASC cohort using the validated Behavioral Dysexecutive Syndrome Inventory, interpreted using GREFEX criteria, as well as confounding factors (depression, anxiety, severity of the neurological deficit, and gait disorders). mVLSM analysis was used to define neuroimaging determinants and was repeated after controlling for confounding factors. Apathy was present for 120 patients (36.9%, 95% CI: 31.7-42.2). Stepwise linear regression identified three factors associated with apathy: depressive symptoms (R2 = .3, p = .0001), cognitive impairment (R2 = .015, p = .02), and neurological deficit (R2 = .110, p = .0001). Accordingly, only 9 (7.5%) patients had apathy without a confounding factor, i.e., isolated apathy. In conventional VLSM analysis, apathy was associated with a large number of subcortical lesions that were no longer considered after controlling for confounding factors. Strategic site analysis identified five regions associated with isolated apathy: the F3 orbitalis pars, left amygdala, left thalamus, left pallidum, and mesencephalon. mVLSM analysis identified four strategic sites associated with apathy: the right corticospinal tract (R2 = .11; p = .0001), left frontostriatal tract (R2 = .11; p = .0001), left thalamus (R2 = .04; p = .0001), and left amygdala (R2 = .01; p = .013). These regions remained significant after controlling for confounding factors but explained a lower amount of variance. These findings indicate that poststroke apathy is more strongly associated with depression, neurological deficit, and cognitive impairment than with stroke lesions locations, at least using VLSM analysis.

Published
2023
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18. In Individuals With Subjective Cognitive Decline, Age, Memory and Speed Scores at Baseline Predict Progression to Cognitive Impairment

Author

Alexandre, Perron, Martine, Roussel, Sandrine, Wannepain-Despretz, Mélanie, Barbay, Agnès, Devendeville, Olivier, Godefroy, and Daniela, Andriuta

Subjects
Psychiatry and Mental health, Clinical Psychology, Disease Progression, Humans, Cognitive Dysfunction, Prospective Studies, Neuropsychological Tests, Geriatrics and Gerontology, Gerontology, Retrospective Studies
Abstract

Some patients with subjective cognitive decline (SCD) progress to neurocognitive disorders (NCD), whereas others remain stable; however, the neuropsychological determinants of this progression have not been identified. Our objective was to examine baseline neuropsychological indicators that could discriminate between stable SCD Versus progression toward an NCD. We retrospectively included patients consulting for SCD at a university medical center's memory center (Amiens, France) who had undergone 3 or more neuropsychological assessments. Among the 80 patients with SCD, 11 had progressed to an NCD. The combination of age, memory, and speed scores at the baseline assessment predicted the progression of SCD with a sensitivity of 91%, and a negative predictive value of 98%. The present results constitute a first step (pending prospective studies) toward helping physicians to identify cases of SCD at risk of progression and, in particular, identifying patients with SCD who will not progress by examining baseline neuropsychological indicators. ClinicalTrials.gov ID: NCT04880252.

Published
2022
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23. Clinical and Imaging Determinants of Neurocognitive Disorders in Post-Acute COVID-19 Patients with Cognitive Complaints

Author

Daniela Andriuta, Cherifa Si-Ahmed, Martine Roussel, Jean-Marc Constans, Malek Makki, Ardalan Aarabi, Damien Basille, Claire Andrejak, and Olivier Godefroy

Subjects
General Neuroscience, Leukoaraiosis, Neurocognitive Disorders, COVID-19, General Medicine, Neuropsychological Tests, Magnetic Resonance Imaging, White Matter, Oxygen, Psychiatry and Mental health, Clinical Psychology, Cognition, Humans, Geriatrics and Gerontology
Abstract

Background: Neurocognitive disorders (NCDs) are a part of the post-acute coronavirus disease (COVID-19) syndrome. No study has specifically evaluated NCDs in post-acute COVID-19 patients with cognitive complaints or their MRI determinants. Objective: To characterize NCDs in post-acute COVID-19 patients with cognitive complaints. The secondary objectives were to assess their clinical and MRI determinants. Methods: We included 46 patients with a post-acute COVID-19 cognitive complaint referred to the Amiens University Hospital Memory Center. They underwent a neuropsychological assessment and 36 had cerebral MRI. The G3 overall summary score was the sum of the mean z scores for the executive function, language, and action speed domains. Neuropsychological profiles were compared in a general linear model. Clinical determinants were analyzed by stepwise linear regression. White matter hyperintensities (WMH) masks were analyzed using parcel-based WMH symptom mapping to identify the locations of WMHs associated with cognitive performance. Results: Repeated ANOVA showed a group effect (p = 0.0001) due to overall lower performance for patients and a domain effect (p = 0.0001) due to a lower (p = 0.007) action speed score. The G3 overall summary score was significantly associated with solely the requirement for oxygen (R2 = 0.319, p = 0.031). WHMs were associated with the G3 overall summary score in the following structures, all right-sided (p

Published
2022

24. Determinants of disability at 6 months after stroke: The GRECogVASC Study

Author

Sophie, Tasseel-Ponche, Mélanie, Barbay, Martine, Roussel, Adnane, Lamrani, Thibaud, Sader, Audrey, Arnoux-Courselle, Sandrine, Canaple, Chantal, Lamy, Claire, Leclercq, Ardalan, Aarabi, Alexis, Schnitzler, Alain Pierre, Yelnik, and Olivier, Godefroy

Subjects
Stroke, Disability Evaluation, Time Factors, Headache, Humans, Disabled Persons
Abstract

The aim of this study was to determine the contributions of background disorders responsible for participation restriction as indexed by a structured interview for the modified Rankin Scale (mRS-SI).A subset of 256 patients was assessed at 6 months after stroke using the National Institutes of Health Stroke Scale (NIHSS), gait score, comprehensive cognitive battery (yielding a global cognitive Z-score), behavioral dysexecutive disorders (DDs), anxiety and depressive symptoms, epilepsy, and headache. Following bivariate analyses, determinants of participation restriction were selected using ordinal regression analysis with partial odds.Poststroke participation restriction (mRS-SI score 1) was observed in 59% of the patients. In bivariate analyses, mRS-SI score was associated with prestroke mRS-SI score, 6-month NIHSS score, gait score, global cognitive Z-score, behavioral DDs, and presence of anxiety and depression (all: p = 0.0001; epilepsy: p =0.3; headache: p = 0.7). After logistic regression analysis, NIHSS score was associated with increasing mRS-SI score (p = 0.00001). Prestroke mRS-SI score (p = 0.00001), behavioral DDs (p = 0.0008) and global cognitive Z-score (p = 0.01) were associated with both mRS-SI score 1 and mRS-SI score 2. In addition, gait score was associated with mRS-SI score 2 (p = 0.00001). This model classified 85% of mRS-SI scores correctly (p = 0.001). Structural equation modeling showed the contributions of gait limitation (standardized coefficient [SC]: 0.68; p = 0.01), prestroke mRS-SI (SC: 0.41; p = 0.01), severity of neurological impairment (SC: 0.16; p = 0.01), global cognitive Z-score (SC: -0.14; p = 0.05), and behavioral DDs (SC: 0.13; p = 0.01).These results provide a statistical model of weights of determinants responsible for poststroke participation restriction and highlight a new independent determinant: behavioral DDs.

Published
2022

25. Poststroke action slowing: Motor and attentional impairments and their imaging determinants. Evidence from lesion-symptom mapping, disconnection and fMRI activation studies

Author

Elisa Ouin, Martine Roussel, Ardalan Aarabi, Audrey Arnoux, Sophie Tasseel-Ponche, Daniela Andriuta, Michel Thiebaut de Schotten, Monica N. Toba, Malek Makki, and Olivier Godefroy

Subjects
Stroke, Brain Mapping, Behavioral Neuroscience, Cognitive Neuroscience, Reaction Time, Humans, Attention, Cognitive Dysfunction, Experimental and Cognitive Psychology, Magnetic Resonance Imaging, Psychomotor Performance
Abstract

Although action slowing is the main cognitive impairment in stroke survivors, its mechanisms and determinants are still poorly understood. The objectives of the present study were to determine the mechanisms of post-stroke action slowing (using validated, highly specific simple reaction time (SRT) and tapping tests) and identify its imaging determinants (using multivariate lesion-symptom mapping (mLSM)).Action speed in the GRECogVASC cohort was assessed using finger tapping and SRT tests performed with both hands and analyzed using previously validated indices. Imaging determinants were identified using validated mLSM analyses and disconnection analysis and compared to those of an fMRI activation meta-analytic database.Both the tapping time and SRT were 10.7% slower for the 394 patients (p = 0.0001) than for the 786 controls, without a group × test interaction (p = 0.2). The intra-individual distribution curve was characterized by a rightward shift with an unaltered attentional peak. The mLSM analyses showed tapping to be associated with lesions in the frontostriatal tract (p = 0.0007). The SRT was associated with lesions in the frontostriatal tract (p = 0.04) and the orbital part of F3 (p = 0.0001). The SRT-tapping index was associated with lesions in the orbital part of F3 (p = 0.0001). All lesions were located in the right hemisphere only and were responsible for the disconnection of several structures involved in motor preparation, initiation, and speed. A comparison with fMRI activation meta-analytic data highlighted mostly the same regions, including the orbital part of F3, the ventral and dorsal parts of F1, and the premotor and cingulate regions in the right hemisphere.Our results confirm the marked impairment of action speed in stroke and show that the primary mechanism is motor slowing and that it is related to lesions in the right frontostriatal tract. A deficit in sustained alertness accounted for action slowing in the subgroup with lesions in the right orbital part of F3. Our SRT and mLSM results were in accordance with the fMRI activation data. Thus, stroke induces slowing in the broad network associated with SRT tasks by disrupting the frontostriatal tract and, to a lesser extent, other sites involved in attention.

Published
2022
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26. Abstract PR005: Targeting EP300 and CBP for therapeutic benefit in pediatric solid tumors

Author

Adam D. Durbin, Noha Shendy, Audrey Mercier, Yang Zhang, Melissa J. Bikowitz, Logan H. Sigua, Sarah Robinson, Tingjian Wang, Barbara Jonchere, A. Thomas Look, Mark W. Zimmerman, Martine Roussel, Brian J. Abraham, Ernst Schonbrunn, Kimberly Stegmaier, and Jun Qi

Subjects
Cancer Research, Oncology
Abstract

Gene expression is regulated by promoters and enhancers marked by histone H3 lysine 27 acetylation (H3K27ac), which is established by the paralogous, multidomain-containing histone acetyltransferases (HAT) EP300 and CBP. These enzymes display overlapping regulatory roles in untransformed cells, but less characterized roles in cancer cells. We demonstrate that the majority of high-risk pediatric neuroblastoma (NB) depends on EP300, whereas CBP has a limited role. To disrupt EP300, we developed a proteolysis-targeting chimera (PROTAC) compound termed “JQAD1” that selectively targets EP300 for degradation. JQAD1 treatment causes loss of H3K27ac at the enhancers that regulate NB master transcription factors, and drives rapid NB apoptosis, with limited toxicity to untransformed cells where CBP may compensate. In parallel, we demonstrate that EP300 and CBP have subdomain-specific functions, with enriched activity for individual domains in distinct tumor lineages. These data provide a foundation for interrogation of these histone acetyltransferases in distinct tumor types and new strategies for therapeutic disruption of subdomain and scaffolding activities of these multidomain proteins in cancer. Citation Format: Adam D. Durbin, Noha Shendy, Audrey Mercier, Yang Zhang, Melissa J. Bikowitz, Logan H. Sigua, Sarah Robinson, Tingjian Wang, Barbara Jonchere, A. Thomas Look, Mark W. Zimmerman, Martine Roussel, Brian J. Abraham, Ernst Schonbrunn, Kimberly Stegmaier, Jun Qi. Targeting EP300 and CBP for therapeutic benefit in pediatric solid tumors. [abstract]. In: Proceedings of the AACR Special Conference: Cancer Epigenomics; 2022 Oct 6-8; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2022;82(23 Suppl_2):Abstract nr PR005.

Published
2022
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30. MEDB-42. GermlineElp1 deficiency promotes genomic instability and survival of granule neuron progenitors primed for SHH medulloblastoma pathogenesis

Author

Jesus Garcia-Lopez, Shiekh Tanveer Ahmad, Yiran Li, Brian Gudenas, Marija Kojic, Friedrik Manz, Barbara Jonchere, Anand Mayasundari, Aaron Pitre, Jennifer Hadley, Leena Paul, Melissa Batts, Brandon Bianski, Christopher Tinkle, Brent Orr, Zoran Rankovic, Giles Robinson, Martine Roussel, Brandon Wainwright, Lena Kutscher, Hong Lin, and Paul Northcott

Subjects
Cancer Research, Oncology, Neurology (clinical)
Abstract

Germline loss-of-function (LOF) mutations in Elongator complex protein 1 (ELP1) are found in 15-20% of childhood SHH medulloblastoma (MB) and are exceedingly rare in non-SHH-MB or other cancers. ELP1 germline carriers that develop SHH-MB harbor frequent somatic PTCH1 mutations and universally sustain loss-of-heterozygosity of the remaining ELP1 allele through chromosome 9q deletion. ELP1 functions as a scaffolding subunit of the Elongator complex that is required for posttranscriptional modification of tRNAs and maintenance of efficient translational elongation and protein homeostasis. However, the molecular, biochemical, and cellular mechanisms by which ELP1/Elongator LOF contribute to SHH-MB tumorigenesis remain largely unknown. Herein, we report that mice harboring germline Elp1 monoallelic loss (i.e., Elp1+/-) exhibit hallmark features of malignant predisposition in developing cerebellar granule neuron progenitors (GNPs), the lineage-of-origin for SHH-MB. Elp1+/- GNPs are characterized by increased replication stress-induced DNA damage, upregulation of the homologous recombination repair pathway, aberrant cell cycle, and attenuation of p53-dependent apoptosis. CRISPR/Cas9-mediated Elp1 and Ptch1 gene targeting in mouse GNPs reproduces highly penetrant SHH-MB tumors recapitulating the molecular and phenotypic features of patient tumors. Reactivation of the p53 pathway through MDM2 and PAK4 inhibitors promotes selective cell death in patient-derived xenograft tumors (PDX) harboring deleterious ELP1 mutations. Together, our findings reveal that germline Elp1 deficiency heightens genomic instability and survival in GNPs, providing a mechanistic model for the subgroup-restricted pattern of predisposition and malignancy associated with pathogenic ELP1 germline carriers. These results provide rationale for further preclinical studies evaluating drugs that overcome p53 pathway inhibition in ELP1-associated SHH-MB and a renewed outlook for improving treatment options for affected children and their families.*, # Contributed equally

Published
2022
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33. Identification of genetic variants associated with Huntington's disease progression

