Neural correlates of set-shifting: decomposing executive functions in schizophrenia

Neural correlates of set-shifting: decomposing executive functions in schizophrenia


J Psychiatry Neurosci 2010; 35(5): 321-329

Andreas Wilmsmeier, MD; Patricia Ohrmann, MD; Thomas Suslow, PhD; Ansgar Siegmund, MD; Katja Koelkebeck, MD; Matthias Rothermundt, MD; Harald Kugel, PhD; Volker Arolt, MD; Jochen Bauer, MSc; Anya Pedersen, PhD

Wilmsmeier, Ohrmann, Suslow, Siegmund, Koelkebeck, Rothermundt, Arolt, Bauer, Pedersen — Department of Psychiatry; Kugel — Department of Clinical Radiology; Pedersen — Department of Psychology, University of Muenster, Muenster, Germany


Background: Although there is considerable evidence that patients with schizophrenia have impaired executive functions, the neural mechanisms underlying these deficits are unclear. Generation and selection is one of the basic mechanisms of executive functioning. We investigated the neural correlates of this mechanism by means of functional magnetic resonance imaging (fMRI) in patients with schizophrenia and healthy controls.

Methods: We used the Wisconsin Card Sorting Test (WCST) in an event-related fMRI study to analyze neural activation patterns during the distinct components of the WCST in 36 patients with schizophrenia and 28 controls. We focused our analyses on the process of set-shifting. After participants received negative feedback, they had to generate and decide on a new sorting rule.

Results: A widespread activation pattern encompassing the inferior and middle frontal gyrus, parietal, temporal and occipital cortices, anterior cingulate cortex (ACC), supplementary motor area, insula, caudate, thalamus and brainstem was observed in patients with schizophrenia after negative versus positive feedback, whereas in healthy controls, significant activation clusters were more confined to the cortical areas. Significantly increased activation in the rostral ACC after negative feedback and in the dorsal ACC during matching after negative feedback were observed in schizophrenia patients compared with controls. Controls showed activation in the bilateral dorsolateral prefrontal cortex (Brodmann area 46), whereas schizophrenia patients showed activation in the right dorsolateral prefrontal cortex only.

Limitations: All patients were taking neuroleptic medication, which has an impact on cognitive function as well as on dopaminergic and serotonergic prefrontal metabolism.

Conclusions: Our data suggest that, in patients with schizophrenia, set-shifting is associated with increased activation in the rostral and dorsal ACC, reflecting higher emotional and cognitive demands, respectively.

Submitted Dec. 13, 2009; Revised Feb. 28, Apr. 13, 2010; Accepted Apr. 13, 2010.

Competing interests: None declared

Contributors: Drs. Wilmsmeier, Ohrmann and Pedersen and Mr. Bauer conceived the study and its design. They, along with Drs. Siegmund, Koelkebeck, Rothermudt and Kugel acquired the data, which was analyzed by Drs. Wilmsmeier, Ohrmann, Kugel and Pedersen and Mr. Bauer. Drs. Wilmsmeier, Ohrmann and Pedersen and Mr. Bauer wrote the manuscript, which was critically revised by all other authors. All of the authors approved the final version submitted for publication.

DOI: 10.1503/jpn.090181

Correspondence to: Dr. P. Ohrmann, Department of Psychiatry, University of Muenster, Albert-Schweitzer-Str. 11, D – 48149 Muenster, Germany;