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

• Published in: Nature communications Vol. 10; no. 1; p. 1536
• Main Authors: Widge, A. S., Zorowitz, S., Basu, I., Paulk, A. C., Cash, S. S., Eskandar, E. N., Deckersbach, T., Miller, E. K., Dougherty, D. D.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 04-04-2019; Nature Publishing Group; Nature Portfolio
• Subjects: 631/378/1689/1414; 631/378/1689/4032; 692/699/476; 692/700/565/545/379; 9/26; Adult; Aged; Brain; Clinical trials; Cognition; Cognitive ability; Control tasks; Deep Brain Stimulation; Depressive Disorder, Major - therapy; Female; Human performance; Humanities and Social Sciences; Humans; Internal Capsule; Male; Medical research; Mental depression; Mental disorders; Middle Aged; multidisciplinary; Neostriatum; Obsessive compulsive disorder; Obsessive-Compulsive Disorder - therapy; Prefrontal cortex; Prefrontal Cortex - physiology; Science; Science (multidisciplinary); Stimulation; Theta rhythms; Treatment Outcome
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-019-09557-4

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.
Deep brain stimulation (DBS) is a promising treatment for psychiatric disorders, but its mechanism in relieving symptoms is unclear. Here, the authors show that DBS of ventral internal capsule/ventral striatum (VCVS) may act by enhancing prefrontal cortex oscillations that in turn enhance cognitive control.