Slow Gamma Suppression Correlates with Therapeutic Response to Anterior Thalamic Deep Brain Stimulation in Intractable Epilepsy

Abstract In drug-resistant epilepsy patients who undergo anterior thalamic deep brain stimulation (ANT-DBS), efficacy is assessed months after therapy initiation and clinicians have no guidance when choosing stimulation parameters due to the lack of real-time biomarkers. Here, we identified acute and chronic suppression of slow gamma oscillations (SGOs) (20–50Hz) in the ANT as a novel electrophysiological biomarker correlated with therapeutic response. Through analysis of an ongoing prospective ANT-DBS parameter optimization trial (N=11), 6/7 participants exhibiting SGOs were responders. Progressive suppression (“gamma fade”) of SGOs under chronic stimulation correlated with long-term seizure reduction in 5/6 responders. Acute stimulation in-clinic with multiple settings suppressed SGOs in 4/5 responders, challenging fixed-programming paradigms, with only one responder using the clinical gold standard parameters at the last follow-up visit. These findings establish SGO suppression as a potential multiscale biomarker for responder identification, parameter titration, and therapeutic tracking for precise, biomarker-guided intervention. Competing Interest Statement Zachary Sanger was a part time graduate student intern at Medtronic during a portion of time while conducting this work. The internship work was not related to any research shown here and his time conducting this work was supported through the project's funding. Clinical Trial NCT05493722 Funding Statement This work has been supported by the National Institute of Neurological Disorders and Stroke (U01NS124616). Zachary Sanger is a 2024–2025 MnDrive Brain Conditions Fellow and his time conducting research reported in this publication was supported by the University of Minnesota′s MnDRIVE (Minnesota′s Discovery, Research and Innovation Economy) initiative. Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Ethics committee/IRB of the University of Minnesota gave ethical approval for this work. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes