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1. Association between superior longitudinal fasciculus, motor recovery, and motor outcome after stroke: a cohort study

Author

Thomas Jacquemont, Romain Valabregue, Lina Daghsen, Eric Moulton, Chiara Zavanone, Jean Charles Lamy, and Charlotte Rosso

Subjects
stroke, motor recovery, motor outcome, superior longitudinal fasciculus, fractional anisotropy, diffusion tensor, Neurology. Diseases of the nervous system, RC346-429
Abstract

IntroductionParieto-frontal interactions are mediated by the superior longitudinal fasciculus (SLF) and are crucial to integrate visuomotor information and mediate fine motor control. In this study, we aimed to characterize the relation of white matter integrity of both parts of the SLF (SLF I and SLF II) to both motor outcome and recovery and its evolution over time in stroke patients with upper limb motor deficits.Materials and methodsFractional anisotropy (FA) values over the SLF I, SLF II, and corticospinal tract (CST) and upper limb motor performance evaluated by both the upper limb Fugl-Meyer Assessment score and maximum grip strength were measured for 16 patients at 3 weeks, 6 weeks, and 12 weeks poststroke. FA changes were assessed over time using repeated-measures Friedman ANOVA, and correlations between motor recovery, motor outcome at 12 weeks, and FA values in the CST, SLF I, and SLF II at 3 weeks were performed using Spearman's rank-order correlation.ResultsFA values in the affected hemisphere's SLF I and SLF II at 3 weeks correlated with motor recovery at 12 weeks when assessed by the Fugl-Meyer Assessment for upper limb extremity (rho: 0.502, p: 0.04 and rho: 0.510, p: 0.04, respectively) but not when assessed by grip strength. FA values in the SLF I and SLF II were not correlated with motor outcomes. FA values in the SLF II in the affected hemisphere changed significantly over time (p: 0.016).ConclusionBoth SLF I and SLF II appeared to participate in poststroke motor recovery of complex movements but not in the motor outcome. These results argue that visually/spatially oriented motor tasks as well as more complex motor tasks using parietal associative areas should be used for poststroke rehabilitation strategies.

Published
2023
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2. The sooner the better: clinical and neural correlates of impulsive choice in Tourette disorder

Author

Cyril Atkinson-Clement, Astrid de Liege, Yanica Klein, Benoit Beranger, Romain Valabregue, Cecile Delorme, Emmanuel Roze, Emilio Fernandez-Egea, Andreas Hartmann, Trevor W. Robbins, and Yulia Worbe

Subjects
Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571
Abstract

Abstract Reward sensitivity has been suggested as one of the central pathophysiological mechanisms in Tourette disorder. However, the subjective valuation of a reward by introduction of delay has received little attention in Tourette disorder, even though it has been suggested as a trans-diagnostic feature of numerous neuropsychiatric disorders. We aimed to assess delay discounting in Tourette disorder and to identify its brain functional correlates. We evaluated delayed discounting and its brain functional correlates in a large group of 54 Tourette disorder patients and 31 healthy controls using a data-driven approach. We identified a subgroup of 29 patients with steeper reward discounting, characterised by a higher burden of impulse-control disorders and a higher level of general impulsivity compared to patients with normal behavioural performance or to controls. Reward discounting was underpinned by resting-state activity of a network comprising the orbito-frontal, cingulate, pre-supplementary motor area, temporal and insular cortices, as well as ventral striatum and hippocampus. Within this network, (i) lower connectivity of pre-supplementary motor area with ventral striatum predicted a higher impulsivity and a steeper reward discounting and (ii) a greater connectivity of pre-supplementary motor area with anterior insular cortex predicted steeper reward discounting and more severe tics. Overall, our results highlight the heterogeneity of the delayed reward processing in Tourette disorder, with steeper reward discounting being a marker of burden in impulsivity and impulse control disorders, and the pre-supplementary motor area being a hub region for the delay discounting, impulsivity and tic severity.

Published
2021
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3. Cerebellar and basal ganglia structural connections in humans: Effect of aging and relation with memory and learning

Author

Vineeth Radhakrishnan, Cecile Gallea, Romain Valabregue, Syam Krishnan, Chandrasekharan Kesavadas, Bejoy Thomas, Praveen James, Ramshekhar Menon, and Asha Kishore

Subjects
aging, memory, learning, cerebellum, basal ganglia, tractography, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571
Abstract

IntroductionThe cerebellum and basal ganglia were initially considered anatomically distinct regions, each connected via thalamic relays which project to the same cerebral cortical targets, such as the motor cortex. In the last two decades, transneuronal viral transport studies in non-human primates showed bidirectional connections between the cerebellum and basal ganglia at the subcortical level, without involving the cerebral cortical motor areas. These findings have significant implications for our understanding of neurodevelopmental and neurodegenerative diseases. While these subcortical connections were established in smaller studies on humans, their evolution with natural aging is less understood.MethodsIn this study, we validated and expanded the previous findings of the structural connectivity within the cerebellum-basal ganglia subcortical network, in a larger dataset of 64 subjects, across different age ranges. Tractography and fixel-based analysis were performed on the 3 T diffusion-weighted dataset using Mrtrix3 software, considering fiber density and cross-section as indicators of axonal integrity. Tractography of the well-established cerebello-thalamo-cortical tract was conducted as a control. We tested the relationship between the structural white matter integrity of these connections with aging and with the performance in different domains of Addenbrooke’s Cognitive Examination.ResultsTractography analysis isolated connections from the dentate nucleus to the contralateral putamen via the thalamus, and reciprocal tracts from the subthalamic nucleus to the contralateral cerebellar cortex via the pontine nuclei. Control tracts of cerebello-thalamo-cortical tracts were also isolated, including associative cerebello-prefrontal tracts. A negative linear relationship was found between the fiber density of both the ascending and descending cerebellum-basal ganglia tracts and age. Considering the cognitive assessments, the fiber density values of cerebello-thalamo-putaminal tracts correlated with the registration/learning domain scores. In addition, the fiber density values of cerebello-frontal and subthalamo-cerebellar (Crus II) tracts correlated with the cognitive assessment scores from the memory domain.ConclusionWe validated the structural connectivity within the cerebellum-basal ganglia reciprocal network, in a larger dataset of human subjects, across wider age range. The structural features of the subcortical cerebello-basal ganglia tracts in human subjects display age-related neurodegeneration. Individual morphological variability of cerebellar tracts to the striatum and prefrontal cortex was associated with different cognitive functions, suggesting a functional contribution of cerebellar tracts to cognitive decline with aging. This study offers new perspectives to consider the functional role of these pathways in motor learning and the pathophysiology of movement disorders involving the cerebellum and striatum.

Published
2023
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4. Multiparametric in vivo analyses of the brain and spine identify structural and metabolic biomarkers in men with adrenomyeloneuropathy

Author

Isaac M. Adanyeguh, Xiaofang Lou, Eavan McGovern, Marie-Pierre Luton, Magali Barbier, Elise Yazbeck, Romain Valabregue, Dinesh Deelchand, Pierre-Gilles Henry, and Fanny Mochel

Subjects
Adrenomyeloneuropathy, Spinal cord imaging, Metabolite cycling, Fixel-based analysis, Imaging biomarkers, Spinal cord toolbox, Computer applications to medicine. Medical informatics, R858-859.7, Neurology. Diseases of the nervous system, RC346-429
Abstract

Objective: Progressive myelopathy causes severe handicap in men with adrenomyeloneuropathy (AMN), an X-linked disorder due to ABCD1 pathogenic variants. At present, treatments are symptomatic but disease-modifying therapies are under evaluation. Given the small effect size of clinical scales in AMN, biomarkers with higher effect size are needed. Here we used high-resolution magnetic resonance techniques to identify non-invasive in vivo biomarkers of the brain and spine with high effect sizes. Methods: We performed a multiparametric imaging and spectroscopy study in 23 male patients with AMN (age: 44 ± 11) and 23 male controls (age: 43 ± 11) of similar age and body-mass index. We combined (i) macrostructural analyses of the spine, using cross-sectional area (CSA) and magnetization transfer ratio (MTR), (ii) microstructural analyses of the spine and the brain, using diffusion tensor and the newly developed fixel-based analysis, and (iii) advanced metabolic analyses of the spine using metabolite cycling coupled to a semi-LASER sequences. Results: Macrostructural alterations (decrease in CSA and MTR) were observed in patients at all spinal cord levels studied (C1-T2 for CSA and C1-C5 for MTR) (p

Published
2021
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5. Iron Imaging as a Diagnostic Tool for Parkinson's Disease: A Systematic Review and Meta-Analysis

Author

Nadya Pyatigorskaya, Clara B. Sanz-Morère, Rahul Gaurav, Emma Biondetti, Romain Valabregue, Mathieu Santin, Lydia Yahia-Cherif, and Stéphane Lehéricy

Subjects
substantia nigra, iron, Parkinson's disease, QSM, SWI, R2*, Neurology. Diseases of the nervous system, RC346-429
Abstract

Background: Parkinson's disease (PD) is a progressive neurodegenerative disease whose main neuropathological feature is the loss of dopaminergic neurons of the substantia nigra (SN). There is also an increase in iron content in the SN in postmortem and imaging studies using iron-sensitive MRI techniques. However, MRI results are variable across studies.Objectives: We performed a systematic meta-analysis of SN iron imaging studies in PD to better understand the role of iron-sensitive MRI quantification to distinguish patients from healthy controls. We also studied the factors that may influence iron quantification and analyzed the correlations between demographic and clinical data and iron load.Methods: We searched PubMed and ScienceDirect databases (from January 1994 to December 2019) for studies that analyzed iron load in the SN of PD patients using T2*, R2*, susceptibility weighting imaging (SWI), or quantitative susceptibility mapping (QSM) and compared the values with healthy controls. Details for each study regarding participants, imaging methods, and results were extracted. The effect size and confidence interval (CI) of 95% were calculated for each study as well as the pooled weighted effect size for each marker over studies. Hence, the correlations between technical and clinical metrics with iron load were analyzed.Results: Forty-six articles fulfilled the inclusion criteria including 27 for T2*/R2* measures, 10 for SWI, and 17 for QSM (3,135 patients and 1,675 controls). Eight of the articles analyzed both R2* and QSM. A notable effect size was found in the SN in PD for R2* increase (effect size: 0.84, 95% CI: 0.60 to 1.08), for SWI measurements (1.14, 95% CI: 0.54 to 1.73), and for QSM increase (1.13, 95% CI: 0.86 to 1.39). Correlations between imaging measures and Unified Parkinson's Disease Rating Scale (UPDRS) scores were mostly observed for QSM.Conclusions: The consistent increase in MRI measures of iron content in PD across the literature using R2*, SWI, or QSM techniques confirmed that these measurements provided reliable markers of iron content in PD. Several of these measurements correlated with the severity of motor symptoms. Lastly, QSM appeared more robust and reproducible than R2* and more suited to multicenter studies.

Published
2020
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6. Autosomal dominant cerebellar ataxias: Imaging biomarkers with high effect sizes

Author

Isaac M. Adanyeguh, Vincent Perlbarg, Pierre-Gilles Henry, Daisy Rinaldi, Elodie Petit, Romain Valabregue, Alexis Brice, Alexandra Durr, and Fanny Mochel

Subjects
Computer applications to medicine. Medical informatics, R858-859.7, Neurology. Diseases of the nervous system, RC346-429
Abstract

Objective: As gene-based therapies may soon arise for patients with spinocerebellar ataxia (SCA), there is a critical need to identify biomarkers of disease progression with effect sizes greater than clinical scores, enabling trials with smaller sample sizes. Methods: We enrolled a unique cohort of patients with SCA1 (n = 15), SCA2 (n = 12), SCA3 (n = 20) and SCA7 (n = 10) and 24 healthy controls of similar age, sex and body mass index. We collected longitudinal clinical and imaging data at baseline and follow-up (mean interval of 24 months). We performed both manual and automated volumetric analyses. Diffusion tensor imaging (DTI) and a novel tractography method, called fixel-based analysis (FBA), were assessed at follow-up. Effect sizes were calculated for clinical scores and imaging parameters. Results: Clinical scores worsened as atrophy increased over time (p 1.2) compared to clinical scores (

Published
2018
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7. Interpretable deep learning for the prognosis of long-term functional outcome post-stroke using acute diffusion weighted imaging

Author

Eric Moulton, Romain Valabregue, Michel Piotin, Gaultier Marnat, Suzana Saleme, Bertrand Lapergue, Stephane Lehericy, Frederic Clarencon, and Charlotte Rosso

Subjects
Neurology, Neurology (clinical), Cardiology and Cardiovascular Medicine
Abstract

Advances in deep learning can be applied to acute stroke imaging to build powerful and explainable prediction models that could supersede traditionally used biomarkers. We aimed to evaluate the performance and interpretability of a deep learning model based on convolutional neural networks (CNN) in predicting long-term functional outcome with diffusion-weighted imaging (DWI) acquired at day 1 post-stroke. Ischemic stroke patients (n = 322) were included from the ASTER and INSULINFARCT trials as well as the Pitié-Salpêtrière registry. We trained a CNN to predict long-term functional outcome assessed at 3 months with the modified Rankin Scale (dichotomized as good [mRS ≤ 2] vs. poor [mRS ≥ 3]) and compared its performance to two logistic regression models using lesion volume and ASPECTS. The CNN contained an attention mechanism, which allowed to visualize the areas of the brain that drove prediction. The deep learning model yielded a significantly higher area under the curve (0.83 95%CI [0.78–0.87]) than lesion volume (0.78 [0.73–0.83]) and ASPECTS (0.77 [0.71–0.83]) (p

Published
2022
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8. Fixel‐Based Analysis Reveals Whole‐Brain White Matter Abnormalities in Cervical Dystonia

Author

Giuseppe A. Zito, Clément Tarrano, Salim Ouarab, Prasanthi Jegatheesan, Asya Ekmen, Benoît Béranger, Romain Valabregue, Cécile Hubsch, Sophie Sangla, Cécilia Bonnet, Cécile Delorme, Aurélie Méneret, Bertrand Degos, Floriane Bouquet, Marion Apoil Brissard, Marie Vidailhet, Dominique Hasboun, Yulia Worbe, Emmanuel Roze, and Cécile Gallea

Subjects
Neurology, Neurology (clinical)
Published
2023
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9. Cerebello-Motor Paired Associative Stimulation and Motor Recovery in Stroke: a Randomized, Sham-Controlled, Double-Blind Pilot Trial

Author

Charlotte Rosso, Eric Jr Moulton, Claire Kemlin, Sara Leder, Jean-Christophe Corvol, Sophien Mehdi, Mickael A. Obadia, Mickael Obadia, Marion Yger, Elena Meseguer, Vincent Perlbarg, Romain Valabregue, Serena Magno, Pavel Lindberg, Sabine Meunier, and Jean-Charles Lamy

Subjects
Stroke, Pharmacology, Treatment Outcome, Double-Blind Method, Cerebellum, Stroke Rehabilitation, Humans, Original Article, Pilot Projects, Pharmacology (medical), Neurology (clinical), Transcranial Magnetic Stimulation
Abstract

Cerebellum is a key structure for functional motor recovery after stroke. Enhancing the cerebello-motor pathway by paired associative stimulation (PAS) might improve upper limb function. Here, we conducted a randomized, double-blind, sham-controlled pilot trial investigating the efficacy of a 5-day treatment of cerebello-motor PAS coupled with physiotherapy for promoting upper limb motor function compared to sham stimulation. The secondary objectives were to determine in the active treated group (i) whether improvement of upper limb motor function was associated with changes in corticospinal excitability or changes in functional activity in the primary motor cortex and (ii) whether improvements were correlated to the structural integrity of the input and output pathways. To that purpose, hand dexterity and maximal grip strength were assessed along with TMS recordings and multimodal magnetic resonance imaging, before the first treatment, immediately after the last one and a month later. Twenty-seven patients were analyzed. Cerebello-motor PAS was effective compared to sham in improving hand dexterity (p: 0.04) but not grip strength. This improvement was associated with increased activation in the ipsilesional primary motor cortex (p: 0.04). Moreover, the inter-individual variability in clinical improvement was partly explained by the structural integrity of the afferent (p: 0.06) and efferent pathways (p: 0.02) engaged in this paired associative stimulation (i.e., cortico-spinal and dentato-thalamo-cortical tracts). In conclusion, cerebello-motor-paired associative stimulation combined with physiotherapy might be a promising approach to enhance upper limb motor function after stroke. Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT 02284087. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13311-022-01205-y.

