Publications by authors named "Vincent Perlbarg"

43 Publications

Global mean diffusivity: A radiomarker discriminating good outcome long term after traumatic brain injury.

Ann Phys Rehabil Med 2021 Mar 8;64(2):101433. Epub 2021 Feb 8.

AP-HP, Hôpitaux Universitaires Pitié-Salpêtrière-Charles Foix, Neurosurgical Department, NeuroIntensive Care Unit, Paris, France; Sorbonne Université, Groupe de Recherche Clinique Biosfast, Paris, France.

Background: Traumatic brain injury (TBI) is a chronic pathology responsible for cognitive disorders impacting outcome. Global clinical outcome several years after TBI may be associated with anatomical sequelae. Anatomical lesions are not well described because characterizing diffuse axonal injury and brain atrophy require using specific MRI sequences with quantitative measures. The best radiologic parameter to describe the lesions long term after TBI is not known.

Objective: We aimed to first, assess the global volumetric and diffusion parameters related to long-term outcome after TBI and second, define the most discriminating parameter.

Methods: In this observational study, we included 96 patients with severe TBI and 22 healthy volunteers. The mean delay after TBI was 63.2 months [range 31-119]. The Glasgow Outcome Scale Extended (GOS-E) was used to assess the global long-term clinical outcome. All patients underwent multimodal MRI with measures of brain volume, ventricle volume, global fractional anisotropy (FA) and global mean diffusivity (MD).

Results: All 96 participants had significant impairment in global FA, global MD, brain volume and ventricle volume as compared with the 22 controls (P<0.01). Only global MD significantly differed between the "good recovery" group (GOS-E score 7-8) and the other two groups: GOS-E scores 3-4 and 5-6. Brain volume significantly differed between the GOS-E 7-8 and 3-4 groups. Global MD was the most discriminating radiological parameter for the "good recovery" group versus other patients, long term after TBI. FA appeared less relevant at this time. Global atrophy was higher in patients than controls but lacked reliability to discriminate groups of patients.

Conclusion: Global mean diffusivity seems a more promising radiomarker than global FA for discriminating good outcome long term after TBI. Further work is needed to understand the evolution of these long-term radiological parameters after TBI.
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http://dx.doi.org/10.1016/j.rehab.2020.08.002DOI Listing
March 2021

Habituation of auditory startle reflex is a new sign of minimally conscious state.

Brain 2020 07;143(7):2154-2172

Institut du Cerveau et de la Moelle épinière - ICM, Inserm U1127, CNRS UMR 7225, F-75013, Paris, France.

Neurological examination of non-communicating patients relies on a few decisive items that enable the crucial distinction between vegetative state (VS)-also coined unresponsive wakefulness syndrome (UWS)-and minimally conscious state. Over the past 10 years, this distinction has proven its diagnostic value as well as its important prognostic value on consciousness recovery. However, clinicians are currently limited by three factors: (i) the current behavioural repertoire of minimally conscious state items is limited and restricted to a few cognitive domains in the goldstandard revised version of the Coma Recovery Scale; (ii) a proportion of ∼15-20% clinically VS/UWS patients are actually in a richer state than VS/UWS as evidenced by functional brain imaging; and (iii) the neurophysiological and cognitive interpretation of each minimally conscious state item is still unclear and debated. In the current study we demonstrate that habituation of the auditory startle reflex (hASR) tested at bedside constitutes a novel, simple and powerful behavioural sign that can accurately distinguish minimally conscious state from VS/UWS. In addition to enlarging the minimally conscious state items repertoire, and therefore decreasing the low sensitivity of current behavioural measures, we also provide an original and rigorous description of the neurophysiological basis of hASR through a combination of functional (high density EEG and 18F-fluorodeoxyglucose PET imaging) and structural (diffusion tensor imaging MRI) measures. We show that preservation of hASR is associated with the functional and structural integrity of a brain-scale fronto-parietal network, including prefrontal regions related to control of action and inhibition, and meso-parietal areas associated with minimally conscious and conscious states. Lastly, we show that hASR predicts 6-month improvement of consciousness. Taken together, our results show that hASR is a cortically-mediated behaviour, and suggest that it could be a new clinical item to clearly and accurately identify non-communicating patients who are in the minimally conscious state.
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http://dx.doi.org/10.1093/brain/awaa159DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7364741PMC
July 2020

Long-term cognitive disability after traumatic brain injury: Contribution of the DEX relative questionnaires.

Neuropsychol Rehabil 2020 Dec 22;30(10):1905-1924. Epub 2019 May 22.

Sorbonne Université, CNRS, INSERM, Laboratoire d'Imagerie Biomédicale, LIB, Paris, France.

Executive functions are high-level cognitive processes commonly impaired after severe traumatic brain injury (sTBI), which may be associated with persistent anosognosia. The dysexecutive questionnaire (DEX) was designed to assess different domains of executive functioning in daily life. Two versions of the DEX exist (DEX-S completed by the patient, DEX-O completed by a relative) to compare cognitive complaints and patient's awareness. This work was aimed at studying the relevance of DEX-O for assessing daily-life limitations, the persistence of anosognosia and its association with global disability (GOSE) and magnetic resonance imaging (MRI) markers of brain alterations. Sixty-three patients (and relatives) were included within 63.4 months (±20.7) after sTBI. DEX-S and DEX-O scores were significantly positively correlated. We obtained significant correlations between DEX-S and episodic memory and phasic alert but not with executive assessment, GOSE and diffusion MRI markers. DEX-O was significantly correlated with executive function, episodic memory, attention (phasic alert sustained and divided attention), with the GOSE and the volume of the body of the corpus callosum (MRI marker). Anosognosia score (DEX-O minus DEX-S) correlated with mean diffusivity measure. These results highlight the clinical interest of DEX-O in assessing long-term disability.
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http://dx.doi.org/10.1080/09602011.2019.1618345DOI Listing
December 2020

Deep structural brain lesions associated with consciousness impairment early after hemorrhagic stroke.

Sci Rep 2019 03 12;9(1):4174. Epub 2019 Mar 12.

Department of Neurology, Critical Care Neurology, Columbia University, New York, NY, USA.

