Failure to deactivate in the prefrontal cortex in schizophrenia: dysfunction of the default mode network?

Psychol Med. 2008 Aug;38(8):1185-93. doi: 10.1017/S0033291708003565. Epub 2008 May 29.

Abstract

Background: Functional imaging studies using working memory tasks have documented both prefrontal cortex (PFC) hypo- and hyperactivation in schizophrenia. However, these studies have often failed to consider the potential role of task-related deactivation.

Method: Thirty-two patients with chronic schizophrenia and 32 age- and sex-matched normal controls underwent functional magnetic resonance imaging (fMRI) scanning while performing baseline, 1-back and 2-back versions of the n-back task. Linear models were used to obtain maps of activations and deactivations in the groups.

Results: The controls showed activation in the expected frontal regions. There were also clusters of deactivation, particularly in the anterior cingulate/ventromedial PFC and the posterior cingulate cortex/precuneus. Compared to the controls, the schizophrenic patients showed reduced activation in the right dorsolateral prefrontal cortex (DLPFC) and other frontal areas. There was also an area in the anterior cingulate/ventromedial PFC where the patients showed apparently greater activation than the controls. This represented a failure of deactivation in the schizophrenic patients. Failure to activate was a function of the patients' impaired performance on the n-back task, whereas the failure to deactivate was less performance dependent.

Conclusions: Patients with schizophrenia show both failure to activate and failure to deactivate during performance of a working memory task. The area of failure of deactivation is in the anterior prefrontal/anterior cingulate cortex and corresponds to one of the two midline components of the 'default mode network' implicated in functions related to maintaining one's sense of self.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Diagnostic and Statistical Manual of Mental Disorders
  • Female
  • Humans
  • Magnetic Resonance Imaging
  • Male
  • Memory Disorders / diagnosis
  • Memory Disorders / epidemiology
  • Memory Disorders / physiopathology
  • Middle Aged
  • Nerve Net / physiopathology*
  • Prefrontal Cortex / physiopathology*
  • Schizophrenia / diagnosis
  • Schizophrenia / epidemiology
  • Schizophrenia / physiopathology*