Published
2022
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10. Multivariate prediction of functional outcome using lesion topography characterized by acute diffusion tensor imaging

Author

Eric Moulton, Romain Valabregue, Stéphane Lehéricy, Yves Samson, and Charlotte Rosso

Subjects
Computer applications to medicine. Medical informatics, R858-859.7, Neurology. Diseases of the nervous system, RC346-429
Abstract

The relationship between stroke topography and functional outcome has largely been studied with binary manual lesion segmentations. However, stroke topography may be better characterized by continuous variables capable of reflecting the severity of ischemia, which may be more pertinent for long-term outcome. Diffusion Tensor Imaging (DTI) constitutes a powerful means of quantifying the degree of acute ischemia and its potential relation to functional outcome. Our aim was to investigate whether using more clinically pertinent imaging parameters with powerful machine learning techniques could improve prediction models and thus provide valuable insight on critical brain areas important for long-term outcome. Eighty-seven thrombolyzed patients underwent a DTI sequence at 24 h post-stroke. Functional outcome was evaluated at 3 months post-stroke with the modified Rankin Score and was dichotomized into good (mRS ≤ 2) and poor (mRS > 2) outcome. We used support vector machines (SVM) to classify patients into good vs. poor outcome and evaluate the accuracy of different models built with fractional anisotropy, mean diffusivity, axial diffusivity, radial diffusivity asymmetry maps, and lesion segmentations in combination with lesion volume, age, recanalization status, and thrombectomy treatment. SVM classifiers built with axial diffusivity maps yielded the best accuracy of all imaging parameters (median [IQR] accuracy = 82.8 [79.3–86.2]%), compared to that of lesion segmentations (76.7 [73.3–82.8]%) when predicting 3-month functional outcome. The analysis revealed a strong contribution of clinical variables, notably – in descending order – lesion volume, thrombectomy treatment, and recanalization status, in addition to the deep white matter at the crossroads of major white matter tracts, represented by brain regions where model weights were highest. Axial diffusivity is a more appropriate imaging marker to characterize stroke topography for predicting long-term outcome than binary lesion segmentations. Keywords: Acute stroke, Prediction, Prognosis, Functional outcome, Diffusion tensor imaging

Published
2019
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11. The Influence of Preprocessing Steps on Graph Theory Measures Derived from Resting State fMRI

Author

Fatma Gargouri, Fathi Kallel, Sebastien Delphine, Ahmed Ben Hamida, Stéphane Lehéricy, and Romain Valabregue

Subjects
graph theory, preprocessing, resting-state fMRI, control quality, tCompCor, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571
Abstract

Resting state functional MRI (rs-fMRI) is an imaging technique that allows the spontaneous activity of the brain to be measured. Measures of functional connectivity highly depend on the quality of the BOLD signal data processing. In this study, our aim was to study the influence of preprocessing steps and their order of application on small-world topology and their efficiency in resting state fMRI data analysis using graph theory. We applied the most standard preprocessing steps: slice-timing, realign, smoothing, filtering, and the tCompCor method. In particular, we were interested in how preprocessing can retain the small-world economic properties and how to maximize the local and global efficiency of a network while minimizing the cost. Tests that we conducted in 54 healthy subjects showed that the choice and ordering of preprocessing steps impacted the graph measures. We found that the csr (where we applied realignment, smoothing, and tCompCor as a final step) and the scr (where we applied realignment, tCompCor and smoothing as a final step) strategies had the highest mean values of global efficiency (eg). Furthermore, we found that the fscr strategy (where we applied realignment, tCompCor, smoothing, and filtering as a final step), had the highest mean local efficiency (el) values. These results confirm that the graph theory measures of functional connectivity depend on the ordering of the processing steps, with the best results being obtained using smoothing and tCompCor as the final steps for global efficiency with additional filtering for local efficiency.

Published
2018
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12. Cerebello-Cortical Differences in Effective Connectivity of the Dominant and Non-dominant Hand during a Visuomotor Paradigm of Grip Force Control

Author

Eric Moulton, Cécile Galléa, Claire Kemlin, Romain Valabregue, Marc A. Maier, Pavel Lindberg, and Charlotte Rosso

Subjects
dynamic causal modeling, fMRI, handedness, cerebellum, visuomotor, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571
Abstract

Structural and functional differences are known to exist within the cortical sensorimotor networks with respect to the dominant vs. non-dominant hand. Similarly, the cerebellum, a key structure in the sensorimotor network with its cerebello-cortical connections, has been reported to respond differently when using the dominant vs. non-dominant hand. Several groups have already investigated causal interactions during diverse motor paradigms using effective connectivity but few have studied the larger visuomotor network, including key structures such as the parietal cortex and the cerebellum, with both hands. Moreover, the effect of force level on such interactions is still unclear. We therefore sought to determine the hemispheric asymmetries in the cerebello-cortical sensorimotor network in right-handers at two force levels (5% and 10% maximum voluntary contraction) for both hands. Cerebello-cortical modulations were investigated in 28 healthy, right-handed volunteers by determining the effective connectivity during a visuomotor task at two force levels under fMRI. A network was built consisting of the left and right primary motor (M1), ventral premotor (PMv) and posterior parietal cortices (PPC), in addition to the supplementary motor area (SMA), and the ipsilateral cerebellum (Cer) to the hand performing the motor task. Task performance (precision of isometric grip force tracking) did not differ between hands, nor did task-related activations in the sensorimotor areas apart from the contralateral primary motor cortex. However, during visuomotor control of the non-dominant hand, connectivity analysis revealed causal modulations between (i) the ipsilateral cerebellum and SMA, and (ii) the ipsilatearl cerebellum and contralateral PPC, which was not the case when using the dominant hand. These cerebello-cortical modulations for the non-dominant hand were more present at the higher of the two force levels. We conclude that precision force generation executed with the non-dominant hand, compared to the dominant hand, may require enhanced cerebello-cortical interaction to ensure equivalent left-right task performance.

Published
2017
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13. Spatiotemporal changes in substantia nigra neuromelanin content in Parkinson’s disease

Author

Isabelle Arnulf, Rahul Gaurav, Matthew Hutchison, Lydia Yahia-Cherif, Romain Valabregue, Claire Ewenczyk, Emma Biondetti, Graziella Mangone, Chantal François, Stéphane Lehéricy, Marie Vidailhet, Jean-Christophe Corvol, and Nadya Pyatigorskaya

Subjects
Pathology, medicine.medical_specialty, Parkinson's disease, medicine.diagnostic_test, business.industry, Parkinsonism, Substantia nigra, Magnetic resonance imaging, Striatum, Disease, medicine.disease, REM sleep behavior disorder, 030218 nuclear medicine & medical imaging, 03 medical and health sciences, 0302 clinical medicine, nervous system, Neuromelanin, medicine, Neurology (clinical), business, 030217 neurology & neurosurgery
Abstract

This study aimed to investigate the spatiotemporal changes in neuromelanin-sensitive MRI signal in the substantia nigra and their relation to clinical scores of disease severity in patients with early or progressing Parkinson’s disease and patients with idiopathic rapid eye movement sleep behaviour disorder (iRBD) exempt of Parkinsonian signs compared to healthy control subjects. Longitudinal T1-weighted anatomical and neuromelanin-sensitive MRI was performed in two cohorts, including patients with iRBD, patients with early or progressing Parkinson’s disease, and control subjects. Based on the aligned substantia nigra segmentations using a study-specific brain anatomical template, parametric maps of the probability of a voxel belonging to the substantia nigra were calculated for patients with various degrees of disease severity and controls. For each voxel in the substantia nigra, probability map of controls, correlations between signal-to-noise ratios on neuromelanin-sensitive MRI in patients with iRBD and Parkinson’s disease and clinical scores of motor disability, cognition and mood/behaviour were calculated. Our results showed that in patients, compared to the healthy control subjects, the volume of the substantia nigra was progressively reduced for increasing disease severity. The neuromelanin signal changes appeared to start in the posterolateral motor areas of the substantia nigra and then progressed to more medial areas of this region. The ratio between the volume of the substantia nigra in patients with Parkinson’s disease relative to the controls was best fitted by a mono-exponential decay. Based on this model, the pre-symptomatic phase of the disease started at 5.3 years before disease diagnosis, and 23.1% of the substantia nigra volume was lost at the time of diagnosis, which was in line with previous findings using post-mortem histology of the human substantia nigra and radiotracer studies of the human striatum. Voxel-wise patterns of correlation between neuromelanin-sensitive MRI signal-to-noise ratio and motor, cognitive and mood/behavioural clinical scores were localized in distinct regions of the substantia nigra. This localization reflected the functional organization of the nigrostriatal system observed in histological and electrophysiological studies in non-human primates (motor, cognitive and mood/behavioural domains). In conclusion, neuromelanin-sensitive MRI enabled us to assess voxel-wise modifications of substantia nigra’s morphology in vivo in humans, including healthy controls, patients with iRBD and patients with Parkinson’s disease, and identify their correlation with nigral function across all motor, cognitive and behavioural domains. This insight could help assess disease progression in drug trials of disease modification.

Published
2020
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14. Simultaneous proton density, T 1 , T 2 , and flip‐angle mapping of the brain at 7 T using multiparametric 3D SSFP imaging and parallel‐transmission universal pulses

Author

Denis Le Bihan, Lisa Leroi, L. Hertz-Pannier, Vincent Gras, Ludovic de Rochefort, Romain Valabregue, Franck Mauconduit, Alexandre Vignaud, Mathilde Ripart, Emilie Poirion, Nicolas Boulant, Mathieu Santin, Service NEUROSPIN (NEUROSPIN), Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Institut 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), Centre de résonance magnétique biologique et médicale (CRMBM), Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)-Centre National de la Recherche Scientifique (CNRS), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), and Assistance Publique - Hôpitaux de Marseille (APHM)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS)

Subjects
[SDV.IB.IMA]Life Sciences [q-bio]/Bioengineering/Imaging, [SDV]Life Sciences [q-bio], relaxometry, Universal Pulses, Parallel transmission, quantitative MRI, 030218 nuclear medicine & medical imaging, [SPI]Engineering Sciences [physics], 03 medical and health sciences, 0302 clinical medicine, Flip angle, Universal Pulses 2, Robustness (computer science), Effective diffusion coefficient, Radiology, Nuclear Medicine and imaging, Image resolution, [PHYS]Physics [physics], Physics, T2, T1, Specific absorption rate, Pulse sequence, Steady-state free precession imaging, Computational physics, Parallel communication, 030217 neurology & neurosurgery
Abstract

International audience; Purpose: Performing simultaneous quantitative MRI at ultra-high field is challenging, as B0 and B1 + heterogeneities as well as Specific Absorption Rate increase. Too large deviations of flip angle from the target can induce biases and impair signal-to-noise ratio in the quantification process. In this work, we use calibration-free parallel transmission, a dedicated pulse sequence parameter optimization and signal fitting to recover 3D proton density, flip angle, T1 and T2 maps over the whole brain, in a clinically suitable time. Methods: Eleven optimized contrasts were acquired with an unbalanced Steady-State Free Precession sequence by varying flip angle amplitude and radiofrequency phase cycling increment, at a 1.0x1.0x3.0mm 3 resolution. Acquisition time was of 16min36sec for the whole brain. Parallel transmission and Universal Pulses were used to mitigate B1 + heterogeneity to improve the results' reliability over six healthy volunteers (3 females/males, age 22.6±2.7 years-old). Quantification of the physical parameters was performed by fitting acquired contrasts to the simulated ones using the Bloch-Torrey equations with a realistic diffusion coefficient. Results: Whole-brain 3D maps of effective flip angle, PD and relaxation times were estimated. Parallel transmission improved the robustness of the results at 7T. Results were in accordance with literature and with measurements from standard methods. Conclusion: These preliminary results show robust PD, FA, T1 and T2 map retrieval. Other parameters, such as Apparent Diffusion Coefficient, could be assessed. With further optimization in the acquisition, scan time could be reduced and spatial resolution increased to bring this multi-parametric quantification method to clinical research routine at 7-tesla.

Published
2020
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15. Analysis of task-based functional MRI data preprocessed with fMRIPrep

Author

Mathias Goncalves, Jessey Wright, Yaroslav O. Halchenko, Craig A. Moodie, James D. Kent, Oscar Esteban, Tal Yarkoni, Karolina Finc, Matthew Cieslak, Daniel E. P. Gomez, Nir Jacoby, Satrajit S. Ghosh, Hrvoje Stojic, Elizabeth DuPre, Romain Valabregue, Franziskus Liem, Ross Blair, Christopher J. Markiewicz, Sebastian Urchs, Krzysztof J. Gorgolewski, Rastko Ciric, Inge K Amlien, Alejandro de la Vega, Russell A. Poldrack, Zhifang Ye, William Hedley Thompson, and Taylor Salo

Subjects
Computer science, Rest, Image processing, Article, General Biochemistry, Genetics and Molecular Biology, 030218 nuclear medicine & medical imaging, Workflow, 03 medical and health sciences, 0302 clinical medicine, Software, Neuroimaging, Image Processing, Computer-Assisted, medicine, Animals, Humans, Preprocessor, 030304 developmental biology, Protocol (science), 0303 health sciences, Neural correlates of consciousness, medicine.diagnostic_test, business.industry, Brain, Pattern recognition, Reference Standards, Data structure, Magnetic Resonance Imaging, Artificial intelligence, Functional magnetic resonance imaging, business, 030217 neurology & neurosurgery
Abstract

Functional magnetic resonance imaging (fMRI) is a standard tool to investigate the neural correlates of cognition. fMRI noninvasively measures brain activity, allowing identification of patterns evoked by tasks performed during scanning. Despite the long history of this technique, the idiosyncrasies of each dataset have led to the use of ad-hoc preprocessing protocols customized for nearly every different study. This approach is time-consuming, error-prone, and unsuitable for combining datasets from many sources. Here we showcasefMRIPrep(http://fmriprep.org), a robust tool to prepare human fMRI data for statistical analysis. This software instrument addresses the reproducibility concerns of the established protocols for fMRI preprocessing. By leveraging the Brain Imaging Data Structure (BIDS) to standardize both the input datasets —MRI data as stored by the scanner— and the outputs —data ready for modeling and analysis—,fMRIPrepis capable of preprocessing a diversity of datasets without manual intervention. In support of the growing popularity offMRIPrep, this protocol describes how to integrate the tool in a task-based fMRI investigation workflow.

Published
2020
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16. The Brain Network of Naming: A Lesson from Primary Progressive Aphasia.

Author

Raffaella Migliaccio, Claire Boutet, Romain Valabregue, Sophie Ferrieux, Marie Nogues, Stéphane Lehéricy, Didier Dormont, Richard Levy, Bruno Dubois, and Marc Teichmann

Subjects
Medicine, Science
Abstract

OBJECTIVE:Word finding depends on the processing of semantic and lexical information, and it involves an intermediate level for mapping semantic-to-lexical information which also subserves lexical-to-semantic mapping during word comprehension. However, the brain regions implementing these components are still controversial and have not been clarified via a comprehensive lesion model encompassing the whole range of language-related cortices. Primary progressive aphasia (PPA), for which anomia is thought to be the most common sign, provides such a model, but the exploration of cortical areas impacting naming in its three main variants and the underlying processing mechanisms is still lacking. METHODS:We addressed this double issue, related to language structure and PPA, with thirty patients (11 semantic, 12 logopenic, 7 agrammatic variant) using a picture-naming task and voxel-based morphometry for anatomo-functional correlation. First, we analyzed correlations for each of the three variants to identify the regions impacting naming in PPA and to disentangle the core regions of word finding. We then combined the three variants and correlation analyses for naming (semantic-to-lexical mapping) and single-word comprehension (lexical-to-semantic mapping), predicting an overlap zone corresponding to a bidirectional lexical-semantic hub. RESULTS AND CONCLUSIONS:Our results showed that superior portions of the left temporal pole and left posterior temporal cortices impact semantic and lexical naming mechanisms in semantic and logopenic PPA, respectively. In agrammatic PPA naming deficits were rare, and did not correlate with any cortical region. Combined analyses revealed a cortical overlap zone in superior/middle mid-temporal cortices, distinct from the two former regions, impacting bidirectional binding of lexical and semantic information. Altogether, our findings indicate that lexical/semantic word processing depends on an anterior-posterior axis within lateral-temporal cortices, including an anatomically intermediate hub dedicated to lexical-semantic integration. Within this axis our data reveal the underpinnings of anomia in the PPA variants, which is of relevance for both diagnosis and future therapy strategies.