The purpose of this study was to determine the significance of deep structural lesions for impairment of consciousness following hemorrhagic stroke and recovery at ICU discharge. Our study focused on deep lesions that previously were implicated in studies of disorders of consciousness. We analyzed MRI measures obtained within the first week of the bleed and command following throughout the ICU stay. A machine learning approach was applied to identify MRI findings that best predicted the level consciousness. From 158 intracerebral hemorrhage patients that underwent MRI, one third was unconscious at the time of MRI and half of these patients recovered consciousness by ICU discharge. Deep structural lesions predicted both, impairment and recovery of consciousness, together with established measures of mass effect. Lesions in the midbrain peduncle and pontine tegmentum alongside the caudate nucleus were implicated as critical structures. Unconscious patients predicted to recover consciousness by ICU discharge had better long-term functional outcomes than those predicted to remain unconscious.
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http://dx.doi.org/10.1038/s41598-019-41042-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6414498PMC
March 2019

Alterations of the nigrostriatal pathway in a 6-OHDA rat model of Parkinson's disease evaluated with multimodal MRI.

PLoS One 2018 6;13(9):e0202597. Epub 2018 Sep 6.

UPMC / INSERM UMR975, Brain and Spine Institute, Paris, France.

Parkinson's disease is characterized by neurodegeneration of the dopaminergic neurons in the substantia nigra pars compacta. The 6-hydroxydopamine (6-OHDA) rat model has been used to study neurodegeneration in the nigro-striatal dopaminergic system. The goal of this study was to evaluate the reliability of diffusion MRI and resting-state functional MRI biomarkers in monitoring neurodegeneration in the 6-OHDA rat model assessed by quantitative histology. We performed a unilateral injection of 6-OHDA in the striatum of Sprague Dawley rats to produce retrograde degeneration of the dopamine neurons in the substantia nigra pars compacta. We carried out a longitudinal study with a multi-modal approach combining structural and functional MRI together with quantitative histological validation to follow the effects of the lesion. Functional and structural connectivity were assessed in the brain of 6-OHDA rats and sham rats (NaCl injection) at 3 and 6 weeks post-lesioning using resting-state functional MRI and diffusion-weighted. Our results showed (i) increased functional connectivity in ipsi- and contra-lesioned regions of the cortico-basal ganglia network pathway including the motor cortex, the globus pallidus, and the striatum regions at 3 weeks; (ii) increased fractional anisotropy (FA) in the ipsi- and contralateral striatum of the 6-OHDA group at 3 weeks, and increased axial diffusivity (AD) and mean diffusivity in the ipsilateral striatum at 6 weeks; (iii) a trend for increased FA in both substantia nigra of the 6-OHDA group at 3 weeks. Optical density measurements of tyrosine-hydroxylase (TH) staining of the striatum showed good correlations with the FA and AD measurements in the striatum. No correlations were found between the number of TH-stained dopaminergic neurons and MRI measurements in the substantia nigra. This study suggested that (i) FA and AD were reliable biomarkers to evaluate neurodegeneration in the cortico-basal ganglia network of the 6-OHDA model, (ii) diffusion MRI and resting-state functional MRI (rsfMRI) were not sensitive enough to detect changes in the substantia nigra in this model.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0202597PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6126820PMC
February 2019

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

Aliment Pharmacol Ther 2018 10 4;48(8):863-874. Epub 2018 Sep 4.

Brain-Liver Pitié-Salpêtrière Study Group (BLIPS), Groupe Hospitalier Pitié-Salpêtrière Charles Foix, Paris, France.

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 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.
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http://dx.doi.org/10.1111/apt.14938DOI Listing
October 2018

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

Neuroimage Clin 2018 14;19:858-867. Epub 2018 Jun 14.

INSERM U 1127, CNRS UMR 7225, Sorbonne Universités, UPMC Univ Paris 06 UMR S 1127, Institut du Cerveau et de la Moelle épinière, ICM, F-75013 Paris, France; AP-HP, Pitié-Salpêtrière University Hospital, Department of Genetics, Paris, France; University Pierre and Marie Curie, Neurometabolic Research Group, Paris, France. Electronic address:

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 ( = 15), SCA2 ( = 12), SCA3 ( = 20) and SCA7 ( = 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 ( < 0.05). However, atrophy of cerebellum and pons showed very large effect sizes (>1.2) compared to clinical scores (<0.8). FBA, applied for the first time to SCA, was sensitive to microstructural cross-sectional differences that were not captured by conventional DTI metrics, especially in the less studied SCA7 group. FBA also showed larger effect sizes than DTI metrics.

Conclusion: This study showed that volumetry outperformed clinical scores to measure disease progression in SCA1, SCA2, SCA3 and SCA7. Therefore, we advocate the use of volumetric biomarkers in therapeutic trials of autosomal dominant ataxias. In addition, FBA showed larger effect size than DTI to detect cross-sectional microstructural alterations in patients relative to controls.
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http://dx.doi.org/10.1016/j.nicl.2018.06.011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6005808PMC
January 2019

Treatment with chenodeoxycholic acid in cerebrotendinous xanthomatosis: clinical, neurophysiological, and quantitative brain structural outcomes.

J Inherit Metab Dis 2018 09 20;41(5):799-807. Epub 2018 Mar 20.

Centre de Référence Neurométabolique Adulte, Groupe Hospitalier Pitié-Salpêtrière, Paris, France.

Background: Cerebrotendinous xanthomatosis (CTX) is a rare neurodegenerative disease related to sterols metabolism. It affects both central and peripheral nervous systems but treatment with chenodeoxycholic acid (CDCA) has been reported to stabilize clinical scores and improve nerve conduction parameters. Few quantitative brain structural studies have been conducted to assess the effect of CDCA in CTX.

Methods And Results: We collected retrospectively clinical, neurophysiological, and quantitative brain structural data in a cohort of 14 patients with CTX treated by CDCA over a mean period of 5 years. Plasma cholestanol levels normalized under treatment with CDCA within a few months. We observed a significant clinical improvement in patients up to 25 years old, whose treatment was initiated less than 15 years after the onset of neurological symptoms. Conversely, patients whose treatment was initiated more than 25 years after neurological disease onset continued their clinical deterioration. Eleven patients presented with a length-dependent peripheral neuropathy, whose electrophysiological parameters improved significantly under CDCA. Volumetric analyses in a subset of patients showed no overt volume loss under CDCA. Moreover, diffusion weighted imaging showed improved fiber integrity of the ponto-cerebellar and the internal capsule with CDCA. CDCA was well tolerated in all patients with CTX.

Conclusion: CDCA may reverse the pathophysiological process in patients with CTX, especially if treatment is initiated early in the disease process. Besides tendon xanthoma, this study stresses the need to consider plasma cholestanol measurement in any patient with infantile chronic diarrhea and/or jaundice, juvenile cataract, learning disability and/or autism spectrum disorder, pyramidal signs, cerebellar syndrome or peripheral neuropathy.
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http://dx.doi.org/10.1007/s10545-018-0162-7DOI Listing
September 2018

Use of brain diffusion tensor imaging for the prediction of long-term neurological outcomes in patients after cardiac arrest: a multicentre, international, prospective, observational, cohort study.

