Decreased limbic and increased fronto-parietal connectivity in unmedicated patients with obsessive-compulsive disorder

Hum Brain Mapp. 2014 Nov;35(11):5617-32. doi: 10.1002/hbm.22574. Epub 2014 Jul 12.

Abstract

Obsessive-compulsive disorder (OCD) is characterized by recurrent intrusive thoughts and ritualized, repetitive behaviors, or mental acts. Convergent experimental evidence from neuroimaging and neuropsychological studies supports an orbitofronto-striato-thalamo-cortical dysfunction in OCD. Moreover, an over excitability of the amygdala and over monitoring of thoughts and actions involving the anterior cingulate, frontal and parietal cortex has been proposed as aspects of pathophysiology in OCD. We chose a data driven, graph theoretical approach to investigate brain network organization in 17 unmedicated OCD patients and 19 controls using resting-state fMRI. OCD patients showed a decreased connectivity of the limbic network to several other brain networks: the basal ganglia network, the default mode network, and the executive/attention network. The connectivity within the limbic network was also found to be decreased in OCD patients compared to healthy controls. Furthermore, we found a stronger connectivity of brain regions within the executive/attention network in OCD patients. This effect was positively correlated with disease severity. The decreased connectivity of limbic regions (amygdala, hippocampus) may be related to several neurocognitive deficits observed in OCD patients involving implicit learning, emotion processing and expectation, and processing of reward and punishment. Limbic disconnection from fronto-parietal regions relevant for (re)-appraisal may explain why intrusive thoughts become and/or remain threatening to patients but not to healthy subjects. Hyperconnectivity within the executive/attention network might be related to OCD symptoms such as excessive monitoring of thoughts and behavior as a dysfunctional strategy to cope with threat and uncertainty.

Keywords: degree; fMRI; functional connectivity; graph analysis; network analysis; network modules; obsessive-compulsive disorder.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Female
  • Frontal Lobe / blood supply
  • Frontal Lobe / pathology*
  • Humans
  • Image Processing, Computer-Assisted
  • Limbic System / blood supply
  • Limbic System / pathology*
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Nerve Net / blood supply
  • Nerve Net / pathology*
  • Obsessive-Compulsive Disorder / pathology*
  • Oxygen
  • Statistics as Topic
  • Statistics, Nonparametric
  • Temporal Lobe / blood supply
  • Temporal Lobe / pathology*
  • Young Adult

Substances

  • Oxygen