William H. Theodore, M.D.

Senior Investigator

Clinical Epilepsy Section


Building 10, Room 5N250
10 Center Drive
Bethesda, MD 20892-1408



Research Topics

The Epilepsy Research Branch seeks to improve treatment of epilepsy by understanding the mechanisms of action of antiepileptic drugs, as well as developing new methods for evaluation and treatment. The two sections, Neuronal Excitability and Clinical Epilepsy, collaborate to study the relationship between drug actions at the cellular and subcellular level and clinical effects, both on seizure control and neuropsychological function.

The NINDS Clinical Epilepsy Section (CES) conducts research on the evaluation and treatment of uncontrolled epilepsy, emphasizing non-invasive approaches to localization of epileptic foci and cognitive mapping. The techniques employed include video-EEG monitoring, transcranial magnetic stimulation (TMS), positron emission tomography (PET), and magnetic resonance imaging (MRI), including functional MRI and MR spectroscopy. We use multimodality image co-registration, and statistical parametric mapping, as well as other image analysis techniques. In addition to drug trials, In a double-blind trial, we are exploring the use of transcranial magnetic stimulation, a novel approach to treatment of focal epilepsy.

Current studies include a trial of the therapeutic effect of rTMS on neocortical epileptic foci. We are using PET to study 5HT-1A receptors in localization-related epilepsy, and in patients with both epilepsy and depression. We are using diffusion weighted MRI and BOLD to study the extent of neuronal injury associated with seizures in rats exposed to specific glutamate receptor subtype agonists. In a collaboration with Johns Hopkins University we are investigating the role of the anterior temporal cortex in semantic processing, the amygdala in affective processing, and the effect of white matter pathway resection on cognitive outcome after temporal lobectomy. With Columbia University, we are investigating structural and functional correlates of epilepsy in LGI1 positive kindreds.


Dr. Theodore received his B.A. degree from Harvard College and M.D. degree from Columbia University College of Physicians and Surgeons. After a medical internship and residency, and a neurology residency at Mount Sinai School of Medicine, he came to the National Institutes of Health for a fellowship in Epilepsy and Clinical Neurophysiology. He is board certified in Internal Medicine, Neurology, and Clinical Neurophysiology. In 1988 he became Chief of the Clinical Epilepsy Section, NINDS. He received the American Epilepsy Society Outstanding Clinical Investigator Award in 1991. Dr. Theodore's section is investigating new therapeutic approaches to uncontrolled epilepsy, and using neuroimaging techniques to study cerebral metabolism, neuropharmacology, and functional cognitive anatomy.

Selected Publications

  1. Goldenholz DM, Moss R, Scott J, Auh S, Theodore WH. Confusing placebo effect with natural history in epilepsy: A big data approach. Ann Neurol. 2015;78(3):329-36.

  2. Siddiqi OK, Elafros MA, Sikazwe I, Birbeck GL, Kalungwana L, Potchen MJ, Bositis CM, Koralnik IJ, Theodore WH. Acute EEG findings in HIV-infected Zambian adults with new-onset seizure. Neurology. 2015;84(13):1317-22.

  3. Austermuehle A, Cocjin J, Reynolds R, Agrawal S, Sepeta L, Gaillard WD, Zaghloul KA, Inati S, Theodore WH. Language functional MRI and direct cortical stimulation in epilepsy preoperative planning. Ann Neurol. 2017;81(4):526-537.

  4. Gershen LD, Zanotti-Fregonara P, Dustin IH, Liow JS, Hirvonen J, Kreisl WC, Jenko KJ, Inati SK, Fujita M, Morse CL, Brouwer C, Hong JS, Pike VW, Zoghbi SS, Innis RB, Theodore WH. Neuroinflammation in Temporal Lobe Epilepsy Measured Using Positron Emission Tomographic Imaging of Translocator Protein. JAMA Neurol. 2015;72(8):882-8.

  5. Berl MM, Zimmaro LA, Khan OI, Dustin I, Ritzl E, Duke ES, Sepeta LN, Sato S, Theodore WH, Gaillard WD. Characterization of atypical language activation patterns in focal epilepsy. Ann Neurol. 2014;75(1):33-42.

This page was last updated on November 25th, 2014