Combining Intensive Exposure and Response Prevention Therapy With Accelerated Transcranial Magnetic Stimulation to Treat Patients With Severe Obsessive-Compulsive Disorder

Background:The efficacy of focal TMS for depression likely depends on targeting the ideal brain circuit.Unlike focal TMS, the H1-coil, commonly used in clinical practice, is believed to target broadly and deeply.It is unclear whether this breadth facilitates or impedes circuit-based targeting.Methods: We retrospectively analyzed 97 depressed patients who received at least 19 TMS sessions, and had incidentally completed a structural brain MRI.Patients were treated with 1980 pulses at 18Hz, with the H1-coil positioned 6cm anterior to the motor hotspot, adjusted 1cm posteriorly if intolerable.Depression was measured using the Quick Inventory of Depressive Symptomatology.The electric field (E-field) was modeled using SimNIBS, and stimulated circuits were estimated via a normative connectome database (n=1000).Results: TMS E-fields that improved depression were preferentially connected to a distinct brain circuit, validated with out-ofsample cross-validation (p=0.0005).This circuit was significantly similar to an a priori causal depression circuit derived from focal TMS, DBS, and lesion studies (spatial r=0.59, p=0.04).TMS E-fields with greater connectivity to the depression circuit led to greater symptom improvement (r=0.41,p < 0.001).In post-hoc analyses, overlap of the H1 E-field with the depression circuit progressively increased with more posterior coil positioning.Peak overlap with the circuit was 4cm anterior to the motor hotspot.Discussion: Targeting specific depression circuitry may be feasible with the H1 deep TMS coil.More posterior coil positioning improves E-field overlap with the depression circuit, with peak overlap at 4cm anterior to the motor hotspot.Prospective studies are needed to validate these findings.