Published
2016
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17. The sooner the better: clinical and neural correlates of impulsive choice in Tourette disorder

Author

Emmanuel Roze, Cecile Delorme, Trevor W. Robbins, Yulia Worbe, Emilio Fernandez-Egea, Cyril Atkinson-Clement, Benoit Beranger, Romain Valabregue, Andreas Hartmann, Astrid de Liege, Yanica Klein, Atkinson-Clement, Cyril [0000-0001-9499-3485], Robbins, Trevor [0000-0003-0642-5977], Apollo - University of Cambridge Repository, Robbins, Trevor W [0000-0003-0642-5977], Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Centre De Référence National 'Syndrome Gilles de la Tourette', Pôle des Maladies du Système Nerveux [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre de Neuro-Imagerie de Recherche (CENIR), Service de Neurologie [CHU Pitié-Salpêtrière], IFR70-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), University of Cambridge [UK] (CAM), Unité de neurophysiologie [CHU Saint-Antoine], CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)

Subjects
Tics, Hippocampus, Neurosciences. Biological psychiatry. Neuropsychiatry, Impulsivity, Insular cortex, 03 medical and health sciences, Cellular and Molecular Neuroscience, 0302 clinical medicine, 631/477/2811, Reward, Reward sensitivity, Human behaviour, medicine, Humans, Insular Cortex, Biological Psychiatry, 692/699/476, 030304 developmental biology, 0303 health sciences, Neural correlates of consciousness, Discounting, Ventral striatum, article, medicine.disease, Magnetic Resonance Imaging, Psychiatry and Mental health, medicine.anatomical_structure, Delay Discounting, Impulsive Behavior, 59/57, 59/36, medicine.symptom, 631/378, Psychiatric disorders, Psychology, Neuroscience, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, 030217 neurology & neurosurgery, psychological phenomena and processes, Tourette Syndrome, RC321-571
Abstract

Funder: Fondation pour la Recherche M��dicale (Foundation for Medical Research in France); doi: https://doi.org/10.13039/501100002915, Reward sensitivity has been suggested as one of the central pathophysiological mechanisms in Tourette disorder. However, the subjective valuation of a reward by introduction of delay has received little attention in Tourette disorder, even though it has been suggested as a trans-diagnostic feature of numerous neuropsychiatric disorders. We aimed to assess delay discounting in Tourette disorder and to identify its brain functional correlates. We evaluated delayed discounting and its brain functional correlates in a large group of 54 Tourette disorder patients and 31 healthy controls using a data-driven approach. We identified a subgroup of 29 patients with steeper reward discounting, characterised by a higher burden of impulse-control disorders and a higher level of general impulsivity compared to patients with normal behavioural performance or to controls. Reward discounting was underpinned by resting-state activity of a network comprising the orbito-frontal, cingulate, pre-supplementary motor area, temporal and insular cortices, as well as ventral striatum and hippocampus. Within this network, (i) lower connectivity of pre-supplementary motor area with ventral striatum predicted a higher impulsivity and a steeper reward discounting and (ii) a greater connectivity of pre-supplementary motor area with anterior insular cortex predicted steeper reward discounting and more severe tics. Overall, our results highlight the heterogeneity of the delayed reward processing in Tourette disorder, with steeper reward discounting being a marker of burden in impulsivity and impulse control disorders, and the pre-supplementary motor area being a hub region for the delay discounting, impulsivity and tic severity.

Published
2021
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18. Hyperglycaemia, insulin therapy and critical penumbral regions for prognosis in acute stroke: further insights from the INSULINFARCT trial.

Author

Charlotte Rosso, Christine Pires, Jean-Christophe Corvol, Flore Baronnet, Sophie Crozier, Anne Leger, Sandrine Deltour, Romain Valabregue, Mélika Amor-Sahli, Stéphane Lehéricy, Didier Dormont, and Yves Samson

Subjects
Medicine, Science
Abstract

BackgroundRecently, the concept of 'clinically relevant penumbra' was defined as an area saved by arterial recanalization and correlated with stroke outcome. This clinically relevant penumbra was located in the subcortical structures, especially the periventricular white matter. Our aims were to confirm this hypothesis, to investigate the impact of admission hyperglycemia and of insulin treatment on the severity of ischemic damages in this area and to study the respective contributions of infarct volume and ischemic damage severity of the clinically relevant penumbra on 3-month outcome.MethodsWe included 99 patients from the INSULINFARCT trial. Voxel-Based Analysis was carried on the Apparent Diffusion Coefficient (ADC) maps obtained at day one to localize the regions, which were more damaged in patients i) with poor clinical outcomes at three months and ii) without arterial recanalization. We determined the intersection of the detected areas, which represents the clinically relevant penumbra and investigated whether hyperglycemic status and insulin regimen affected the severity of ischemic damages in this area. We performed logistic regression to examine the contribution of infarct volume or early ADC decrease in this strategic area on 3-month outcome.FindingsLower ADC values were found in the corona radiata in patients with poor prognosis (p< 0.0001) and in those without arterial recanalization (p< 0.0001). The tracking analysis showed that lesions in this area interrupted many important pathways. ADC values in this area were lower in hyperglycemic than in normoglycemic patients (average decrease of 41.6 ± 20.8 x10(-6) mm2/s) and unaffected by the insulin regimen (p: 0.10). ADC values in the clinically relevant penumbra, but not infarct volumes, were significant predictors of 3-month outcome.ConclusionThese results confirm that the deep hemispheric white matter is part of the clinically relevant penumbra and show that hyperglycaemia exacerbates the apparition of irreversible ischemic damage within 24 hours in this area. However, early intensive insulin therapy fails to protect this area from infarction.Trial registrationClinicalTrials.gov NCT00472381.

Published
2015
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19. Axial Diffusivity of the Corona Radiata at 24 Hours Post-Stroke: A New Biomarker for Motor and Global Outcome.

Author

Eric Moulton, Mélika Amor-Sahli, Vincent Perlbarg, Christine Pires, Sophie Crozier, Damien Galanaud, Romain Valabregue, Marion Yger, Flore Baronnet-Chauvet, Yves Samson, Didier Dormont, and Charlotte Rosso

Subjects
Medicine, Science
Abstract

Fractional anisotropy (FA) is an effective marker of motor outcome at the chronic stage of stroke yet proves to be less efficient at early time points. This study aims to determine which diffusion metric in which location is the best marker of long-term stroke outcome after thrombolysis with diffusion tensor imaging (DTI) at 24 hours post-stroke. Twenty-eight thrombolyzed patients underwent DTI at 24 hours post-stroke onset. Ipsilesional and contralesional FA, mean (MD), axial (AD), and radial (RD) diffusivities values were calculated in different Regions-of-Interest (ROIs): (1) the white matter underlying the precentral gyrus (M1), (2) the corona radiata (CoRad), (3) the posterior limb of the internal capsule (PLIC) and (4) the cerebral peduncles (CP). NIHSS scores were acquired at admission, day 1, and day 7; modified Rankin Scores (mRS) at 3 months. Significant decreases were found in FA, MD, and AD of the ipsilesional CoRad and M1. MD and AD were also significantly lower in the PLIC. The ratio of ipsi and contralesional AD of the CoRad (CoRad-rAD) was the strongest diffusion parameter correlated with motor NIHSS scores on day 7 and with the mRS at 3 months. A Receiver-Operator Curve analysis yielded a model for the CoRad-rAD to predict good outcome based on upper limb NIHSS motor scores and mRS with high specificity and sensitivity. FA values were not correlated with clinical outcome. In conclusion, axial diffusivity of the CoRad from clinical DTI at 24 hours post-stroke is the most appropriate diffusion metric for quantifying stroke damage to predict outcome, suggesting the importance of early axonal damage.

Published
2015
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20. Acute Diffusivity Biomarkers for Prediction of Motor and Language Outcome in Mild-to-Severe Stroke Patients

Author

Romain Valabregue, Christine Pires, Mélika Amor-Sahli, Serena Magno, Charlotte Rosso, Stéphane Lehéricy, Anne Leger, Eric A. Moulton, and Yves Samson

Subjects
Male, medicine.medical_specialty, Motor Disorders, Pyramidal Tracts, computer.software_genre, 050105 experimental psychology, White matter, 03 medical and health sciences, 0302 clinical medicine, Physical medicine and rehabilitation, Voxel, Aphasia, medicine, Humans, Arcuate fasciculus, 0501 psychology and cognitive sciences, Stroke, Aged, Advanced and Specialized Nursing, medicine.diagnostic_test, business.industry, 05 social sciences, Magnetic resonance imaging, Recovery of Function, Middle Aged, medicine.disease, Diffusion Tensor Imaging, medicine.anatomical_structure, Corticospinal tract, Female, Neurology (clinical), medicine.symptom, Cardiology and Cardiovascular Medicine, business, computer, 030217 neurology & neurosurgery, Diffusion MRI
Abstract

Background and Purpose— Early severity of stroke symptoms—especially in mild-to-severe stroke patients—are imperfect predictors of long-term motor and aphasia outcome. Motor function and language processing heavily rely on the preservation of important white matter fasciculi in the brain. Axial diffusivity (AD) from the diffusion tensor imaging model has repeatedly shown to accurately reflect acute axonal damage and is thus optimal to probe the integrity of important white matter bundles and their relationship with long-term outcome. Our aim was to investigate the independent prognostic value of the AD of white matter tracts in the motor and language network evaluated at 24 hours poststroke for motor and aphasia outcome at 3 months poststroke. Methods— Seventeen (motor cohort) and 28 (aphasia cohort) thrombolyzed patients with initial mild-to-severe stroke underwent a diffusion tensor imaging sequence at 24 hours poststroke. Motor and language outcome were evaluated at 3 months poststroke with a composite motor score and the aphasia handicap scale. We first used stepwise regression to determine which classic (age, initial motor or aphasia severity, and lesion volume) and imaging (ratio of affected/unaffected AD of motor and language fasciculi) factors were related to outcome. Second, to determine the specificity of our a priori choices of fasciculi, we performed voxel-based analyses to determine if the same, additional, or altogether new regions were associated with long-term outcome. Results— The ratio of AD in the corticospinal tract was the sole predictor of long-term motor outcome, and the ratio of AD in the arcuate fasciculus—along with age and initial aphasia severity—was an independent predictor of 3-month aphasia outcome. White matter regions overlapping with these fasciculi naturally emerged in the corresponding voxel-based analyses. Conclusions— AD of the corticospinal tract and arcuate fasciculus are effective biomarkers of long-term motor and aphasia outcome, respectively.

Published
2019
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21. Medial prefrontal disengagement during self-focus in formerly depressed patients prone to rumination

Author

Frédéric Limosin, Philippe Fossati, Philip Gorwood, Nicolas Hoertel, Romain Valabregue, Jean-Yves Rotge, Cédric Lemogne, Caroline Dubertret, Christophe Guerin-Langlois, Ayna Baladi Nejad, Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Université Paris Descartes - Faculté de Médecine (UPD5 Médecine), Université Paris Descartes - Paris 5 (UPD5), and Université Paris Diderot - Paris 7 (UPD7)

Subjects
Adult, Male, [SDV]Life Sciences [q-bio], media_common.quotation_subject, Prefrontal Cortex, Neuropsychological Tests, Young Adult, 03 medical and health sciences, 0302 clinical medicine, medicine, Humans, Personality, Disengagement theory, Prefrontal cortex, Anterior cingulate cortex, Depression (differential diagnoses), media_common, Psychiatric Status Rating Scales, Brain Mapping, Depressive Disorder, Major, Depression, business.industry, Cognition, Middle Aged, medicine.disease, Magnetic Resonance Imaging, 030227 psychiatry, Psychiatry and Mental health, Clinical Psychology, Rumination, Cognitive, medicine.anatomical_structure, Rumination, Major depressive disorder, Female, medicine.symptom, business, 030217 neurology & neurosurgery, Clinical psychology
Abstract

Background Medial prefrontal cortex (MPFC) activity during self-referential processing has been associated with rumination and found aberrant in depression. We investigated whether this aberrant activity reflects a trait marker that persists in remitted patients. Methods Twenty-five patients fully remitted from major depression for at least 6 months, and 29 matched healthy controls were scanned with fMRI while presented with personality trait words in two conditions: Self condition asked whether the trait described themselves; General condition asked whether the trait was generally desirable. Contrasts-of-interest were examined in a factorial model and rumination correlates were examined in 2-sample t-tests with Ruminative Response Style score as covariate. All findings were reported at a conservative p Results Self-referential processing increased anterior cortical midline activity to a similar extent in both groups. Dorsal anterior cingulate cortex (MNI(x,y,z) = -12,20,26) and dorsal MPFC (MNI(x,y,z) = -6,46,40) activity during self-referential processing was positively associated with rumination in healthy control subjects and negatively associated with rumination in remitted patients. Limitations A longitudinal design tracking the relationship between rumination and MPFC activity would have aided the interpretation of our findings as to whether high ruminators are exhibiting an adaptive process to maintain remission or whether it represents a maladaptive process considering that high ruminators have an increased vulnerability for relapse. Conclusions The association between increased anterior cortical midline activity during self-referential processing and rumination differentiated healthy controls from formerly depressed patients. Self-referential neural processing during remission from depression may depend on the cognitive tendencies to ruminate.

Published
2019
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22. Cystathionine as a marker for 1p/19q codeleted gliomas by in vivo magnetic resonance spectroscopy

Author

Małgorzata Marjańska, Marc Sanson, Lucien Tchara, Anna Luisa Di Stefano, Romain Valabregue, Stéphane Lehéricy, Francesca Branzoli, Clément Pontoizeau, Chris Ottolenghi, Dinesh K. Deelchand, and Aurélie Kamoun

Subjects
Adult, Male, In vivo magnetic resonance spectroscopy, Cancer Research, Magnetic Resonance Spectroscopy, Brain tumor, 1p/19q Codeletion, Young Adult, 03 medical and health sciences, Cystathionine, 0302 clinical medicine, In vivo, Glioma, Biomarkers, Tumor, Tumor Cells, Cultured, medicine, Humans, Neoplasm Invasiveness, Prospective Studies, Phosphoglycerate dehydrogenase, Phosphoglycerate Dehydrogenase, Aged, Cell Proliferation, biology, Brain Neoplasms, Chemistry, Middle Aged, Prognosis, medicine.disease, Cystathionine beta synthase, Survival Rate, Real-time polymerase chain reaction, Oncology, Chromosomes, Human, Pair 1, 030220 oncology & carcinogenesis, Basic and Translational Investigations, biology.protein, Cancer research, Female, Neurology (clinical), Chromosome Deletion, Chromosomes, Human, Pair 19, 030217 neurology & neurosurgery, Follow-Up Studies
Abstract

Background Codeletion of chromosome arms 1p and 19q (1p/19q codeletion) highly benefits diagnosis and prognosis in gliomas. In this study, we investigated the effect of 1p/19q codeletion on cancer cell metabolism and evaluated possible metabolic targets for tailored therapies. Methods We combined in vivo 1H (proton) magnetic resonance spectroscopy (MRS) measurements in human gliomas with the analysis of a series of standard amino acids by liquid chromatography-mass spectroscopy (LC-MS) in human glioma biopsies. Sixty-five subjects with low-grade glioma were included in the study: 31 underwent the MRI/MRS examination, 47 brain tumor tissue samples were analyzed with LC-MS, and 33 samples were analyzed for gene expression with quantitative PCR. Additionally, we performed metabolic tracer experiments in cell models with 1p deletion. Results We report the first in vivo detection of cystathionine by MRS in 1p/19q codeleted gliomas. Selective accumulation of cystathionine was observed in codeleted gliomas in vivo, in brain tissue samples, as well as in cells harboring heterozygous deletions for serine- and cystathionine-pathway genes located on 1p: phosphoglycerate dehydrogenase (PHGDH) and cystathionine gamma-lyase (CTH). Quantitative PCR analyses showed 40-50% lower expression of both PHGDH and CTH in 1p/19q codeleted gliomas compared with their non-codeleted counterparts. Conclusions Our results provide strong evidence of a selective vulnerability of codeleted gliomas to serine and glutathione depletion and point to cystathionine as a possible noninvasive marker of treatment response.