Lancet Neurol 2018 04 27;17(4):317-326. Epub 2018 Feb 27.

CNRS, INSERM, Laboratoire d'Imagerie Biomédicale, Sorbonne Université, Paris, France; AP-HP, Hôpital Pitié-Salpêtrière, Sorbonne Université, Paris, France. Electronic address:

Background: Prediction of neurological outcome after cardiac arrest is a major challenge. The aim of this study was to assess whether quantitative whole-brain white matter fractional anisotropy (WWM-FA) measured by diffusion tensor imaging between day 7 and day 28 after cardiac arrest can predict long-term neurological outcome.

Methods: This prospective, observational, cohort study (part of the MRI-COMA study) was done in 14 centres in France, Italy, and Belgium. We enrolled patients aged 18 years or older who had been unconscious for at least 7 days after cardiac arrest into the derivation cohort. The following year, we recruited the validation cohort on the same basis. We also recruited a minimum of five healthy volunteers at each centre for the normalisation procedure. WWM-FA values were compared with standard criteria for unfavourable outcome, conventional MRI sequences (fluid-attenuated inversion recovery and diffusion-weighted imaging), and proton magnetic resonance spectroscopy. The primary outcome was the best achieved Glasgow-Pittsburgh Cerebral Performance Categories (CPC) at 6 months, dichotomised as favourable (CPC 1-2) and unfavourable outcome (CPC 3-5). Prognostication performance was assessed by the area under the receiver operating characteristic (ROC) curves and compared between groups. This study was registered with ClinicalTrials.gov, number NCT00577954.

Findings: Between Oct 1, 2006, and June 30, 2014, 185 patients were enrolled in the derivation cohort, of whom 150 had an interpretable multimodal MRI and were included in the analysis. 33 (22%) patients had a favourable neurological outcome at 6 months. Prognostic accuracy, as quantified by the area under the ROC curve, was significantly higher with the normalised WWM-FA value (area under the ROC curve 0·95, 95% CI 0·91-0·98) than with the standard criteria for unfavourable outcome or other MRI sequences. In a subsequent validation cohort of 50 patients (enrolled between April 1, 2015, and March 31, 2016), a normalised WWM-FA value lower than 0·91, set from the derivation cohort, had a negative predictive value of 71·4% (95% CI 41·9-91·6) and a positive predictive value of 100% (90·0-100), with 89·7% sensitivity (75·8-97·1) and 100% specificity (69·1-100) for the prediction of unfavourable outcome.

Interpretation: In patients who are unconscious 7 days after cardiac arrest, the normalised WWM-FA value, measured by diffusion tensor imaging, could be used to accurately predict neurological outcome at 6 months. This evidence requires confirmation from future large-scale trials with a strict protocol of withdrawal or limitation-of-care decisions and time window for MRI.

Funding: French Ministry of Health, French National Agency for Research, Italian Ministry of Health, and Regione Lombardia.
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http://dx.doi.org/10.1016/S1474-4422(18)30027-9DOI Listing
April 2018

A strategy for multimodal data integration: application to biomarkers identification in spinocerebellar ataxia.

Brief Bioinform 2018 11;19(6):1356-1369

Bioinformatics and Biostatistics Core Facility of the Brain and Spine Institute, La Pitié-Salpêtriére Hospital, Paris, France.

The growing number of modalities (e.g. multi-omics, imaging and clinical data) characterizing a given disease provides physicians and statisticians with complementary facets reflecting the disease process but emphasizes the need for novel statistical methods of data analysis able to unify these views. Such data sets are indeed intrinsically structured in blocks, where each block represents a set of variables observed on a group of individuals. Therefore, classical statistical tools cannot be applied without altering their organization, with the risk of information loss. Regularized generalized canonical correlation analysis (RGCCA) and its sparse generalized canonical correlation analysis (SGCCA) counterpart are component-based methods for exploratory analyses of data sets structured in blocks of variables. Rather than operating sequentially on parts of the measurements, the RGCCA/SGCCA-based integrative analysis method aims at summarizing the relevant information between and within the blocks. It processes a priori information defining which blocks are supposed to be linked to one another, thus reflecting hypotheses about the biology underlying the data blocks. It also requires the setting of extra parameters that need to be carefully adjusted.Here, we provide practical guidelines for the use of RGCCA/SGCCA. We also illustrate the flexibility and usefulness of RGCCA/SGCCA on a unique cohort of patients with four genetic subtypes of spinocerebellar ataxia, in which we obtained multiple data sets from brain volumetry and magnetic resonance spectroscopy, and metabolomic and lipidomic analyses. As a first step toward the extraction of multimodal biomarkers, and through the reduction to a few meaningful components and the visualization of relevant variables, we identified possible markers of disease progression.
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http://dx.doi.org/10.1093/bib/bbx060DOI Listing
November 2018

Early Functional Connectome Integrity and 1-Year Recovery in Comatose Survivors of Cardiac Arrest.

Radiology 2018 Apr 18;287(1):247-255. Epub 2017 Oct 18.

From the Departments of Radiology and Radiological Science (H.I.S., R.D.S.), Anesthesiology and Critical Care Medicine (Y.H., R.D.S.), Neurology (Y.H., R.D.S.), and Neurosurgery (R.D.S.), Johns Hopkins University School of Medicine, 600 N Wolfe St, Phipps 455, Baltimore, MD 21287; Department of Biostatistics, Indiana University Fairbanks School of Public Health, Indianapolis, Ind (S.L.); Department of Neurology, Tufts University School of Medicine, Boston, Mass (J.K.); Institut du Cerveau et de la Moelle Épinière, Groupe Hospitalier Pitié-Salpêtrière, Paris, France (A.D.); Coma Science Group and Department of Neurology, University of Liège, Liège, Belgium (C.D.P., S.L.); Departments of Anesthesia Resuscitation (R.C.) and Neuroradiology (B.J.), Centre Hospitalier Universitaire, Clermont-Ferrand, France; Functional Imaging Laboratory U678, Faculté de Médecine Pierre et Marie Curie, Paris, France (H.B., V.P.); F.M. Kirby Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, Md (J.P.); Medical Resuscitation Service (C.E.L.), Department of Neuroradiology (D.G.), and Neurosurgical Resuscitation Service (L.V., L.P.), Groupe Hospitalier Pitié-Salpêtrière, Assistance Publique-Hôpitaux de Paris, and Université Pierre et Marie Curie, Paris, France; and Department of Biostatistics, Johns Hopkins Bloomberg School of Public Health, Baltimore, Md (B.C.).

