title: Global resting-state functional magnetic resonance imaging analysis identifies frontal cortex, striatal, and cerebellar dysconnectivity in obsessive-compulsive disorder.
abstract: BACKGROUND
  Obsessive-compulsive disorder (OCD) is associated with regional hyperactivity in cortico-striatal circuits. However, the large-scale patterns of abnormal neural connectivity remain uncharacterized. Resting-state functional connectivity studies have shown altered connectivity within the implicated circuitry, but they have used seed-driven approaches wherein a circuit of interest is defined a priori. This limits their ability to identify network abnormalities beyond the prevailing framework. This limitation is particularly problematic within the prefrontal cortex (PFC), which is large and heterogeneous and where a priori specification of seeds is therefore difficult. A hypothesis-neutral, data-driven approach to the analysis of connectivity is vital.
  
  
  METHODS
  We analyzed resting-state functional connectivity data collected at 3T in 27 OCD patients and 66 matched control subjects with a recently developed data-driven global brain connectivity (GBC) method, both within the PFC and across the whole brain.
  
  
  RESULTS
  We found clusters of decreased connectivity in the left lateral PFC in both whole-brain and PFC-restricted analyses. Increased GBC was found in the right putamen and left cerebellar cortex. Within regions of interest in the basal ganglia and thalamus, we identified increased GBC in dorsal striatum and anterior thalamus, which was reduced in patients on medication. The ventral striatum/nucleus accumbens exhibited decreased global connectivity but increased connectivity specifically with the ventral anterior cingulate cortex in subjects with OCD.
  
  
  CONCLUSIONS
  These findings identify previously uncharacterized PFC and basal ganglia dysconnectivity in OCD and reveal differentially altered GBC in dorsal and ventral striatum. Results highlight complex disturbances in PFC networks, which could contribute to disrupted cortical-striatal-cerebellar circuits in OCD.
authors: Department of Psychiatry, Yale University; Abraham Ribicoff Research Facilities, Yale University; NIAAA Center for the Translational Neuroscience of Alcoholism, Yale University.
authors: Alan
authors: A
authors: Anticevic
authors: Department of Psychiatry, Yale University.
authors: Sien
authors: S
authors: Hu
authors: Department of Psychiatry, Yale University.
authors: Sheng
authors: S
authors: Zhang
authors: Department of Psychiatry, Yale University; University Psychiatric Hospital Vrapce, University of Zagreb, Zagreb, Croatia.
authors: Aleksandar
authors: A
authors: Savic
authors: Department of Psychiatry, Yale University.
authors: Eileen
authors: E
authors: Billingslea
authors: Department of Psychiatry, Yale University.
authors: Suzanne
authors: S
authors: Wasylink
authors: Department of Psychology, University of Ljubljana, Ljubljana, Slovenia.
authors: Grega
authors: G
authors: Repovs
authors: Washington University, St. Louis, Missouri.
authors: Michael W
authors: MW
authors: Cole
authors: Department of Psychiatry, Yale University.
authors: Sarah
authors: S
authors: Bednarski
authors: Department of Psychiatry, Yale University; NIAAA Center for the Translational Neuroscience of Alcoholism, Yale University.
authors: John H
authors: JH
authors: Krystal
authors: Department of Psychiatry, Yale University; Child Study Center, Yale University.
authors: Michael H
authors: MH
authors: Bloch
authors: Department of Psychiatry, Yale University; Department of Neurobiology, Yale University; Interdepartmental Neuroscience Program, Yale University.
authors: Chiang-Shan R
authors: CS
authors: Li
authors: Department of Psychiatry, Yale University; Department of Psychology, Yale University; Child Study Center, Yale University; Abraham Ribicoff Research Facilities, Yale University; Interdepartmental Neuroscience Program, Yale University. Electronic address: christopher.pittenger@yale.edu.
authors: Christopher
authors: C
authors: Pittenger
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001921:Brain / Q000187:drug effects / Q000503:physiopathology; D001931:Brain Mapping / Q000379:methods; D002531:Cerebellum / Q000187:drug effects / Q000503:physiopathology*; D003342:Corpus Striatum / Q000187:drug effects / Q000503:physiopathology*; D005260:Female; D005625:Frontal Lobe / Q000187:drug effects / Q000503:physiopathology*; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009434:Neural Pathways / Q000187:drug effects / Q000503:physiopathology; D009771:Obsessive-Compulsive Disorder / Q000188:drug therapy / Q000503:physiopathology* / Q000628:therapy; D012146:Rest / Q000502:physiology*; D055815:Young Adult
keywords: Basal ganglia; functional connectivity; global connectivity; obsessive-compulsive disorder; prefrontal cortex; resting-state fMRI