Published
2019
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24. Dopamine denervation in the functional territories of the striatum: a new MR and atlas-based 123I-FP-CIT SPECT quantification method

Author

Aurélie Kas, Sara Fernandez-Vidal, David Grabli, M-O Habert, Stéphane Lehéricy, Graziella Mangone, Nicolas Villain, J Aubert, O Jaubert, G. Bera, Romain Valabregue, J-C Corvol, Marie Vidailhet, 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), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Laboratoire d'Imagerie Biomédicale (LIB), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), and VILLAIN, Nicolas

Subjects
Parkinson's disease, [SDV.IB.IMA]Life Sciences [q-bio]/Bioengineering/Imaging, striatum, Partial volume, idiopathic rapid eye movement sleep behavioral disorder, Striatum, Nucleus accumbens, Dopamine, Basal ganglia, Medicine, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Biological Psychiatry, Denervation, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, business.industry, Dopaminergic, medicine.disease, Psychiatry and Mental health, [SDV.IB.IMA] Life Sciences [q-bio]/Bioengineering/Imaging, Neurology, nervous system, 123 I-FP-CIT SPECT, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Neurology (clinical), business, Neuroscience, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, medicine.drug
Abstract

International audience; Current quantification methods of 123I-FP-CIT SPECT rely on anatomical parcellation of the striatum. We propose here to implement a new method based on MRI segmentation and functional atlas of the basal ganglia (MR-ATLAS) that could provide a reliable quantification within the sensorimotor, associative, and limbic territories of the striatum. Patients with Parkinson’s disease (PD), idiopathic rapid eye movement sleep behavioral disorder (iRBD), and healthy controls underwent 123I-FP-CIT SPECT, MRI, motor, and cognitive assessments. SPECT data were corrected for partial volume effects and registered to a functional atlas of the striatum to allow quantification in every functional region of the striatum (nucleus accumbens, limbic, associative, and sensorimotor parts of the striatum). The MR-ATLAS quantification method is proved to be reliable in every territory of the striatum. In addition, good correlations were found between cognitive dysexecutive tests and the binding within the functional (limbic) territories of the striatum using the MR-ATLAS method, slightly better than correlations found using the anatomical quantification method. This new MR-ATLAS method provides a robust and useful tool for studying the dopaminergic system in PD, particularly with respect to cognitive functions. It may also be relevant to further unravel the relationship between dopaminergic denervation and cognitive or behavioral symptoms.

Published
2021
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25. The spatiotemporal changes in dopamine, neuromelanin and iron characterizing Parkinson's disease

Author

Mathieu Santin, Nicolas Villain, I. Arnulf, Stéphane Lehéricy, Smaranda Leu-Semenescu, Emma Biondetti, Miquel Vila, Jean-Christophe Corvol, Marie-Odile Habert, Pauline Dodet, Graziella Mangone, M. Vidailhet, Rahul Gaurav, Lydia Yahia-Cherif, Romain Valabregue, Matthew Hutchison, Nadya Pyatigorskaya, Institut du Cerveau = Paris Brain Institute (ICM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Università degli studi 'G. d'Annunzio' Chieti-Pescara [Chieti-Pescara] (Ud'A), Center for NeuroImaging Research-Human MRI Neuroimaging core facility for clinical research [ICM Paris] (CENIR), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Centre d'investigation clinique Biothérapie [CHU Pitié-Salpêtrière] (CIC-BTi), Centre d'investigation clinique pluridisciplinaire [CHU Pitié Salpêtrière] (CIC-P 1421), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de Neurologie [CHU Pitié-Salpêtrière], IFR70-CHU Pitié-Salpêtrière [AP-HP], Service de Neuroradiologie [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Laboratoire d'Imagerie Biomédicale (LIB), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Service de Médecine nucléaire [CHU Pitié-Salpétrière], Service de Pathologies du sommeil [CHU Pitié-Salpêtrière], Universitat Autònoma de Barcelona (UAB), Vall d’Hebron Research Institute (VHIR), Centro de Investigacion Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Instituto de Salud Carlos III [Madrid] (ISC), Institució Catalana de Recerca i Estudis Avançats (ICREA), HAL-SU, Gestionnaire, Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Center for NeuroImaging Research - CENIR, Sorbonne Université (SU), Centre d’Investigation Clinique en Biothérapies [CHU Pitié-Salpêtrière] (CIC-BT), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de médecine nucléaire [CHU Pitié-Salpétrière], Service des Pathologies du sommeil [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Institut Català de la Salut, [Biondetti E, Gaurav R] Sorbonne Université, Institut du Cerveau - Paris Brain Institute - ICM, INSERM, CNRS, Paris, France. ICM, Centre de NeuroImagerie de Recherche - CENIR, Paris, France. ICM, Team 'Movement Investigations and Therapeutics' (MOV'IT), Paris, France. [Santin MD, Valabrègue R] Sorbonne Université, Institut du Cerveau - Paris Brain Institute - ICM, INSERM, CNRS, Paris, France. ICM, Centre de NeuroImagerie de Recherche - CENIR, Paris, France. [Mangone G] Sorbonne Université, Institut du Cerveau - Paris Brain Institute - ICM, INSERM, CNRS, Paris, France. Assistance Publique Hôpitaux de Paris, Hôpital Pitié-Salpêtrière, Department of Neurology, Centre d'Investigation Clinique Neurosciences, Paris, France. Assistance Publique Hôpitaux de Paris, Hôpital Pitié-Salpêtrière, Department of Neurology, Paris, France. [Pyatigorskaya N] Sorbonne Université, Institut du Cerveau - Paris Brain Institute - ICM, INSERM, CNRS, Paris, France. ICM, Team 'Movement Investigations and Therapeutics' (MOV'IT), Paris, France. Assistance Publique Hôpitaux de Paris, Hôpital Pitié-Salpêtrière, Department of Neuroradiology, Paris, France. [Vila M] Grup de Recerca en Malalties Neurodegeneratives, Vall d'Hebron Institut de Recerca (VHIR), Barcelona, Spain. Center for Networked Biomedical Research on Neurodegenerative Diseases (CIBERNED). Departament de Bioquímica i Biologia Molecular, Universitat Autònoma de Barcelona, Bellaterra, Spain. Catalan Institution for Research and Advanced Studies (ICREA), 08010 Barcelona, Spain, and Vall d'Hebron Barcelona Hospital Campus

Subjects
Male, Parkinson's disease, Time Factors, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, aminoácidos, péptidos y proteínas::aminoácidos::aminoácidos cíclicos::aminoácidos aromáticos::tirosina::melaninas [COMPUESTOS QUÍMICOS Y DROGAS], Striatum, Imaging, 030218 nuclear medicine & medical imaging, Cohort Studies, 0302 clinical medicine, iron, enfermedades del sistema nervioso::enfermedades del sistema nervioso central::enfermedades cerebrales::enfermedades de los ganglios basales::trastornos parkinsonianos::enfermedad de Parkinson [ENFERMEDADES], Medicine, Longitudinal Studies, Prospective Studies, dopamine transporter, biology, AcademicSubjects/SCI01870, Dopaminergic, imaging, Middle Aged, Organic Chemicals::Amines::Biogenic Amines::Biogenic Monoamines::Dopamine [CHEMICALS AND DRUGS], Magnetic Resonance Imaging, Substantia Nigra, Dopamine transporter, Neurones dopaminèrgiques, Nervous System Diseases::Central Nervous System Diseases::Brain Diseases::Basal Ganglia Diseases::Parkinsonian Disorders::Parkinson Disease [DISEASES], Female, neuromelanin, dopamine, Amino Acids, Peptides, and Proteins::Amino Acids::Amino Acids, Cyclic::Amino Acids, Aromatic::Tyrosine::Melanins [CHEMICALS AND DRUGS], medicine.drug, Iron, Substantia nigra, Neuromelanin, 03 medical and health sciences, Dopamine, parkinson disease, Parkinson, Malaltia de - Imatgeria per ressonància magnètica, Humans, Other subheadings::Other subheadings::/diagnostic imaging [Other subheadings], Aged, Melanins, business.industry, Pars compacta, pars compacta, [SDV.NEU.NB] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Otros calificadores::Otros calificadores::/diagnóstico por imagen [Otros calificadores], Original Articles, medicine.disease, Corpus Striatum, compuestos orgánicos::aminas::aminas biógenas::monoaminas biógenas::dopamina [COMPUESTOS QUÍMICOS Y DROGAS], nervous system, biology.protein, Parkinson’s disease, AcademicSubjects/MED00310, Neurology (clinical), business, Neuroscience, 030217 neurology & neurosurgery
Abstract

In Parkinson’s disease, there is a progressive reduction in striatal dopaminergic function, and loss of neuromelanin-containing dopaminergic neurons and increased iron deposition in the substantia nigra. We tested the hypothesis of a relationship between impairment of the dopaminergic system and changes in the iron metabolism. Based on imaging data of patients with prodromal and early clinical Parkinson’s disease, we assessed the spatiotemporal ordering of such changes and relationships in the sensorimotor, associative and limbic territories of the nigrostriatal system. Patients with Parkinson’s disease (disease duration < 4 years) or idiopathic REM sleep behaviour disorder (a prodromal form of Parkinson’s disease) and healthy controls underwent longitudinal examination (baseline and 2-year follow-up). Neuromelanin and iron sensitive MRI and dopamine transporter single-photon emission tomography were performed to assess nigrostriatal levels of neuromelanin, iron, and dopamine. For all three functional territories of the nigrostriatal system, in the clinically most and least affected hemispheres separately, the following was performed: cross-sectional and longitudinal intergroup difference analysis of striatal dopamine and iron, and nigral neuromelanin and iron; in Parkinson’s disease patients, exponential fitting analysis to assess the duration of the prodromal phase and the temporal ordering of changes in dopamine, neuromelanin or iron relative to controls; and voxel-wise correlation analysis to investigate concomitant spatial changes in dopamine-iron, dopamine-neuromelanin and neuromelanin-iron in the substantia nigra pars compacta. The temporal ordering of dopaminergic changes followed the known spatial pattern of progression involving first the sensorimotor, then the associative and limbic striatal and nigral regions. Striatal dopaminergic denervation occurred first followed by abnormal iron metabolism and finally neuromelanin changes in the substantia nigra pars compacta, which followed the same spatial and temporal gradient observed in the striatum but shifted in time. In conclusion, dopaminergic striatal dysfunction and cell loss in the substantia nigra pars compacta are interrelated with increased nigral iron content., Using multi-modal imaging (MRI and SPECT) in patients with prodromal and early clinical Parkinson’s disease, Biondetti et al. reveal dopaminergic changes, abnormal iron metabolism and neuromelanin changes first in the sensorimotor, then the associative and finally the limbic regions of the nigrostriatal system.

Published
2021
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26. Longitudinal Changes in Neuromelanin MRI Signal in Parkinson's Disease: A Progression Marker

Author

Lydia Yahia-Cherif, Romain Valabregue, Jesse M. Cedarbaum, Marie Vidailhet, Rahul Gaurav, Jean-Christophe Corvol, Stéphane Lehéricy, Claire Ewenczyk, Emma Biondetti, R. Matthew Hutchison, Nadya Pyatigorskaya, Graziella Mangone, Gestionnaire, Hal Sorbonne Université, Institut du Cerveau = Paris Brain Institute (ICM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Center for NeuroImaging Research-Human MRI Neuroimaging core facility for clinical research [ICM Paris] (CENIR), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Service de Neuroradiologie [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Biogen Inc. [Cambridge, MA, USA], Service de Neurologie [CHU Pitié-Salpêtrière], IFR70-CHU Pitié-Salpêtrière [AP-HP], Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Centre de Neuro-Imagerie de Recherche (CENIR), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Service de neurologie 1 [CHU Pitié-Salpétrière], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), and Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)

Subjects
Male, 0301 basic medicine, medicine.medical_specialty, Movement disorders, Parkinson's disease, [SDV]Life Sciences [q-bio], Urology, Substantia nigra, Regular Issue Articles, 03 medical and health sciences, 0302 clinical medicine, Neuromelanin, medicine, Humans, Prospective Studies, Research Articles, parkinsonism, Melanins, neuroimaging, Pars compacta, business.industry, Parkinsonism, Parkinson Disease, medicine.disease, Magnetic Resonance Imaging, 3. Good health, Substantia Nigra, [SDV] Life Sciences [q-bio], 030104 developmental biology, Neurology, Case-Control Studies, neurodegenerative disorders, Cohort, biomarker, Biomarker (medicine), Female, Neurology (clinical), medicine.symptom, business, Biomarkers, 030217 neurology & neurosurgery, Research Article
Abstract

International audience; BackgroundDevelopment of reliable and accurate imaging biomarkers of dopaminergic cell neurodegeneration is necessary to facilitate therapeutic drug trials in Parkinson's disease (PD). Neuromelanin‐sensitive MRI techniques have been effective in detecting neurodegeneration in the substantia nigra pars compacta (SNpc). The objective of the current study was to investigate longitudinal neuromelanin signal changes in the SNpc in PD patients.MethodsIn this prospective, longitudinal, observational case–control study, we included 140 PD patients and 64 healthy volunteers divided into 2 cohorts. Cohort I included 99 early PD patients (disease duration, 1.5 ± 1.0 years) and 41 healthy volunteers analyzed at baseline (V1), where 79 PD patients and 32 healthy volunteers were rescanned after 2.0 ± 0.2 years of follow‐up (V2). Cohort II included 41 progressing PD patients (disease duration, 9.3 ± 3.7 years) and 23 healthy volunteers at V1, where 30 PD patients were rescanned after 2.4 ± 0.5 years of follow‐up. Subjects were scanned at 3 T MRI using 3‐dimensional T1‐weighted and neuromelanin‐sensitive imaging. Regions of interest were delineated manually to calculate SN volumes, volumes corrected by total intracranial volume, signal‐to‐noise ratio, and contrast‐to‐noise ratio.ResultsResults showed (1) significant reduction in volume and volume corrected by total intracranial volume between visits, greater in progressing PD than nonsignificant changes in healthy volunteers; (2) no significant effects of visit for signal intensity (signal‐to‐noise ratio); (3) significant interaction in volume between group and visit; (4) greater volume corrected by total intracranial volume at baseline in female patients and greater decrease in volume and increase in the contrast‐to‐noise ratio in progressing female PD patients compared with male patients; and (5) correlations between neuromelanin SN changes and disease severity and duration.ConclusionsWe observed a progressive and measurable decrease in neuromelanin‐based SN signal and volume in PD, which might allow a direct noninvasive assessment of progression of SN loss and could represent a target biomarker for disease‐modifying treatments. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society

Published
2021
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27. Contribution of corticospinal tract and functional connectivity in hand motor impairment after stroke.

Author

Charlotte Rosso, Romain Valabregue, Yohan Attal, Patricia Vargas, Marie Gaudron, Flore Baronnet, Eric Bertasi, Frédéric Humbert, Anne Peskine, Vincent Perlbarg, Habib Benali, Stéphane Lehéricy, and Yves Samson

Subjects
Medicine, Science
Abstract

BackgroundMotor outcome after stroke is associated with reorganisation of cortical networks and corticospinal tract (CST) integrity. However, the relationships between motor severity, CST damage, and functional brain connectivity are not well understood. Here, the main objective was to study the effect of CST damage on the relationship between functional motor network connectivity and hand motor function in two groups of stroke patients: the severely (n=8) and the mildly impaired (n=14).MethodsTwenty-two carotid stroke patients with motor deficits were studied with magnetic resonance imaging (MRI) at 3 weeks, at 3 and 6 months. Healthy subjects (n=28) were scanned once. The CST injury was assessed by fractional anisotropy values. Functional connectivity was studied from a whole-hand grip task fMRI in a cortical and cerebellar motor network. Functional connectivity indexes were computed between these regions at each time point. The relationship between hand motor strength, ipsilesional CST damage and functional connectivity from the primary motor cortex (M1) was investigated using global and partial correlations.FindingsIn mildly impaired patients, cortico-cortical connectivity was disturbed at three weeks but returned to a normal pattern after 3 months. Cortico-cerebellar connectivity was still decreased at 6 months. In severely impaired patients, the cortico-cortical connectivity tended to return to a normal pattern, but the cortico-cerebellar connectivity was totally abolished during the follow-up. In the entire group of patients, the hand motor strength was correlated to the ipsilesional functional connectivity from M1. Partial correlations revealed that these associations were not anymore significant when the impact of CST damage was removed, except for the ipsilesional M1-contralateral cerebellum connectivity.ConclusionFunctional brain connectivity changes can be observed, even in severely impaired patients with no recovery. Upper limb function is mainly explained by the CST damage and by the ipsilesional cortico-cerebellar connectivity.