Purpose To assess whether early brain functional connectivity is associated with functional recovery 1 year after cardiac arrest (CA). Materials and Methods Enrolled in this prospective multicenter cohort were 46 patients who were comatose after CA. Principal outcome was cerebral performance category at 12 months, with favorable outcome (FO) defined as cerebral performance category 1 or 2. All participants underwent multiparametric structural and functional magnetic resonance (MR) imaging less than 4 weeks after CA. Within- and between-network connectivity was measured in dorsal attention network (DAN), default-mode network (DMN), salience network (SN), and executive control network (ECN) by using seed-based analysis of resting-state functional MR imaging data. Structural changes identified with fluid-attenuated inversion recovery and diffusion-weighted imaging sequences were analyzed by using validated morphologic scales. The association between connectivity measures, structural changes, and the principal outcome was explored with multivariable modeling. Results Patients underwent MR imaging a mean 12.6 days ± 5.6 (standard deviation) after CA. At 12 months, 11 patients had an FO. Patients with FO had higher within-DMN connectivity and greater anticorrelation between SN and DMN and between SN and ECN compared with patients with unfavorable outcome, an effect that was maintained after multivariable adjustment. Anticorrelation of SN-DMN predicted outcomes with higher accuracy than fluid-attenuated inversion recovery or diffusion-weighted imaging scores (area under the receiver operating characteristic curves, respectively, 0.88, 0.74, and 0.71). Conclusion MR imaging-based measures of cerebral functional network connectivity obtained in the acute phase of CA were independently associated with FO at 1 year, warranting validation as early markers of long-term recovery potential in patients with anoxic-ischemic encephalopathy. RSNA, 2017.
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http://dx.doi.org/10.1148/radiol.2017162161DOI Listing
April 2018

Anatomical and functional correlates of cortical motor threshold of the dominant hand.

Brain Stimul 2017 Sep - Oct;10(5):952-958. Epub 2017 May 17.

Inserm U 1127, CNRS UMR 7225, Sorbonne Universités, UPMC Univ Paris 06, UMR S 1127, Institut du Cerveau et de la Moelle épinière, ICM, F-75013, Paris, France; Centre de Neuro-imagerie de Recherche, CENIR, F-75013, Paris, France.

Background: Resting Motor threshold (rMT) provides information about cortical motor excitability. Interestingly, the influences of the structural or functional variability of the motor system on the rMT inter-individual variability have been poorly investigated.

Objective/hypothesis: To investigate relationships between rMT and measures of brain structures and function of the motor system. The hypothesis is that cortical excitability not only depends on the primary motor cortex (M1) but also on the integration of information originating from its vicinity such as premotor (PMd and SMA) and post-central (S1) cortices.

Methods: We measured brain structures, including grey and white matter properties (cortical volume and fiber coherence respectively), and functional interaction (resting-state functional connectivity-FC) in areas contributing to the corticospinal tract axons, i. e, M1, S1, SMA and PMd in the dominant hemisphere of 21 healthy subjects.

Results: The rMT was inversely correlated with the FC between PMd and M1 (r = -0.496, 95%CI: -0.764; -0.081; p = 0.02) and the grey matter volume of the dominant hemisphere (r = -0.463, 95%CI: -0.746; -0.039; p = 0.03). The multiple regression analysis model retained the FC between M1 and PMd (coefficient: -25 ± 9) as well as the grey matter volume of the dominant hemisphere (coefficient: -0.15 ± 0.06) explaining 44% of the variance of the rMT (p: 0.005). When adding age and coil-to-cortex distance, two factors known to influence rMT, the model reached a R2 of 75% (p: 0.0001).

Conclusions: These results underline the major role of the PMd and the cortico-cortical connections toward M1 in the excitation of the corticospinal fibers likely through trans-synaptic pathways.
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http://dx.doi.org/10.1016/j.brs.2017.05.005DOI Listing
April 2018

Default mode and task-positive networks connectivity during the N-Back task in remitted depressed patients with or without emotional residual symptoms.

Hum Brain Mapp 2017 Jul 8;38(7):3491-3501. Epub 2017 Apr 8.

Sorbonne Universités, UPMC Univ Paris 06, Inserm, CNRS, APHP, Institut du cerveau et de la moelle (ICM)-Hôpital Pitié Salpêtrière, Boulevard de l'hôpital, Paris, France.

Clinical remission of depression may be associated with emotional residual symptoms. We studied the association of emotional blunting, rumination with neural networks dynamics in remitted depressed patients and cognitive performance during an N-Back task. Twenty-six outpatients in remission of depression (Hamilton Depressive rating scale score <7) performed an N-Back task during fMRI assessment. All patients had been treated by paroxetine for a minimum of 4 months. Two subgroups of patients [Nonemotionally blunted (NEB) = 14 and emotionally blunted (EB) = 12] were determined. To identify functional network maps across participants, the Network Detection using Independent Component Analysis approach was employed. Within and between Task Positive Network (TPN) and Default Mode Network (DMN) connectivity were assessed and related to variability of performance on the N-Back task and rumination. EB and NEB patients were not different for the level of accurate responses at the N-Back. However over the entire working memory task, the negative correlation between DMN and TPN was significantly lower in the EB than NEB group and was differently related to cognitive performance and rumination. The stronger the negative correlation between DMN and TPN was, the less variable the reaction time during 3-Back task in NEB patients. Moreover the greater the negative correlation between DMN and TPN was, the lower the rumination score in EB patients. Emotional blunting may be associated with compromised monitoring of rumination and cognitive functioning in remitted depressed patients through altered cooperation between DMN and TPN. The study suggests clinical remission in depression is associated with biological heterogeneity. Hum Brain Mapp 38:3491-3501, 2017. © 2017 Wiley Periodicals, Inc.
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http://dx.doi.org/10.1002/hbm.23603DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6866887PMC
July 2017

Brain Gray Matter MRI Morphometry for Neuroprognostication After Cardiac Arrest.

