BIONIC: Discovering Thalamic Connectivity and Using It to Treat Epilepsy

In this talk, Dr. Nick Gregg presents cutting‑edge work on mapping thalamic networks to develop personalized neuromodulation therapies for drug‑resistant epilepsy. He begins with the case of a patient who continued to suffer daily seizures despite a frontal lobectomy and anterior thalamic DBS—highlighting the limitations of current one‑target‑fits‑all approaches. Dr. Gregg explains that unlike movement disorders with predictable circuits, each person’s seizure network is unique, and seizures occur too infrequently—and are too often forgotten—to serve as reliable biomarkers. Instead, his team uses interictal discharges (short‑latency biomarkers occurring many times per minute) and active single‑pulse stimulation to map how different thalamic nuclei communicate with cortex in real time. Through thalamic SEEG recordings across 10 patients, Gregg’s group shows how tiny differences in electrode location—sometimes just millimeters—engage entirely different networks (motor, limbic, pulvinar‑based, etc.). These connectivity fingerprints reveal which thalamic targets are most likely to influence an individual’s specific seizure circuit, enabling patient‑specific DBS targeting rather than generic placement. He also demonstrates that high‑frequency thalamic stimulation can suppress epileptic discharges in real time—and that the degree of suppression is strongly predicted by baseline connectivity strength. Duration matters: short stimulation produces little change, while longer stimulation induces sub‑acute neuroplasticity that reduces excitability, offering insight into why DBS effects for epilepsy often unfold over hours to days. Dr. Gregg closes by outlining a roadmap toward biomarker‑targeted, precision neuromodulation—mirroring the real‑time tuning used in Parkinson’s surgery but powered by electrophysiology rather than motor testing. This approach, now expanding to multicenter trials, could dramatically accelerate therapy optimization for epilepsy and other neurological conditions lacking fast clinical feedback. 00:00 Introduction to Dr. Nick Gregg 00:30 Case Study: Persistent Seizures Despite Surgery & DBS 01:32 The Challenge of Drug-Resistant Epilepsy 02:15 Limits of Conventional DBS & The Need for New Targets 03:16 Unique Seizure Networks & Unreliable Seizure Biomarkers 04:01 Passive & Active Electrophysiological Biomarkers 05:39 SEEG + Thalamic Sampling for Network Mapping 06:20 Study Design: Baseline Mapping → High-Frequency Stim → Remapping 07:17 Thalamocortical Connectivity Differences Across Nuclei 09:34 Using Connectivity to Predict Circuit Engagement & Therapeutic Targets 10:34 Biomarker Suppression During Thalamic Stimulation 12:04 Neuroplasticity: Why Longer-Duration DBS Modulates Excitability 14:41 Toward Biomarker-Targeted Precision Neuromodulation From Mayo Clinic to your inbox (free): https://www.mayoclinic.org/patient-visitor-guide/newsletters Visit Mayo Clinic: https://www.mayoclinic.org Connect with Mayo Clinic: Facebook: https://www.facebook.com/mayoclinic Instagram: https://www.instagram.com/mayoclinic X: https://x.com/MayoClinic Threads: https://www.threads.net/@mayoclinic