Target Engagement in a Head-to-head Clinical Trial of Dysphoric versus Anxiosomatic TMS Targets

Functional connectivity (FC) is increasingly used to measure target engagement following transcranial magnetic stimulation (TMS), but whether FC changes are specific to the TMS target remains unclear. We examined FC before and after TMS in patients with depression and anxiety (N=29) enrolled in a randomized trial targeting a dysphoric vs. anxiosomatic circuit. We tested whether: 1) TMS selectively modulated FC within the targeted circuit; 2) baseline TMS site FC to the targeted circuit predicted FC changes; 3) either metric correlated with symptom improvement. We found that: 1) FC decreased in both circuits, but effects were not clearly target-specific; 2) FC to the targeted circuit correlated with FC changes; 3) FC to the targeted circuit, not FC changes, correlated with symptom improvement. Results were driven by the anxiosomatic target group, likely due to heterogeneity in dysphoric circuit properties. These results have implications for using FC to target TMS and measure engagement.