Published
2013
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28. Tau PET imaging, MRI and cognitive progression in subjects with progressive amnesia and suspected non‐Alzheimer pathophysiology (SNAP)

Author

Fabien Caillé, Julien Lagarde, Michel Bottlaender, Marie Sarazin, Philippe Gervais, Romain Valabregue, Lorraine Hamelin, and Pauline Olivieri

Subjects
Epidemiology, business.industry, Health Policy, Snap, Amnesia, Cognition, Pathophysiology, Psychiatry and Mental health, Cellular and Molecular Neuroscience, Developmental Neuroscience, Neuroimaging, Medicine, Neurology (clinical), Geriatrics and Gerontology, medicine.symptom, business, Neuroscience
Published
2020
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29. Locus coeruleus signal intensity in progressive amnesia due to suspected non‐Alzheimer pathophysiology (SNAP)

Author

Stéphane Lehéricy, Romain Valabregue, Philippe Gervais, Michel Bottlaender, Marie Sarazin, Fabien Caillé, Pauline Olivieri, and Julien Lagarde

Subjects
Epidemiology, business.industry, Health Policy, Snap, Amnesia, Pathophysiology, Psychiatry and Mental health, Cellular and Molecular Neuroscience, Developmental Neuroscience, Neuroimaging, Medicine, Locus coeruleus, Neurology (clinical), Geriatrics and Gerontology, Signal intensity, medicine.symptom, business, Neuroscience
Published
2020
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30. Dissociation in reactive and proactive inhibitory control in Myoclonus dystonia

Author

Vanessa Brochard, Cyril Atkinson-Clement, Yulia Worbe, David Grabli, Stéphane Thobois, Jean‐Michel Pedespan, Nicolas Wattiez, Christine Tranchant, Romain Valabregue, Pierre Krystkoviak, Emmanuel Roze, Bertrand Degos, Clément Tarrano, Emmanuelle Apartis, Charlotte Rosso, Cécile Delorme, Camille-Albane Porte, Luc Defebvre, Jean-Luc Houeto, Marie Vidailhet, Eavan McGovern, Jean-Christophe Corvol, Pierre Pouget, Adrian Degardin, Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Hôpital Côte de Nacre [CHU Caen], CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Université de Caen Normandie (UNICAEN), Normandie Université (NU), Centre d'investigation clinique Neurosciences [CHU Pitié Salpêtrière] (CIC Neurosciences), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Neurophysiologie Respiratoire Expérimentale et Clinique (UMRS 1158), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), St Vincent's University Hospital, Institut des sciences cognitives Marc Jeannerod - Centre de neuroscience cognitive - UMR5229 (CNC), Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, Hospices Civils de Lyon (HCL), Hôpital neurologique et neurochirurgical Pierre Wertheimer [CHU - HCL], Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Fédération de Médecine Translationnelle de Strasbourg (FMTS), Université de Strasbourg (UNISTRA), Hôpital Avicenne [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpitaux Paris Seine-Saint-Denis [Bobigny], CHU de Bordeaux Pellegrin [Bordeaux], CHU Amiens-Picardie, CIC - Poitiers, Université de Poitiers-Centre hospitalier universitaire de Poitiers (CHU Poitiers)-Direction Générale de l'Organisation des Soins (DGOS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier de Tourcoing, Troubles cognitifs dégénératifs et vasculaires - U 1171 (TCDV), Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Recherche de l'Institut du Cerveau et de la Moelle épinière (CRICM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), CHU Saint-Antoine [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Neurophysiologie Respiratoire Expérimentale et Clinique, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut du Cerveau = Paris Brain Institute (ICM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Université de Caen Normandie - UFR Santé (UNICAEN Santé), Normandie Université (NU)-Normandie Université (NU), Centre d'investigation clinique pluridisciplinaire [CHU Pitié Salpêtrière] (CIC-P 1421), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Service de neurologie [Poitiers], Centre hospitalier universitaire de Poitiers (CHU Poitiers), CHU Lille, Service de Neurologie [CHU Saint-Antoine], Atkinson-Clement, Cyril, Service de pédiatrie, CHU Pellegrin, Département de neurologie[Lille], Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service de neurologie et pathologie du mouvement, Hôpital Roger Salengro [Lille]-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Equipe NEMESIS - Centre de Recherches de l'Institut du Cerveau et de la Moelle épinière (NEMESIS-CRICM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Institut des sciences cognitives Marc Jeannerod - Centre de neuroscience cognitive - UMR5229 (ISC-MJ), and ANR-18-CE37-0008,CADETS,Cognition et développement cérébral chez adolescents avec Syndrome de Gilles de la Tourette(2018)

Subjects
Male, Myoclonus, 0301 basic medicine, Deep Brain Stimulation, medicine.medical_treatment, lcsh:Medicine, Stop signal, Synaptic Transmission, Comorbidities, [SCCO]Cognitive science, 0302 clinical medicine, lcsh:Science, ComputingMilieux_MISCELLANEOUS, Dystonia, Multidisciplinary, Inhibition, Psychological, Dystonic Disorders, Proactive Inhibition, Neurological manifestations, Facilitation, Female, medicine.symptom, Adult, medicine.medical_specialty, Deep brain stimulation, Dissociative Disorders, Globus Pallidus, Inhibitory postsynaptic potential, Article, Young Adult, 03 medical and health sciences, Internal medicine, Reaction Time, medicine, Humans, Movement disorders, Reactive inhibition, business.industry, [SCCO.NEUR]Cognitive science/Neuroscience, lcsh:R, Reactive Inhibition, [SCCO] Cognitive science, medicine.disease, nervous system diseases, 030104 developmental biology, Endocrinology, nervous system, lcsh:Q, business, Neurological disorders, 030217 neurology & neurosurgery
Abstract

Myoclonus-dystonia (MD) is a syndrome characterized by myoclonus of subcortical origin and dystonia, frequently associated with psychiatric comorbidities. The motor and psychiatric phenotypes of this syndrome likely result from cortico-striato-thamalo-cerebellar-cortical pathway dysfunction. We hypothesized that reactive and proactive inhibitory control may be altered in these patients. Using the Stop Signal Task, we assessed reactive and proactive inhibitory control in MD patients with (n = 12) and without (n = 21) deep brain stimulation of the globus pallidus interna and compared their performance to matched healthy controls (n = 24). Reactive inhibition was considered as the ability to stop an already initiated action and measured using the stop signal reaction time. Proactive inhibition was assessed through the influence of several consecutive GO or STOP trials on decreased response time or inhibitory process facilitation. The proactive inhibition was solely impaired in unoperated MD patients. Patients with deep brain stimulation showed impairment in reactive inhibition, independent of presence of obsessive–compulsive disorders. This impairment in reactive inhibitory control correlated with intrinsic severity of myoclonus (i.e. pre-operative score). The results point to a dissociation in reactive and proactive inhibitory control in MD patients with and without deep brain stimulation of the globus pallidus interna.

Published
2020
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31. Automated Categorization of Parkinsonian Syndromes Using Magnetic Resonance Imaging in a Clinical Setting

Author

Louise-Laure Mariani, Marie Villotte, Alexis Brice, Lydia Yahia-Cherif, Lydia Chougar, Romain Valabregue, Christine Payan, David Grabli, Emma Biondetti, Rahul Gaurav, Olivier Colliot, Johann Faouzi, Nadya Pyatigorskaya, Gwendoline Dupont, Stéphane Lehéricy, Ines Piot, Jean-Christophe Corvol, Florence Cormier, M. Vidailhet, Bertrand Degos, Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Service de Neuroradiologie [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université, Centre de Neuro-Imagerie de Recherche (CENIR), Université de Paris - Faculté de Médecine Paris Centre (UP Médecine Paris Centre), Université de Paris (UP), Service des Maladies du Système Nerveux [CHU Pitié-Salpêtrière], Service de neurochirurgie [CHU de Dijon], Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), BESPIM, Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Centre interdisciplinaire de recherche en biologie (CIRB), Collège de France (CdF (institution))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Hôpital Avicenne [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Algorithms, models and methods for images and signals of the human brain (ARAMIS), Sorbonne Université (SU)-Inria de Paris, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Center for NeuroImaging Research-Human MRI Neuroimaging core facility for clinical research [ICM Paris] (CENIR), Université Paris Cité - UFR Médecine Paris Centre [Santé] (UPC Médecine Paris Centre), Université Paris Cité (UPC), Pôle des Maladies du Système Nerveux [CHU Pitié-Salpêtrière] (Pôle MSN), Labex MemoLife, École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Collège de France (CdF (institution))-Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), PARK-AI, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Université de Paris - UFR Médecine Paris Centre [Santé] (UP Médecine Paris Centre), École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS Paris), Institut du Cerveau = Paris Brain Institute (ICM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Institut du Cerveau = Paris Brain Institute (ICM), 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)-Centre National de la Recherche Scientifique (CNRS), UFR Médecine [Santé] - Université Paris Cité (UFR Médecine UPCité), Université Paris Cité (UPCité), Service de neurochirurgie [CHU Dijon], and ANR-19-P3IA-0001,PRAIRIE,PaRis Artificial Intelligence Research InstitutE(2019)

Subjects
0301 basic medicine, medicine.medical_specialty, Parkinson's disease, multiple system atrophy, Progressive supranuclear palsy, Diagnosis, Differential, 03 medical and health sciences, 0302 clinical medicine, Physical medicine and rehabilitation, Parkinsonian Disorders, medicine, Humans, multimodal magnetic resonance imaging, Receiver operating characteristic, medicine.diagnostic_test, business.industry, Parkinsonism, Magnetic resonance imaging, progressive supranuclear palsy, medicine.disease, Magnetic Resonance Imaging, 3. Good health, nervous system diseases, machine learning algorithm, 030104 developmental biology, Diffusion Tensor Imaging, Neurology, Categorization, nervous system, Cohort, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Neurology (clinical), Supranuclear Palsy, Progressive, business, 030217 neurology & neurosurgery, Diffusion MRI
Abstract

Background Machine learning algorithms using magnetic resonance imaging (MRI) data can accurately discriminate parkinsonian syndromes. Validation in patients recruited in routine clinical practice is missing. Objective The aim of this study was to assess the accuracy of a machine learning algorithm trained on a research cohort and tested on an independent clinical replication cohort for the categorization of parkinsonian syndromes. Methods Three hundred twenty-two subjects, including 94 healthy control subjects, 119 patients with Parkinson's disease (PD), 51 patients with progressive supranuclear palsy (PSP) with Richardson's syndrome, 35 with multiple system atrophy (MSA) of the parkinsonian variant (MSA-P), and 23 with MSA of the cerebellar variant (MSA-C), were recruited. They were divided into a training cohort (n = 179) scanned in a research environment and a replication cohort (n = 143) examined in clinical practice on different MRI systems. Volumes and diffusion tensor imaging (DTI) metrics in 13 brain regions were used as input for a supervised machine learning algorithm. To harmonize data across scanners and reduce scanner-dependent effects, we tested two types of normalizations using patient data or healthy control data. Results In the replication cohort, high accuracies were achieved using volumetry in the classification of PD-PSP, PD-MSA-C, PSP-MSA-C, and PD-atypical parkinsonism (balanced accuracies: 0.840-0.983, area under the receiver operating characteristic curves: 0.907-0.995). Performances were lower for the classification of PD-MSA-P, MSA-C-MSA-P (balanced accuracies: 0.765-0.784, area under the receiver operating characteristic curve: 0.839-0.871) and PD-PSP-MSA (balanced accuracies: 0.773). Performance using DTI was improved when normalizing by controls, but remained lower than that using volumetry alone or combined with DTI. Conclusions A machine learning approach based on volumetry enabled accurate classification of subjects with early-stage parkinsonism, examined on different MRI systems, as part of their clinical assessment. © 2020 International Parkinson and Movement Disorder Society.

Published
2020
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32. Impulsive prepotent actions and tics in Tourette disorder underpinned by a common neural network

Author

Yulia Worbe, Benoit Beranger, Trevor W. Robbins, Romain Valabregue, Camille-Albane Porte, Yanica Klein, Cyril Atkinson-Clement, Cécile Delorme, Cecile Gallea, Astrid de Liege, Andreas Hartmann, Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Centre De Référence National 'Syndrome Gilles de la Tourette', Pôle des Maladies du Système Nerveux [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre de Neuro-Imagerie de Recherche (CENIR), University of Cambridge [UK] (CAM), Unité de neurophysiologie [CHU Saint-Antoine], CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Robbins, Trevor W [0000-0003-0642-5977], Worbe, Yulia [0000-0001-5903-9370], and Apollo - University of Cambridge Repository

Subjects
0301 basic medicine, Adult, medicine.medical_specialty, Tics, [SDV]Life Sciences [q-bio], Caudate nucleus, Audiology, Impulsivity, Article, 03 medical and health sciences, Cellular and Molecular Neuroscience, 0302 clinical medicine, Neuroimaging, mental disorders, medicine, Attention deficit hyperactivity disorder, Humans, Vocal tics, Molecular Biology, Functional connectivity, medicine.disease, Psychiatry and Mental health, 030104 developmental biology, Tic Disorders, Impulsive Behavior, Neural Networks, Computer, medicine.symptom, Large group, Psychology, Psychiatric disorders, 030217 neurology & neurosurgery, Neuroscience, Tourette Syndrome
Abstract

Tourette disorder (TD), which is characterized by motor and vocal tics, is not in general considered as a product of impulsivity, despite a frequent association with attention deficit hyperactivity disorder and impulse control disorders. It is unclear which type of impulsivity, if any, is intrinsically related to TD and specifically to the severity of tics. The waiting type of motor impulsivity, defined as the difficulty to withhold a specific action, shares some common features with tics. In a large group of adult TD patients compared to healthy controls, we assessed waiting motor impulsivity using a behavioral task, as well as structural and functional underpinnings of waiting impulsivity and tics using multi-modal neuroimaging protocol. We found that unmedicated TD patients showed increased waiting impulsivity compared to controls, which was independent of comorbid conditions, but correlated with the severity of tics. Tic severity did not account directly for waiting impulsivity, but this effect was mediated by connectivity between the right orbito-frontal cortex with caudate nucleus bilaterally. Waiting impulsivity in unmedicated patients with TD also correlated with a higher gray matter signal in deep limbic structures, as well as connectivity with cortical and with cerebellar regions on a functional level. Neither behavioral performance nor structural or functional correlates were related to a psychometric measure of impulsivity or impulsive behaviors in general. Overall, the results suggest that waiting impulsivity in TD was related to tic severity, to functional connectivity of orbito-frontal cortex with caudate nucleus and to structural changes within limbic areas.

Published
2020
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33. The supplementary motor area modulates interhemispheric interactions during movement preparation

Author

Elodie Hainque, Cecilia Bonnet, Vanessa Brochard, Emmanuel Roze, Constance Flamand-Roze, Oriane Trouillard, Jean-Charles Lamy, Cecile Gallea, Stéphane Lehéricy, Isabelle Dusart, Romain Valabregue, Cécile Hubsch, Benoît Béranger, Traian Popa, Jean-Louis Golmard, Pierre Bitoun, Marie Vidailhet, Bertrand Degos, Norbert Brüggemann, Quentin Welniarz, Sabine Meunier, and Aurélie Méneret

Subjects
Adult, Male, Adolescent, Movement, medicine.medical_treatment, Intention, Mirror movements, Functional Laterality, 050105 experimental psychology, Hand movements, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Healthy volunteers, Coordinated movement, medicine, Humans, 0501 psychology and cognitive sciences, Radiology, Nuclear Medicine and imaging, Research Articles, Movement Disorders, Radiological and Ultrasound Technology, Supplementary motor area, Movement (music), business.industry, 05 social sciences, Motor Cortex, Middle Aged, Evoked Potentials, Motor, SMA, Magnetic Resonance Imaging, Transcranial Magnetic Stimulation, Healthy Volunteers, Transcranial magnetic stimulation, medicine.anatomical_structure, Neurology, Female, Neurology (clinical), Anatomy, business, Neuroscience, Psychomotor Performance, 030217 neurology & neurosurgery
Abstract

The execution of coordinated hand movements requires complex interactions between premotor and primary motor areas in the two hemispheres. The supplementary motor area (SMA) is involved in movement preparation and bimanual coordination. How the SMA controls bimanual coordination remains unclear, although there is evidence suggesting that the SMA could modulate interhemispheric interactions. With a delayed‐response task, we investigated interhemispheric interactions underlying normal movement preparation and the role of the SMA in these interactions during the delay period of unimanual or bimanual hand movements. We used functional MRI and transcranial magnetic stimulation in 22 healthy volunteers (HVs), and then in two models of SMA dysfunction: (a) in the same group of HVs after transient disruption of the right SMA proper by continuous transcranial magnetic theta‐burst stimulation; (b) in a group of 22 patients with congenital mirror movements (CMM), whose inability to produce asymmetric hand movements is associated with SMA dysfunction. In HVs, interhemispheric connectivity during the delay period was modulated according to whether or not hand coordination was required for the forthcoming movement. In HVs following SMA disruption and in CMM patients, interhemispheric connectivity was modified during the delay period and the interhemispheric inhibition was decreased. Using two models of SMA dysfunction, we showed that the SMA modulates interhemispheric interactions during movement preparation. This unveils a new role for the SMA and highlights its importance in coordinated movement preparation.

