Epilepsy is the most common brain disorder worldwide with no age, racial, social class, national, or geographic boundaries. It affects 67 million people, 85% of whom live in developing countries. Refractory (uncontrolled) epilepsy and misdiagnosis are two major challenges in the field of epilepsy worldwide. Despite decades of research, new antiepileptic drugs (AEDs), and advances in surgical therapy, many patients suffer from uncontrollable epilepsy or the side effects of AEDs and surgical treatment. Furthermore, misdiagnosis of epilepsy is very common in patients of all ages. Misdiagnosis of epilepsy can lead to serious complications as seizures and antiepileptic drugs can cause cognitive impairments and behavioral problems. There is growing evidence that brain stimulation may be used as a potential therapy for refractory epilepsy. However, the therapeutic results of stimulation are not proven. Existing stimulation approaches demonstrate suboptimal effect or involve significant risks. Presently, the primary diagnostic tool for epilepsy is conventional electroencephalography (EEG) which suffers from poor sensitivity/specificity, a root cause of misdiagnosis because it leads to inaccurate spike and seizure detection and foci localization. To address these problems, our long-term research goals are, through multi-disciplinary collaboration between the U.S. and Mexico, to develop (1) a tripolar concentric ring electrode (TCRE) based noninvasive transcutaneous focal stimulation (TFS) neuromodulation system for epilepsy therapy, and (2) a TCRE EEG system to improve epilepsy diagnosis. Preliminary studies generated promising results, thus warrant further investigation. The proposed techniques are cost effective and noninvasive, which are particularly advantageous for use in low-to-mid income countries because they reduce the financial burden and surgical risks caused by implantable devices. To achieve the long-term goals, the objectives of the current R21 proposal are to assess needs in Mexico, initiate preliminary studies and training, and plan, prepare, and assemble the information and data for a more comprehensive R01 submission. The team has made a preliminary assessment of the epilepsy research and medical needs in Mexico. Based on this pre-assessment, the following Specific Aims are designed to accomplish the proposal objectives:
Aim 1 - Finalize the assessment of epilepsy research capacity and training needs in Mexico.
Aim 2 - Develop multi-disciplinary collaboration to build Mexico research and clinical capacity in epilepsy.
Aim 3 - Acquire preliminary data that will prepare the team for a follow-up R01 submission.
Aim 4 - Integrate capacity building and collaborator training. Successful completion of the proposed research will change methods, treatments, and technologies in the field of epilepsy. This grant will help build sustainable research capacity in Mexico in epilepsy and neurological disorders in general.

Public Health Relevance

For epilepsy control, successful demonstration of the effects of transcutaneous focal stimulation (TFS) will potentially change the current paradigms to noninvasive TFS for alternative or additive epilepsy therapy. For diagnosis, in the short-term, we expect the benefits of tripolar concentric ring electrodes (TCREs) to significantly improve the interpretability of EEG and, in the long-term, to advance epilepsy diagnosis.

National Institute of Health (NIH)
Fogarty International Center (FIC)
Exploratory/Developmental Grants (R21)
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Special Emphasis Panel (ZRG1-BDCN-Z (50))
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Michels, Kathleen M
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University of Rhode Island
Engineering (All Types)
Schools of Engineering
United States
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Santana-Gomez, Cesar E; Alcantara-Gonzalez, David; Luna-Munguia, Hiram et al. (2015) Transcranial focal electrical stimulation reduces seizure activity and hippocampal glutamate release during status epilepticus. Conf Proc IEEE Eng Med Biol Soc 2015:6586-9
Santana-Gómez, César E; Alcántara-González, David; Luna-Munguía, Hiram et al. (2015) Transcranial focal electrical stimulation reduces the convulsive expression and amino acid release in the hippocampus during pilocarpine-induced status epilepticus in rats. Epilepsy Behav 49:33-9
Luby, Matthew D; Makeyev, Oleksandr; Besio, Walter G (2014) Chronic transcranial focal stimulation from tripolar concentric ring electrodes does not disrupt memory formation in rats. Conf Proc IEEE Eng Med Biol Soc 2014:6139-42
Makeyev, Oleksandr; Ding, Quan; Martínez-Juárez, Iris E et al. (2013) Multiple sensor integration for seizure onset detection in human patients comparing conventional disc versus novel tripolar concentric ring electrodes. Conf Proc IEEE Eng Med Biol Soc 2013:17-20
Besio, Walter; Cuellar-Herrera, Manola; Luna-Munguia, Hiram et al. (2013) Effects of transcranial focal electrical stimulation alone and associated with a sub-effective dose of diazepam on pilocarpine-induced status epilepticus and subsequent neuronal damage in rats. Epilepsy Behav 28:432-6
Makeyev, Oleksandr; Ding, Quan; Kay, Steven M et al. (2013) Toward improving the Laplacian estimation with novel multipolar concentric ring electrodes. Conf Proc IEEE Eng Med Biol Soc 2013:1486-9
Rogel-Salazar, G; Luna-Munguia, H; Stevens, K E et al. (2013) Transcranial focal electrical stimulation via tripolar concentric ring electrodes does not modify the short- and long-term memory formation in rats evaluated in the novel object recognition test. Epilepsy Behav 27:154-8