Neural Correlates of Global and Specific Cognitive Deficits in Schizophrenia

Cognitive deficits are a core feature of schizophrenia, but the neural mechanisms that contribute to these characteristics are not fully understood. This study investigated whether volume of the dorsal lateral prefrontal cortex (DLPFC), hippocampus, and white matter were associated with impairment in specific cognitive domains, including executive functioning, working memory, verbal memory, verbal fluency, processing speed, versus global functioning. The multi-site data used in this study was collected from the Bipolar and Schizophrenia Network on Intermediate Phenotypes (B-SNIP), and consisted of 206 healthy controls and 247 individuals with either schizophrenia or schizoaffective disorder. The neuroimaging data was segmented based on the Destrieux atlas in FreeSurfer. Linear regression analyses revealed that DLPFC volume was positively associated with executive functioning and processing speed, but not with working memory or verbal memory. Hippocampal volume was positively associated with executive functioning, working memory, and verbal memory, but not with verbal fluency. White matter volume was positively associated with processing speed, but not verbal fluency. Volume of all three brain structures were also associated with global cognitive functioning. However, DLPFC, hippocampal, and white matter volume were significantly associated with executive functioning even when controlling for global cognition, identifying a specific relationship. These findings suggest that volume of the DLPFC, hippocampus, and white matter are associated with both the global cognitive deficit in schizophrenia and with executive functioning, but may not have specific relationships to other cognitive domains over and above the global deficit.