Correlational analysis reveals differences in functional connectivity in patients with schizophrenia during working memory task performance

Deanna M Barch, Grega Repovš
Department of Psychology, Washington University in Saint Louis, 63130 MO, USA

Individuals with schizophrenia reliably show abnormalities in appropriate task-related activation of a network of regions typically implicated in working memory studies. However, less is known about the degree to which these abnormalities reflect disturbed functional connectivity among the critical elements of the working memory network. We examined task-related functional connectivity in schizophrenia using two approaches: 1) within-subjects across time during performance of verbal and non-verbal working memory tasks, reflecting the trial by trial fluctuations in the coordinated activity of regions involved in working memory; and 2) across participants, reflecting individual differences in the degree to which participants are able to co-activate regions involved in the working memory network. FMRI data during performance of word and face 2-back working memory tasks was acquired from 38 individuals with DSM-IV schizophrenia and 38 demographically similar healthy controls. All the data were preprocessed using standard fMRI methods. A set of 11 regions (bilateral dorsal lateral PFC, inferior PFC, PPC, cerebellum, and thalamus, and ACC) were selected that showed significant activity in both word and face working memory in both patients and controls. The within-subject connectivity analyses indicated that individuals with schizophrenia showed reduced connectivity during both word and face working memory between bilateral DLPFC regions and other cortical regions (inferior PFC, dorsal PPC and ACC), and trend levels reductions in the connections between DLPFC and subcoritical regions. There were no group differences in the degree of connectivity between the other cortical regions or among subcoritical regions. The between subject correlations showed a different pattern of enhanced connectivity of left DLPFC and right inferior PFC with the two thalamic regions, and reduced connectivity between the two cerebellar regions. We hypothesize that the reduced within subject connectivity demonstrated by individuals with schizophrenia reflects impairments in the trial-by-trial ability to appropriate coordinate activity between DLPFC regions and other cortical nodes of the working memory network. In contrast, the enhanced between subject correlations may reflect the fact that individuals with schizophrenia tend to show altered activity across a range of working memory related regions.

In contrast, the enhanced between subject correlations may reflect systematic, state related changes in the recruitment/coupling of the regions during working memory performance.