Shape features of working memory-related deep-brain regions differentiate high and low community functioning in schizophrenia

Abstract

We have previously shown that schizophrenia (SCZ) participants with high community functioning demonstrate better verbal working memory (vWM) performance relative to those with low community functioning. In the present study, we investigated whether neuroanatomical differences in regions supporting vWM also exist between schizophrenia groups that vary on community functioning. Utilizing magnetic resonance imaging, shape features of deep-brain nuclei known to be involved in vWM were calculated in samples of high functioning (HF-SCZ, n = 23) and low functioning schizophrenia participants (LF-SCZ, n = 18), as well as in a group of healthy control participants (CON, n = 45). Large deformation diffeomorphic metric mapping was employed to characterize surface anatomy of the caudate nucleus, globus pallidus, hippocampus, and thalamus. Statistical analyses involved linear mixed-effects models and vertex-wise contrast mapping to assess between-group differences in structural shape features, and Pearson correlations to evaluate relationships between shape metrics and vWM performance. We found significant between-group main effects in deep-brain surface anatomy across all structures. Post-hoc comparisons revealed HF-SCZ and LF-SCZ groups significantly differed on both caudate and hippocampal shape, however, significant correlations with vWM were only observed in hippocampal shape for both SCZ groups. Specifically, more abnormal hippocampal deformation was associated with lower vWM suggesting hippocampal shape is both a neural substrate for vWM deficits and a potential biomarker to predict or monitor the efficacy of cognitive rehabilitation. These findings add to a growing body of literature related to functional outcomes in schizophrenia by demonstrating unique shape patterns across the spectrum of community functioning in SCZ.