Targeting depression circuitry with H1 coil Transcranial Magnetic Stimulation: a retrospective circuit mapping study

The efficacy of transcranial magnetic stimulation (TMS) for depression may depend on targeting specific brain circuits. However, this has not been tested for TMS with the H1 coil, a widely used device believed to target more broadly and deeply than TMS with figure-of-8 coils. This study examined whether targeting a specific brain circuit with H1 coil TMS treatment may impact depressive symptom improvement. We retrospectively analyzed data from 97 patients at McLean Hospital, who received at least 19 TMS sessions and had incidentally completed an anatomical brain MRI. We modeled each patient's electric (E-)field using SimNIBS and estimated the connectivity of the E-field using a normative connectome (n = 1000), which was correlated with depression improvement as measured by the Quick Inventory of Depressive Symptomatology. H1 E-fields improving depression were preferentially connected to a distinct brain circuit, validated with leave-one-out cross-validation (p = 0.0005). This circuit was significantly similar to a predefined causal depression circuit (spatial r = 0.59, p = 0.04) derived from TMS, deep brain stimulation, and lesion studies. E-fields with greater connectivity similarity to this circuit led to greater symptom improvement (r = 0.41, p < 0.001). Post-hoc analyses revealed that more posterior coil positioning increases H1 E-field overlap with the depression circuit, with high overlap at scalp locations 3-6 cm anterior to the motor hotspot. Thus, H1 coil stimulation sites that improve depression converge on a common causal depression circuit. Prospective studies are needed to validate these findings.