The long-range objectives of this research include establishment of more universal criteria for neocortical epilepsy surgery in children, with the assistance of quantitative analysis of intracranial EEG and neuroimaging data, as well as understanding of the mechanisms of ictal epileptic discharges seen on EEG in pediatric neocortical epilepsy using in vivo quantitative multimodality analyses. The training aspects of this proposal focus on progression to independence as a researcher. The educational plan include supervised research in quantitative analyses of intracranial EEG and neuroimaging as well as formal training and experience in applied biostatistics, data management, and the ethical conduct of research. One-fifth of epilepsy in children is medically intractable. A subset of children with intractable neocortical epilepsy have benefited from respective surgery of the presumed epileptogenic zone. Yet, the chance of long-term seizure-free outcome by respective brain surgery is reported as low as 50% in children with extra temporal lobe epilepsy. Objective delineation of abnormalities on positron emission tomography (PET) imaging has recently yielded better surgical outcomes (-80% seizure-free) in our institute, but even this is not optimum. The applicant hypothesizes that an epileptic brain has a spatial gradient of epileptogenicity and that some of the failed surgery may have been due to the incomplete resection of epileptogenic cortex, which is missed by imaging studies and optimal EEG analysis. The concept of a gradient of epileptogenicity is supported by observations that 1) some patients experience seizure recurrence several years after resection of the presumed epileptogenic zone, including neuroimaging abnormalities and 2) discontinuation of antiepileptic drugs after apparently successful epilepsy surgery induce seizure recurrence in one-third of patients. Since EEG parameters retain continuous values among intracranial electrodes, we will determine whether surgical outcome is correlated with the degree of neurophysiological abnormalities in the cortex not respected by surgery, and establish the cutoff threshold resulting in the best surgical outcome in children with neocortical epilepsy (including epileptic spasms). Epileptic seizures are represented as sustained rhythmic ictal discharges on EEG, of which underlying mechanisms are unknown. Since ictal discharges typically show synchronization and propagation to other brain regions, in vitro analysis of isolated human brain tissues may not be representative of the entire epileptic circuitry. In contrast, in vivo quantitative analyses of ictal electrographic changes in children with neocortical partial seizures, using intracranial EEG and functional neuroimaging data will provide a different perspective regarding the mechanism and clinical significance of ictal discharges on the EEG. Ultimately, such knowledge may lead to better surgical and pharmaco-therapies for seizure disorders. If funded, the applicant will achieve the necessary training in an excellent environment to develop into an independent investigator. ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Mentored Patient-Oriented Research Career Development Award (K23)
Project #
5K23NS047550-03
Application #
7062072
Study Section
NST-2 Subcommittee (NST)
Program Officer
Fureman, Brandy E
Project Start
2004-07-01
Project End
2009-04-30
Budget Start
2006-05-01
Budget End
2007-04-30
Support Year
3
Fiscal Year
2006
Total Cost
$154,652
Indirect Cost
Name
Wayne State University
Department
Pediatrics
Type
Schools of Medicine
DUNS #
001962224
City
Detroit
State
MI
Country
United States
Zip Code
48202
Motoi, Hirotaka; Miyakoshi, Makoto; Abel, Taylor J et al. (2018) Phase-amplitude coupling between interictal high-frequency activity and slow waves in epilepsy surgery. Epilepsia 59:1954-1965
Nakai, Yasuo; Jeong, Jeong-Won; Brown, Erik C et al. (2017) Three- and four-dimensional mapping of speech and language in patients with epilepsy. Brain 140:1351-1370
Chugani, Harry T; Ilyas, Mohammed; Kumar, Ajay et al. (2015) Surgical treatment for refractory epileptic spasms: The Detroit series. Epilepsia 56:1941-9
Ueda, Keisuke; Brown, Erik C; Kojima, Katsuaki et al. (2015) Mapping mental calculation systems with electrocorticography. Clin Neurophysiol 126:39-46
Cho-Hisamoto, Yoshimi; Kojima, Katsuaki; Brown, Erik C et al. (2015) Gamma activity modulated by naming of ambiguous and unambiguous images: intracranial recording. Clin Neurophysiol 126:17-26
Asano, Eishi (2014) Contribution of research on 'Epilepsy & behavior' to the refinement of functional brain atlas in four dimensions. Epilepsy Behav 40:86-8
Brown, Erik C; Jeong, Jeong-Won; Muzik, Otto et al. (2014) Evaluating the arcuate fasciculus with combined diffusion-weighted MRI tractography and electrocorticography. Hum Brain Mapp 35:2333-47
Brown, Erik C; Muzik, Otto; Rothermel, Robert et al. (2014) Evaluating signal-correlated noise as a control task with language-related gamma activity on electrocorticography. Clin Neurophysiol 125:1312-23
Kojima, Katsuaki; Brown, Erik C; Matsuzaki, Naoyuki et al. (2013) Animal category-preferential gamma-band responses in the lower- and higher-order visual areas: intracranial recording in children. Clin Neurophysiol 124:2368-77
Kojima, Katsuaki; Brown, Erik C; Matsuzaki, Naoyuki et al. (2013) Gamma activity modulated by picture and auditory naming tasks: intracranial recording in patients with focal epilepsy. Clin Neurophysiol 124:1737-44

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