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

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.