Psychological Medicine

Original Articles

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

E. Pomarol-Cloteta1a2 c1, R. Salvadora1a2a3, S. Sarróa1a2a4, J. Gomara1a2, F. Vilaa3, Á. Martíneza3, A. Guerreroa1, J. Ortiz-Gila1, B. Sans-Sansaa1, A. Capdevilaa3, J. M. Cebamanosa1 and P. J. McKennaa1a2a5

a1 Benito Menni Complex Assistencial en Salut Mental, Barcelona, Spain

a2 Centro de Investigación Biomédica en Red de Salud Mental (CIBERSam), Spain

a3 Fundació Sant Joan de Déu, Barcelona, Spain

a4 Psychiatry and Clinical Psychology Programme, Universitat Autònoma de Barcelona, Barcelona, Spain

a5 Department of Psychological Medicine, University of Glasgow, Gartnavel Royal Hospital, UK


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.

(Received July 26 2007)

(Revised March 26 2008)

(Accepted April 11 2008)

(Online publication May 29 2008)


c1 Address for correspondence: E. Pomarol-Clotet, M.D., Ph.D., Benito Menni Complex Assistencial en Salut Mental, Barcelona, Spain. (Email: