Connectivity between personalized rTMS targets and stimulated normative functional brain networks as a marker of treatment response in OCD

Resting-state functional connectivity (FC) is increasingly recognized as an important determinant of the therapeutic effects of repetitive transcranial magnetic stimulation (rTMS). In major depressive disorder, FC between the stimulation site and disorder-relevant brain circuits has been linked to treatment outcome. However, FC-based predictors of rTMS efficacy in obsessive-compulsive disorder (OCD) remain poorly understood.

In this study, we used normative network mapping based on a large resting-state fMRI reference dataset (N = 491) to normative stimulated networks whose pretreatment connectivity with the rTMS target was associated with clinical outcome in OCD. We also examined changes in target-to-network connectivity following treatment. The clinical sample comprised 19 OCD individuals that were treated with high-frequency rTMS over the DLPFC and 21 OCD individuals treated over the preSMA.

For DLPFC stimulation, stronger pretreatment FC between the target and the positively coupled stimulated network predicted greater symptom improvement. This association was primarily driven by connectivity with frontoparietal regions. In contrast, for preSMA stimulation, stronger FC between the target and the negatively coupled stimulated network predicted better clinical outcome, driven by connectivity with the precuneus, posterior cingulate cortex, and inferior parietal cortex. Across both stimulation targets, greater reductions in FC between the target and regions within the positively coupled stimulated network following treatment were associated with symptom improvement.

These findings provide new insight into the network-level mechanisms underlying rTMS efficacy in OCD and highlight the potential of connectivity-informed approaches to optimize target selection and improve treatment outcomes.