This study investigates the potential for temporally-interfering electric field stimulation (TIEFS) to treat epilepsy. In this case series within and between subjects design, the impact of TIEFS on epilepsy biomarkers was studied in patients with medial temporal lobe epilepsy.

Secondary analyses examine the underlying physiological effects of TIEF on local brain activity and brain networks.

Participants Patients with drug-resistant focal epilepsy and a clinical diagnosis of medial temporal epilepsy undergoing invasive intracranial electrophysiology studies will be consented in accord with institutional review boards at Emory University, Saint-Anne University Hospital, and the Institute of Neurosurgery and Neurointervention, Semmelweis University. The determination of medial temporal epilepsy is based on clinical semiology, EEG, PET, MRI, and invasive electrophysiology. Across all centers, patients underwent the stimulation protocols 6 to 10 days post-implantation after patient-specific electric field modeling to determine TIEFS electrode placement.

Patients then undergo two sessions of TIEFS on separate days, one sham (aligned carriers), and one active (with an offset in frequency between the carriers to provide a lower-frequency modulation envelope at the anatomical target.

Inclusion Criteria:

• Patients undergoing invasive intracranial EEG studies

Exclusion Criteria:

• None

Deidentified IPD will be shared with other researchers at the completion of the study.

IPD in this study consists of the anatomical location of electrode contacts, electrophysiological recordings, field models of the carrier fields and interference envelope. IPD also includes neuroimaging, and key data from the clinical neurophysiology reports.

All data will be fully de-identified.

At the completion of the studies.

Data will be shared upon request to the investigative team for non-commercial and academic use.