Crit Care Med 2017 Aug;45(8):e763-e771

1Department of Anaesthesiology and Critical Care, Critical Care Unit, University Teaching Hospital of Purpan, Place du Dr Baylac, Toulouse Cedex 9, France.2Critical Care and Anaesthesiology Department, University Teaching Hospital of Purpan, Place du Dr Baylac, Toulouse Cedex 9, France.3Toulouse NeuroImaging Center, Toulouse University, Inserm, UPS, France.4Department of Anaesthesiology and Critical Care, Critical Care Unit, Hopital Dieu Hospital, Narbonne, France.5Department of Anaesthesiology and Critical Care, School of medicine and Surgery, University Milano Bicocca and Hospital San Gerardo, Monza, Italy.6Department of Neuroradiology, University Hospital of Clermont-Ferrand, Clermont-Ferrand, France.7Department of Anaesthesiology and Critical Care, University Hospital of Clermont-Ferrand, Clermont-Ferrand, France.8Laboratoire d'Imagerie Biomédicale (UMR S 1146/UMR 7371), Université Pierre-et-Marie-Curie-Paris 06, Paris, France.9Critical Care and Anaesthesiology Department, Groupe Hospitalier Pitié-Salpétrière, APHP, Paris, France.10Department of Neuroradiology, Groupe Hospitalier Pitié-Salpétrière, APHP, Paris, France.11Cyclotron Research Center and Department of Neurology, University Hospital and University of Liège, Liège, Belgium.12Algology and Palliative Care Department, University Hospital and University of Liège, Liège, Belgium.

Objectives: We hypothesize that the combined use of MRI cortical thickness measurement and subcortical gray matter volumetry could provide an early and accurate in vivo assessment of the structural impact of cardiac arrest and therefore could be used for long-term neuroprognostication in this setting.

Design: Prospective cohort study.

Setting: Five Intensive Critical Care Units affiliated to the University in Toulouse (France), Paris (France), Clermont-Ferrand (France), Liège (Belgium), and Monza (Italy).

Patients: High-resolution anatomical T1-weighted images were acquired in 126 anoxic coma patients ("learning" sample) 16 ± 8 days after cardiac arrest and 70 matched controls. An additional sample of 18 anoxic coma patients, recruited in Toulouse, was used to test predictive model generalization ("test" sample). All patients were followed up 1 year after cardiac arrest.

Interventions: None.

Measurements And Main Results: Cortical thickness was computed on the whole cortical ribbon, and deep gray matter volumetry was performed after automatic segmentation. Brain morphometric data were employed to create multivariate predictive models using learning machine techniques. Patients displayed significantly extensive cortical and subcortical brain volumes atrophy compared with controls. The accuracy of a predictive classifier, encompassing cortical and subcortical components, has a significant discriminative power (learning area under the curve = 0.87; test area under the curve = 0.96). The anatomical regions which volume changes were significantly related to patient's outcome were frontal cortex, posterior cingulate cortex, thalamus, putamen, pallidum, caudate, hippocampus, and brain stem.

Conclusions: These findings are consistent with the hypothesis of pathologic disruption of a striatopallidal-thalamo-cortical mesocircuit induced by cardiac arrest and pave the way for the use of combined brain quantitative morphometry in this setting.
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http://dx.doi.org/10.1097/CCM.0000000000002379DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5515639PMC
August 2017

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

Hum Brain Mapp 2016 11;37(11):4112-4128

Institut Du Cerveau Et De La Moelle Épinière - ICM, Centre De NeuroImagerie De Recherche - CENIR, Paris, France.

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 37:4112-4128, 2016. © 2016 Wiley Periodicals, Inc.
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http://dx.doi.org/10.1002/hbm.23299DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6867429PMC
November 2016

CATI: A Large Distributed Infrastructure for the Neuroimaging of Cohorts.

Neuroinformatics 2016 07;14(3):253-64

INSERM U708, Neuroepidemiology, CIC-EC7 & Bordeaux University, Bordeaux, France.

This paper provides an overview of CATI, a platform dedicated to multicenter neuroimaging. Initiated by the French Alzheimer's plan (2008-2012), CATI is a research project called on to provide service to other projects like an industrial partner. Its core mission is to support the neuroimaging of large populations, providing concrete solutions to the increasing complexity involved in such projects by bringing together a service infrastructure, the know-how of its expert academic teams and a large-scale, harmonized network of imaging facilities. CATI aims to make data sharing across studies easier and promotes sharing as much as possible. In the last 4 years, CATI has assisted the clinical community by taking charge of 35 projects so far and has emerged as a recognized actor at the national and international levels.
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http://dx.doi.org/10.1007/s12021-016-9295-8DOI Listing
July 2016

Functional Connectivity of Ventral and Dorsal Visual Streams in Posterior Cortical Atrophy.

J Alzheimers Dis 2016 ;51(4):1119-30

INSERM U 1127, CNRS UMR 7225, Sorbonne Universités, and Université Pierre et Marie Curie-Paris 6, UMR S 1127, Institut du Cerveau et de la Moelle épinière (ICM), F-75013 Paris, France.

Background: Posterior cortical atrophy (PCA) induces progressive dysfunction of ventral and dorsal visual networks. Little is known, however, about corresponding changes in functional connectivity (FC).

Objectives: To investigate FC changes in the visual networks, their relationship with cortical atrophy, and the association with Alzheimer's disease (AD) pathology.

Methods: Ten PCA patients and 28 age-matched controls participated in the study. Using resting state fMRI, we measured FC in ventral and dorsal cortical visual networks, defined on the basis of a priori knowledge of long-range white matter connections. To assess the relationships with AD, we determined AD biomarkers in cerebrospinal fluid and FC in the default mode network (DMN), which is vulnerable to AD pathology. Voxel-based morphometry analysis assessed the pattern of grey matter (GM) atrophy.

Results: PCA patients showed GM atrophy in bilateral occipital and inferior parietal regions. PCA patients had lower FC levels in a ventral network than controls, but higher FC in inferior components of the dorsal network. In particular, the increased connectivity correlated with greater GM atrophy in occipital regions. All PCA patients had positive cerebrospinal fluid biomarkers for AD; however, FC in global DMN did not differ from controls.

Conclusions: FC in PCA reflects brain structure in a non-univocal way. Hyperconnectivity of dorsal networks may indicate aberrant communication in response to posterior brain atrophy or processes of neural resilience during the initial stage of brain dysfunction. The lack of difference from controls in global DMN FC highlights the atypical nature of PCA with respect to typical AD.
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http://dx.doi.org/10.3233/JAD-150934DOI Listing
December 2016

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

PLoS One 2015 12;10(11):e0142910. Epub 2015 Nov 12.

Centre de Recherche de l'Institut du Cerveau et de la Moelle épinière, Paris, France.

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.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0142910PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4642950PMC
July 2016

Lateral Temporal Lobe: An Early Imaging Marker of the Presymptomatic GRN Disease?

J Alzheimers Dis 2015 ;47(3):751-9

Sorbonne Universités, UPMC Université Paris 06, UMR S 1127, ICM, Paris, France.

