Role of the insula in rTMS response for depression

Background: The insula has a significant impact on interoception and depression. This study aims to explore the role of the insula in mediating treatment responses to high-frequency repetitive transcranial magnetic stimulation (rTMS) targeting the left dorsolateral prefrontal cortex (DLPFC). Methods: Twenty-five patients with either bipolar disorder (BD, n = 15) or major depressive disorder (MDD, n = 10) were recruited. All subjects were aged between 20 and 70, with a minimum score of 18 on the 24-item Hamilton Rating Scale for Depression (HDRS-24). Each patient received 12 sessions of rTMS treatment using a figure-eight-shaped coil at 10 Hz high-frequency stimulation intensity, targeted to the left DLPFC. Resting-state functional magnetic resonance imaging was conducted before and after the rTMS treatment to assess changes in insula-seeded functional connectivity. Results: Both BD and MDD patients experienced significant reductions in depressive symptoms following rTMS therapy. The respective response rates at weeks 4, 8 and 12 were 64.0 %, 64.0 % and 68.0 % and remission rates were 40.0 %, 36.0 % and 44.0 %. Decreases in functional connectivity between the right anterior insula and right calcarine were significantly larger in the remitters than in the non-remitters (p = 0.013). Additionally, a higher baseline functional connectivity between the right anterior insula and right superior temporal gyrus correlated with better treatment outcome. Limitations: The small sample size of 25 participants is small. Conclusion: Our findings highlight the potential role of the insula in depression and suggest that insula-seeded functional connectivity could serve as a predictive biomarker for rTMS efficacy.