Epilepsy is one of the most prevalent neurological disorders. Patients with epilepsy experience recurrent seizures that can cause a variety of symptoms ranging from auras to loss of consciousness. Epilepsy is characterized by the abnormal firing of large numbers of neurons and current therapeutic agents cannot control seizures in 25% of all epileptic patients. We have previously shown that a novel brain stimulation method targeting fiber tracts (fornix) instead of grey matter at low frequency (1-20Hz) is effective to suppress seizures in animal models and patients with mesial temporal lobe epilepsy (MTLE). We propose to target another prominent fiber tract, the corpus callosum (CC) to suppress cortical seizures and to compare this technology to two state-the-art methods that stimulate at high frequency either the focus directly or the anterior nucleus of the thalamus. Specifically, we propose to determine if stimulation of the CC at low frequency can decrease focal seizures by selectively activating the CC fibers innervating the focus in an acute model (Aim 1) or in focal chronic model of epilepsy with tetanus toxin (Aim 2). We then propose to determine if fiber tract stimulation can improve seizure control of activity generated by multiple foci compared to stimulation of the anterior nucleus of the thalamus (Aim3) or with kainic acid in chronic model (Aim4). Finally, we will study the mechanisms of the CC stimulation using in-vitro cortical brain slices obtained from animals in previous aims. The project will be carried with a collaboration between scientists, engineers and clinicians and if successful could be translated into a novel patient-specific therapeutic modality for the control of cortical seizures in patients with intractable epilepsy.

Public Health Relevance

Many patients with epilepsy have seizures that cannot be treated by drugs or surgery and current stimulation methods do not provide significant relief. We propose to develop a novel stimulation method that relies on the stimulation of the corpus callosum, a fiber tract that connects the two sides of the brain to suppress cortical seizures. This methods is based on a previous method we have developed to treat seizures arising in the limbic system. 1

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS114120-02
Application #
10059285
Study Section
Acute Neural Injury and Epilepsy Study Section (ANIE)
Program Officer
Churn, Severn Borden
Project Start
2019-12-01
Project End
2024-11-30
Budget Start
2020-12-01
Budget End
2021-11-30
Support Year
2
Fiscal Year
2021
Total Cost
Indirect Cost
Name
Case Western Reserve University
Department
Biomedical Engineering
Type
Schools of Medicine
DUNS #
077758407
City
Cleveland
State
OH
Country
United States
Zip Code
44106