Effect of personalized dorsolateral prefrontal cortex neuromodulation on default mode connectivity and working memory in schizophrenia spectrum disorders

Abstract

Schizophrenia spectrum disorders (SSD) are marked by working memory impairments associated with abnormal functional brain connectivity. Although transcranial magnetic stimulation (TMS) shows promise in modulating dysconnectivity patterns and improving cognitive symptoms, current protocols often lack target personalization, overlooking significant variability in functional network topography between individuals. Twenty-two individuals with SSD and cognitive deficits underwent 20Hz repetitive TMS to the left lateral prefrontal cortex. Personalized TMS targeted regions with the strongest central executive-default mode network (CEN-DMN) antagonism, while standardized TMS focused on the EEG F3 site. Resting-state fMRI scans were conducted pre- and post-TMS sessions to evaluate changes in CEN-DMN connectivity, and working memory performance was assessed after the post-TMS fMRI scan. Both TMS protocols failed to significantly alter CEN-DMN connectivity or improve cognitive function, which may be due to the low reliability of the biomarker used for personalized targeting. However, stronger DMN intra-network connectivity at the stimulation site was positively correlated with a reduction in CEN-DMN connectivity and improved working memory performance. These findings highlight the need for more extensive fMRI data for better target determination, and suggest that targeting left prefrontal areas with higher DMN connectivity could more effectively modulate functional connectivity and improve working memory performance through TMS.