Deep brain stimulation of the internal capsule enhances human cognitive control and prefrontal cortex function

A S Widge; S Zorowitz; I Basu; A C Paulk; S S Cash; E N Eskandar; T Deckersbach; E K Miller; D D Dougherty

doi:10.1038/s41467-019-09557-4

Deep brain stimulation of the internal capsule enhances human cognitive control and prefrontal cortex function

Nat Commun. 2019 Apr 4;10(1):1536. doi: 10.1038/s41467-019-09557-4.

Authors

A S Widge^{1

2

3}, S Zorowitz^{4

5}, I Basu⁴, A C Paulk⁶, S S Cash⁶, E N Eskandar^{7

8}, T Deckersbach⁴, E K Miller⁹, D D Dougherty⁴

Affiliations

¹ Department of Psychiatry, Massachusetts General Hospital and Harvard Medical School, 149 13th St, Boston, MA, 02129, USA. awidge@umn.edu.
² Picower Institute for Learning and Memory, Massachusetts Institute of Technology, 43 Vassar St, Cambridge, MA, 02139, USA. awidge@umn.edu.
³ University of Minnesota, 2001 6th St SE, Minneapolis, MN, 55455, USA. awidge@umn.edu.
⁴ Department of Psychiatry, Massachusetts General Hospital and Harvard Medical School, 149 13th St, Boston, MA, 02129, USA.
⁵ Princeton Neuroscience Institute, Princeton, NJ, 08540, USA.
⁶ Department of Neurology, Massachusetts General Hospital and Harvard Medical School, 55 Fruit St, Boston, MA, 02114, USA.
⁷ Department of Neurological Surgery, Massachusetts General Hospital and Harvard Medical School, 55 Fruit St, Boston, MA, 02114, USA.
⁸ Department of Neurological Surgery, Albert Einstein College of Medicine-Montefiore Medical Center, Bronx, NY, 10467, USA.
⁹ Picower Institute for Learning and Memory, Massachusetts Institute of Technology, 43 Vassar St, Cambridge, MA, 02139, USA.

Abstract

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.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

Adult
Aged
Cognition*
Deep Brain Stimulation*
Depressive Disorder, Major / therapy*
Female
Humans
Internal Capsule*
Male
Middle Aged
Obsessive-Compulsive Disorder / therapy*
Prefrontal Cortex / physiology*
Treatment Outcome

Abstract

Publication types

MeSH terms

Grants and funding