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bioRxiv · 10.1101/2025.11.15.688471

Ephaptic coupling and power fluctuations in depression

Pinotsis, D.·Alagapan, S.·Sarikhani, P.·Nauvel, T.·Rozell, C.·Mayberg, H.
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Abstract

The initial therapeutic exposure to DBS during implantation surgery has reproducible acute behavioral effects that carry over without further stimulation. We analyzed LFP data from the first month following brief therapeutic intraoperative DBS. Data were recorded from the subcallosal cingulate cortex (SCC). 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 two 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 two measures seem to split low vs. high HDRS scores within a small patient cohort. They are motivated by the cytoelectric coupling hypothesis, that 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.

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Pinotsis, D., Alagapan, S., Sarikhani, P., Nauvel, T., Rozell, C., Mayberg, H.. 2025-11-16. Ephaptic coupling and power fluctuations in depression. https://doi.org/10.1101/2025.11.15.688471

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