Cingulo-Opercular Connectivity Enhances the Repeatability of Transcranial Magnetic Stimulation Target Maps

The effectiveness of transcranial magnetic stimulation (TMS) in the treatment of major depressive disorder (MDD) may be enhanced through individualized targeting in the dorsolateral prefrontal cortex (DLPFC). Recent clinical trials have used TMS targeting based on the subgenual anterior cingulate cortex (sgACC) or right anterior insula (rAI) functional connectivity. However, the repeatability of such individual targeting may present significant challenges for feasibility. We aimed to compare the repeatability of the novel depression core network model-based (CNM) target maps with the sgACC functional connectivity-based and the rAI effective connectivity-based target maps. We further tested whether using a movie stimulus increases the feasibility of individualized functional connectivity-based targeting. In a final sample of 31 patients with treatment-resistant MDD, the repeatability of the target maps was computed as the within-subject spatial correlation among imaging sessions in the DLPFC. Repeatability was compared across the connectivity models. Furthermore, repeatability, head movement, and subjective alertness and comfortableness during functional magnetic resonance imaging (fMRI) were compared between movie and resting-state acquisition. The CNM functional connectivity-based DLPFC target maps were more repeatable than the sgACC- or rAI-based target maps when using a movie stimulus. In particular, the cingulo-opercular seeds from the CNM produced target maps with high repeatability in both resting-state and movie stimulus conditions. Compared with the resting-state, the movie stimulus reduced head movement during fMRI but did not enhance repeatability at a statistically significant level. Our findings support future investigations of multiseed functional connectivity targeting methods, including those focused on the cingulo-opercular regions. These findings also encourage further research on the use of engaging naturalistic stimuli to enhance the feasibility of individualized TMS targeting.