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Ephaptic coupling and power fluctuations in depression

Pinotsis, D. A. ORCID: 0000-0002-6865-8103, Alagapan, S., Sarikhani, P. , Nauvel, T., Rozell, C. J. & Mayberg, H. S. (2026). Ephaptic coupling and power fluctuations in depression. Cerebral Cortex, 36(3), doi: 10.1093/cercor/bhag019

Abstract

The initial therapeutic exposure to Deep Brain Stimulation (DBS) during implantation surgery has reproducible acute behavioral effects that carry over without further stimulation. We analyzed local field potential (LFP) data from the first month following brief therapeutic intraoperative DBS. Data were recorded from the subcallosal cingulate cortex. During this month, no further stimulation was applied. Recent studies have identified beta power fluctuations in LFP data as an acute putative depression biomarker of this exposure. However, a detailed description of neural dynamics underlying brain power fluctuations is missing. Here, we consider how these fluctuations are related to brain itinerancy, that is, neural activity changes between stable and unstable states. We also provide a proof of principle study that these dynamics can be described using 2 new dynamical systems measures: instability frequency and relative wandering time. These capture interactions between neural activity and the mesoscale oscillatory electric fields generated by it. The 2 measures seem to split low vs. high Hamilton Depression Rating Scale scores within a small patient cohort. They are motivated by the cytoelectric coupling hypothesis, which suggests that efficient information processing results from mesoscale electric fields and that the re-emergence of depression symptoms might result from altered electric fields. Whether the new measures reflect general mechanisms of rapid antidepressant action remains to be tested.

Publication Type: Article
Additional Information: © The Author(s) 2026. Published by Oxford University Press. All rights reserved. This is a pre-copyedited, author-produced version of an article accepted for publication in Cerebral Cortex following peer review. The version of record Dimitrios A Pinotsis, Sankaraleengam Alagapan, Parisa Sarikhani, Tanya Nauvel, Christopher J Rozell, Helen S Mayberg, Ephaptic coupling and power fluctuations in depression, Cerebral Cortex, Volume 36, Issue 3, March 2026 is available online at: https://doi.org/10.1093/cercor/bhag019
Publisher Keywords: DBS, depression, electric fields, Lyapunov exponents
Subjects: R Medicine > RC Internal medicine > RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry
Departments: School of Health & Medical Sciences
School of Health & Medical Sciences > Department of Psychology & Neuroscience
SWORD Depositor:
[thumbnail of paper F2.pdf] Text - Accepted Version
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