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

Nicolas Rüsch, Ilaria Spoletini, Marko Wilke, Pietro Bria, Margherita Di Paola, Fulvia Di Iulio, Giovanni Martinotti, Carlo Caltagirone, Gianfranco Spalletta

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish
Pages (from-to)79-89
Number of pages11
JournalSchizophrenia Research
Issue number1-3
Publication statusPublished - Jul 2007


  • Dorsolateral prefrontal cortex
  • Executive functioning
  • Schizophrenia
  • Voxel-based morphometry
  • Wisconsin Card Sorting Test

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Behavioral Neuroscience
  • Biological Psychiatry
  • Neurology
  • Psychology(all)


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