Published
2019
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34. Automated classification of neurodegenerative parkinsonian syndromes using multimodal magnetic resonance imaging in a clinical setting

Author

Emma Biondetti, Louise-Laure Mariani, Johann Faouzi, Bertrand Degos, Alexis Brice, M. Vidailhet, Jean-Christophe Corvol, Lydia Chougar, Marie Villotte, Olivier Colliot, Gwendoline Dupont, Nadya Pyatigorskaya, Romain Valabregue, David Grabli, Florence Cormier, Stéphane Lehéricy, Christine Payan, Ines Piot, and Rahul Gaurav

Subjects
medicine.medical_specialty, medicine.diagnostic_test, business.industry, Parkinsonism, Magnetic resonance imaging, medicine.disease, Training cohort, nervous system diseases, 030218 nuclear medicine & medical imaging, Parkinsonian syndromes, 03 medical and health sciences, 0302 clinical medicine, Physical medicine and rehabilitation, stomatognathic system, nervous system, Categorization, mental disorders, Replication (statistics), Research environment, Cohort, medicine, business, 030217 neurology & neurosurgery
Abstract

BackgroundSeveral studies have shown that machine learning algorithms using MRI data can accurately discriminate parkinsonian syndromes. Validation under clinical conditions is missing.ObjectivesTo evaluate the accuracy for the categorization of parkinsonian syndromes of a machine learning algorithm trained with a research cohort and tested on an independent clinical replication cohort.Methods361 subjects, including 94 healthy controls, 139 patients with PD, 60 with PSP with Richardson’s syndrome, 41 with MSA of the parkinsonian variant (MSA-P) and 27 with MSA of the cerebellar variant (MSA-P), were recruited. They were divided into a training cohort (n=179) scanned in a research environment, and a replication cohort (n=182), scanned in clinical conditions on different MRI systems. Volumes and DTI metrics in 13 brain regions were used as input for a supervised machine learning algorithm.ResultHigh accuracy was achieved using volumetry in the classification of PD versus PSP, PD versus MSA-P, PD versus MSA-C, PD versus atypical parkinsonian syndromes and PSP versus MSA-C in both cohorts, although slightly lower in the replication cohort (balanced accuracy: 0.800 to 0.915 in the training cohort; 0.741 to 0.928 in the replication cohort). Performance was lower in the classification of PSP versus MSA-P and MSA-P versus MSA-C. When adding DTI metrics, the performance tended to increase in the training cohort, but not in the replication cohort.ConclusionsA machine learning approach based on volumetric and DTI data can accurately classify subjects with early-stage parkinsonism, scanned on different MRI systems, in the setting of their clinical workup.

Published
2020
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35. Multimodal magnetic resonance imaging investigation of basal forebrain damage and cognitive deficits in Parkinson's disease

Author

M. Vidailhet, Claire Ewenczyk, Stéphane Lehéricy, Marie Sarazin, Fatma Gargouri, Nadya Pyatigorskaya, Lydia Yahia-Cherif, Romain Valabregue, Cecile Gallea, Marie Mongin, Gestionnaire, Hal Sorbonne Université, Sorbonne Université (SU), Sorbonne Université - Faculté de Médecine (SU FM), Center for NeuroImaging Research-Human MRI Neuroimaging core facility for clinical research [ICM Paris] (CENIR), Institut du Cerveau = Paris Brain Institute (ICM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Service de Neurologie [CHU Pitié-Salpêtrière], IFR70-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de Neuroradiologie [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Centre Hospitalier Sainte Anne [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Imagerie Moléculaire in Vivo (IMIV - U1023 - ERL9218), Service Hospitalier Frédéric Joliot (SHFJ), Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre de Neuro-Imagerie de Recherche (CENIR), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Service de neurologie 1 [CHU Pitié-Salpétrière], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)

Subjects
Male, cognition, 0301 basic medicine, Parkinson's disease, Basal Forebrain, [SDV.IB.IMA]Life Sciences [q-bio]/Bioengineering/Imaging, resting state fMRI, Neuropsychological Tests, Multimodal Imaging, diffusion MRI, Executive Function, 03 medical and health sciences, 0302 clinical medicine, cholinergic, Cortex (anatomy), Neural Pathways, medicine, Humans, Cognitive Dysfunction, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Prefrontal cortex, Research Articles, Aged, Brain Mapping, Basal forebrain, Resting state fMRI, business.industry, functional connectivity, Fornix, Parkinson Disease, Middle Aged, medicine.disease, Executive functions, Magnetic Resonance Imaging, acetylcholine, Olfactory bulb, [SDV.IB.IMA] Life Sciences [q-bio]/Bioengineering/Imaging, 030104 developmental biology, medicine.anatomical_structure, nervous system, Neurology, Female, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Neurology (clinical), business, Neuroscience, 030217 neurology & neurosurgery, Research Article
Abstract

Background Cognitive deficits in Parkinson's disease (PD) may result from damage in the cortex as well as in the dopaminergic, noradrenergic, and cholinergic inputs to the cortex. Cholinergic inputs to the cortex mainly originate from the basal forebrain and are clustered in several regions, called Ch1 to Ch4, that project to the hippocampus (Ch1‐2), the olfactory bulb (Ch3), and the cortex and amygdala (Ch4). Objective We investigated changes in basal forebrain and their role in cognitive deficits in PD. Methods We studied 52 nondemented patients with PD (Hoehn & Yahr 1‐2) and 25 age‐matched healthy controls using diffusion and resting state functional MRI. Results PD patients had a loss of structural integrity within the Ch1‐2 and Ch3‐4 nuclei of the basal forebrain as well as in the fornix. Tractography showed that the probability of anatomical connection was decreased in PD between Ch3‐4 and the associative prefrontal cortex, occipital cortex, and peri‐insular regions. There was a reduction in functional connectivity between Ch1‐2 and the bilateral hippocampi and parahippocampal gyri, the left middle and superior temporal gyri, and the left fusiform gyrus and between Ch3‐4 and the right inferior frontal gyrus and the right and left thalamus. In Ch1‐2, loss of structural integrity and connectivity correlated with scores at the memory tests, whereas changes in Ch3‐4 correlated with scores of global cognition and executive functions. Conclusion This study highlights the association between deficits of different cholinergic nuclei of the basal forebrain and the extent of cognitive impairments in nondemented PD patients. © 2018 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.

Published
2018
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36. Comparison of spatial normalization strategies of diffusion MRI data for studying motor outcome in subacute-chronic and acute stroke

Author

Claire Kemlin, Charlotte Rosso, Belen Diaz, Stéphane Lehéricy, Sara Leder, Yves Samson, Eric A. Moulton, and Romain Valabregue

Subjects
Male, Normalization (statistics), medicine.medical_specialty, Cognitive Neuroscience, Pyramidal Tracts, 030218 nuclear medicine & medical imaging, Lesion, White matter, Correlation, 03 medical and health sciences, Nerve Fibers, 0302 clinical medicine, Physical medicine and rehabilitation, Fractional anisotropy, medicine, Humans, Aged, Aged, 80 and over, Movement Disorders, business.industry, Middle Aged, Stroke, Diffusion Magnetic Resonance Imaging, medicine.anatomical_structure, Neurology, Acute Disease, Chronic Disease, Corticospinal tract, Spatial normalization, Female, medicine.symptom, business, 030217 neurology & neurosurgery, Diffusion MRI
Abstract

A common means of studying motor recovery in stroke patients is to extract Diffusion Tensor Imaging (DTI) parameters from the corticospinal tract (CST) and correlate them with clinical outcome scores. To that purpose, conducting group-level analyses through spatial normalization has become a popular approach. However, the reliability of such analyses depends on the accuracy of the particular registration strategy employed. To date, most studies have employed scalar-based registration using either high-resolution T1 images or Fractional Anisotropy (FA) maps to warp diffusion data to a common space. However, more powerful registration algorithms exist for aligning major white matter structures, such as Fiber Orientation Distribution (FOD)-based registration. Regardless of the strategy chosen, automatic normalization algorithms are prone to distortions caused by stroke lesions. While lesion masking is a common means to lessen such distortions, the extent of its effect on tract-related DTI parameters and their correlation with motor outcome has yet to be determined. Here, we aimed to address these concerns by first investigating the effect of common T1 and FA-based registration as well as novel FOD-based registration algorithms with and without lesion masking on lesion load and DTI parameter extraction of the CST in datasets typically acquired for subacute-chronic and acute stroke patients. Second, we studied how differences in these procedures influenced correlation strength between CST damage (through DTI parameters) and motor outcome. Our results showed that, for high-quality subacute-chronic stroke data, FOD-based registration captured significantly higher lesion loads and significantly larger FA asymmetries in the CST. This was also associated with significantly stronger correlations in motor outcome with respect to T1 or FA-based registration methods. For acute data acquired in a clinical setting, there were few observed differences, suggesting that commonly employed FA-based registration is appropriate for group-level analyses.

Published
2018
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37. Combined diffusion tensor imaging and magnetic resonance spectroscopy to predict neurological outcome before transjugular intrahepatic portosystemic shunt

Author

Marika Rudler, Damien Galanaud, Dominique Thabut, Philippe Cluzel, Vincent Perlbarg, Małgorzata Marjańska, Nicolas Weiss, Maxime Mallet, Simona Tripon, and Romain Valabregue

Subjects
Cirrhosis, Hepatology, medicine.diagnostic_test, business.industry, medicine.medical_treatment, Gastroenterology, Magnetic resonance imaging, medicine.disease, Asymptomatic, 03 medical and health sciences, 0302 clinical medicine, Ascites, Fractional anisotropy, medicine, 030211 gastroenterology & hepatology, Pharmacology (medical), medicine.symptom, Nuclear medicine, business, Hepatic encephalopathy, Transjugular intrahepatic portosystemic shunt, 030217 neurology & neurosurgery, Diffusion MRI
Abstract

Background Hepatic encephalopathy (HE) may occur after transjugular intrahepatic portosystemic shunt (TIPSS) placement. Multimodal magnetic resonance imaging (MRI), combining anatomical sequences, diffusion tensor imaging (DTI) and 1 H magnetic resonance spectroscopy, is modified in cirrhotic patients. Aims To describe multimodal MRI images before TIPSS, to assess if TIPSS induces changes in multimodal MRI, and to find predictors of HE after TIPSS in patients with cirrhosis. Methods Consecutive cirrhotic patients with an indication for TIPSS were prospectively screened. Diagnosis of minimal HE was performed using psychometric HE test score. Multimodal MRI was performed before and 3 months after TIPSS placement. Results Twenty-five consecutive patients were analysed (median age = 59, male gender 76%, median Child-Pugh score = 8 [5-8], MELD score = 12 [9-17], indication for TIPSS placement: ascites/secondary prophylaxis of variceal bleeding/other 20/3/2), no HE/minimal HE/overt HE: 21/4/0. 8/25 patients developed HE after TIPSS. Before TIPSS placement, metabolite concentrations were different in patients with or without minimal HE (lower myo-inositol, mI, higher glutamate/glutamine), but there were no differences in DTI data. TIPSS placement induced changes in metabolite concentrations even in asymptomatic patients, but not in DTI metrics. Baseline fractional anisotropy was significantly lower in patients who developed HE after TIPSS in five regions of interest. Conclusions TIPSS placement induced significant changes in cerebral metabolites, even in asymptomatic patients. Patients who developed HE after TIPSS displayed lower fractional anisotropy before TIPSS. Brain MRI with DTI acquisition may help selecting patients at risk of HE.

Published
2018
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38. Elucidating the Structural and Functional Correlates of Upper-Limb Poststroke Motor Impairment

Author

Vanessa Brochard, Yves Samson, Claire Kemlin, Charlotte Rosso, Mickael A. Obadia, Sara Leder, Jean-Charles Lamy, Marion Houot, Elena Meseguer, Romain Valabregue, Marion Yger, Jean-Christophe Corvol, and Eric A. Moulton

Subjects
Adult, Male, medicine.medical_specialty, medicine.medical_treatment, Pyramidal Tracts, 030204 cardiovascular system & hematology, Corpus callosum, Brain Ischemia, Corpus Callosum, Upper Extremity, 03 medical and health sciences, 0302 clinical medicine, Physical medicine and rehabilitation, medicine, Humans, Stroke, Neurorehabilitation, Aged, Aged, 80 and over, Advanced and Specialized Nursing, Hand Strength, business.industry, Functional Neuroimaging, Motor Cortex, Middle Aged, Evoked Potentials, Motor, medicine.disease, Magnetic Resonance Imaging, Transcranial Magnetic Stimulation, Transcranial magnetic stimulation, Diffusion Tensor Imaging, medicine.anatomical_structure, Laterality, Upper limb, Female, Neurology (clinical), Primary motor cortex, Cardiology and Cardiovascular Medicine, business, 030217 neurology & neurosurgery, Motor cortex
Abstract

Background and Purpose— Many studies have attempted to bring to light the neural correlates of poststroke motor impairment, but few have used multimodal approach to explain it. The aim of this study was to elucidate neural structural and functional correlates of upper limb motor impairment by combining electrophysiological, anatomic, and functional neuroimaging data. Methods— Forty ischemic stroke patients (median [min–max] age: 63 [33–82] years, time poststroke: 3.5 [1.1–58] months) with unilateral upper limb weakness were included. The upper limb motor impairment was defined by a motor composite score. Simple linear analysis followed by multiple linear regression analysis were performed to identify which variables (corticospinal excitability, laterality indices within the primary motor cortex or corticospinal [CST], and corpus callosum tracts integrity) were the best explaining factors of upper limb motor impairment. Results— There was a significant correlation between the resting motor threshold ratio and CST damage ( r = −0.50 [95% CI, −0.70 to −0.22]; P r = −0.73 [95% CI, −0.85 to −0.54]; P P Conclusions— The implementation of quantitative neurophysiological measurements such as the resting motor threshold as a surrogate marker of impairment could be considered in neurorehabilitation trials.

Published
2019
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39. Automated Acquisition Planning for Magnetic Resonance Spectroscopy in Brain Cancer

Author

Marc Sanson, Romain Valabregue, Anna Luisa Di Stefano, Francesca Branzoli, Małgorzata Marjańska, Patrick J. Bolan, Stéphane Lehéricy, Sara L. Saunders, Lucia Nichelli, and Mehmet Akcakaya

Subjects
In vivo magnetic resonance spectroscopy, Computer science, business.industry, Nuclear magnetic resonance spectroscopy, computer.software_genre, Convolutional neural network, Response to treatment, Article, 030218 nuclear medicine & medical imaging, Brain cancer, Lesion, 03 medical and health sciences, 0302 clinical medicine, Voxel, medicine, Computer vision, Artificial intelligence, medicine.symptom, business, computer, 030217 neurology & neurosurgery
Abstract

In vivo magnetic resonance spectroscopy (MRS) can provide clinically valuable metabolic information from brain tumors that can be used for prognosis and monitoring response to treatment. Unfortunately, this technique has not been widely adopted in clinical practice or even clinical trials due to the difficulty in acquiring and analyzing the data. In this work we propose a computational approach to solve one of the most critical technical challenges: the problem of quickly and accurately positioning an MRS volume of interest (a cuboid voxel) inside a tumor using MR images for guidance. The proposed automated method comprises a convolutional neural network to segment the lesion, followed by a discrete optimization to position an MRS voxel optimally within the lesion. In a retrospective comparison, the novel automated method is shown to provide improved lesion coverage compared to manual voxel placement.