Author

Davina J Hensman Moss, Antonio F Pardiñas, Douglas Langbehn, Kitty Lo, Blair R Leavitt, Raymund Roos, Alexandra Durr, Simon Mead, Peter Holmans, Lesley Jones, Sarah J Tabrizi, A Coleman, R Dar Santos, J Decolongon, A Sturrock, E Bardinet, C Jauff Ret, D Justo, S Lehericy, C Marelli, K Nigaud, R Valabrègue, SJA van den Bogaard, E M Dumas, J van der Grond, EP t'Hart, C Jurgens, M-N Witjes-Ane, N Arran, J Callaghan, C Stopford, C Frost, R Jones, N Hobbs, N Lahiri, R Ordidge, G Owen, T Pepple, J Read, M Say, E Wild, A Patel, N C Fox, C Gibbard, I Malone, H Crawford, D Whitehead, S Keenan, D M Cash, C Berna, N Bechtel, S Bohlen, A Hoff Man, P Kraus, E Axelson, C Wang, T Acharya, S Lee, W Monaco, C Campbell, S Queller, K Whitlock, M Campbell, E Frajman, C Milchman, A O'Regan, I Labuschagne, J Stout, B Landwehrmeyer, D Craufurd, R Scahill, S Hicks, C Kennard, H Johnson, A Tobin, HD Rosas, R Reilmann, B Borowsky, C Pourchot, S C Andrews, Anne-Catherine Bachoud-Lévi, Anna Rita Bentivoglio, Ida Biunno, Raphael Bonelli, Jean-Marc Burgunder, Stephen Dunnett, Joaquim Ferreira, Olivia Handley, Arvid Heiberg, Torsten Illmann, G. Bernhard Landwehrmeyer, Jamie Levey, Maria A. Ramos-Arroyo, Jørgen Nielsen, Susana Pro Koivisto, Markku Päivärinta, Raymund A.C. Roos, A Rojo Sebastián, Sarah Tabrizi, Wim Vandenberghe, Christine Verellen-Dumoulin, Tereza Uhrova, Jan Wahlström, Jacek Zaremba, Verena Baake, Katrin Barth, Monica Bascuñana Garde, Sabrina Betz, Reineke Bos, Jenny Callaghan, Adrien Come, Leonor Correia Guedes, Daniel Ecker, Ana Maria Finisterra, Ruth Fullam, Mette Gilling, Lena Gustafsson, Olivia J Handley, Carina Hvalstedt, Christine Held, Kerstin Koppers, Claudia Lamanna, Matilde Laurà, Asunción Martínez Descals, Saül Martinez-Horta, Tiago Mestre, Sara Minster, Daniela Monza, Lisanne Mütze, Martin Oehmen, Michael Orth, Hélène Padieu, Laurent Paterski, Nadia Peppa, Martina Di Renzo, Amandine Rialland, Niini Røren, Pavla Šašinková, Erika Timewell, Jenny Townhill, Patricia Trigo Cubillo, Wildson Vieira da Silva, Marleen R van Walsem, Carina Whalstedt, Marie-Noelle Witjes-Ané, Grzegorz Witkowski, Abigail Wright, Daniel Zielonka, Eugeniusz Zielonka, Paola Zinzi, Raphael M. Bonelli, Sabine Lilek, Karen Hecht, Brigitte Herranhof, Anna Holl, Hans-Peter Kapfhammer, Michael Koppitz, Markus Magnet, Nicole Müller, Daniela Otti, Annamaria Painold, Karin Reisinger, Monika Scheibl, Helmut Schöggl, Jasmin Ullah, Eva-Maria Braunwarth, Florian Brugger, Lisa Buratti, Eva-Maria Hametner, Caroline Hepperger, Christiane Holas, Anna Hotter, Anna Hussl, Christoph Müller, Werner Poewe, Klaus Seppi, Fabienne Sprenger, Gregor Wenning, Andrea Boogaerts, Godelinde Calmeyn, Isabelle Delvaux, Dirk Liessens, Nele Somers, Michel Dupuit, Cécile Minet, Dominique van Paemel, Pascale Ribaï, Dimphna van Reijen, Jirí Klempír, Veronika Majerová, Jan Roth, Irena Stárková, Lena E. Hjermind, Oda Jacobsen, Jørgen E. Nielsen, Ida Unmack Larsen, Tua Vinther-Jensen, Heli Hiivola, Hannele Hyppönen, Kirsti Martikainen, Katri Tuuha, Philippe Allain, Dominique Bonneau, Marie Bost, Bénédicte Gohier, Marie-Anne Guérid, Audrey Olivier, Adriana Prundean, Clarisse Scherer-Gagou, Christophe Verny, Blandine Babiloni, Sabrina Debruxelles, Charlotte Duché, Cyril Goizet, Laetitia Jameau, Danielle Lafoucrière, Umberto Spampinato, Rekha Barthélémy, Christelle De Bruycker, Maryline Cabaret Anne-Sophie Carette, Eric Decorte Luc Defebvre, Marie Delliaux, Arnaud Delval, Alain Destee, Kathy Dujardin, Marie-Hélène Lemaire, Sylvie Manouvrier, Mireille Peter, Lucie Plomhouse, Bernard Sablonnière, Clémence Simonin, Stéphanie Thibault-Tanchou, Isabelle Vuillaume, Marcellin Bellonet, Hassan Berrissoul, Stéphanie Blin, Françoise Courtin, Cécile Duru, Véronique Fasquel, Olivier Godefroy, Pierre Krystkowiak, Béatrice Mantaux, Martine Roussel, Sandrine Wannepain, Jean-Philippe Azulay, Marie Delfini, Alexandre Eusebio, Frédérique Fluchere, Laura Mundler, Mathieu Anheim, Celine Julié, Ouhaid Lagha Boukbiza, Nadine Longato, Gabrielle Rudolf, Christine Tranchant, Marie-Agathe Zimmermann, Christoph Michael Kosinski, Eva Milkereit, Daniela Probst, Kathrin Reetz, Christian Sass, Johannes Schiefer, Christiane Schlangen, Cornelius J. Werner, Harald Gelderblom, Josef Priller, Harald Prüß, Eike Jakob Spruth, Gisa Ellrichmann, Lennard Herrmann, Rainer Hoffmann, Barbara Kaminski, Peter Kotz, Christian Prehn, Carsten Saft, Herwig Lange, Robert Maiwald, Matthias Löhle, Antonia Maass, Simone Schmidt, Cecile Bosredon, Alexander Storch, Annett Wolz, Martin Wolz, Philipp Capetian, Johann Lambeck, Birgit Zucker, Kai Boelmans, Christos Ganos, Walburgis Heinicke, Ute Hidding, Jan Lewerenz, Alexander Münchau, Jenny Schmalfeld, Lars Stubbe, Simone Zittel, Gabriele Diercks, Dirk Dressler, Heike Gorzolla, Christoph Schrader, Pawel Tacik, Michael Ribbat, Bernhard Longinus, Katrin Bürk, Jens Carsten Möller, Ida Rissling, Mark Mühlau, Alexander Peinemann, Michael Städtler, Adolf Weindl, Juliane Winkelmann, Cornelia Ziegler, Natalie Bechtel, Heike Beckmann, Stefan Bohlen, Eva Hölzner, Ralf Reilmann, Stefanie Rohm, Silke Rumpf, Sigrun Schepers, Natalia Weber, Matthias Dose, Gabriele Leythäuser, Ralf Marquard, Tina Raab, Alexandra Wiedemann, Andrea Buck, Julia Connemann, Carolin Geitner, Andrea Kesse, Bernhard Landwehrmeyer, Christina Lang, Franziska Lezius, Solveig Nepper, Anke Niess, Ariane Schneider, Daniela Schwenk, Sigurd Süßmuth, Sonja Trautmann, Patrick Weydt, Claudia Cormio, Vittorio Sciruicchio, Claudia Serpino, Marina de Tommaso, Sabina Capellari, Pietro Cortelli, Roberto Galassi, Giovanni Rizzo, Roberto Poda, Cesa Scaglione, Elisabetta Bertini, Elena Ghelli, Andrea Ginestroni, Francesca Massaro, Claudia Mechi, Marco Paganini, Silvia Piacentini, Silvia Pradella, Anna Maria Romoli, Sandro Sorbi, Giovanni Abbruzzese, Monica Bandettini di Poggio, Giovanna Ferrandes, Paola Mandich, Roberta Marchese, Alberto Albanese, Daniela Di Bella, Anna Castaldo, Stefano Di Donato, Cinzia Gellera, Silvia Genitrini, Caterina Mariotti, Lorenzo Nanetti, Dominga Paridi, Paola Soliveri, Chiara Tomasello, Giuseppe De Michele, Luigi Di Maio, Marco Massarelli, Silvio Peluso, Alessandro Roca, Cinzia Valeria Russo, Elena Salvatore, Pierpaolo Sorrentino, Enrico Amico, Mariagrazia Favellato, Annamaria Griguoli, Irene Mazzante, Martina Petrollini, Ferdinando Squitieri, Barbara D'Alessio, Chiara Esposito, Rita Bentivoglio, Marina Frontali, Arianna Guidubaldi, Tamara Ialongo, Gioia Jacopini, Carla Piano, Silvia Romano, Francesco Soleti, Maria Spadaro, Monique S.E. van Hout, Marloes E. Verhoeven, Jeroen P.P. van Vugt, A. Marit de Weert, J.J.W. Bolwijn, M. Dekker, B. Kremer, K.L. Leenders, J.C.H. van Oostrom, Simon J.A. van den Bogaard, Eve M. Dumas, Ellen P. 't Hart, Berry Kremer, C.C.P. Verstappen, Olaf Aaserud, Jan Frich C, Ragnhild Wehus, Kathrine Bjørgo, Madeleine Fannemel, Per F. Gørvell, Eirin Lorentzen, Lars Retterstøl, Bodil Stokke, Inga Bjørnevoll, Sigrid Botne Sando, Artur Dziadkiewicz, Malgorzata Nowak, Piotr Robowski, Emilia Sitek, Jaroslaw Slawek, Witold Soltan, Michal Szinwelski, Magdalena Blaszcyk, Magdalena Boczarska-Jedynak, Ewelina Ciach-Wysocka, Agnieszka Gorzkowska, Barbara Jasinska-Myga, Gabriela Klodowska-Duda, Gregorz Opala, Daniel Stompel, Krzysztof Banaszkiewicz, Dorota Bocwinska, Kamila Bojakowska-Jaremek, Malgorzata Dec, Malgorzata Krawczyk, Monika Rudzinska, Elzbieta Szczygiel, Andrzej Szczudlik, Anna Wasielewska, Magdalena Wójcik, Anna Bryl, Anna Ciesielska, Aneta Klimberg, Jerzy Marcinkowski, Husam Samara, Justyna Sempolowicz, Anna Gogol, Piotr Janik, Hubert Kwiecinski, Zygmunt Jamrozik, Jakub Antczak, Katarzyna Jachinska, Wioletta Krysa, Maryla Rakowicz, Przemyslaw Richter, Rafal Rola, Danuta Ryglewicz, Halina Sienkiewicz-Jarosz, Iwona Stepniak, Anna Sulek, Elzbieta Zdzienicka, Karolina Zieora-Jakutowicz, Joaquim J Ferreira, Miguel Coelho, Tiago Mendes, Anabela Valadas, Carlos Andrade, Miguel Gago, Carolina Garrett, Maria Rosália Guerra, Carmen Durán Herrera, Patrocinio Moreno Garcia, Miquel Aguilar Barbera, Dolors Badenes Guia, Laura Casas Hernanz, Judit López Catena, Pilar Quiléz Ferrer, Ana Rojo Sebastián, Gemma Tome Carruesco, Jordi Bas, Núria Busquets, Matilde Calopa, Misericordia Floriach Robert, Celia Mareca Viladrich, Jesús Miguel Ruiz Idiago, Antonio Villa Riballo, Esther Cubo, Cecilia Gil Polo, Natividad Mariscal, Perez Jessica Rivadeneyra, Francisco Barrero, Blas Morales, María Fenollar, Rocío García-Ramos García, Paloma Ortega, Clara Villanueva, Javier Alegre, Mónica Bascuñana, Juan Garcia Caldentey, Marta Fatás Ventura, Guillermo García Ribas, Justo García de Yébenes, José Luis López-Sendón Moreno, Fernando Alonso Frech, Pedro J García Ruíz, Asunción Martínez-Descals, Rosa Guerrero, María José Saiz Artiga, Vicenta Sánchez, María Fuensanta Noguera Perea, Lorenza Fortuna, Salvadora Manzanares, Gema Reinante, María Martirio Antequera Torres, Laura Vivancos Moreau, Sonia González González, Luis Menéndez Guisasola, Carlos Salvador, Esther Suaréz San Martín, Inés Legarda Ramirez, Aranzazú Gorospe, Mónica Rodriguez Lopera, Penelope Navas Arques, María José Torres Rodríguez, Barbara Vives Pastor, Itziar Gaston, Maria Dolores Martinez-Jaurrieta, Jose Manuel Garcia Moreno, Carolina Mendez Lucena, Fatima Damas, Hermoso Eva Pacheco Cortegana, José Chacón Peña, Luis Redondo, Fátima Carrillo, María Teresa Cáceres, Pablo Mir, María José Lama Suarez, Laura Vargas-González, Maria E. Bosca, Francisco Castera Brugada, Juan Andres Burguera, Anabel Campos, Garcia Carmen Peiró Vilaplana, Peter Berglund, Radu Constantinescu, Gunnel