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’ mechanism(s) of action are unclear. One clue to those mechanisms may lie in the efficacy of ventral internal capsule/ventral striatum (VCVS) DBS in both major depression (MDD) and obsessive-compulsive disorder (OCD). MDD and OCD both involve deficits in cognitive control. Cognitive control depends on prefrontal cortex (PFC) regions that project into the VCVS. Here, we show that VCVS DBS’ effect is explained in part by enhancement of PFC-driven cognitive control. DBS improves human subjects’ performance on a cognitive control task and increases theta (5–8Hz) oscillations in both medial and lateral PFC. The theta increase predicts subjects’ clinical outcomes. Our results suggest a possible mechanistic approach to DBS therapy, based on tuning stimulation to optimize these neurophysiologic phenomena.
Bibliographical noteFunding Information:
We gratefully acknowledge technical assistance from Amanda Arulpragasam, Andrew Corse, Nina Levar, and Tommi Raij with subject recruitment and data collection. Graphical elements in Fig. 1a include photography by Elias Levy re-used under CC-BY. This work was supported by grants from the Brain & Behavior Research Foundation (A.S.W.), Picower Family Foundation (A.S.W., E.K.M.), MIT Picower Institute Innovation Fund (E.K.M.), Defense Advanced Research Projects Agency (DARPA) under Cooperative Agreement Number W911NF-14-2-0045 issued by the Army Research Organization (ARO) contracting office in support of DARPA’s SUBNETS Program (A.S.W., D.D.D., E.N.E., S.Z., T.D.), Office of Naval Research MURI N00014-16-1-2832 (E.K.M.), and National Institutes of Health (R21MH109722, A.S.W.; R03MH111320, A.S.W. and D.D.D.; UH3NS100548, A. S.W., D.D.D., E.N.E., and T.D.; R37MH087027, E.K.M.). The views, opinions, and findings expressed are those of the authors. They should not be interpreted as representing the official views or policies of the Department of Defense, Department of Health & Human Services, any other branch of the U.S. Government, or any other funding entity.
© 2019, The Author(s).