The preclinical stage of frontotemporal lobar degeneration (FTLD) is not well characterized. We conducted a brain metabolism (FDG-PET) and structural (cortical thickness) study to detect early changes in asymptomatic GRN mutation carriers (aGRN+) that were evaluated longitudinally over a 20-month period. At baseline, a left lateral temporal lobe hypometabolism was present in aGRN+ without any structural changes. Importantly, this is the first longitudinal study and, across time, the metabolism more rapidly decreased in aGRN+ in lateral temporal and frontal regions. The main structural change observed in the longitudinal study was a reduction of cortical thickness in the left lateral temporal lobe in carriers. A limit of this study is the relatively small sample (n = 16); nevertheless, it provides important results. First, it evidences that the pathological processes develop a long time before clinical onset, and that early neuroimaging changes might be detected approximately 20 years before the clinical onset of disease. Second, it suggests that metabolic changes are detectable before structural modifications and cognitive deficits. Third, both the baseline and longitudinal studies provide converging results implicating lateral temporal lobe as early involved in GRN disease. Finally, our study demonstrates that structural and metabolic changes could represent possible biomarkers to monitor the progression of disease in the presymptomatic stage toward clinical onset.
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http://dx.doi.org/10.3233/JAD-150270DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4923734PMC
July 2016

Neuroanatomical basis of paroxysmal sympathetic hyperactivity: a diffusion tensor imaging analysis.

Brain Inj 2015 7;29(4):455-61. Epub 2015 Jan 7.

Department of Neurology and Emergency Medicine, Oregon Health & Science University , Portland, OR , USA .

Primary Objective: Paroxysmal sympathetic hyperactivity (PSH) is observed in a sub-set of patients with moderate-to-severe traumatic brain injury (TBI). The neuroanatomical basis of PSH is poorly understood. It is hypothesized that PSH is linked to changes in connectivity within the central autonomic network.

Research Design: Retrospective analysis in a sub-set of patients from a multi-centre, prospective cohort study Methods and procedures: Adult patients who were <3 weeks after severe TBI were enrolled and screened for PSH using a standard definition. Patients underwent multimodal MRI, which included quantitative diffusion tensor imaging.

Main Outcomes And Results: Principal component analysis (PCA) was used to resolve the set of tracts into components. Ability to predict PSH was evaluated via area under the receiver operating characteristic (AUROC) and tree-based classification analyses. Among 102 enrolled patients, 16 met criteria for PSH. The first principle component was significantly associated (p = 0.024, AUROC = 0.867) with PSH status even after controlling for age and admission GCS. In a classification tree analysis, age, GCS and decreased FA in the splenium of the corpus callosum and in the right posterior limb of the internal capsule discriminated PSH vs no PSH with an AUROC of 0.933.

Conclusions: Disconnection involving the posterior corpus callosum and of the posterior limb of the internal capsule may play a role in the pathogenesis or expression of PSH.
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http://dx.doi.org/10.3109/02699052.2014.995229DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4397147PMC
March 2016

Characteristics of the default mode functional connectivity in normal ageing and Alzheimer's disease using resting state fMRI with a combined approach of entropy-based and graph theoretical measurements.

Neuroimage 2014 Nov 9;101:778-86. Epub 2014 Aug 9.

Laboratoire d'Imagerie Fonctionnelle, UMR-S 678, INSERM-UPMC, Paris, France; Laboratoire International de Neuroimagerie et Modélisation, Montréal, Québec, Canada.

Cognitive decline in normal ageing and Alzheimer's disease (AD) emerges from functional disruption in the coordination of large-scale brain systems sustaining cognition. Integrity of these systems can be examined by correlation methods based on analysis of resting state functional magnetic resonance imaging (fMRI). Here we investigate functional connectivity within the default mode network (DMN) in normal ageing and AD using resting state fMRI. Images from young and elderly controls, and patients with AD were processed using spatial independent component analysis to identify the DMN. Functional connectivity was quantified using integration and indices derived from graph theory. Four DMN sub-systems were identified: Frontal (medial and superior), parietal (precuneus-posterior cingulate, lateral parietal), temporal (medial temporal), and hippocampal (bilateral). There was a decrease in antero-posterior interactions (lower global efficiency), but increased interactions within the frontal and parietal sub-systems (higher local clustering) in elderly compared to young controls. This decreased antero-posterior integration was more pronounced in AD patients compared to elderly controls, particularly in the precuneus-posterior cingulate region. Conjoint knowledge of integration measures and graph indices in the same data helps in the interpretation of functional connectivity results, as comprehension of one measure improves with understanding of the other. The approach allows for complete characterisation of connectivity changes and could be applied to other resting state networks and different pathologies.
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http://dx.doi.org/10.1016/j.neuroimage.2014.08.003DOI Listing
November 2014

Age-related changes in functional network connectivity associated with high levels of verbal fluency performance.

Cortex 2014 Sep 8;58:123-38. Epub 2014 Jun 8.

Centre de recherche, Institut universitaire de gériatrie de Montréal, Montréal, Québec, Canada; Faculty of Medicine, Université de Montréal, Montréal, Québec, Canada. Electronic address:

The relative preservation of receptive language abilities in older adults has been associated with adaptive changes in cerebral activation patterns, which have been suggested to be task-load dependent. However, the effects of aging and task demands on the functional integration of neural networks contributing to speech production abilities remain largely unexplored. In the present functional neuroimaging study, data-driven spatial independent component analysis and hierarchical measures of integration were used to explore age-related changes in functional connectivity among cortical areas contributing to semantic, orthographic, and automated word fluency tasks in healthy young and older adults, as well as to assess the effect of age and task demands on the functional integration of a verbal fluency network. The results showed that the functional integration of speech production networks decreases with age, while at the same time this has a marginal effect on behavioral outcomes in high-performing older adults. Moreover, a significant task demand/age interaction was found in functional connectivity within the anterior and posterior subnetworks of the verbal fluency network. These results suggest that local changes in functional integration among cortical areas supporting lexical speech production are modulated by age and task demands.
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http://dx.doi.org/10.1016/j.cortex.2014.05.007DOI Listing
September 2014

Brain networks disconnection in early multiple sclerosis cognitive deficits: an anatomofunctional study.

Hum Brain Mapp 2014 Sep 31;35(9):4706-17. Epub 2014 Mar 31.

Université Pierre et Marie Curie-Paris 6, Centre de Recherche de l'Institut du Cerveau et de la Moelle épinière, UMR-S975, Paris, F-75013, France; Inserm, U975, Paris, F-75013, France; CNRS, UMR 7225, Paris, France; AP-HP, Hôpital de la Salpêtrière, Hôpital Tenon, F-75020, Paris, France.

