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Closed-loop neurostimulation for the treatment of psychiatric disorders

Neuropsychopharmacology volume 49, pages 163–178 (2024)Cite this article

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Abstract

Despite increasing prevalence and huge personal and societal burden, psychiatric diseases still lack treatments which can control symptoms for a large fraction of patients. Increasing insight into the neurobiology underlying these diseases has demonstrated wide-ranging aberrant activity and functioning in multiple brain circuits and networks. Together with varied presentation and symptoms, this makes one-size-fits-all treatment a challenge. There has been a resurgence of interest in the use of neurostimulation as a treatment for psychiatric diseases. Initial studies using continuous open-loop stimulation, in which clinicians adjusted stimulation parameters during patient visits, showed promise but also mixed results. Given the periodic nature and fluctuations of symptoms often observed in psychiatric illnesses, the use of device-driven closed-loop stimulation may provide more effective therapy. The use of a biomarker, which is correlated with specific symptoms, to deliver stimulation only during symptomatic periods allows for the personalized therapy needed for such heterogeneous disorders. Here, we provide the reader with background motivating the use of closed-loop neurostimulation for the treatment of psychiatric disorders. We review foundational studies of open- and closed-loop neurostimulation for neuropsychiatric indications, focusing on deep brain stimulation, and discuss key considerations when designing and implementing closed-loop neurostimulation.

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Fig. 1: Symptoms of psychiatric diseases can be continuous or episodic.
Fig. 2: Considerations of temporal dynamics when designing closed-loop neurostimulation.

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Acknowledgements

The authors thank members of the Departments of Psychiatry and Behavioral Sciences, Neurology, and Neurological Surgery at the University of California, San Francisco for thoughtful discussion related to the present and future of therapeutic neurostimulation.

Funding

This work was supported by the Ray and Dagmar Dolby Family Fund through the Department of Psychiatry at UCSF. JLC is funded by R25MH060482. JMF is funded by the Doris Duke Charitable Foundation (grant #2021090).

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Authors and Affiliations

  1. Department of Neurological Surgery, University of California, San Francisco, CA, USA

    Kristin K. Sellers, Ankit N. Khambhati & Edward F. Chang

  2. Weill Institute for Neurosciences, University of California, San Francisco, CA, USA

    Kristin K. Sellers, Joshua L. Cohen, Ankit N. Khambhati, Joline M. Fan, A. Moses Lee, Edward F. Chang & Andrew D. Krystal

  3. Department of Psychiatry and Behavioral Sciences, University of California, San Francisco, CA, USA

    Joshua L. Cohen, A. Moses Lee & Andrew D. Krystal

  4. Department of Neurology, University of California, San Francisco, CA, USA

    Joline M. Fan

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Contributions

KKS, JLC, ANK, JMF, AML, EFC, and ADK made substantial contributions to the conception or design of the work. KKS, JLC, ANK, JMF, AML and ADK drafted the work or revised it critically for important intellectual content. KKS, JLC, ANK, JMF, AML, EFC, and ADK approved the final version to be published. EFC and ADK agreed to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

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Correspondence to Andrew D. Krystal.

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Competing interests

ADK Grant Support: Janssen Pharmaceuticals, Axsome Pharmaceutics, Attune, Harmony, Neurocrine Biosciences, Reveal Biosensors; Consulting; Axsome Therapeutics, Big Health, Eisai, Evecxia, Harmony Biosciences, Idorsia, Janssen Pharmaceuticals, Jazz Pharmaceuticals, Millenium Pharmaceuticals, Merck, Neurocrine Biosciences, Neurawell Therapeutics, Otsuka Pharmaceuticals, Sage, Takeda, Angelini, Genentech. JLC served as a consultant for OptionsMD. The other authors declare no competing interests.

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Sellers, K.K., Cohen, J.L., Khambhati, A.N. et al. Closed-loop neurostimulation for the treatment of psychiatric disorders. Neuropsychopharmacol. 49, 163–178 (2024). https://doi.org/10.1038/s41386-023-01631-2

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