Brain stimulation and brain lesions converge on common causal circuits in neuropsychiatric disease

Damage to specific brain circuits can cause specific neuropsychiatric symptoms. Therapeutic stimulation to these same circuits may modulate these symptoms. To determine if these circuits converge, we studied depression severity after brain lesions (n=461, five datasets), transcranial magnetic stimulation (TMS) (n=151, four datasets), and deep brain stimulation (DBS) (n=101, five datasets). Lesions and stimulation sites most associated with depression severity were connected to a similar brain circuit across all 14 datasets (p<0.001). Circuits derived from lesions, DBS, and TMS were similar (p<0.0005), as were circuits derived from patients with major depression versus other diagnoses (p<0.001). Connectivity to this circuit predicted out-of-sample antidepressant efficacy of TMS and DBS sites (p<0.0001). In an independent analysis, 29 lesions and 95 stimulation sites converged on a distinct circuit for motor symptoms of Parkinson’s disease (p<0.05). We conclude that lesions, TMS, and DBS converge on common brain circuitry that may represent improved neurostimulation targets for depression and other disorders.