Published
2020
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40. MRI monitoring of temperature and displacement for transcranial focus ultrasound applications

Author

Valéry Ozenne, Harry Ahnine, Stéphane Lehéricy, Pierre Bour, Romain Valabregue, Mathieu Santin, Bruno Quesson, Jean-François Aubry, Charlotte Constans, Pierre Pouget, IHU-LIRYC, Université Bordeaux Segalen - Bordeaux 2-CHU Bordeaux [Bordeaux], Institut Langevin - Ondes et Images (UMR7587) (IL), Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Laboratoire d'Imagerie Paramétrique (LIP), Université Pierre et Marie Curie - Paris 6 (UPMC)-IFR58-Centre National de la Recherche Scientifique (CNRS), Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Centre de Recherche de l'Institut du Cerveau et de la Moelle épinière (CRICM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut de rythmologie et modélisation cardiaque [Pessac] (IHU Liryc), Centre de recherche Cardio-Thoracique de Bordeaux [Bordeaux] (CRCTB), Université Bordeaux Segalen - Bordeaux 2-CHU Bordeaux [Bordeaux]-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Bordeaux [Bordeaux]-Université Bordeaux Segalen - Bordeaux 2, Institut Langevin - Ondes et Images, Université Paris Diderot - Paris 7 (UPD7)-ESPCI ParisTech-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-CHU Pitié-Salpêtrière [APHP], Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [APHP]-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), and Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)

Subjects
Materials science, Acoustic radiation force imaging, [SDV.IB.IMA]Life Sciences [q-bio]/Bioengineering/Imaging, Ultrasonic Therapy, Cognitive Neuroscience, Brain imaging, Neuroimaging, Thermometry, Magnetic resonance guided high intensity focused ultrasound, Proton resonance frequency shift, 050105 experimental psychology, Displacement (vector), lcsh:RC321-571, Body Temperature, 03 medical and health sciences, [SCCO]Cognitive science, 0302 clinical medicine, Animals, Computer Simulation, 0501 psychology and cognitive sciences, Acoustic radiation force, lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry, Image resolution, ComputingMilieux_MISCELLANEOUS, Echo-Planar Imaging, business.industry, 05 social sciences, Ultrasound, Brain, Sound power, Frame rate, Macaca mulatta, Transducer, Neurology, Measurement uncertainty, [SDV.IB]Life Sciences [q-bio]/Bioengineering, business, Magnetic resonance thermometry, 030217 neurology & neurosurgery, Biomedical engineering
Abstract

Background Transcranial focus ultrasound applications applied under MRI-guidance benefit from unrivaled monitoring capabilities, allowing the recording of real-time anatomical information and biomarkers like the temperature rise and/or displacement induced by the acoustic radiation force. Having both of these measurements could allow for better targeting of brain structures, with improved therapy monitoring and safety. Method We investigated the use of a novel MRI-pulse sequence described previously in Bour et al., (2017) to quantify both the displacement and temperature changes under various ultrasound sonication conditions and in different regions of the brain. The method was evaluated in vivo in a non-human primate under anesthesia using a single-element transducer (f = 850 kHz) in a setting that could mimic clinical applications. Acquisition was performed at 3 T on a clinical imaging system using a modified single-shot gradient echo EPI sequence integrating a bipolar motion-sensitive encoding gradient. Four slices were acquired sequentially perpendicularly or axially to the direction of the ultrasound beam with a 1-Hz update frequency and an isotropic spatial resolution of 2-mm. A total of twenty-four acquisitions were performed in three different sets of experiments. Measurement uncertainty of the sequence was investigated under different acoustic power deposition and in different regions of the brain. Acoustic simulation and thermal modeling were performed and compared to experimental data. Results The sequence simultaneously provides relevant information about the focal spot location and visualization of heating of brain structures: 1) The sequence localized the acoustic focus both along as well as perpendicular to the ultrasound direction. Tissue displacements ranged from 1 to 2 μm. 2) Thermal rise was only observed at the vicinity of the skull. Temperature increase ranged between 1 and 2 °C and was observed delayed relative the sonication due to thermal diffusion. 3) The fast frame rate imaging was able to highlight magnetic susceptibility artifacts related to breathing, for the most caudal slices. We demonstrated that respiratory triggering successfully restored the sensitivity of the method (from 0.7 μm to 0.2 μm). 4) These results were corroborated by acoustic simulations. Conclusions The current rapid, multi-slice acquisition and real-time implementation of temperature and displacement visualization may be useful in clinical practices. It may help defining operational safety margins, improving therapy precision and efficacy. Simulations were in good agreement with experimental data and may thus be used prior treatment for procedure planning.

Published
2020
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41. Deep brain activation patterns involved in virtual gait without and with a doorway: An fMRI study

Author

Carine Karachi, Brian Lau, Mélanie Pélégrini-Issac, Romain Valabregue, Jason Sellers, Cecile Gallea, Pierre Leboucher, Marie-Laure Welter, Véronique Marchal, Eric Bertasi, Eric Bardinet, Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Laboratoire d'Imagerie Biomédicale (LIB), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Centre de Neuro-Imagerie de Recherche (CENIR), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Plateforme PRISME [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Service de neurophysiologie [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Service de Neurochirurgie [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Research was funded by the 'Investissements d’Avenir' (investing in the future) program ANR-10-IAIHU-06. This work was supported by a grant from the 'Régie Autonome des Transports Parisiens' (RATP) and the grant ANR 'Technologie de la Santé' [N˚ ANR-GUI-AAP-05 ECOTECH]. The contribution of JS was supported by an ATIP-Avenir grant to BL from the Mairie de Paris., Institut du Cerveau = Paris Brain Institute (ICM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Center for NeuroImaging Research-Human MRI Neuroimaging core facility for clinical research [ICM Paris] (CENIR), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], and Bodescot, Myriam

Subjects
Male, Cerebellum, Physiology, Red nucleus, [SDV.IB.IMA]Life Sciences [q-bio]/Bioengineering/Imaging, Deep Brain Stimulation, medicine.medical_treatment, Walking, Basal Ganglia, Diagnostic Radiology, 0302 clinical medicine, Gait (human), Thalamus, Functional Magnetic Resonance Imaging, Basal ganglia, Medicine and Health Sciences, Image Processing, Computer-Assisted, Gait, Cerebral Cortex, Brain Mapping, Multidisciplinary, Radiology and Imaging, 05 social sciences, Brain, Magnetic Resonance Imaging, medicine.anatomical_structure, Medicine, Female, Brainstem, Anatomy, Gait Analysis, Psychology, Locomotion, Research Article, Adult, Deep brain stimulation, Imaging Techniques, Science, Neuroimaging, Research and Analysis Methods, 050105 experimental psychology, Young Adult, 03 medical and health sciences, Diagnostic Medicine, medicine, Humans, 0501 psychology and cognitive sciences, Biological Locomotion, [SCCO.NEUR]Cognitive science/Neuroscience, [SCCO.NEUR] Cognitive science/Neuroscience, Biology and Life Sciences, Spinal cord, [SDV.IB.IMA] Life Sciences [q-bio]/Bioengineering/Imaging, Caudate Nucleus, Neuroscience, human activities, 030217 neurology & neurosurgery
Abstract

International audience; The human gait program involves many brain areas such as motor cortices, cerebellum, basal ganglia, brainstem, and spinal cord. The mesencephalic locomotor region (MLR), which contains the pedunculopontine (PPN) and cuneiform (CN) nuclei, is thought to be one of the key supraspinal gait generators. In daily life activities, gait primarily occurs in complex conditions, such as through narrow spaces, or while changing direction or performing motor or cognitive tasks. Here, we aim to explore the activity of these subcortical brain areas while walking through narrow spaces, using functional MRI in healthy volunteers and designing a virtual reality task mimicking walking down a hallway, without and with an open doorway to walk through. As a control, we used a virtual moving walkway in the same environment. Twenty healthy volunteers were scanned. Fifteen subjects were selected for second level analysis based on their ability to activate motor cortices. Using the contrast Gait versus Walkway, we found activated clusters in motor cortices, cerebellum, red nucleus, thalamus, and the left MLR including the CN and PPN. Using the contrast Gait with Doorway versus Walkway with Doorway, we found activated clusters in motor cortices, left putamen, left internal pallidum, left substantia nigra, right subthalamic area, and bilateral MLR involving the CN and PPN. Our results suggest that unobstructed gait involves a motor network including the PPN whereas gait through a narrow space requires the additional participation of basal ganglia and bilateral MLR, which may encode environmental cues to adapt locomotion.

Published
2019
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42. Effect of Intermittent Theta Burst Stimulation on the Neural Processing of Emotional Stimuli in Healthy Volunteers

Author

Christian Gaudeau-Bosma, Florence Durand, Palmyre Schenin-King Andrianisaina, Noomane Bouaziz, Dominique Januel, Romain Valabregue, Fanny Thomas, Charles Laidi, René Benadhira, Maxence Thomas, Virginie Moulier, Clémence Isaac, Unité de Recherche Clinique de l'Hôpital de Ville-Evrard [Neuilly-sur-​Marne] (URCVE), Etablissement public de santé de Ville-Evrard (EPS), Centre Hospitalier du Rouvray (Etablissement Spécialisé en Santé Mentale - CH Rouvray), Centre Hospitalier Les Murets [La Queue-en-Brie] (CHLM), 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), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Unité de recherche en NeuroImagerie Applicative Clinique et Translationnelle (UNIACT), Service NEUROSPIN (NEUROSPIN), Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Fondation FondaMental [Créteil], Pôle de Psychiatrie [Hôpital Henri Mondor], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital H. Mondor - A. Chenevier, Gestionnaire, Hal Sorbonne Université, Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), and Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay

Subjects
medicine.medical_specialty, Brain activity and meditation, [SDV]Life Sciences [q-bio], brain, medicine.medical_treatment, emotion, Stimulation, Audiology, Article, 03 medical and health sciences, 0302 clinical medicine, rTMS, Medicine, business.industry, iTBS, Emotional stimuli, Healthy subjects, General Medicine, 030227 psychiatry, [SDV] Life Sciences [q-bio], Transcranial magnetic stimulation, Theta burst, Mood, healthy subjects, Neural processing, business, 030217 neurology & neurosurgery
Abstract

International audience; Background: Intermittent theta burst stimulation (iTBS) is a form of repetitive transcranial magnetic stimulation that has shown to be effective in treatment-resistant depression. Through studying the effect of iTBS on healthy subjects, we wished to attain a greater understanding of its impact on the brain. Our objective was to assess whether 10 iTBS sessions altered the neural processing of emotional stimuli, mood and brain anatomy in healthy subjects. Methods: In this double-blind randomized sham-controlled study, 30 subjects received either active iTBS treatment (10 sessions, two sessions a day) or sham treatment over the left dorsolateral prefrontal cortex. Assessments of mood, structural magnetic resonance imaging (MRI) and functional MRI (fMRI) were performed before and after iTBS sessions. During the fMRI, three different categories of stimuli were presented: positive, negative and neutral photographs. Results: This study showed that, during the presentation of negative stimuli (compared with neutral stimuli), 10 sessions of iTBS increased activity in the left anterior insula. However, iTBS did not induce any change in mood, regional gray matter volume or cortical thickness. Conclusions: iTBS modifies healthy subjects’ brain activity in a key region that processes emotional stimuli. (AFSSAPS: ID-RCB 2010A01032-37).

Published
2021
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43. Longitudinal changes in functional connectivity of cortico-basal ganglia networks in manifests and premanifest huntington's disease

Author

Alexandra Durr, Fatma Gargouri, Vincent Perlbarg, Lydia Yahia-Cherif, Ahmed Ben Hamida, Romain Valabregue, Habib Benali, Sara Fernandez-Vidal, Arnaud Messé, Peter McColgan, Sarah J. Tabrizi, and Stéphane Lehéricy

Subjects
Random graph, Radiological and Ultrasound Technology, 05 social sciences, Cognition, Graph theory, Neurological disorder, medicine.disease, 050105 experimental psychology, 03 medical and health sciences, 0302 clinical medicine, Neurology, Betweenness centrality, Huntington's disease, Basal ganglia, medicine, 0501 psychology and cognitive sciences, Radiology, Nuclear Medicine and imaging, sense organs, Neurology (clinical), Anatomy, skin and connective tissue diseases, Psychology, Neuroscience, 030217 neurology & neurosurgery, Stroop effect
Abstract

Huntington's disease (HD) is a genetic neurological disorder resulting in cognitive and motor impairments. We evaluated the longitudinal changes of functional connectivity in sensorimotor, associative and limbic cortico-basal ganglia networks. We acquired structural MRI and resting-state fMRI in three visits one year apart, in 18 adult HD patients, 24 asymptomatic mutation carriers (preHD) and 18 gender- and age-matched healthy volunteers from the TRACK-HD study. We inferred topological changes in functional connectivity between 182 regions within cortico-basal ganglia networks using graph theory measures. We found significant differences for global graph theory measures in HD but not in preHD. The average shortest path length (L) decreased, which indicated a change toward the random network topology. HD patients also demonstrated increases in degree k, reduced betweeness centrality bc and reduced clustering C. Changes predominated in the sensorimotor network for bc and C and were observed in all circuits for k. Hubs were reduced in preHD and no longer detectable in HD in the sensorimotor and associative networks. Changes in graph theory metrics (L, k, C and bc) correlated with four clinical and cognitive measures (symbol digit modalities test, Stroop, Burden and UHDRS). There were no changes in graph theory metrics across sessions, which suggests that these measures are not reliable biomarkers of longitudinal changes in HD. preHD is characterized by progressive decreasing hub organization, and these changes aggravate in HD patients with changes in local metrics. HD is characterized by progressive changes in global network interconnectivity, whose network topology becomes more random over time. Hum Brain Mapp, 2016. © 2016 Wiley Periodicals, Inc.

Published
2016
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44. Multivariate prediction of functional outcome using lesion topography characterized by acute diffusion tensor imaging

Author

Charlotte Rosso, Stéphane Lehéricy, Eric A. Moulton, Romain Valabregue, Yves Samson, Institut du Cerveau = Paris Brain Institute (ICM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Center for NeuroImaging Research-Human MRI Neuroimaging core facility for clinical research [ICM Paris] (CENIR), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Service de Neuroradiologie [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service d'Urgences Cérébro-Vasculaires [CHU Pitié-Salpêtrière], Gestionnaire, Hal Sorbonne Université, Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Centre de Neuro-Imagerie de Recherche (CENIR), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), and Service des Urgences Cérébro-Vasculaires [CHU Pitié-Salpétriêre]

Subjects
Male, Support Vector Machine, [SDV.IB.IMA]Life Sciences [q-bio]/Bioengineering/Imaging, lcsh:RC346-429, Brain Ischemia, 0302 clinical medicine, Acute stroke, Diagnosis, Computer-Assisted, Stroke, Thrombectomy, Aged, 80 and over, 05 social sciences, Radial diffusivity, Regular Article, Middle Aged, Functional outcome, Prognosis, Outcome (probability), medicine.anatomical_structure, Diffusion tensor imaging, Neurology, lcsh:R858-859.7, Female, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Radiology, medicine.symptom, medicine.medical_specialty, Cognitive Neuroscience, lcsh:Computer applications to medicine. Medical informatics, 050105 experimental psychology, White matter, Lesion, 03 medical and health sciences, Fractional anisotropy, medicine, Humans, 0501 psychology and cognitive sciences, Radiology, Nuclear Medicine and imaging, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], lcsh:Neurology. Diseases of the nervous system, Aged, business.industry, medicine.disease, [SDV.IB.IMA] Life Sciences [q-bio]/Bioengineering/Imaging, Multivariate Analysis, Multivariate prediction, Neurology (clinical), business, Prediction, 030217 neurology & neurosurgery, Diffusion MRI
Abstract

The relationship between stroke topography and functional outcome has largely been studied with binary manual lesion segmentations. However, stroke topography may be better characterized by continuous variables capable of reflecting the severity of ischemia, which may be more pertinent for long-term outcome. Diffusion Tensor Imaging (DTI) constitutes a powerful means of quantifying the degree of acute ischemia and its potential relation to functional outcome. Our aim was to investigate whether using more clinically pertinent imaging parameters with powerful machine learning techniques could improve prediction models and thus provide valuable insight on critical brain areas important for long-term outcome. Eighty-seven thrombolyzed patients underwent a DTI sequence at 24 h post-stroke. Functional outcome was evaluated at 3 months post-stroke with the modified Rankin Score and was dichotomized into good (mRS ≤ 2) and poor (mRS > 2) outcome. We used support vector machines (SVM) to classify patients into good vs. poor outcome and evaluate the accuracy of different models built with fractional anisotropy, mean diffusivity, axial diffusivity, radial diffusivity asymmetry maps, and lesion segmentations in combination with lesion volume, age, recanalization status, and thrombectomy treatment. SVM classifiers built with axial diffusivity maps yielded the best accuracy of all imaging parameters (median [IQR] accuracy = 82.8 [79.3–86.2]%), compared to that of lesion segmentations (76.7 [73.3–82.8]%) when predicting 3-month functional outcome. The analysis revealed a strong contribution of clinical variables, notably – in descending order – lesion volume, thrombectomy treatment, and recanalization status, in addition to the deep white matter at the crossroads of major white matter tracts, represented by brain regions where model weights were highest. Axial diffusivity is a more appropriate imaging marker to characterize stroke topography for predicting long-term outcome than binary lesion segmentations. Keywords: Acute stroke, Prediction, Prognosis, Functional outcome, Diffusion tensor imaging