Severe cognitive impairment involving multiple cognitive domains can occur early during the course of multiple sclerosis (MS). We investigated resting state functional connectivity changes in large-scale brain networks and related structural damage underlying cognitive dysfunction in patients with early MS. Patients with relapsing MS (3-5 years disease duration) were prospectively assigned to two groups based on a standardized neuropsychological evaluation: (1) cognitively impaired group (CI group, n = 15), with abnormal performances in at least 3 tests; (2) cognitively preserved group (CP group, n = 20) with normal performances in all tests. Patients and age-matched healthy controls underwent a multimodal 3T magnetic resonance imaging (MRI) including anatomical T1 and T2 images, diffusion imaging and resting state functional MRI. Structural MRI analysis revealed that CI patients had a higher white matter lesion load compared to CP and a more severe atrophy in gray matter regions highly connected to networks involved in cognition. Functional connectivity measured by integration was increased in CP patients versus controls in attentional networks (ATT), while integration was decreased in CI patients compared to CP both in the default mode network (DMN) and ATT. An anatomofunctional study within the DMN revealed that functional connectivity was mostly altered between the medial prefrontal cortex (MPFC) and the posterior cingulate cortex (PCC) in CI patients compared to CP and controls. In a multilinear regression model, functional correlation between MPFC and PCC was best predicted by PCC atrophy. Disconnection in the DMN and ATT networks may deprive the brain of compensatory mechanisms required to face widespread structural damage.
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http://dx.doi.org/10.1002/hbm.22505DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6869493PMC
September 2014

Combining spatial independent component analysis with regression to identify the subcortical components of resting-state FMRI functional networks.

Brain Connect 2014 Apr;4(3):181-92

1 Inserm/UPMC Univ Paris 6, UMR-S 678, Laboratoire d'Imagerie Fonctionnelle , Paris, France .

Functional brain networks are sets of cortical, subcortical, and cerebellar regions whose neuronal activities are synchronous over multiple time scales. Spatial independent component analysis (sICA) is a widespread approach that is used to identify functional networks in the human brain from functional magnetic resonance imaging (fMRI) resting-state data, and there is now a general agreement regarding the cortical regions involved in each network. It is well known that these cortical regions are preferentially connected with specific subcortical functional territories; however, subcortical components (SC) have not been observed whether in a robust or in a reproducible manner using sICA. This article presents a new method to analyze resting-state fMRI data that enables robust and reproducible association of subcortical regions with well-known patterns of cortical regions. The approach relies on the hypothesis that the time course in subcortical regions is similar to that in cortical regions belonging to the same network. First, sICA followed by hierarchical clustering is performed on cortical time series to extract group functional cortical networks. Second, these networks are complemented with related subcortical areas based on the similarity of their time courses, using an individual general linear model and a random-effect group analysis. Two independent resting-state fMRI datasets were processed, and the SC of both datasets overlapped by 69% to 99% depending on the network, showing the reproducibility and the robustness of our approach. The relationship between SC and functional cortical networks was consistent with functional territories (sensorimotor, associative, and limbic) from an immunohistochemical atlas of the basal ganglia.
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http://dx.doi.org/10.1089/brain.2013.0160DOI Listing
April 2014

White matter changes in comatose survivors of anoxic ischemic encephalopathy and traumatic brain injury: comparative diffusion-tensor imaging study.

Radiology 2014 Feb 7;270(2):506-16. Epub 2013 Nov 7.

From the Department of Neuroradiology (A.W.v.d.E., D.D., D.G.), the Neurosurgical ICU (P.S., L.P.), and the Medical ICU (C.E.L.), Hôpital Pitié-Salpêtrière, Assistance Publique-Hôpitaux de Paris, 47-83 boulevard de l'Hôpital, 75651 Paris Cedex 13, France; Departments of Radiology (A.W.v.d.E.) and Neurology (P.E.V.), Radboud University Nijmegen Medical Centre, Nijmegen, the Netherlands; INSERM, UMRS 678, Université Pierre et Marie Curie-Paris 6, Paris, France (V.P., H.B.); Department of Radiology, Massachusetts General Hospital, Boston, Mass (O.K., J.D., R.G.); Division of Neuroscience Critical Care, Department of Anesthesiology Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, Md (R.D.S.); Department of Neuroradiology, Guy de Chauliac Hospital, Montpellier, France (N.M.d.C.); Department of Neuroradiology, Roger Salengro Hospital, Lille, France (C.D.); Department of Neuroradiology, Centre Hospitalier Universitaire, Rouen, France (E.T.); and Cyclotron Research Center, University of Liège, Liège, Belgium (S.L., A.V.).

Purpose: To analyze white matter pathologic abnormalities by using diffusion-tensor (DT) imaging in a multicenter prospective cohort of comatose patients following cardiac arrest or traumatic brain injury (TBI).

Materials And Methods: Institutional review board approval and informed consent from proxies and control subjects were obtained. DT imaging was performed 5-57 days after insult in 49 cardiac arrest and 40 TBI patients. To control for DT imaging-processing variability, patients' values were normalized to those of 111 control subjects. Automated segmentation software calculated normalized axial diffusivity (λ1) and radial diffusivity (λ⊥) in 19 predefined white matter regions of interest (ROIs). DT imaging variables were compared by using general linear modeling, and side-to-side Pearson correlation coefficients were calculated. P values were corrected for multiple testing (Bonferroni).

Results: In central white matter, λ1 differed from that in control subjects in six of seven TBI ROIs and five of seven cardiac arrest ROIs (all P < .01). The λ⊥ differed from that in control subjects in all ROIs in both patient groups (P < .01). In hemispheres, λ1 was decreased compared with that in control subjects in three of 12 TBI ROIs (P < .05) and nine of 12 cardiac arrest ROIs (P < .01). The λ⊥ was increased in all TBI ROIs (P < .01) and in seven of 12 cardiac arrest ROIs (P < .05). Cerebral hemisphere λ1 was lower in cardiac arrest than in TBI in six of 12 ROIs (P < .01), while λ⊥ was higher in TBI than in cardiac arrest in eight of 12 ROIs (P < .01). Diffusivity values were symmetrically distributed in cardiac arrest (P < .001 for side-to-side correlation) but not in TBI patients.

Conclusion: DT imaging findings are consistent with the known predominance of cerebral hemisphere axonal injury in cardiac arrest and chiefly central myelin injury in TBI. This consistency supports the validity of DT imaging for differentiating axon and myelin damage in vivo in humans.
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http://dx.doi.org/10.1148/radiol.13122720DOI Listing
February 2014

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

PLoS One 2013 27;8(9):e73164. Epub 2013 Sep 27.