Fredlund, Ulrika Høsterey-Ugander, Petra Linnsand, Liselotte Neleborn-Lingefjärd, Magnus Wentzel, Ghada Loutfi, Carina Olofsson, Eva-Lena Stattin, Laila Westman, Birgitta Wikström, Yanik Stebler, Alain Kaelin, Irene Romero, Michael Schüpbach, Sabine Weber Zaugg, Maria Hauer, Roman Gonzenbach, Hans H. Jung, Violeta Mihaylova, Jens Petersen, Roisin Jack, Kirsty Matheson, Zosia Miedzybrodzka, Daniela Rae, Sheila A Simpson, Fiona Summers, Alexandra Ure, Vivien Vaughan, Shahbana Akhtar, Jenny Crooks, Adrienne Curtis, Jenny de Souza, John Piedad, Hugh Rickards, Jan Wright, Elizabeth Coulthard, Louise Gethin, Beverley Hayward, Kasia Sieradzan, Matthew Armstrong, Roger A. Barker, Deidre O'Keefe, Anna Di Pietro, Kate Fisher, Anna Goodman, Susan Hill, Ann Kershaw, Sarah Mason, Nicole Paterson, Lucy Raymond, Rachel Swain, Natalie Valle Guzman, Monica Busse, Cynthia Butcher, Catherine Clenaghan, Sarah Hunt, Una Jones, Hanan Khalil, Michael Owen, Kathleen Price, Anne Rosser, Maureen Edwards, Carrie Ho, Teresa Hughes, Marie McGill, Pauline Pearson, Mary Porteous, Paul Smith, Peter Brockie, Jillian Foster, Nicola Johns, Sue McKenzie, Jean Rothery, Gareth Thomas, Shona Yates, Liz Burrows, Carol Chu, Amy Fletcher, Deena Gallantrae, Stephanie Hamer, Alison Harding, Stefan Klöppel, Alison Kraus, Fiona Laver, Monica Lewis, Mandy Longthorpe, Ivana Markova, Ashok Raman, Nicola Robertson, Mark Silva, Aileen Thomson, Sue Wild, Pam Yardumian, Carole Evans, Deena Gallentrae, Emma Hobson, Stuart Jamieson, Hannah Musgrave, Liz Rowett, Jean Toscano, Colin Bourne, Jackie Clapton, Carole Clayton, Heather Dipple, Dawn Freire-Patino, Janet Grant, Diana Gross, Caroline Hallam, Julia Middleton, Ann Murch, Catherine Thompson, Sundus Alusi, Rhys Davies, Kevin Foy, Emily Gerrans, Louise Pate, Thomasin Andrews, Andrew Dougherty, Charlotte Golding, Fred Kavalier, Hana Laing, Alison Lashwood, Dene Robertson, Deborah Ruddy, Alastair Santhouse, Anna Whaite, Stefania Bruno, Karen Doherty, Salman Haider, Davina Hensman, Nayana Lahiri, Marianne Novak, Aakta Patel, Elisabeth Rosser, Rachel Taylor, Thomas Warner, Edward Wild, Natalie Arran, Judith Bek, David Craufurd, Marianne Hare, Liz Howard, Susan Huson, Liz Johnson, Mary Jones, Helen Murphy, Emma Oughton, Lucy Partington-Jones, Dawn Rogers, Andrea Sollom, Julie Snowden, Cheryl Stopford, Jennifer Thompson, Iris Trender-Gerhard, Nichola Verstraelen, Leann Westmoreland, Richard Armstrong, Kathryn Dixon, Andrea H Nemeth, Gill Siuda, Ruth Valentine, David Harrison, Max Hughes, Andrew Parkinson, Beverley Soltysiak, Oliver Bandmann, Alyson Bradbury, Paul Gill, Helen Fairtlough, Kay Fillingham, Isabella Foustanos, Mbombe Kazoka, Kirsty O'Donovan, Cat Taylor, Katherine Tidswell, Oliver Quarrell, Puay Ngoh Lau, Emmanul Pica, Louis Tan, Univ Angers, Okina, Moss, Davina J. Hensman, Tabrizi, Sarah J, Mead, Simon, Kitty, Lo, Pardiã±as, Antonio F, Holmans, Peter, Jones, Lesley, Langbehn, Dougla, Coleman, A., Santos, R. Dar, Decolongon, J., Sturrock, A., Bardinet, E., Ret, C. Jauff, Justo, D., Lehericy, S., Marelli, C., Nigaud, K., Valabrãgue, R., van den Bogaard, S. J. A., Dumas, E. M., van der Grond, J., T'Hart, E. P., Jurgens, C., Witjes-Ane, M. -. N., Arran, N., Callaghan, J., Stopford, C., Frost, C., Jones, R., Hobbs, N., Lahiri, N., Ordidge, R., Owen, G., Pepple, T., Read, J., Say, M., Wild, E., Patel, A., Fox, N. C., Gibbard, C., Malone, I., Crawford, H., Whitehead, D., Keenan, S., Cash, D. M., Berna, C., Bechtel, N., Bohlen, S., Man, A. Hoff, Kraus, P., Axelson, E., Wang, C., Acharya, T., Lee, S., Monaco, W., Campbell, C., Queller, S., Whitlock, K., Campbell, M., Frajman, E., Milchman, C., O'Regan, A., Labuschagne, I., Stout, J., Landwehrmeyer, B., Craufurd, D., Scahill, R., Hicks, S., Kennard, C., Johnson, H., Tobin, A., Rosas, H. D., Reilmann, R., Borowsky, B., Pourchot, C., Andrews, S. C., Bachoud-Lévi, Anne-Catherine, Bentivoglio, Anna Rita, Biunno, Ida, Bonelli, Raphael, Burgunder, Jean-Marc, Dunnett, Stephen, Ferreira, Joaquim, Handley, Olivia, Heiberg, Arvid, Illmann, Torsten, Landwehrmeyer, G. Bernhard, Levey, Jamie, Ramos-Arroyo, Maria A., Nielsen, Jã¸rgen, Koivisto, Susana Pro, Pã¤ivã¤rinta, Markku, Roos, Raymund A. C., Sebastiã¡n, A. Rojo, Tabrizi, Sarah, Vandenberghe, Wim, Verellen-Dumoulin, Christine, Uhrova, Tereza, Wahlstrã¶m, Jan, Zaremba, Jacek, Baake, Verena, Barth, Katrin, Garde, Monica Bascuñana, Betz, Sabrina, Bos, Reineke, Callaghan, Jenny, Come, Adrien, Guedes, Leonor Correia, Ecker, Daniel, Finisterra, Ana Maria, Fullam, Ruth, Gilling, Mette, Gustafsson, Lena, Handley, Olivia J, Hvalstedt, Carina, Held, Christine, Koppers, Kerstin, Lamanna, Claudia, Laurã , Matilde, Descals, Asunción Martínez, Martinez-Horta, Saã¼l, Mestre, Tiago, Minster, Sara, Monza, Daniela, Mã¼tze, Lisanne, Oehmen, Martin, Orth, Michael, Padieu, Hã©lãne, Paterski, Laurent, Peppa, Nadia, Di Renzo, Martina, Rialland, Amandine, Rã¸ren, Niini, Å aå¡inkovã¡, Pavla, Timewell, Erika, Townhill, Jenny, Cubillo, Patricia Trigo, da Silva, Wildson Vieira, van Walsem, Marleen R, Whalstedt, Carina, Witjes-Ané, Marie-Noelle, Witkowski, Grzegorz, Wright, Abigail, Zielonka, Daniel, Zielonka, Eugeniusz, Zinzi, Paola, Bonelli, Raphael M., Lilek, Sabine, Hecht, Karen, Herranhof, Brigitte, Holl, Anna, Kapfhammer, Hans-Peter, Koppitz, Michael, Magnet, Marku, Mã¼ller, Nicole, Otti, Daniela, Painold, Annamaria, Reisinger, Karin, Scheibl, Monika, Schã¶ggl, Helmut, Ullah, Jasmin, Braunwarth, Eva-Maria, Brugger, Florian, Buratti, Lisa, Hametner, Eva-Maria, Hepperger, Caroline, Holas, Christiane, Hotter, Anna, Hussl, Anna, Mã¼ller, Christoph, Poewe, Werner, Seppi, Klau, Sprenger, Fabienne, Wenning, Gregor, Boogaerts, Andrea, Calmeyn, Godelinde, Delvaux, Isabelle, Liessens, Dirk, Somers, Nele, Dupuit, Michel, Minet, Cã©cile, van Paemel, Dominique, Ribaã¯, Pascale, van Reijen, Dimphna, Klempã­r, Jirã­, Majerovã¡, Veronika, Roth, Jan, Stã¡rkovã¡, Irena, Hjermind, Lena E., Jacobsen, Oda, Nielsen, Jørgen E., Larsen, Ida Unmack, Vinther-Jensen, Tua, Hiivola, Heli, Hyppã¶nen, Hannele, Martikainen, Kirsti, Tuuha, Katri, Allain, Philippe, Bonneau, Dominique, Bost, Marie, Gohier, Bã©nã©dicte, Guã©rid, Marie-Anne, Olivier, Audrey, Prundean, Adriana, Scherer-Gagou, Clarisse, Verny, Christophe, Babiloni, Blandine, Debruxelles, Sabrina, Duchã©, Charlotte, Goizet, Cyril, Jameau, Laetitia, Lafoucriãre, Danielle, Spampinato, Umberto, Barthã©lã©my, Rekha, De Bruycker, Christelle, Carette, Maryline Cabaret Anne-Sophie, Defebvre, Eric Decorte Luc, Delliaux, Marie, Delval, Arnaud, Destee, Alain, Dujardin, Kathy, Lemaire, Marie-HélÃne, Manouvrier, Sylvie, Peter, Mireille, Plomhouse, Lucie, Sablonniãre, Bernard, Simonin, Clã©mence, Thibault-Tanchou, Stã©phanie, Vuillaume, Isabelle, Bellonet, Marcellin, Berrissoul, Hassan, Blin, Stã©phanie, Courtin, Franã§oise, Duru, Cã©cile, Fasquel, Vã©ronique, Godefroy, Olivier, Krystkowiak, Pierre, Mantaux, Bã©atrice, Roussel, Martine, Wannepain, Sandrine, Azulay, Jean-Philippe, Delfini, Marie, Eusebio, Alexandre, Fluchere, Frã©dã©rique, Mundler, Laura, Anheim, Mathieu, Juliã©, Celine, Boukbiza, Ouhaid Lagha, Longato, Nadine, Rudolf, Gabrielle, Tranchant, Christine, Zimmermann, Marie-Agathe, Kosinski, Christoph Michael, Milkereit, Eva, Probst, Daniela, Reetz, Kathrin, Sass, Christian, Schiefer, Johanne, Schlangen, Christiane, Werner, Cornelius J., Gelderblom, Harald, Priller, Josef, Prã¼ã , Harald, Spruth, Eike Jakob, Ellrichmann, Gisa, Herrmann, Lennard, Hoffmann, Rainer, Kaminski, Barbara, Kotz, Peter, Prehn, Christian, Saft, Carsten, Lange, Herwig, Maiwald, Robert, Lã¶hle, Matthia, Maass, Antonia, Schmidt, Simone, Bosredon, Cecile, Storch, Alexander, Wolz, Annett, Wolz, Martin, Capetian, Philipp, Lambeck, Johann, Zucker, Birgit, Boelmans, Kai, Ganos, Christo, Heinicke, Walburgi, Hidding, Ute, Lewerenz, Jan, Mã¼nchau, Alexander, Schmalfeld, Jenny, Stubbe, Lar, Zittel, Simone, Diercks, Gabriele, Dressler, Dirk, Gorzolla, Heike, Schrader, Christoph, Tacik, Pawel, Ribbat, Michael, Longinus, Bernhard, Bã¼rk, Katrin, Mã¶ller, Jens Carsten, Rissling, Ida, Mã¼hlau, Mark, Peinemann, Alexander, Stã¤dtler, Michael, Weindl, Adolf, Winkelmann, Juliane, Ziegler, Cornelia, Bechtel, Natalie, Beckmann, Heike, Bohlen, Stefan, Hã¶lzner, Eva, Reilmann, Ralf, Rohm, Stefanie, Rumpf, Silke, Schepers, Sigrun, Weber, Natalia, Dose, Matthia, Leythã¤user, Gabriele, Marquard, Ralf, Raab, Tina, Wiedemann, Alexandra, Buck, Andrea, Connemann, Julia, Geitner, Carolin, Kesse, Andrea, Landwehrmeyer, Bernhard, Lang, Christina, Lezius, Franziska, Nepper, Solveig, Niess, Anke, Schneider, Ariane, Schwenk, Daniela, Sã¼ã muth, Sigurd, Trautmann, Sonja, Weydt, Patrick, Cormio, Claudia, Sciruicchio, Vittorio, Serpino, Claudia, de Tommaso, Marina, Capellari, Sabina, Cortelli, Pietro, Galassi, Roberto, Rizzo, Giovanni, Poda, Roberto, Scaglione, Cesa, Bertini, Elisabetta, Ghelli, Elena, Ginestroni, Andrea, Massaro, Francesca, Mechi, Claudia, Paganini, Marco, Piacentini, Silvia, Pradella, Silvia, Romoli, Anna Maria, Sorbi, Sandro, Abbruzzese, Giovanni, di Poggio, Monica Bandettini, Ferrandes, Giovanna, Mandich, Paola, Roberta, Marchese, Albanese, Alberto, Di Bella, Daniela, Castaldo, Anna, Di Donato, Stefano, Gellera, Cinzia, Genitrini, Silvia, Mariotti, Caterina, Nanetti, Lorenzo, Paridi, Dominga, Soliveri, Paola, Tomasello, Chiara, De Michele, Giuseppe, Di Maio, Luigi, Massarelli, Marco, Peluso, Silvio, Roca, Alessandro, Russo, Cinzia