Published
2019
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45. Early alteration of the locus coeruleus in phenotypic variants of Alzheimer’s disease

Author

Michel Bottlaender, Stéphane Lehéricy, Marie Sarazin, Pierre Macé, Fabien Caillé, Philippe Gervais, Julien Lagarde, Romain Valabregue, Adeline Michel, Pauline Olivieri, Université Sorbonne Paris Cité (USPC), Imagerie Moléculaire in Vivo (IMIV - U1023 - ERL9218), Service Hospitalier Frédéric Joliot (SHFJ), Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Centre Hospitalier Sainte Anne [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut du Cerveau = Paris Brain Institute (ICM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Center for NeuroImaging Research-Human MRI Neuroimaging core facility for clinical research [ICM Paris] (CENIR), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Unité de recherche en NeuroImagerie Applicative Clinique et Translationnelle (UNIACT), Service NEUROSPIN (NEUROSPIN), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Centre de Neuro-Imagerie de Recherche (CENIR), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), and Gestionnaire, Hal Sorbonne Université

Subjects
0301 basic medicine, Male, Amyloid, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Logopenic aphasia, Neurosciences. Biological psychiatry. Neuropsychiatry, Disease, Brief Communication, 03 medical and health sciences, 0302 clinical medicine, Alzheimer Disease, medicine, Humans, RC346-429, Aged, business.industry, General Neuroscience, Prodromal Stage, [SDV.NEU.NB] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Middle Aged, medicine.disease, Phenotype, Pathophysiology, 030104 developmental biology, Locus coeruleus, Female, Locus Coeruleus, Neurology (clinical), Tauopathy, Neurology. Diseases of the nervous system, business, Brief Communications, Neuroscience, 030217 neurology & neurosurgery, RC321-571
Abstract

International audience; Neuropathological studies showed early locus coeruleus (LC) neuronal loss associated with tauopathy in Alzheimer's Disease (AD). We used the LC signal intensity (LC-I) on 3T MRI to assess the LC integrity in AD (n = 37) and controls (n = 17). The LC-I was decreased in AD regardless of typical (amnesic) and atypical presentation (logopenic aphasia/visuo-spatial deficit), from the prodromal stage, and independently of the amyloid load measured by PiB-PET. The LC-I was correlated with memory performance of typical AD. This supports the pathophysiological model in which the LC plays a critical role in AD and may thus be a potential therapeutic target.

Published
2019
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46. Evolution of neocortical folding: A phylogenetic comparative analysis of MRI from 34 primate species

Author

Omer Faruk Gulban, Roberto Toro, Katja Heuer, Romain Valabregue, Anastasia Osoianu, Marc Herbin, Pierre-Louis Bazin, Mathieu Santin, Toro, Roberto, Génétique humaine et fonctions cognitives - Human Genetics and Cognitive Functions (GHFC (UMR_3571 / U-Pasteur_1)), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Max Planck Institute for Human Cognitive and Brain Sciences [Leipzig] (IMPNSC), Max-Planck-Gesellschaft, Centre de Recherches Interdisciplinaires (CRI), Université Paris Cité (UPCité), Maastricht University [Maastricht], Spinoza Center for Neuroimaging [Amsterdam], Netherlands Institute for Neuroscience (NIN), Royal Netherlands Academy of Arts and Sciences (KNAW), Centre de Recherche de l'Institut du Cerveau et de la Moelle épinière (CRICM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), 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), Muséum national d'Histoire naturelle (MNHN), Mécanismes Adaptatifs et Evolution (MECADEV), Muséum national d'Histoire naturelle (MNHN)-Centre National de la Recherche Scientifique (CNRS), KH was supported by the Max Planck International Research Network on Ageing and the Max Planck Institute for Human Cognitive and Brain Sciences. OFG was supported by NWO VIDI grant 864-13-012., We thank Marion Fouquet and Nicolas Traut for their help with the quality control and selection of the human data from ABIDE. We thank Helen D'Arcueil, Alex de Crespigny, Emmanuel Gilissen and Chet Sherwood for allowing us to make accessible their MRI data in the Brain Catalogue. We thank Spencer Arbuckle and Andrew Pruszynski for sharing their macaque data with us and making it openly available. Data acquisition was funded by the MNHN programme e-Museum. The development of BrainBox was supported by the Wellcome Trust through the Open Science Prize., Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris]-Université de Paris (UP), Université de Paris (UP), Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Audition, RS: FPN CN 2, Brain and Cognition, and Brein en Cognitie (Psychologie, FMG)

Subjects
SELECTION, Primates, Evolution, Cognitive Neuroscience, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, MODELS, SEGMENTATION, Lemur, Neocortex, Experimental and Cognitive Psychology, Context (language use), Neuroimaging, PREFRONTAL CORTEX, GYRIFICATION, 050105 experimental psychology, 03 medical and health sciences, 0302 clinical medicine, CEREBRAL-CORTEX, biology.animal, THICKNESS, medicine, Animals, 0501 psychology and cognitive sciences, Primate, GREAT APES, Gyrification, Phylogeny, 030304 developmental biology, VOLUMES, 0303 health sciences, Phylogenesis, biology, Phylogenetic tree, Cerebrum, 05 social sciences, [SDV.NEU.NB] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, HUMANS, Phylogenetic comparative methods, Phenotype, Biological Evolution, Magnetic Resonance Imaging, Folding (chemistry), Neuroanatomy, Neuropsychology and Physiological Psychology, medicine.anatomical_structure, Evolutionary biology, Psychology, 030217 neurology & neurosurgery
Abstract

We conducted a comparative analysis of primate cerebral size and neocortical folding using magnetic resonance imaging data from 65 individuals belonging to 34 different species. We measured several neocortical folding parameters and studied their evolution using phylogenetic comparative methods. Our results suggest that the most likely model for neuroanatomical evolution is one where differences appear randomly (the Brownian Motion model), however, alternative models cannot be completely ruled out. We present estimations of the ancestral primate phenotypes as well as estimations of the rates of phenotypic change. Based on the Brownian Motion model, the common ancestor of primates may have had a folded cerebrum similar to that of a small lemur such as the aye-aye. Finally, we observed a non-linear relationship between fold wavelength and fold depth with cerebral volume. In particular, gyrencephalic primate neocortices across different groups exhibited a strikingly stable fold wavelength of about 12 mm (± 20%), despite a 20-fold variation in cerebral volume. We discuss our results in the context of current theories of neocortical folding.

Published
2019
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47. Simultaneous multi-parametric mapping of total sodium concentration, T1, T2 and ADC at 7 T using a multi-contrast unbalanced SSFP

Author

Michel Luong, Edouard Chazel, Denis Le Bihan, Franck Mauconduit, Lisa Leroi, Romain Valabregue, Cécile Rabrait-Lerman, Mathieu Santin, Eric Giacomini, Arthur Coste, Fawzi Boumezbeur, Ludovic de Rochefort, Julien Valette, Cyril Poupon, Alexandre Vignaud, Service NEUROSPIN (NEUROSPIN), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, Centre de résonance magnétique biologique et médicale (CRMBM), Assistance Publique - Hôpitaux de Marseille (APHM)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Centre d'Exploration Métabolique par Résonance Magnétique [Hôpital de la Timone - AP-HM] (CEMEREM), Assistance Publique - Hôpitaux de Marseille (APHM)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS)-Assistance Publique - Hôpitaux de Marseille (APHM)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS)- Hôpital de la Timone [CHU - APHM] (TIMONE), Aix Marseille Université (AMU), Centre National de la Recherche Scientifique (CNRS), Centre de Neuro-Imagerie de Recherche (CENIR), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Siemens Healthineers [Saint-Denis], Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)-Centre National de la Recherche Scientifique (CNRS), Hôpital de la Timone [CHU - APHM] (TIMONE)-Centre de résonance magnétique biologique et médicale (CRMBM), Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)-Centre National de la Recherche Scientifique (CNRS), Center for NeuroImaging Research-Human MRI Neuroimaging core facility for clinical research [ICM Paris] (CENIR), Institut du Cerveau = Paris Brain Institute (ICM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), de Rochefort, Ludovic, and Centre d'Exploration Métabolique par Résonance Magnétique [Hôpital de la Timone - APHM] (CEMEREM)

Subjects
Materials science, [SPI] Engineering Sciences [physics], Sodium, Diffusion, [SDV]Life Sciences [q-bio], Biomedical Engineering, Biophysics, chemistry.chemical_element, 030218 nuclear medicine & medical imaging, [PHYS] Physics [physics], 03 medical and health sciences, [SPI]Engineering Sciences [physics], 0302 clinical medicine, Flip angle, Effective diffusion coefficient, Radiology, Nuclear Medicine and imaging, ComputingMilieux_MISCELLANEOUS, [PHYS]Physics [physics], Multi parametric, Relaxation (NMR), Steady-state free precession imaging, [SDV] Life Sciences [q-bio], Amplitude, chemistry, Biological system, 030217 neurology & neurosurgery
Abstract

Purpose Quantifying multiple NMR properties of sodium could be of benefit to assess changes in cellular viability in biological tissues. A proof of concept of Quantitative Imaging using Configuration States (QuICS) based on a SSFP sequence with multiple contrasts was implemented to extract simultaneously 3D maps of applied flip angle (FA), total sodium concentration, T1, T2, and Apparent Diffusion Coefficient (ADC). Methods A 3D Cartesian Gradient Recalled Echo (GRE) sequence was used to acquire 11 non-balanced SSFP contrasts at a 6 × 6 × 6 mm3 isotropic resolution with carefully-chosen gradient spoiling area, RF amplitude and phase cycling, with TR/TE = 20/3.2 ms and 25 averages, leading to a total acquisition time of 1 h 18 min. A least-squares fit between the measured and the analytical complex signals was performed to extract quantitative maps from a mono-exponential model. Multiple sodium phantoms with different compositions were studied to validate the ability of the method to measure sodium NMR properties in various conditions. Results Flip angle maps were retrieved. Relaxation times, ADC and sodium concentrations were estimated with controlled precision below 15%, and were in accordance with measurements from established methods and literature. Conclusion The results illustrate the ability to retrieve sodium NMR properties maps, which is a first step toward the estimation of FA, T1, T2, concentration and ADC of 23Na for clinical research. With further optimization of the acquired QuICS contrasts, scan time could be reduced to be suitable with in vivo applications.

Published
2018
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48. Comparative Study of MRI Biomarkers in the Substantia Nigra to Discriminate Idiopathic Parkinson Disease

Author

Claire Ewenczyk, Marie Mongin, M. Vidailhet, Benoît Magnin, Lydia Yahia-Cherif, Romain Valabregue, Cyril Poupon, Nadya Pyatigorskaya, Dario Arnaldi, and Stéphane Lehéricy

Subjects
Male, Substantia nigra, Neuroimaging, Sensitivity and Specificity, 030218 nuclear medicine & medical imaging, 03 medical and health sciences, 0302 clinical medicine, Computer-Assisted, Neuromelanin, Fractional anisotropy, Image Interpretation, Computer-Assisted, Medicine, Humans, Radiology, Nuclear Medicine and imaging, Aged, Female, Magnetic Resonance Imaging, Melanins, Middle Aged, Parkinson Disease, Substantia Nigra, Image Interpretation, business.industry, Adult Brain, Radial diffusivity, Individual level, Mr imaging, Hyperintensity, nervous system, Neurology (clinical), Nuclear medicine, business, 030217 neurology & neurosurgery, Diffusion MRI
Abstract

BACKGROUND AND PURPOSE: Several new MR imaging techniques have shown promising results in patients with Parkinson disease; however, the comparative diagnostic values of these measures at the individual level remain unclear. Our aim was to compare the diagnostic value of MR imaging biomarkers of substantia nigra damage for distinguishing patients with Parkinson disease from healthy volunteers. MATERIALS AND METHODS: Thirty-six patients and 20 healthy volunteers were prospectively included. The MR imaging protocol at 3T included 3D T2-weighted and T1-weighted neuromelanin-sensitive images, diffusion tensor images, and R2* mapping. T2* high-resolution images were also acquired at 7T to evaluate the dorsal nigral hyperintensity sign. Quantitative analysis was performed using ROIs in the substantia nigra drawn manually around the area of high signal intensity on neuromelanin-sensitive images and T2-weighted images. Visual analysis of the substantia nigra neuromelanin-sensitive signal intensity and the dorsolateral nigral hyperintensity on T2* images was performed. RESULTS: There was a significant decrease in the neuromelanin-sensitive volume and signal intensity in patients with Parkinson disease. There was also a significant decrease in fractional anisotropy and an increase in mean, axial, and radial diffusivity in the neuromelanin-sensitive substantia nigra at 3T and a decrease in substantia nigra volume on T2* images. The combination of substantia nigra volume, signal intensity, and fractional anisotropy in the neuromelanin-sensitive substantia nigra allowed excellent diagnostic accuracy (0.93). Visual assessment of both substantia nigra dorsolateral hyperintensity and neuromelanin-sensitive images had good diagnostic accuracy (0.91 and 0.86, respectively). CONCLUSIONS: The combination of neuromelanin signal and volume changes with fractional anisotropy measurements in the substantia nigra showed excellent diagnostic accuracy. Moreover, the high diagnostic accuracy of visual assessment of substantia nigra changes using dorsolateral hyperintensity analysis or neuromelanin-sensitive signal changes indicates that these techniques are promising for clinical practice.

Published
2018

49. P1-321: IMPACT OF THE RIGHT UNCINATE FASCICULUS ON LOW-AWARENESS: INTERACTION WITH AGE

Author

Stéphane Epelbaum, Marion Houot, Bruno Dubois, Federica Cacciamani, Romain Valabregue, and Katia Andrade

Subjects
Right uncinate fasciculus, Psychiatry and Mental health, Cellular and Molecular Neuroscience, Developmental Neuroscience, Epidemiology, business.industry, Health Policy, Medicine, Neurology (clinical), Anatomy, Geriatrics and Gerontology, business
Published
2019
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50. Single-voxel1H spectroscopy in the human hippocampus at 3 T using the LASER sequence: characterization of neurochemical profile and reproducibility

Author

Najib Allaïli, Edward J. Auerbach, Stéphane Lehéricy, Lydia Yahia-Cherif, Romain Valabregue, Philippe Fossati, Maritza Jabourian, Vincent Guillemot, Eric Bardinet, and Małgorzata Marjańska

Subjects
Pathology, medicine.medical_specialty, Reproducibility, Chemistry, Intraclass correlation, Coefficient of variation, Hippocampus, computer.software_genre, Creatine, Glutamine, chemistry.chemical_compound, Nuclear magnetic resonance, Neurochemical, nervous system, Voxel, medicine, Molecular Medicine, Radiology, Nuclear Medicine and imaging, computer, Spectroscopy
Abstract

The hippocampus is crucial for long-term episodic memory and learning. It undergoes structural change in aging and is sensitive to neurodegenerative and psychiatric diseases. MRS studies have seldom been performed in the hippocampus due to technical challenges. The reproducibility of MRS in the hippocampus has not been evaluated at 3 T. The purpose of the present study was to quantify the concentration of metabolites in a small voxel placed in the hippocampus and evaluate the reproducibility of the quantification. Spectra were measured in a 2.4 mL voxel placed in the left hippocampus covering the body and most of the tail of the structure in 10 healthy subjects across three different sessions and quantified using LCModel. High-quality spectra were obtained, which allowed a reliable quantification of 10 metabolites including glutamate and glutamine. Reproducibility of MRS was evaluated with coefficient of variation, standard errors of measurement, and intraclass correlation coefficients. All of these measures showed improvement with increased number of averages. Changes of less than 5% in concentration of N-acetylaspartate, choline-containing compounds, and total creatine and of less than 10% in concentration of myo-inositol and the sum of glutamate and glutamine can be confidently detected between two measurements in a group of 20 subjects. A reliable and reproducible neurochemical profile of the human hippocampus was obtained using MRS at 3 T in a small hippocampal volume.

Published
2015
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