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Biol Psychiatry. 2014 Apr 15;75(8):595-605. doi: 10.1016/j.biopsych.2013.10.021. Epub 2013 Nov 4.

Global resting-state functional magnetic resonance imaging analysis identifies frontal cortex, striatal, and cerebellar dysconnectivity in obsessive-compulsive disorder.

Author information

  • 1Department of Psychiatry, Yale University; Abraham Ribicoff Research Facilities, Yale University; NIAAA Center for the Translational Neuroscience of Alcoholism, Yale University.
  • 2Department of Psychiatry, Yale University.
  • 3Department of Psychiatry, Yale University; University Psychiatric Hospital Vrapce, University of Zagreb, Zagreb, Croatia.
  • 4Department of Psychology, University of Ljubljana, Ljubljana, Slovenia.
  • 5Washington University, St. Louis, Missouri.
  • 6Department of Psychiatry, Yale University; NIAAA Center for the Translational Neuroscience of Alcoholism, Yale University.
  • 7Department of Psychiatry, Yale University; Child Study Center, Yale University.
  • 8Department of Psychiatry, Yale University; Department of Neurobiology, Yale University; Interdepartmental Neuroscience Program, Yale University.
  • 9Department 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.

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.

© 2013 Society of Biological Psychiatry Published by Society of Biological Psychiatry All rights reserved.

KEYWORDS:

Basal ganglia; functional connectivity; global connectivity; obsessive-compulsive disorder; prefrontal cortex; resting-state fMRI

PMID:
24314349
[PubMed - indexed for MEDLINE]
PMCID:
PMC3969771
Free PMC Article
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