The NINDS and several epilepsy organizations have established benchmarks that emphasize the need to develop new therapeutic strategies and optimize current approaches to treat and cure epilepsy. Mesial temporal lobe epilepsy (MTLE) with hippocampal sclerosis (HS) is the most common type of pharmacoresistant epilepsy. Patients with this type of epilepsy are often treated surgically, but surgical outcome studies indicate too many patients continue to have postoperative seizures. Surgical resection is based on determining the epileptogenic zone (EZ), i.e. the brain areas necessary and sufficient for generating spontaneous seizures, and surgical failure is believed to result from an incomplete resection of the EZ. The fundamental challenge in defining the EZ is that it can not be measured directly, but is inferred from diagnostic tests, most important of which is localization of sites of ictal onset and early propagation and the presence of an epileptogenic lesion. Our recent work using advanced structural imaging in patients with MTLE found specific spatial patterns and levels of hippocampal atrophy that were associated with different types of ictal onset. These data indicate there could be several types of MTLE with HS and each associated with specific anatomical abnormalities, ictal and interictal electrophysiological disturbances and clinical features. If this hypothesis is correct, then a combination of these measures of epileptogenicity could define the EZ and provide important information on prognosis for a seizure-free surgical outcome. The proposed studies will use structural imaging and functional measures in an attempt to accurately delineate the EZ in patients with MTLE. Specifically, first, we will quantitatively evaluate the spatial patterns and levels of hippocampal and neocortical gray matter atrophy in patients with different types of depth electrode-recorded ictal onsets and clinical features. Second, we will characterize pathological high frequency oscillations (pHFOs) and localize their sites of generation in hippocampal and neocortical networks that include areas of ictal onset and early propagation and remote areas. Studies by us and others suggest pHFOs represent fundamental neuronal disturbances responsible for spontaneous seizure genesis, and because these abnormal events occur during interictal as well as during ictal periods, recording pHFOs will allow us to identify areas of epileptogenicity more rapidly than capturing seizures. And third, we will determine whether a combination of these measures of epileptogenicity accurately defines the EZ by correlating their removal with seizure-free surgical outcomes. We anticipate completion of these specific aims will develop safer, more accurate and less expensive approaches to defining the EZ and increase the likelihood for postoperative seizure freedom. In addition, we expect that the results of the proposed studies will provide valuable insights into the fundamental neuronal basis of the EZ in MTLE.

Public Health Relevance

Individuals with poorly controlled epilepsy, as well as their families and communities, sustain considerable physical, social and economic costs. This study is designed to identify specific anatomical and electrophysiological disturbances that define the brain areas capable of generating spontaneous seizures in order to more clearly understand mechanisms of seizure genesis, improve surgical treatment and develop new therapies to eliminate seizures and the burden of epilepsy.

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
Research Project (R01)
Project #
Application #
Study Section
Acute Neural Injury and Epilepsy Study Section (ANIE)
Program Officer
Fureman, Brandy E
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of California Los Angeles
Schools of Medicine
Los Angeles
United States
Zip Code
Lopour, Beth A; Staba, Richard J; Stern, John M et al. (2016) Characterization of long-range functional connectivity in epileptic networks by neuronal spike-triggered local field potentials. J Neural Eng 13:026031
Weiss, Shennan Aibel; Alvarado-Rojas, Catalina; Bragin, Anatol et al. (2016) Ictal onset patterns of local field potentials, high frequency oscillations, and unit activity in human mesial temporal lobe epilepsy. Epilepsia 57:111-21
Bragin, Anatol; Li, Lin; Almajano, Joyel et al. (2016) Pathologic electrographic changes after experimental traumatic brain injury. Epilepsia 57:735-45
Weiss, Shennan A; Orosz, Iren; Salamon, Noriko et al. (2016) Ripples on spikes show increased phase-amplitude coupling in mesial temporal lobe epilepsy seizure-onset zones. Epilepsia 57:1916-1930
Reid, Aylin Y; Bragin, Anatol; Giza, Christopher C et al. (2016) The progression of electrophysiologic abnormalities during epileptogenesis after experimental traumatic brain injury. Epilepsia 57:1558-1567
Memarian, Negar; Kim, Sally; Dewar, Sandra et al. (2015) Multimodal data and machine learning for surgery outcome prediction in complicated cases of mesial temporal lobe epilepsy. Comput Biol Med 64:67-78
Menendez de la Prida, Liset; Staba, Richard J; Dian, Joshua A (2015) Conundrums of high-frequency oscillations (80-800 Hz) in the epileptic brain. J Clin Neurophysiol 32:207-19
Staba, Richard J; Stead, Matt; Worrell, Gregory A (2014) Electrophysiological biomarkers of epilepsy. Neurotherapeutics 11:334-46
Reid, Aylin Y; Staba, Richard J (2014) Limbic networks: clinical perspective. Int Rev Neurobiol 114:89-120
Gloss, David; Nolan, Sarah J; Staba, Richard (2014) The role of high-frequency oscillations in epilepsy surgery planning. Cochrane Database Syst Rev :CD010235

Showing the most recent 10 out of 19 publications