Optimizing Neuromodulation Therapies for Epilepsy: Identifying the Right Patient, Right Place, and Right Time for Stimulation

PROJECT SUMMARY Responsive neurostimulation (RNS) is used as a treatment for epilepsy that does not respond to medication. However, its effectiveness varies significantly from one patient to another. While it can render some patients almost completely seizure-free, others see no improvement. Additionally, some patients may take years to achieve a reasonable benefit. This project aims to identify factors that determine a patient’s response to RNS, focusing on three specific objectives. Aim 1: Connectivity This aim will utilize patient-specific white-matter connectivity, structural imaging, and stimulation field modeling to identify networks crucial for positive RNS outcomes. Aim 2: Stimulation Timing Given that neuroplasticity likely underpins the gradually improving efficacy of RNS but is hindered during periods of frequent epileptiform activity, this aim will investigate whether periods free from prolonged epileptiform episodes (states with a low risk of seizures) correlate with better long-term RNS outcomes. It will also assess whether delivering stimulation during these low-risk states enhances RNS effectiveness. Aim 3: Background Rhythms This aim will explore circadian fluctuations in background neural activity as a potential predictor of patient response to RNS. Successfully achieving these aims will not only enhance our understanding of neuromodulation in epilepsy but also inspire new trials of innovative closed-loop stimulation algorithms, network-based targeting methodologies, and prognostic tools. In the future, these advancements set a foundation for improving neuromodulation outcomes, accelerating how quickly worthwhile benefits are achieved, and sparing patients unnecessary and ineffective surgeries.