Centre de Recherche de l'Institut du Cerveau et de la Moelle Epinière (CRICM), Université Pierre et Marie Curie, Paris, France ; Inserm, U975; CNRS, UMR 7225, Paris, France ; COGIMAGE, CRICM, Paris, France ; APHP, Urgences Cérébro-Vasculaires, Hôpital Pitié-Salpêtrière, Paris, France ; IFR49, DSV/I2BM/NeuroSpin, Université Paris 11, Gif-sur-yvette, France.

Background: Motor 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).

Methods: Twenty-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.

Findings: In 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.

Conclusion: Functional 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.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0073164PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3785485PMC
July 2014

Resting state networks' corticotopy: the dual intertwined rings architecture.

PLoS One 2013 24;8(7):e67444. Epub 2013 Jul 24.

UMR-S 678, Laboratoire d'Imagerie Fonctionnelle, Inserm Univ. Pierre et Marie Curie, Paris 6, Paris, France.

How does the brain integrate multiple sources of information to support normal sensorimotor and cognitive functions? To investigate this question we present an overall brain architecture (called "the dual intertwined rings architecture") that relates the functional specialization of cortical networks to their spatial distribution over the cerebral cortex (or "corticotopy"). Recent results suggest that the resting state networks (RSNs) are organized into two large families: 1) a sensorimotor family that includes visual, somatic, and auditory areas and 2) a large association family that comprises parietal, temporal, and frontal regions and also includes the default mode network. We used two large databases of resting state fMRI data, from which we extracted 32 robust RSNs. We estimated: (1) the RSN functional roles by using a projection of the results on task based networks (TBNs) as referenced in large databases of fMRI activation studies; and (2) relationship of the RSNs with the Brodmann Areas. In both classifications, the 32 RSNs are organized into a remarkable architecture of two intertwined rings per hemisphere and so four rings linked by homotopic connections. The first ring forms a continuous ensemble and includes visual, somatic, and auditory cortices, with interspersed bimodal cortices (auditory-visual, visual-somatic and auditory-somatic, abbreviated as VSA ring). The second ring integrates distant parietal, temporal and frontal regions (PTF ring) through a network of association fiber tracts which closes the ring anatomically and ensures a functional continuity within the ring. The PTF ring relates association cortices specialized in attention, language and working memory, to the networks involved in motivation and biological regulation and rhythms. This "dual intertwined architecture" suggests a dual integrative process: the VSA ring performs fast real-time multimodal integration of sensorimotor information whereas the PTF ring performs multi-temporal integration (i.e., relates past, present, and future representations at different temporal scales).
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0067444PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3722222PMC
February 2014

Functional connectivity changes in second language vocabulary learning.

Brain Lang 2013 Jan 27;124(1):56-65. Epub 2012 Dec 27.

Centre de Recherche Institut de Gériatrie de Montréal, Montreal, Quebec, Canada.

Functional connectivity changes in the language network (Price, 2010), and in a control network involved in second language (L2) processing (Abutalebi & Green, 2007) were examined in a group of Persian (L1) speakers learning French (L2) words. Measures of network integration that characterize the global integrative state of a network (Marrelec, Bellec et al., 2008) were gathered, in the shallow and consolidation phases of L2 vocabulary learning. Functional connectivity remained unchanged across learning phases for L1, whereas total, between- and within-network integration levels decreased as proficiency for L2 increased. The results of this study provide the first functional connectivity evidence regarding the dynamic role of the language processing and cognitive control networks in L2 learning (Abutalebi, Cappa, & Perani, 2005; Altarriba & Heredia, 2008; Leonard et al., 2011; Parker-Jones et al., 2011). Thus, increased proficiency results in a higher degree of automaticity and lower cognitive effort (Segalowitz & Hulstijn, 2005).
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http://dx.doi.org/10.1016/j.bandl.2012.11.008DOI Listing
January 2013

Default-mode network functional connectivity in aphasia: therapy-induced neuroplasticity.

Brain Lang 2013 Jan 27;124(1):45-55. Epub 2012 Dec 27.

Unité de neuroimagerie fonctionnelle, Research Center, Institut Universitaire de Gériatrie de Montréal, 4565 Queen Mary Road, Montreal, Quebec, Canada.

Previous research on participants with aphasia has mainly been based on standard functional neuroimaging analysis. Recent studies have shown that functional connectivity analysis can detect compensatory activity, not revealed by standard analysis. Little is known, however, about the default-mode network in aphasia. In the current study, we studied changes in the default-mode network in subjects with aphasia who underwent semantic feature analysis therapy. We studied nine participants with chronic aphasia and compared them to 10 control participants. For the first time, we identified the default-mode network using spatial independent component analysis, in participants with aphasia. Intensive therapy improved integration in the posterior areas of the default-mode network concurrent with language improvement. Correlations between integration and improvement did not reach significance, but the trend suggests that pre-therapy integration of the default-mode network may predict therapy outcomes. Functional connectivity allows a better understanding of the impact of semantic feature analysis in aphasia.
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http://dx.doi.org/10.1016/j.bandl.2012.11.004DOI Listing
January 2013

Parkinson's disease patients show reduced cortical-subcortical sensorimotor connectivity.

Mov Disord 2013 Apr 9;28(4):447-54. Epub 2012 Nov 9.

UMR-S975, CRICM-INSERM-UPMC Paris 6, Paris, Île-de-France, France.

Reduced dopamine input to cortical and subcortical brain structures, particularly those in the sensorimotor network, is a hallmark of Parkinson's disease (PD). The extent to which dopamine dysfunction affects connectivity within this and other brain networks remains to be investigated. The purpose of this study was to measure anatomical and functional connectivity in groups of PD patients and controls to determine whether connectivity deficits within the cortico-basal ganglia thalamocortical system could be attributed to PD, particularly in sensorimotor connections. A neuroimaging paradigm involving diffusion-weighted magnetic resonance imaging (MRI) and resting-state functional MRI was implemented in a large cohort of PD patients and control subjects. Probabilistic tractography and functional correlation analyses were performed to map connections between brain structures and to derive indices of connectivity that were then used to compare groups. Anatomical connectivity deficits were demonstrated in PD patients, specifically for sensorimotor connections. Functional deficits were also found in some of the same connections. In addition, functional connectivity was found to increase in associative and limbic connections in PD patients compared with controls. This study lends support to findings regarding the dysfunction of the sensorimotor circuit in PD. As deficits in anatomical and functional connectivity within this circuit were in some cases concordant in PD patients, a possible link between brain structure and function is suggested. Increases in functional connectivity in other cortico-basal ganglia thalamocortical circuits may be indicative of compensatory effects in response to system deficits elsewhere.
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http://dx.doi.org/10.1002/mds.25255DOI Listing
April 2013