title: The neural circuits that generate tics in Tourette's syndrome.
abstract: OBJECTIVE
  The purpose of this study was to examine neural activity and connectivity within cortico-striato-thalamo-cortical circuits and to reveal circuit-based neural mechanisms that govern tic generation in Tourette's syndrome.
  
  
  METHODS
  Functional magnetic resonance imaging data were acquired from 13 individuals with Tourette's syndrome and 21 healthy comparison subjects during spontaneous or simulated tics. Independent component analysis with hierarchical partner matching was used to isolate neural activity within functionally distinct regions of cortico-striato-thalamo-cortical circuits. Granger causality was used to investigate causal interactions among these regions.
  
  
  RESULTS
  The Tourette's syndrome group exhibited stronger neural activity and interregional causality than healthy comparison subjects throughout all portions of the motor pathway, including the sensorimotor cortex, putamen, pallidum, and substantia nigra. Activity in these areas correlated positively with the severity of tic symptoms. Activity within the Tourette's syndrome group was stronger during spontaneous tics than during voluntary tics in the somatosensory and posterior parietal cortices, putamen, and amygdala/hippocampus complex, suggesting that activity in these regions may represent features of the premonitory urges that generate spontaneous tic behaviors. In contrast, activity was weaker in the Tourette's syndrome group than in the healthy comparison group within portions of cortico-striato-thalamo-cortical circuits that exert top-down control over motor pathways (the caudate and anterior cingulate cortex), and progressively less activity in these regions accompanied more severe tic symptoms, suggesting that faulty activity in these circuits may result in their failure to control tic behaviors or the premonitory urges that generate them.
  
  
  CONCLUSIONS
  Our findings, taken together, suggest that tics are caused by the combined effects of excessive activity in motor pathways and reduced activation in control portions of cortico-striato-thalamo-cortical circuits.
authors.affiliation: Magnetic Resonance Imaging Unit, Division of Child and Adolescent Psychiatry, Columbia University, New York, USA. zw2105@columbia.edu
authors.forename: Zhishun
authors.initials: Z
authors.lastname: Wang
authors.forename: Tiago V
authors.initials: TV
authors.lastname: Maia
authors.forename: Rachel
authors.initials: R
authors.lastname: Marsh
authors.forename: Tiziano
authors.initials: T
authors.lastname: Colibazzi
authors.forename: Andrew
authors.initials: A
authors.lastname: Gerber
authors.forename: Bradley S
authors.initials: BS
authors.lastname: Peterson
mesh_terms: D000328:Adult; D002540:Cerebral Cortex / Q000503:physiopathology*; D003342:Corpus Striatum / Q000503:physiopathology*; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009415:Nerve Net / Q000503:physiopathology*; D009434:Neural Pathways / Q000503:physiopathology; D013788:Thalamus / Q000503:physiopathology*; D020323:Tics / Q000503:physiopathology*; D005879:Tourette Syndrome / Q000503:physiopathology*