Gamma suppression correlates with thalamic stimulation therapeutic response in intractable epilepsy

In patients with drug-resistant epilepsy who undergo anterior nucleus of the thalamus (ANT) deep brain stimulation (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 local field potential (LFP) oscillations (SGOs) (20-50 Hz) in the ANT as a novel electrophysiological biomarker correlated with therapeutic response.

Participants enrolled in an ongoing prospective ANT-DBS parameter optimization trial (N = 11) were analyzed retrospectively for the effects of stimulation on ANT LFPs. One-minute baseline and stimulation ANT LFPs were captured across follow-up visits using a Medtronic Percept, testing different stimulation settings around the Stimulation of the Anterior Nucleus of the Thalamus in Epilepsy (SANTE) trial clinical setting (145 Hz, 90 μs) in the clinic. Aperiodic component detrended ANT LFP power spectral density responses during stimulation were compared against each baseline responses. Participants kept a seizure diary, where responders were those who achieved greater than a 50% seizure frequency reduction compared to their pre-DBS seizure frequency.

In the seven participants exhibiting SGOs, six were responders. Progressive suppression ("gamma fade") of SGOs under chronic stimulation correlated with long-term seizure reduction in five of six responders. Acute stimulation in-clinic with multiple settings suppressed SGOs in four of five 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.