Valeria, Salvatore, Elena, Sorrentino, Pierpaolo, Amico, Enrico, Favellato, Mariagrazia, Griguoli, Annamaria, Mazzante, Irene, Petrollini, Martina, Squitieri, Ferdinando, D'Alessio, Barbara, Esposito, Chiara, Bentivoglio, Rita, Frontali, Marina, Guidubaldi, Arianna, Ialongo, Tamara, Jacopini, Gioia, Piano, Carla, Romano, Silvia, Soleti, Francesco, Spadaro, Maria, van Hout, Monique S. E., Verhoeven, Marloes E., van Vugt, Jeroen P. P., de Weert, A. Marit, Bolwijn, J. J. W., Dekker, M., Kremer, B., Leenders, K. L., van Oostrom, J. C. H., van den Bogaard, Simon J. A., Dumas, Eve M., â t Hart, Ellen P., Kremer, Berry, Verstappen, C. C. P., Aaserud, Olaf, Jan Frich, C., Wehus, Ragnhild, Bjã¸rgo, Kathrine, Fannemel, Madeleine, Gã¸rvell, Per F., Lorentzen, Eirin, Retterstã¸l, Lar, Stokke, Bodil, Bjã¸rnevoll, Inga, Sando, Sigrid Botne, Dziadkiewicz, Artur, Nowak, Malgorzata, Robowski, Piotr, Sitek, Emilia, Slawek, Jaroslaw, Soltan, Witold, Szinwelski, Michal, Blaszcyk, Magdalena, Boczarska-Jedynak, Magdalena, Ciach-Wysocka, Ewelina, Gorzkowska, Agnieszka, Jasinska-Myga, Barbara, Klodowska-Duda, Gabriela, Opala, Gregorz, Stompel, Daniel, Banaszkiewicz, Krzysztof, Bocwinska, Dorota, Bojakowska-Jaremek, Kamila, Dec, Malgorzata, Krawczyk, Malgorzata, Rudzinska, Monika, Szczygiel, Elzbieta, Szczudlik, Andrzej, Wasielewska, Anna, Wã³jcik, Magdalena, Bryl, Anna, Ciesielska, Anna, Klimberg, Aneta, Marcinkowski, Jerzy, Samara, Husam, Sempolowicz, Justyna, Gogol, Anna, Janik, Piotr, Kwiecinski, Hubert, Jamrozik, Zygmunt, Antczak, Jakub, Jachinska, Katarzyna, Krysa, Wioletta, Rakowicz, Maryla, Richter, Przemyslaw, Rola, Rafal, Ryglewicz, Danuta, Sienkiewicz-Jarosz, Halina, Stepniak, Iwona, Sulek, Anna, Zdzienicka, Elzbieta, Zieora-Jakutowicz, Karolina, Ferreira, Joaquim J, Coelho, Miguel, Mendes, Tiago, Valadas, Anabela, Andrade, Carlo, Gago, Miguel, Garrett, Carolina, Guerra, Maria Rosália, Herrera, Carmen Durán, Garcia, Patrocinio Moreno, Barbera, Miquel Aguilar, Guia, Dolors Badene, Hernanz, Laura Casa, Catena, Judit López, Ferrer, Pilar Quiléz, Sebastiã¡n, Ana Rojo, Carruesco, Gemma Tome, Bas, Jordi, Busquets, Nãºria, Calopa, Matilde, Robert, Misericordia Floriach, Viladrich, Celia Mareca, Idiago, Jesús Miguel Ruiz, Riballo, Antonio Villa, Cubo, Esther, Polo, Cecilia Gil, Mariscal, Natividad, Rivadeneyra, Perez Jessica, Barrero, Francisco, Morales, Bla, Fenollar, Marã­a, Garcã­a, Rocío García-Ramo, Ortega, Paloma, Villanueva, Clara, Alegre, Javier, Bascuã±ana, Mã³nica, Caldentey, Juan Garcia, Ventura, Marta Fatá, Ribas, Guillermo García, de Yébenes, Justo García, Moreno, José Luis López-Sendón, Frech, Fernando Alonso, Ruã­z, Pedro J. García, Martínez-Descals, Asunciã³n, Guerrero, Rosa, Artiga, María José Saiz, Sã¡nchez, Vicenta, Perea, María Fuensanta Noguera, Fortuna, Lorenza, Manzanares, Salvadora, Reinante, Gema, Torres, María Martirio Antequera, Moreau, Laura Vivanco, González González, Sonia, Guisasola, Luis Menéndez, Salvador, Carlo, Martã­n, Esther Suaréz San, Ramirez, Inés Legarda, Gorospe, Aranzazãº, Lopera, Mónica Rodriguez, Arques, Penelope Nava, Rodrã­guez, María José Torre, Pastor, Barbara Vive, Gaston, Itziar, Martinez-Jaurrieta, Maria Dolore, Moreno, Jose Manuel Garcia, Lucena, Carolina Mendez, Damas, Fatima, Cortegana, Hermoso Eva Pacheco, Peã±a, José Chacón, Redondo, Lui, Carrillo, Fã¡tima, Teresa Cáceres, Marã­a, Mir, Pablo, Suarez, María José Lama, Vargas-González, Laura, Bosca, Maria E., Brugada, Francisco Castera, Burguera, Juan Andre, Campos, Anabel, Vilaplana, Garcia Carmen Peiró, Berglund, Peter, Constantinescu, Radu, Fredlund, Gunnel, Høsterey-Ugander, Ulrika, Linnsand, Petra, Neleborn-Lingefjärd, Liselotte, Wentzel, Magnu, Loutfi, Ghada, Olofsson, Carina, Stattin, Eva-Lena, Westman, Laila, Wikstrã¶m, Birgitta, Stebler, Yanik, Kaelin, Alain, Romero, Irene, Schã¼pbach, Michael, Weber Zaugg, Sabine, Hauer, Maria, Gonzenbach, Roman, Jung, Hans H., Mihaylova, Violeta, Petersen, Jen, Jack, Roisin, Matheson, Kirsty, Miedzybrodzka, Zosia, Rae, Daniela, Simpson, Sheila A, Summers, Fiona, Ure, Alexandra, Vaughan, Vivien, Akhtar, Shahbana, Crooks, Jenny, Curtis, Adrienne, de Souza, Jenny, Piedad, John, Rickards, Hugh, Wright, Jan, Coulthard, Elizabeth, Gethin, Louise, Hayward, Beverley, Sieradzan, Kasia, Armstrong, Matthew, Barker, Roger A., O'Keefe, Deidre, Di Pietro, Anna, Fisher, Kate, Goodman, Anna, Hill, Susan, Kershaw, Ann, Mason, Sarah, Paterson, Nicole, Raymond, Lucy, Swain, Rachel, Guzman, Natalie Valle, Busse, Monica, Butcher, Cynthia, Clenaghan, Catherine, Hunt, Sarah, Jones, Una, Khalil, Hanan, Owen, Michael, Price, Kathleen, Rosser, Anne, Edwards, Maureen, Carrie, Ho, Hughes, Teresa, Mcgill, Marie, Pearson, Pauline, Porteous, Mary, Smith, Paul, Brockie, Peter, Foster, Jillian, Johns, Nicola, Mckenzie, Sue, Rothery, Jean, Thomas, Gareth, Yates, Shona, Burrows, Liz, Chu, Carol, Fletcher, Amy, Gallantrae, Deena, Hamer, Stephanie, Harding, Alison, Klã¶ppel, Stefan, Kraus, Alison, Laver, Fiona, Lewis, Monica, Longthorpe, Mandy, Markova, Ivana, Raman, Ashok, Robertson, Nicola, Silva, Mark, Thomson, Aileen, Wild, Sue, Yardumian, Pam, Evans, Carole, Gallentrae, Deena, Hobson, Emma, Jamieson, Stuart, Musgrave, Hannah, Rowett, Liz, Toscano, Jean, Bourne, Colin, Clapton, Jackie, Clayton, Carole, Dipple, Heather, Freire-Patino, Dawn, Grant, Janet, Gross, Diana, Hallam, Caroline, Middleton, Julia, Murch, Ann, Thompson, Catherine, Alusi, Sundu, Davies, Rhy, Foy, Kevin, Gerrans, Emily, Pate, Louise, Andrews, Thomasin, Dougherty, Andrew, Golding, Charlotte, Kavalier, Fred, Laing, Hana, Lashwood, Alison, Robertson, Dene, Ruddy, Deborah, Santhouse, Alastair, Whaite, Anna, Bruno, Stefania, Doherty, Karen, Haider, Salman, Hensman, Davina, Lahiri, Nayana, Novak, Marianne, Patel, Aakta, Rosser, Elisabeth, Taylor, Rachel, Warner, Thoma, Wild, Edward, Arran, Natalie, Bek, Judith, Craufurd, David, Hare, Marianne, Howard, Liz, Huson, Susan, Johnson, Liz, Jones, Mary, Murphy, Helen, Oughton, Emma, Partington-Jones, Lucy, Rogers, Dawn, Sollom, Andrea, Snowden, Julie, Stopford, Cheryl, Thompson, Jennifer, Trender-Gerhard, Iri, Verstraelen, Nichola, Westmoreland, Leann, Armstrong, Richard, Dixon, Kathryn, Nemeth, Andrea H, Siuda, Gill, Valentine, Ruth, David, Harrison, Hughes, Max, Parkinson, Andrew, Soltysiak, Beverley, Bandmann, Oliver, Bradbury, Alyson, Gill, Paul, Fairtlough, Helen, Fillingham, Kay, Foustanos, Isabella, Kazoka, Mbombe, O'Donovan, Kirsty, Taylor, Cat, Tidswell, Katherine, Quarrell, Oliver, Lau, Puay Ngoh, Pica, Emmanul, Tan, Louis, Amsterdam Neuroscience - Neurodegeneration, Neurology, Biologie Neurovasculaire et Mitochondriale Intégrée (BNMI), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Moss, Davina J Hensman, Lo, Kitty, Pardiñas, Antonio F, Santos, R Dar, Ret, C Jauff, Valabrègue, R., Witjes-Ane, M. -N., Man, A Hoff, Bachoud-Lévi, Anne-Catherine, Nielsen, Jørgen, Päivärinta, Markku, Sebastián, A Rojo, Wahlström, Jan, Garde, Monica Bascuñana, Laurà, Matilde, Descals, Asunción Martínez, Martinez-Horta, Saül, Mütze, Lisanne, Padieu, Hélène, Røren, Niini, Šašinková, Pavla, Witjes-Ané, Marie-Noelle, Müller, Nicole, Schöggl, Helmut, Müller, Christoph, Minet, Cécile, Ribaï, Pascale, Klempír, Jirí, Majerová, Veronika, Stárková, Irena, Nielsen, Jørgen E., Hyppönen, Hannele, Gohier, Bénédicte, Guérid, Marie-Anne, Duché, Charlotte, Lafoucrière, Danielle, Barthélémy, Rekha, Lemaire, Marie-Hélène, Sablonnière, Bernard, Simonin, Clémence, Thibault-Tanchou, Stéphanie, Blin, Stéphanie, Courtin, Françoise, Duru, Cécile, Fasquel, Véronique, Mantaux, Béatrice, Fluchere, Frédérique, Julié, Celine, Prüß, Harald, Löhle, Matthia, Münchau, Alexander, Bürk, Katrin, Möller, Jens Carsten, Mühlau, Mark, Städtler, Michael, Hölzner, Eva, Leythäuser, Gabriele, Süßmuth, Sigurd, Marchese, Roberta, DI MAIO, Luigi, ’t Hart, Ellen P., Bjørgo, Kathrine, Gørvell, Per F., Retterstøl, Lar, Bjørnevoll, Inga, Wójcik, Magdalena, Guerra, Maria Rosália, Herrera, Carmen Durán, Catena, Judit López, Ferrer, Pilar Quiléz, Sebastián, Ana Rojo, Busquets, Núria, Idiago, Jesús Miguel Ruiz, Fenollar, María, García, Rocío García-Ramo, Bascuñana, Mónica, Ventura, Marta Fatá, Ribas, Guillermo García, de Yébenes, Justo García, Moreno, José Luis López-Sendón, Ruíz, Pedro J García, Martínez-Descals, Asunción, Artiga, María José Saiz, Sánchez, Vicenta, Perea, María Fuensanta Noguera, Torres, María Martirio Antequera, González González, Sonia, Guisasola, Luis Menéndez, Martín, Esther Suaréz San, Ramirez, Inés Legarda, Gorospe, Aranzazú, Lopera, Mónica Rodriguez, Rodríguez, María José Torre, Peña, José Chacón, Carrillo, Fátima, Teresa Cáceres, María, Suarez, María José Lama, Vargas-González, Laura, Vilaplana, Garcia Carmen Peiró, Høsterey-Ugander, Ulrika, Neleborn-Lingefjärd, Liselotte, Wikström, Birgitta, Schüpbach, Michael, Ho, Carrie, Klöppel, Stefan, Harrison, David, Cardiff University, University of Iowa [Iowa City], University of British Columbia (UBC), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), UCL, Institute of Neurology [London], National Oceanography Centre [Southampton] (NOC), University of Southampton, 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), IFR de Neuroimagerie Fonctionnelle (IFR 49), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), CHU Amiens-Picardie, Laboratoire de Neurosciences Fonctionnelles et Pathologies - UR UPJV 4559 (LNFP), Université de Picardie Jules Verne (UPJV), CHirurgie, IMagerie et REgénération tissulaire de l’extrémité céphalique - Caractérisation morphologique et fonctionnelle - UR UPJV 7516 (CHIMERE), TRACK-HD investigators, Pardinas, Antonio F, Langbehn, Douglas, Lee, S Hong, TRACK-HD Investigators, and REGISTRY Investigators

