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

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

doi:10.1038/s41467-019-09557-4

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.

Highlights

Deep brain stimulation (DBS) is a circuit-oriented treatment for mental disorders
We show that VCVS DBS enhances cognitive control, that this enhanced control is correlated with the expected prefrontal cortex (PFC) theta oscillations, and that the increased theta power is in turn correlated with clinical recovery
Fourteen subjects (12 major depressive disorder (MDD) and 2 obsessive-compulsive disorder (OCD); Table 1) with VCVS DBS implants performed a variant of the Multi-Source Interference Task (MSIT, Fig. 1a) that included emotional distractors to increase overall cognitive load

Summary

Introduction

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). Of five blinded and sham-controlled DBS clinical trials, two met their primary endpoint, two did not, and one remains unpublished[3,4,5] This ambiguous set of outcomes has limited DBS’ use in mental illness, despite the pressing need for new treatments for these disorders. Current theories focus around resetting of abnormal oscillatory activity, which may alter information transmission in distributed circuits[8,12] This uncertainty suggests that some patients who did not respond in clinical trials likely did not receive an active dose of the study intervention. In clinically successful DBS applications, such as Parkinson disease, the dosing problem can be solved by trial and error

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