Widge, A.S., Zorowitz, S., Basu, I. Paulk, A., Cash, S., Eskandar, E., Deckersbach, T., Miller, E.K., and Dougherty, D. (2019) Deep brain stimulation of the internal capsule enhances human cognitive control and prefrontal cortex function. Nature Communications. https://doi.org/10.1038/s41467-019-09557-4 View PDF
Deep brain stimulation (DBS) is a circuit-oriented treatment for mental disorders. Unfortunately, even well-conducted psychiatric DBS clinical trials have yielded inconsistent symptom relief, in part because DBS’ cognitive and physiologic mechanism(s) of action are unclear. One clue to those mechanisms may lie in DBS’ efficacy in both major depression (MDD) and obsessive-compulsive disorder (OCD) by stimulation of a single brain site, the ventral internal capsule/ventral striatum (VCVS). MDD and OCD both involve deficits in cognitive control. Cognitive control depends on prefrontal cortex (PFC) regions that project into the VCVS. We show that VCVS DBS’ effect is explained in part by enhancement of PFC-driven cognitive control. DBS improved human subjects’ performance on a cognitive control task and increased theta (5-8 Hz) oscillations in both medial and lateral PFC. Further, the theta increase predicted subjects’ clinical outcomes. Our results suggest a possible mechanistic approach to DBS therapy, based on tuning stimulation to optimize these neurophysiologic phenomena.