Epilepsy is one of the most prevalent neurological disorder. Patients with epilepsy experience recurrent seizures that can cause a variety of symptoms ranging from muscle stiffness to loss of consciousness. Partial epilepsy is the most common syndrome in adult epilepsy patients and mesial temporal lobe epilepsy (MTLE) is the most common form of partial epilepsy. Epilepsy is characterized by the abnormal synchronization of large numbers of neurons. Current therapeutic agents cannot control seizures in 25% of all epileptic patients. Although electrical stimulation of the brain has been very effective to suppress some symptoms of Parkinson's disease, the level of seizure suppression by stimulation has been limited. The reason for this low therapeutic outcome could be attributed to an inadequate target for stimulation, lack of understanding of the mechanisms and non-optimum stimulation parameters. We propose to develop a method to suppress seizures by applying electrical stimulation to the commissural fiber tract that innervates both hippocampi (major epileptogenic foci in MTLE) from a single electrode location. Specifically, we propose to 1) evaluate the effect of low frequency stimulation 2) determine the effect of high frequency stimulation 3) study the mechanisms of the effect of stimulation, 4) analyze the spatial extent of the suppression/excitation effect in an intact hippocampal in-vitro preparation and 5) suppress seizures in a drug-free genetic model of epilepsy in mice. Current therapeutic agents are incapable of controlling seizure activity in 25% of all epileptic patients. The results of this neuro-technology project should provide valuable insights into the mechanisms underlying seizure suppression with electrical stimulation as well as establishing the preliminary design for an effective neural prosthesis for the control of seizures in patients with epilepsy.

Public Health Relevance

About 3 million people have been diagnosed with epilepsy and the cost to the society is about $12.5B/year. Yet, only 25% of patients can receive some therapeutic benefits from anti-epileptic medication. We propose to develop an alternative therapeutic modality to surgical resection that relies on electrical stimulation of the brain to control seizures.

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
Research Project (R01)
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Special Emphasis Panel (ZRG1-NT-K (01))
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Fureman, Brandy E
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Case Western Reserve University
Biomedical Engineering
Schools of Engineering
United States
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Chiang, Chia-Chu; Wei, Xile; Ananthakrishnan, Arvind Keshav et al. (2018) Slow moving neural source in the epileptic hippocampus can mimic progression of human seizures. Sci Rep 8:1564
Couturier, Nicholas H; Durand, Dominique M (2018) Corpus callosum low-frequency stimulation suppresses seizures in an acute rat model of focal cortical seizures. Epilepsia 59:2219-2230
Feng, Zhouyan; Wang, Zhaoxiang; Guo, Zheshan et al. (2017) High frequency stimulation of afferent fibers generates asynchronous firing in the downstream neurons in hippocampus through partial block of axonal conduction. Brain Res 1661:67-78
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Zhang, Mingming; Kibler, Andrew B; Gonzales-Reyes, Luis E et al. (2015) Neural activity propagation in an unfolded hippocampal preparation with a penetrating micro-electrode array. J Vis Exp :
Ladas, Thomas P; Chiang, Chia-Chu; Gonzalez-Reyes, Luis E et al. (2015) Seizure reduction through interneuron-mediated entrainment using low frequency optical stimulation. Exp Neurol 269:120-32
Qiu, Chen; Shivacharan, Rajat S; Zhang, Mingming et al. (2015) Can Neural Activity Propagate by Endogenous Electrical Field? J Neurosci 35:15800-11
Tang, Y; Wodlinger, B; Durand, D M (2014) Bayesian spatial filters for source signal extraction: a study in the peripheral nerve. IEEE Trans Neural Syst Rehabil Eng 22:302-11
Feng, Zhouyan; Yu, Ying; Guo, Zheshan et al. (2014) High frequency stimulation extends the refractory period and generates axonal block in the rat hippocampus. Brain Stimul 7:680-9
Chiang, Chia-Chu; Ladas, Thomas P; Gonzalez-Reyes, Luis E et al. (2014) Seizure suppression by high frequency optogenetic stimulation using in vitro and in vivo animal models of epilepsy. Brain Stimul 7:890-9

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