Subjects
0301 basic medicine, Oncology, Registrie, Genome-wide association study, Longitudinal Studie, Disease, Bioinformatics, Severity of Illness Index, Principal Component Analysi, Longitudinal Studies, Registries, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Huntington disease, DNA-Binding Proteins, Settore MED/26 - NEUROLOGIA, Adult, Genome-Wide Association Study, Humans, Huntington Disease, MutS Homolog 3 Protein, Principal Component Analysis, Disease Progression, Neurology (clinical), huntingtin gene, age of onest, Huntington’s disease, Human, medicine.medical_specialty, cag repeat, instability, DNA-Binding Protein, Clinical Neurology, Principal component analysis, Single-nucleotide polymorphism, Biology, 03 medical and health sciences, Huntington's disease, Internal medicine, medicine, SNP, genome-wide association study, medicine.disease, R1, meta-analysis, Minor allele frequency, 030104 developmental biology, Age of onset, Trinucleotide repeat expansion, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract

Background Huntington's disease is caused by a CAG repeat expansion in the huntingtin gene, HTT. Age at onset has been used as a quantitative phenotype in genetic analysis looking for Huntington's disease modifiers, but is hard to define and not always available. Therefore, we aimed to generate a novel measure of disease progression and to identify genetic markers associated with this progression measure. Methods We generated a progression score on the basis of principal component analysis of prospectively acquired longitudinal changes in motor, cognitive, and imaging measures in the 218 indivduals in the TRACK-HD cohort of Huntington's disease gene mutation carriers (data collected 2008–11). We generated a parallel progression score using data from 1773 previously genotyped participants from the European Huntington's Disease Network REGISTRY study of Huntington's disease mutation carriers (data collected 2003–13). We did a genome-wide association analyses in terms of progression for 216 TRACK-HD participants and 1773 REGISTRY participants, then a meta-analysis of these results was undertaken. Findings Longitudinal motor, cognitive, and imaging scores were correlated with each other in TRACK-HD participants, justifying use of a single, cross-domain measure of disease progression in both studies. The TRACK-HD and REGISTRY progression measures were correlated with each other (r=0·674), and with age at onset (TRACK-HD, r=0·315; REGISTRY, r=0·234). The meta-analysis of progression in TRACK-HD and REGISTRY gave a genome-wide significant signal (p=1·12 × 10−10) on chromosome 5 spanning three genes: MSH3, DHFR, and MTRNR2L2. The genes in this locus were associated with progression in TRACK-HD (MSH3 p=2·94 × 10−8 DHFR p=8·37 × 10−7 MTRNR2L2 p=2·15 × 10−9) and to a lesser extent in REGISTRY (MSH3 p=9·36 × 10−4 DHFR p=8·45 × 10−4 MTRNR2L2 p=1·20 × 10−3). The lead single nucleotide polymorphism (SNP) in TRACK-HD (rs557874766) was genome-wide significant in the meta-analysis (p=1·58 × 10−8), and encodes an aminoacid change (Pro67Ala) in MSH3. In TRACK-HD, each copy of the minor allele at this SNP was associated with a 0·4 units per year (95% CI 0·16–0·66) reduction in the rate of change of the Unified Huntington's Disease Rating Scale (UHDRS) Total Motor Score, and a reduction of 0·12 units per year (95% CI 0·06–0·18) in the rate of change of UHDRS Total Functional Capacity score. These associations remained significant after adjusting for age of onset. Interpretation The multidomain progression measure in TRACK-HD was associated with a functional variant that was genome-wide significant in our meta-analysis. The association in only 216 participants implies that the progression measure is a sensitive reflection of disease burden, that the effect size at this locus is large, or both. Knockout of Msh3 reduces somatic expansion in Huntington's disease mouse models, suggesting this mechanism as an area for future therapeutic investigation. Funding The European Commission FP7 NeurOmics project; CHDI Foundation; the Medical Research Council UK; the Brain Research Trust; and the Guarantors of Brain.

Published
2017
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34. Cross-validation of a Shortened Battery for the Assessment of Dysexecutive Disorders in Alzheimer Disease

Author

Olivier, Godefroy, Olivier, Martinaud, Marc, Verny, Chrystèle, Mosca, Hermine, Lenoir, Eric, Bretault, Agnès, Devendeville, Momar, Diouf, Jean-Jacques, Pere, Serge, Bakchine, Jean-Philippe, Delabrousse-Mayoux, Martine, Roussel, and F, Lala

Subjects
Male, Battery (electricity), medicine.medical_specialty, Population, Trail Making Test, Neuropsychological Tests, Audiology, Executive Function, 03 medical and health sciences, 0302 clinical medicine, Alzheimer Disease, medicine, Humans, Cognitive Dysfunction, Psychiatry, education, Categorical variable, Aged, education.field_of_study, Models, Statistical, Receiver operating characteristic, business.industry, Reproducibility of Results, Stepwise regression, medicine.disease, 030227 psychiatry, Cognitive test, Psychiatry and Mental health, Clinical Psychology, Female, Geriatrics and Gerontology, Alzheimer's disease, business, Gerontology, 030217 neurology & neurosurgery
Abstract

The frequency of executive disorders in mild-to-moderate Alzheimer disease (AD) has been demonstrated by the application of a comprehensive battery. The present study analyzed data from 2 recent multicenter studies based on the same executive battery. The objective was to derive a shortened battery by using the GREFEX population as a training dataset and by cross-validating the results in the REFLEX population. A total of 102 AD patients of the GREFEX study (MMSE=23.2±2.9) and 72 patients of the REFLEX study (MMSE=20.8±3.5) were included. Tests were selected and receiver operating characteristic curves were generated relative to the performance of 780 controls from the GREFEX study. Stepwise logistic regression identified 3 cognitive tests (Six Elements Task, categorical fluency and Trail Making Test B error) and behavioral disorders globally referred as global hypoactivity (P=0.0001, all). This shortened battery was as accurate as the entire GREFEX battery in diagnosing dysexecutive disorders in both training group and the validation group. Bootstrap procedure confirmed the stability of AUC. A shortened battery based on 3 cognitive tests and 3 behavioral domains provides a high diagnosis accuracy of executive disorders in mild-to-moderate AD.

Published
2016
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35. Neuroimaging Determinants of Poststroke Cognitive Performance

Author

Laurent, Puy, Mélanie, Barbay, Martine, Roussel, Sandrine, Canaple, Chantal, Lamy, Audrey, Arnoux, Claire, Leclercq, Jean-Louis, Mas, Sophie, Tasseel-Ponche, Jean-Marc, Constans, and Olivier, Godefroy

Subjects
Male, Brain, Neuroimaging, Middle Aged, Neuropsychological Tests, Magnetic Resonance Imaging, Severity of Illness Index, White Matter, Temporal Lobe, Frontal Lobe, Stroke, Cognition, Thalamus, Cerebral Small Vessel Diseases, Humans, Female, Atrophy, Aged
Abstract

Background and Purpose- We aimed to define the neuroimaging determinants of poststroke cognitive performance and their relative contributions among a spectrum of magnetic resonance imaging markers, including lesion burden and strategic locations. Methods- We prospectively included patients with stroke from the GRECogVASC study (Groupe de Réflexion pour l'Évaluation Cognitive Vasculaire) who underwent 3-T magnetic resonance imaging and a comprehensive standardized battery of neuropsychological tests 6 months after the index event. An optimized global cognitive score and neuroimaging markers, including stroke characteristics, cerebral atrophy markers, and small vessel diseases markers, were assessed. Location of strategic strokes was determined using a specifically designed method taking into account stroke size and cerebral atrophy. A stepwise multivariable linear regression model was used to identify magnetic resonance imaging determinants of cognitive performance. Results- Data were available for 356 patients (mean age: 63.67±10.6 years; 326 [91.6%] of the patients had experienced an ischemic stroke). Six months poststroke, 50.8% of patients presented with a neurocognitive disorder. Strategic strokes (right corticospinal tract, left antero-middle thalamus, left arcuate fasciculus, left middle frontal gyrus, and left postero-inferior cerebellum; R

Published
2018

36. Differentiating between Alzheimer's Disease and Vascular Cognitive Impairment: Is the 'Memory Versus Executive Function' Contrast Still Relevant?

Author

Daniela, Andriuta, Martine, Roussel, Mélanie, Barbay, Sandrine, Despretz-Wannepain, Olivier, Godefroy, and Eric, Theunssens

Subjects
Cohort Studies, Diagnosis, Differential, Cerebrovascular Disorders, Executive Function, Memory Disorders, Alzheimer Disease, Memory, Humans, Cognitive Dysfunction, Neuropsychological Tests, Severity of Illness Index, Biomarkers
Abstract

The contrast between memory versus executive function impairments is commonly used to differentiate between neurocognitive disorders (NCDs) due to Alzheimer's disease (AD) and vascular cognitive impairment (VCI). We reconsidered this question because of the current use of AD biomarkers and the recent revision of the criteria for AD, VCI, and dysexecutive syndrome.To establish and compare the neuropsychological profiles in AD (i.e., with positive CSF biomarkers) and in VCI.We included 62 patients with mild or major NCDs due to pure AD (with positive CSF biomarker assays), and 174 patients (from the GRECogVASC cohort) with pure VCI. The neuropsychological profiles were compared after stratification for disease severity (mild or major NCD). We defined a memory-executive function index (the mean z score for the third free recall and the delayed free recall in the Free and Cued Selective Reminding Test minus the mean z score for category fluency and the completion time in the Trail Making Test part B) and determined its diagnostic accuracy.Compared with VCI patients, patients with AD had significantly greater memory impairments (p = 0.001). Executive function was impaired to a similar extent in the two groups (p = 0.11). Behavioral executive disorders were more prominent in the AD group (p = 0.001). Although the two groups differed significant with regard to the memory-executive function index (p 0.001), the latter's diagnostic accuracy was only moderate (sensitivity: 63%, specificity: 87%).Although the contrast between memory and executive function impairments was supported at the group level it does not reliably discriminate between AD and VCI at the individual level.

