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Closing the loop in psychiatric deep brain stimulation: physiology, psychometrics, and plasticity

Neuropsychopharmacology volume 49, pages 138–149 (2024)Cite this article

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Abstract

Deep brain stimulation (DBS) is an invasive approach to precise modulation of psychiatrically relevant circuits. Although it has impressive results in open-label psychiatric trials, DBS has also struggled to scale to and pass through multi-center randomized trials. This contrasts with Parkinson disease, where DBS is an established therapy treating thousands of patients annually. The core difference between these clinical applications is the difficulty of proving target engagement, and of leveraging the wide range of possible settings (parameters) that can be programmed in a given patient’s DBS. In Parkinson’s, patients’ symptoms change rapidly and visibly when the stimulator is tuned to the correct parameters. In psychiatry, those same changes take days to weeks, limiting a clinician’s ability to explore parameter space and identify patient-specific optimal settings. I review new approaches to psychiatric target engagement, with an emphasis on major depressive disorder (MDD). Specifically, I argue that better engagement may come by focusing on the root causes of psychiatric illness: dysfunction in specific, measurable cognitive functions and in the connectivity and synchrony of distributed brain circuits. I overview recent progress in both those domains, and how it may relate to other technologies discussed in companion articles in this issue.

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Fig. 1: Example tracts/tract combinations correlated with DBS response.
Fig. 2: Limbic network mapping for closed loop DBS optimization, adapted from [38].
Fig. 3: Neurostimulation approaches to evoke targeted neuroplasticity.

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Funding

Preparation of this article was supported by R01MH125429, R01MH124687, R01MH123634, UH3NS100548, R01NS120851, R01MH119384, R21DA052568, and the MnDRIVE Brain Conditions Initiative. The views are entirely those of the author(s), not any funding body.

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    Alik S. Widge

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ASW receives DBS device donations from Medtronic and consulting fees related to DBS for psychiatric illness from Abbott. He holds multiple granted and pending patents in the area of closed-loop deep brain stimulation.

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Widge, A.S. Closing the loop in psychiatric deep brain stimulation: physiology, psychometrics, and plasticity. Neuropsychopharmacol. 49, 138–149 (2024). https://doi.org/10.1038/s41386-023-01643-y

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