Prefrontal-thalamic-cerebellar gray matter networks and executive functioning in schizophrenia

OBJECTIVE: Poor executive functioning is a core deficit in schizophrenia and has been linked to frontal lobe alterations. We aimed to identify (1) prefrontal cerebral areas in which decreased volume is linked to executive dysfunction in schizophrenia; and (2) areas throughout the brain that are volumetrically related to the prefrontal area identified in the first analysis, thus detecting more extended volumetric networks associated with executive functioning. METHOD: Fifty-three outpatients with schizophrenia and 62 healthy controls, matched for age, gender and handedness, were recruited. High-resolution images were acquired on a 1.5 tesla scanner and regional gray and white matter volumes were analyzed by voxel-based morphometry within SPM5 (statistical parametric mapping, University College London, UK). Executive functioning was assessed using the Wisconsin Card Sorting Test (WCST). RESULTS: Twenty-one patients with poor executive functioning showed reduced dorsolateral prefrontal and anterior cingulate gray matter volume as compared to 30 patients with high WCST performance, with a maximum effect in the left dorsolateral prefrontal cortex. Left dorsolateral prefrontal gray matter volume predicted WCST performance after controlling for possible confounding effects of global cognitive functioning, verbal attention span, negative symptoms, illness duration and education. In this area, both patient groups had less gray matter than healthy controls. Left dorsolateral prefrontal gray matter volume was positively related to dorsal prefrontal, anterior cingulate and parietal gray matter volume; and negatively related to thalamic, cerebellar, pontine and right parahippocampal gray matter volume. CONCLUSIONS: Volumetric alterations in prefrontal-thalamic-cerebellar gray matter networks may lead to executive dysfunction in schizophrenia.