Published
2018

37. THER-28. A CK1α ACTIVATOR PENETRATES THE BRAIN, AND SHOWS EFFICACY AGAINST DRUG-RESISTANT METASTATIC MEDULLOBLASTOMA

Author

Jezabel Rodriguez, Bin Li, Jun Long, Chen Shen, Fan Yang, Darren Orthon, Sara Collins, Noriyuki Kasahara, Nagi Ayad, Heather McCrea, Martine Roussel, William Weiss, Anthony Capobianco, and David Robbins

Subjects
Cancer Research, animal structures, Oncology, embryonic structures, Neurology (clinical), Translational Therapeutics
Abstract

Although most children with medulloblastoma (MB) are cured of their disease, SONIC HEDGEHOG (SHH) subgroup MB driven by TRP53 mutations is essentially lethal. Casein Kinase 1α (CK1α) phosphorylates and destabilizes GLI transcription factors, thereby inhibiting the key effectors of SHH signaling. We therefore tested a second-generation CK1α activator against, TRP53 mutant, MYCN amplified MB. Our novel CK1α activator inhibited SHH activity in vitro, acting downstream of the vismodegib target SMOOTHENED (SMO), and reduced the viability of sphere cultures derived from SHH MB. SSTC3 accumulated in the brain, inhibited growth of SHH MB tumors, and blocked metastases in a genetically-engineered vismodegib-resistant mouse model of SHH MB. Importantly, SSTC3 attenuated growth and metastasis of orthotopic patient-derived TRP53 mutant, MYCN amplified, SHH subgroup MB xenografts, increasing overall survival. Thus, a CK1α agonist penetrates into the brain, and shows efficacy against metastatic TRP53 mutant MB, which are resistant to existing therapies including the SMO inhibitors currently being evaluated clinically.

Published
2019
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38. Optical design options for hypertelescopes and prototype testing

Author

Wassila Dali-Ali, Thomas Houllier, Yves Bresson, Jordi Pijoan, Bernard Tregon, Rémi Prudhomme, Bruno Lacamp, Arun Surya, Paul D. Nuñez, David Vernet, Erick Bondoux, S. Bosio, Rijuparna Chakraborty, Antoine Labeyrie, Thierry Lépine, Patrick Rabou, Martine Roussel, Pierre Riaud, André Rondi, Denis Mourard, Jerome Maillot, Observatoire de la Côte d'Azur (OCA), Centre National de la Recherche Scientifique (CNRS), Laboratoire Ondes et Matière d'Aquitaine (LOMA), Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), Observatoire des Sciences de l'Univers de Grenoble (OSUG), Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP)-Institut national de recherche en sciences et technologies pour l'environnement et l'agriculture (IRSTEA)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Collège de France (CDF), Collège de France (CdF), Institut d'Optique Graduate School (IOGS), Malbet, F. and CreechEakman, M. J. and Tuthill, P. G., Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS), Observatoire des Sciences de l'Univers de Grenoble (OSUG ), Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Institut national des sciences de l'Univers (INSU - CNRS)-Institut national de recherche en sciences et technologies pour l'environnement et l'agriculture (IRSTEA)-Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Laboratoire d'interférométrie stellaire et exo-planétaire (LISEP), and Centre National de la Recherche Scientifique (CNRS)-Collège de France (CdF (institution))

Subjects
[PHYS.ASTR.IM]Physics [physics]/Astrophysics [astro-ph]/Instrumentation and Methods for Astrophysic [astro-ph.IM], Active galactic nucleus, High resolution, Tracking (particle physics), Space telescopes, 01 natural sciences, Optics, 0103 physical sciences, 010303 astronomy & astrophysics, Physics, [PHYS.PHYS.PHYS-OPTICS]Physics [physics]/Physics [physics]/Optics [physics.optics], [SDU.ASTR]Sciences of the Universe [physics]/Astrophysics [astro-ph], 010308 nuclear & particles physics, business.industry, Testbed, Astrophysics::Instrumentation and Methods for Astrophysics, Optical design, Cameras, Prototyping, Stars, Mirrors, Interferometry, Above ground, Millimeter, business, Beam (structure), Telescopes
Abstract

International audience; Hypertelescopes are large optical interferometric arrays, employing many small mirrors and a miniature pupildensifier before the focal camera, expected to produce direct images of celestial sources at high resolution. Their peculiar imaging properties, initially explored through analytical derivations, had been verified with simulations before testing a full-size testbed instrument. We describe several architectures and optical design solutions and present recent progress made on the Ubaye hypertelescope experiment. Arecibo-like versions with a fixed spherical primary meta-mirror, or an active aspheric one, have a suspended focal beam combiner equipped for pupil-drift accommodation, with a field-mosaic arrangement for observing multiple sources such as exoplanetary systems, globular clusters or active galactic nuclei. We have developed a cable suspension and drive system with tracking accuracy reaching a millimeter at 100m above ground.

Published
2016
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41. Characteristics of Alzheimer's Disease Patients with Severe Executive Disorders

Author

Olivier, Godefroy, Serge, Bakchine, Marc, Verny, Jean-Philippe, Delabrousse-Mayoux, Martine, Roussel, Jean-Jacques, Pere, and M, Guichardon

Subjects
Male, Neuropsychological Tests, Severity of Illness Index, Executive Function, Treatment Outcome, Caregivers, Cost of Illness, Alzheimer Disease, Activities of Daily Living, Prevalence, Humans, Female, Mental Status Schedule, Aged
Abstract

Executive dysfunctions in Alzheimer's disease (AD) have been assessed using variable batteries and/or in selected populations.The primary objective of this observational study was to determine the prevalence and severity of executive dysfunction in AD patients using a previously validated battery. The secondary objective was to determine the characteristics including treatment outcomes of AD patients with severe executive dysfunction.The study included AD patients with mild-to-moderate dementia aged 60 or over, consulting in various clinical settings including memory clinics and requiring the introduction of an antidementia drug. Executive dysfunction was examined using a validated, shortened executive battery.381 patients were included. Executive dysfunctions were observed in 88.2% of the patients (95% CI: 84.9-91.4) and were severe (defined as ≥2/3 impaired scores) in 80.4% (95% CI: 76.9-84.8). Global hypoactivity with apathy was more frequent (p = 0.0001) than impairment in executive function tests. The 308 patients with severe executive dysfunction were older (p = 0.003) and had more severe dementia (p = 0.0001). Similarly, in the subset of 257 patients with mild dementia, individuals with severe executive dysfunction were older (p = 0.003) and had more severe dementia. Global hypoactivity was independently associated with difficulties in IADL and a higher caregiver burden (p = 0.0001 for both). The severity of executive dysfunction did not significantly influence the patients' outcomes at 6 months.Executive dysfunction is a very common disorder in a representative population of patients with mild-to-moderate AD. It was independently correlated with impaired autonomy and increased caregiver burden but did not significantly influence treatment outcomes.

Published
2016

42. Motor and cognitive slowing in multiple sclerosis: An attentional deficit?

Author

Christine Bottin, Olivier Godefroy, Martine Roussel-Pieronne, and Soraya Stoquart-ElSankari

Subjects
Adult, Male, medicine.medical_specialty, Multiple Sclerosis, Accident prevention, Poison control, Motor Activity, Neuropsychological Tests, Audiology, Choice Behavior, Central nervous system disease, Cognition, Reaction Time, Humans, Medicine, Attention, In patient, business.industry, Multiple sclerosis, General Medicine, Middle Aged, medicine.disease, Surgery, Case-Control Studies, Divided attention, Visual Perception, Female, Neurology (clinical), business, Motor Deficit, Psychomotor Performance
Abstract

Action slowing is frequently observed in multiple sclerosis (MS) patients. Several factors may account for response slowing: motor, perceptual, cognitive deficits, global mental slowing. Our objective was to examine mechanisms accounting for action slowing in MS patients.Twenty MS patients, free of visual impairment and of upper limbs sensory-motor deficit underwent previously validated reaction time (RT) tests using visual stimuli. Three tasks were used: (1) motor tapping, (2) simple reaction time (SRT) in a simple and dual task condition, and (3) choice RT (CRT) with varying response probabilities. Results were compared to those of 20 healthy matched subjects.MS patients had: (1) lower motor tapping frequency (p=0.02); (2) SRT lengthening (p=0.001) related to a lower proportion of fast responses (p=0.001) indicating attentional deficit whereas perceptuomotor index was spared (p=0.5), without higher sensitivity to dual task (p=0.9); and (3) CRT lengthening (p=0.001) with spared decision time (p=0.7).This study showed that action slowing of MS patient is mainly related to (1) attentional deficit resulting in inability to maintain high level of rapid actions, and (2) subtle motor slowing even in patients without motor deficit on clinical examination, whereas (3) divided attention and decisional process are preserved.

Published
2010
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43. French adaptation of the vascular cognitive impairment harmonization standards: the GRECOG-VASC study

Author

Olivier, Godefroy, Claire, Leclercq, Martine, Roussel, Christine, Moroni, Véronique, Quaglino, Hélène, Beaunieux, Hervé, Tallia, Claudine, Nédélec-Ciceri, Camille, Bonnin, Catherine, Thomas-Anterion, Jérôme, Varvat, Tatiana, Aboulafia-Brakha, Frédéric, Assal, Mélanie, Planton, CHU Amiens-Picardie, Université de Caen Normandie (UNICAEN), and Normandie Université (NU)

Subjects
Gerontology, MEDLINE, Harmonization, Neuropsychological Tests, 03 medical and health sciences, Executive Function, 0302 clinical medicine, Clinical Protocols, Reaction Time, Medicine, Humans, Stroke/psychology, 030212 general & internal medicine, Cognitive impairment, Adaptation (computer science), ComputingMilieux_MISCELLANEOUS, Language, Cognition Disorders/diagnosis/etiology, [SDV.NEU.PC]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Psychology and behavior, business.industry, [SDV.MHEP.GEG]Life Sciences [q-bio]/Human health and pathology/Geriatry and gerontology, [SCCO.NEUR]Cognitive science/Neuroscience, ddc:616.8, Stroke, Neurology, [SCCO.PSYC]Cognitive science/Psychology, business, Cognition Disorders, 030217 neurology & neurosurgery
Abstract

International audience

Published
2012
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44. Functional consequences of a section of the anterior part of the body of the corpus callosum: evidence from an interhemispheric transcallosal approach

Author

Johann, Peltier, Martine, Roussel, Yasmina, Gerard, Maryse, Lassonde, Hervé, Deramond, Daniel, Le Gars, Daniel Le, Gars, Louis, De Beaumont, Louis De, Beaumont, and Olivier, Godefroy

Subjects
Adult, Male, medicine.medical_specialty, Audiology, Neuropsychological Tests, Corpus callosum, Verbal learning, Procedural memory, Functional Laterality, Developmental psychology, Corpus Callosum, Executive Function, Visual memory, medicine, Reaction Time, Verbal fluency test, Humans, Retrospective Studies, Analysis of Variance, medicine.diagnostic_test, Neuropsychology, Neuropsychological test, Middle Aged, Verbal Learning, Executive functions, Magnetic Resonance Imaging, Neurology, Female, Neurology (clinical), Psychology, Cognition Disorders, Mental Status Schedule, Cerebral Ventricle Neoplasms
Abstract

The aim of this study was to determine the neuropsychological consequences of a middle interhemispheric approach for the removal of tumors of the third or lateral ventricles. A retrospective analysis of eight callosotomized patients for ventricular tumors (three males/five females; mean age: 48.7 ± 11.2 years; education level: 11.9 ± 2.9 years) and eight healthy subjects was performed. An extensive neuropsychological test battery was used to evaluate global intellectual efficiency, memory capacities, executive functions, and interhemispheric transfer of a procedural learning task (serial reaction time task/SRTT). Neuropsychological results showed that: (1) five of eight patients operated through a middle transcallosal approach had disturbances of verbal or visual memory; (2) three of eight patients displayed a dysexecutive cognitive syndrome(two of eight of whom presenting with a deficit of verbal fluency); (3) two of eight patients presented a dysexecutive behavior syndrome; and (4) with regard to the SRTT, although all participants learned the task, in contrast to controls, the callosotomized patients showed an increase in reaction times and an absence of interhemispheric transfer of learning from one hand to the other. The transcallosal approach transects a large number of callosal fibers. This damage accounts for the deficits of memory, the dysexecutive cognitive and behavioral syndrome, and disturbances in interhemispheric transfer of learning.

