title: Longitudinal changes in functional connectivity of cortico-basal ganglia networks in manifests and premanifest huntington's disease.
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 37:4112-4128, 2016. © 2016 Wiley Periodicals, Inc.
authors.affiliation: Institut Du Cerveau Et De La Moelle Épinière - ICM, Centre De NeuroImagerie De Recherche - CENIR, Paris, France.|Institut Du Cerveau Et De La Moelle Épinière - ICM, Sorbonne Universités, UPMC Univ Paris 06, Inserm U1127, CNRS UMR 7225, Paris, France.|Advanced Technologies for Medicine and Signals - ATMS, Ecole Nationale D'Ingénieurs De Sfax - ENIS, Sfax Université, Tunisia.
authors.forename: Fatma
authors.initials: F
authors.lastname: Gargouri
authors.affiliation: Department of Computational Neuroscience, University Medical Center Eppendorf, Hamburg University, Germany.|Sorbonne Universités, UPMC Univ Paris 06, CNRS UMR 7371, Inserm UMR_S 1146, Laboratoire D'Imagerie Biomédicale, Paris, F-75013, France.
authors.forename: Arnaud
authors.initials: A
authors.lastname: Messé
authors.affiliation: Institut Du Cerveau Et De La Moelle Épinière - ICM, Centre De NeuroImagerie De Recherche - CENIR, Paris, France.|Sorbonne Universités, UPMC Univ Paris 06, CNRS UMR 7371, Inserm UMR_S 1146, Laboratoire D'Imagerie Biomédicale, Paris, F-75013, France.|Bioinformatics and Biostatistics platform - ICONICS, Institut Du Cerveau Et De La Moelle Épinière - ICM, Paris, France.
authors.forename: Vincent
authors.initials: V
authors.lastname: Perlbarg
authors.affiliation: Institut Du Cerveau Et De La Moelle Épinière - ICM, Centre De NeuroImagerie De Recherche - CENIR, Paris, France.|Institut Du Cerveau Et De La Moelle Épinière - ICM, Sorbonne Universités, UPMC Univ Paris 06, Inserm U1127, CNRS UMR 7225, Paris, France.
authors.forename: Romain
authors.initials: R
authors.lastname: Valabregue
authors.affiliation: Department of Neurodegenerative Disease, UCL Institute of Neurology, London, WC1N 3BG, UK.
authors.forename: Peter
authors.initials: P
authors.lastname: McColgan
authors.affiliation: Institut Du Cerveau Et De La Moelle Épinière - ICM, Centre De NeuroImagerie De Recherche - CENIR, Paris, France.|Institut Du Cerveau Et De La Moelle Épinière - ICM, Sorbonne Universités, UPMC Univ Paris 06, Inserm U1127, CNRS UMR 7225, Paris, France.
authors.forename: Lydia
authors.initials: L
authors.lastname: Yahia-Cherif
authors.affiliation: Institut Du Cerveau Et De La Moelle Épinière - ICM, Centre De NeuroImagerie De Recherche - CENIR, Paris, France.|Institut Du Cerveau Et De La Moelle Épinière - ICM, Sorbonne Universités, UPMC Univ Paris 06, Inserm U1127, CNRS UMR 7225, Paris, France.
authors.forename: Sara
authors.initials: S
authors.lastname: Fernandez-Vidal
authors.affiliation: Advanced Technologies for Medicine and Signals - ATMS, Ecole Nationale D'Ingénieurs De Sfax - ENIS, Sfax Université, Tunisia.
authors.forename: Ahmed
authors.initials: A
authors.lastname: Ben Hamida
authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, CNRS UMR 7371, Inserm UMR_S 1146, Laboratoire D'Imagerie Biomédicale, Paris, F-75013, France.
authors.forename: Habib
authors.initials: H
authors.lastname: Benali
authors.affiliation: Department of Neurodegenerative Disease, UCL Institute of Neurology, London, WC1N 3BG, UK.
authors.forename: Sarah
authors.initials: S
authors.lastname: Tabrizi
authors.affiliation: Institut Du Cerveau Et De La Moelle Épinière - ICM, Sorbonne Universités, UPMC Univ Paris 06, Inserm U1127, CNRS UMR 7225, Paris, France.|Department of Genetics, APHP, University Hospital Pitié-Salpêtrière, Paris, France.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Durr
authors.affiliation: Institut Du Cerveau Et De La Moelle Épinière - ICM, Centre De NeuroImagerie De Recherche - CENIR, Paris, France. stephane.lehericy@upmc.fr.|Institut Du Cerveau Et De La Moelle Épinière - ICM, Sorbonne Universités, UPMC Univ Paris 06, Inserm U1127, CNRS UMR 7225, Paris, France. stephane.lehericy@upmc.fr.|ICM Team Control of Normal and Abnormal Movement. stephane.lehericy@upmc.fr.|Groupe Hospitalier Pitié-Salpêtrière, Service De Neuroradiologie, Paris, France. stephane.lehericy@upmc.fr.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Lehéricy
mesh_terms: D000328:Adult; D001479:Basal Ganglia / Q000000981:diagnostic imaging* / Q000503:physiopathology*; D001931:Brain Mapping; D002540:Cerebral Cortex / Q000000981:diagnostic imaging* / Q000503:physiopathology*; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D006816:Huntington Disease / Q000000981:diagnostic imaging* / Q000235:genetics / Q000503:physiopathology*; D007091:Image Processing, Computer-Assisted; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009434:Neural Pathways / Q000000981:diagnostic imaging / Q000503:physiopathology; D009929:Organ Size; D062706:Prodromal Symptoms; D012146:Rest; D012720:Severity of Illness Index
keywords: Huntington's disease; cortico-basal ganglia networks; graph theory; resting-state functional MRI