title: Functional immaturity of cortico-basal ganglia networks in Gilles de la Tourette syndrome.
abstract: Gilles de la Tourette syndrome is a clinically heterogeneous disorder with poor known pathophysiology. Recent neuropathological and structural neuroimaging data pointed to the dysfunction of cortico-basal ganglia networks. Nonetheless, it is not clear how these structural changes alter the functional activity of the brain and lead to heterogeneous clinical expressions of the syndrome. The objective of this study was to evaluate global integrative state and organization of functional connections of sensori-motor, associative and limbic cortico-basal ganglia networks, which are likely involved in tics and behavioural expressions of Gilles de la Tourette syndrome. We also tested the hypothesis that specific regions and networks contribute to different symptoms. Data were acquired on 59 adult patients and 27 gender- and age-matched controls using a 3T magnetic resonance imaging scanner. Cortico-basal ganglia networks were constructed from 91 regions of interest. Functional connectivity was quantified using global integration and graph theory measures. We found a stronger functional integration (more interactions among anatomical regions) and a global functional disorganization of cortico-basal ganglia networks in patients with Gilles de la Tourette syndrome compared with controls. All networks were characterized by a shorter path length, a higher number of and stronger functional connections among the regions and by a loss of pivotal regions of information transfer (hubs). The functional abnormalities correlated to tic severity in all cortico-basal ganglia networks, namely in premotor, sensori-motor, parietal and cingulate cortices and medial thalamus. Tic complexity was correlated to functional abnormalities in sensori-motor and associative networks, namely in insula and putamen. Severity of obsessive-compulsive disorder was correlated with functional abnormalities in associative and limbic networks, namely in orbito-frontal and prefrontal dorsolateral cortices. The results suggest that the pattern of functional changes in cortico-basal ganglia networks in patients could reflect a defect in brain maturation. They also support the hypothesis that distinct regions of cortico-basal ganglia networks contribute to the clinical heterogeneity of this syndrome.
authors.affiliation: Inserm, Groupe Hospitalier Pitié-Salpêtrière, Assistance Publique–Hôpitaux de Paris, Centre d’Investigation Clinique CIC 9503, Pôle des Maladies du Système Nerveux, Paris, France. yw327@cam.ac.uk
authors.forename: Yulia
authors.initials: Y
authors.lastname: Worbe
authors.forename: Caroline
authors.initials: C
authors.lastname: Malherbe
authors.forename: Andreas
authors.initials: A
authors.lastname: Hartmann
authors.forename: Mélanie
authors.initials: M
authors.lastname: Pélégrini-Issac
authors.forename: Arnaud
authors.initials: A
authors.lastname: Messé
authors.forename: Marie
authors.initials: M
authors.lastname: Vidailhet
authors.forename: Stéphane
authors.initials: S
authors.lastname: Lehéricy
authors.forename: Habib
authors.initials: H
authors.lastname: Benali
mesh_terms: D000328:Adult; D000704:Analysis of Variance; D001479:Basal Ganglia / Q000098:blood supply / Q000503:physiopathology*; D001931:Brain Mapping; D016022:Case-Control Studies; D002540:Cerebral Cortex / Q000098:blood supply / Q000503:physiopathology*; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008297:Male; D008959:Models, Neurological; D009434:Neural Pathways / Q000098:blood supply / Q000473:pathology; D010100:Oxygen / Q000097:blood; D012044:Regression Analysis; D012720:Severity of Illness Index; D005879:Tourette Syndrome / Q000473:pathology*; D055815:Young Adult
chemical_list: D010100:Oxygen