Published
2011

45. Dysexecutive syndrome: diagnostic criteria and validation study

Author

Olivier, Godefroy, Philippe, Azouvi, Philippe, Robert, Martine, Roussel, Didier, LeGall, Thierry, Meulemans, and P, Vuadens

Subjects
Adult, Male, medicine.medical_specialty, Adolescent, Neuropsychological Tests, Personality Disorders, Executive Function, Young Adult, medicine, Humans, Psychiatry, Aged, Dysexecutive syndrome, Aged, 80 and over, Cognitive disorder, Cognition, Odds ratio, Middle Aged, medicine.disease, Executive functions, Personality disorders, Cognitive test, Neurology, Personal Autonomy, Female, Neurology (clinical), Alzheimer's disease, Psychology, Cognition Disorders, Clinical psychology
Abstract

Objective: Disorders of executive functions are among the most frequent cognitive deficits, but they remain poorly defined and are subject to heterogeneous assessment. To address this major issue, the Groupe de Reflexion sur l'Evaluation des Fonctions Executives (GREFEX) group has proposed criteria for behavioral and cognitive dysexecutive syndromes and has designed a battery including a specific heteroquestionnaire and 7 cognitive tests. We investigated the frequency of behavioral and cognitive dysexecutive disorders in patients suffering from various diseases and the association of these disorders with loss of autonomy. Methods: A total of 461 patients aged between 16 and 90 years with severe traumatic brain injury, stroke, mild cognitive impairment, Alzheimer disease, multiple sclerosis, and Parkinson disease were recruited into this prospective cohort study by 21 centers between September 2003 and June 2006. Behavioral and cognitive dysexecutive disorders were examined using the GREFEX battery. Results: A dysexecutive syndrome was observed in 60% of patients, concerning both behavioral and cognitive domains in 26% and dissociated in 34%. All behavioral and cognitive dysexecutive disorders discriminated (p ¼ 0.001, all) patients from controls. The pattern of cognitive syndrome differed (p ¼ 0.0001) according to the disease. Finally, behavioral (odds ratio (OR), 4.6; 95% confidence interval (CI), 2. 3-9.1; p ¼ 0.0001) and cognitive (OR, 3.36; 95% CI, 1.7-6.6; p ¼ 0.001) dysexecutive syndromes and Mini Mental State Examination score (OR, 0.79; 95% CI, 0.68-0.91; p ¼ 0.002) were independent predictors of loss of autonomy. Interpretation: This study provided criteria of dysexecutive syndrome and showed that both behavioral and cognitive syndromes contribute to loss of autonomy. Profiles vary across patients and diseases, and therefore systematic assessment of behavioral and cognitive disorders in reference to diagnostic criteria is needed. ANN NEUROL 2010;68:855-864

Published
2011

46. MECHANISMS OF PSYCHOMOTOR SLOWING IN SCHIZOPHRENIA

Author

MONESTES, JEAN-LOUIS, Martine, Roussel, Louis, Monestes Jean, Gewnolé, Loas, Virginie, Tourbier, Valérie, Yon, Cyril, Méribault, Godefroy, Olivier, Laboratoire Inter-universitaire de Psychologie : Personnalité, Cognition, Changement Social (LIP-PC2S), and Université Pierre Mendès France - Grenoble 2 (UPMF)-Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])

Subjects
Psychomotor learning, medicine.medical_specialty, business.industry, Schizophrenia (object-oriented programming), [SHS.PSY]Humanities and Social Sciences/Psychology, 030227 psychiatry, 03 medical and health sciences, Psychiatry and Mental health, 0302 clinical medicine, Medicine, business, Psychiatry, 030217 neurology & neurosurgery, Biological Psychiatry, ComputingMilieux_MISCELLANEOUS
Abstract

International audience

Published
2010
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48. TMOD-13GENETICALLY ENGINEERED MOUSE MODELS OF CHOROID PLEXUS TUMORS

Author

Jun Wang, Diana Merino, Brian Murphy, Girish Dhall, Erin Kiehna, Alexander Judkins, Charles Eberhart, Scott Vandenberg, David Ellison, David Malkin, Richard Gilbertson, Martine Roussel, and Robert Wechsler-Reya

Subjects
Cancer Research, Oncology, Neurology (clinical), Abstracts from the 20th Annual Scientific Meeting of the Society for Neuro-Oncology
Published
2015
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49. « AMIENSCOG » : outil informatique à l’interprétation automatique des scores neuropsychologiques et l’exportation vers une base de données

Author

Martine Roussel, Sandrine Wannepain, Annie Routier, Virginie Tourbier, Olivier Godefroy, and null Dsio

Subjects
Neurology, Neurology (clinical)
Abstract

Introduction La dichotomisation manuelle des performances (normal vs pathologique), en fonction des criteres âge et de niveau socioculturel, d’un bilan neuropsychologique est couteuse en temps au regard des nombreux scores. Objectifs L’objectif du travail est de presenter un outil d’assistance informatise, « AMIENSCOG » et de montrer son interet lors de l’evaluation neuropsychologique et en particulier le gain de temps obtenu. Methodes L’interet de cet outil sera illustre en montrant qu’il permet de : – realiser automatiquement la dichotomisation des scores aux tests selon les donnees normatives ; – sauvegarder les donnees, en permettant de les consulter ou les modifier ; – d’exporter les scores et leur interpretation dichotomisee vers une base de donnees. Des analyses de comparaisons des temps de saisie et d’interpretation des scores aux bilans realises manuellement et avec « AMIENSCOG » ont ete effectuees. Resultats Durant la periode de 2008 a 2013, 4473 bilans ont ete effectues totalisant plus de 122000 scores qui ont ete rentres dans « AMIENSCOG » et automatiquement interpretes en normal vs pathologique. Les resultats de la comparaison entre les temps de saisie et l’interpretation des scores, montrent des temps pour « AMIENSCOG » (m = 284 ± 48 s) inferieurs ( p = 0,001) a ceux des bilans realises manuellement ( m = 284 ± 128 s). Discussion Ces resultats montrent que « AMIENSCOG » offre un gain de temps significatif sur la saisie et l’interpretation des scores mais aussi grâce a l’export automatique sur Excel. Il facilite et fiabilise le recueil et l’interpretation des scores automatiquement dichotomises en normal vs pathologique, en produisant une version papier synthetique regroupant les donnees cliniques et les scores en fonction des principales fonctions cognitive. Conclusion « AMIENSCOG » offre une aide precieuse au clinicien et chercheur en permettant un acces plus facile, plus rapide et plus fiable aux donnees neuropsychologiques disponibles avec un export possible vers une base de donnee. Informations complementaires Demonstration en direct possible du logiciel.

Published
2015
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50. Cytokines and sodium induce protein kinase A-dependent cell-surface Na,K-ATPase recruitment via dissociation of NF-kappaB/IkappaB/protein kinase A catalytic subunit complex in collecting duct principal cells

Author

Eric Féraille, Pierre-Yves Martin, David Mordasini, Eric Ogier-Denis, Maria Capovilla, Martine Roussel, Alain Vandewalle, Manlio Vinciguerra, Udo Hasler, Dulbecco Telethon Institute, Telethon Foundation, Centre de recherche biomédicale Bichat-Beaujon (CRB3), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre d'Etudes et d'Expertise sur les Risques, l'Environnement, la Mobilité et l'Aménagement - Direction Ouest (Cerema Direction Ouest), and Centre d'Etudes et d'Expertise sur les Risques, l'Environnement, la Mobilité et l'Aménagement (Cerema)

Subjects
Lipopolysaccharides, Protein subunit, [SDV.BC.BC]Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], Cell Line, Mice, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, NF-KappaB Inhibitor alpha, Animals, Kidney Tubules, Collecting, Na+/K+-ATPase, Protein kinase A, 030304 developmental biology, G alpha subunit, 0303 health sciences, Tumor Necrosis Factor-alpha, Kinase, Cell Membrane, Sodium, NF-kappa B, NF-κB, General Medicine, Cyclic AMP-Dependent Protein Kinases, I-kappa B Kinase, Cell biology, chemistry, Biochemistry, Nephrology, 030220 oncology & carcinogenesis, Cytokines, I-kappa B Proteins, Sodium-Potassium-Exchanging ATPase, Signal transduction, Intracellular
Abstract

International audience; Collecting duct (CD) principal cells are exposed to large physiologic variations of apical Na+ influx as a result of variations of Na(+) intake and extrarenal losses. It was shown previously that increasing intracellular [Na+] induces recruitment of Na,K-ATPase to the cell surface in a protein kinase A (PKA)-dependent manner in both native and cultured renal CD principal cells. As described previously in response to cytokines in nonrenal cells, PKA activation in response to increased intracellular [Na+] was independent of cAMP and required proteasomal activity. With the use of cultured mpkCCD(cL4) cells as a model of CD principal cells, whether cytokines and increased intracellular [Na+] share a common signaling pathway leading to cell-surface Na,K-ATPase recruitment was investigated. Results showed that two potent inducers of NF-kappaB, LPS and TNF-alpha, enhance Na+ transport and induce cell-surface Na,K-ATPase recruitment in mpkCCD(cL4) cells via cAMP-independent PKA activation. In addition, increased intracellular [Na+] after selective plasma membrane permeabilization by a low concentration of the Na+ ionophore amphotericin B (1 microg/ml) induced dissociation of the PKA catalytic subunit from p65-NF-kappaB and IkappaBalpha. Moreover, inhibitors of NF-kappaB/IkappaB dissociation prevented both Na+-dependent stimulation of PKA activity and cell-surface Na,K-ATPase recruitment. Altogether, these results revealed the presence of a novel Na+-dependent intracellular signaling pathway leading to Na,K-ATPase cell-surface recruitment via dissociation of the PKA catalytic subunit from a macromolecular complex that contains NF-kappaB and IkappaBalpha in CD epithelial cells.

Published
2005
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