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State-dependent responses to intracranial brain stimulation in a patient with depression

Abstract

Deep brain stimulation is a promising treatment for severe depression, but lack of efficacy in randomized trials raises questions regarding anatomical targeting. We implanted multi-site intracranial electrodes in a severely depressed patient and systematically assessed the acute response to focal electrical neuromodulation. We found an elaborate repertoire of distinctive emotional responses that were rapid in onset, reproducible, and context and state dependent. Results provide proof of concept for personalized, circuit-specific medicine in psychiatry.

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Fig. 1: Mapping mood across the corticolimbic circuit.
Fig. 2: Characterization of response properties.

Data availability

The source data that support the findings in this report are available in the report itself, in the Supplementary Information and in our publicly available code. Source data are provided with this paper.

Code availability

The code and data used to produce the figures in this paper are available at https://github.com/ScangosLab/PR01.

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Acknowledgements

This work was supported by National Institutes of Health award K23NS110962 (to K.W.S.), a NARSAD Young Investigator grant from the Brain and Behavioral Research Foundation (to K.W.S.) and the Ray and Dagmar Dolby Family Fund through the Department of Psychiatry at the University of California, San Francisco (to K.W.S., A.D.K., E.F.C. and L.P.S.). E.F.C. was supported by the National Institutes of Health (U01NS098971, R01MH114860, R01MH111444, R01DC015504, R01DC01237, UH3 NS109556, UH3NS115631 and R01 NS105675), the New York Stem Cell Foundation, the Howard Hughes Medical Institute, the McKnight Foundation, the Shurl and Kay Curci Foundation and the William K. Bowes Foundation. A.D.K. acknowledges support from the National Institutes of Health (P01AG019724, R01 HL142051-01, R01AG059794, R01DK117953, UH3 NS109556-01 and R01AG060477-01A1), PCORI, Janssen, Jazz, Axsome (AXS-05-301) and Reveal Biosensors. L.P.S. receives support from the National Institutes of Health (U24 DA041123).

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K.W.S., A.D.K. and E.F.C. initiated this work and supervised the study. K.W.S. drafted the manuscript, and G.S.M., K.W.S. and L.P.S. collected and analyzed the data. A.D.K. and E.G.C. finalized the manuscript. All authors approved this work and take responsibility for its integrity.

Corresponding author

Correspondence to Katherine W. Scangos.

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Competing interests

A.D.K. consults for Eisai, Evecxia, Ferring, Galderma, Harmony Biosciences, Idorsia, Jazz, Janssen, Merck, Neurocrine, Pernix, Sage, Takeda, Big Health, Millenium Pharmaceuticals, Otsuka Pharmaceuticals, and Neurawell. All other authors declare no competing interests.

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Peer review information Jerome Staal and Kate Gao were the primary editors on this article and managed its editorial process and peer review in collaboration with the rest of the editorial team.

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Scangos, K.W., Makhoul, G.S., Sugrue, L.P. et al. State-dependent responses to intracranial brain stimulation in a patient with depression. Nat Med 27, 229–231 (2021). https://doi.org/10.1038/s41591-020-01175-8

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