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Interictal High Frequency Oscillations of Epileptogenecity in Pediatric Patients

Award Number: R01NS104116
ORGANIZATION: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 07/01/2019
PERIOD OF PERFORMANCE END DATE: 03/31/2025

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Interictal High Frequency Oscillations of Epileptogenecity in Pediatric Patients - Project Summary Crucial to the success of epilepsy surgery is the availability of a robust presurgical biomarker to identify the epileptogenic zone (EZ). Complete resection of the EZ may lead to medication and seizure freedom. Since the EZ cannot be measured directly, its location is estimated indirectly based on concordant data from a multitude of noninvasive tests. Yet, the results of these tests are often insufficiently concordant or inconclusive. Intracranial electroencephalography (iEEG) serves as the gold standard for the delineation of the seizure onset zone (SOZ). However, the SOZ does not always predict the surgical outcome, and its delineation requires many days of recordings to capture clinical seizures. High-frequency oscillations (HFOs), recorded with iEEG are promising interictal biomarkers of the EZ. Yet, their clinical value for epilepsy surgery is still debated since the HFO-generating area is often relatively large and its complete resection may overlap with eloquent areas. This is often attributed to the presence of physiological HFOs in non-epileptogenic areas. In our recent iEEG study, we showed that interictal HFOs are initiated by an onset generator and spread to other brain areas over time. This generator constitutes a promising interictal biomarker of the EZ since its resection is associated with good surgical outcome. Despite the copious literature on HFOs, the clinical value of HFOs for surgery has been only investigated using iEEG, which presents serious limitations due to its invasiveness and its limited spatial sampling. This application aims to noninvasively localize interictal HFOs with high-density electroencephalography (HD-EEG) and magnetoencephalography (MEG) in children with medically refractory epilepsy (MRE), distinguish pathological from physiological HFOs, and assess the noninvasive localization of the HFO-onset generator with respect to the surgical resection and patients’ outcome. Our hypothesis is that HD-EEG and MEG can distinguish pathological from physiological HFOs non-invasively and can localize the HFO-onset generator whose removal leads to better surgical outcome than the removal of the area of secondary spread. To test our hypothesis, we specifically aim to: (i) assess the ability of HD-EEG and MEG to localize HFOs; (ii) differentiate physiological (nHFOs) from pathological (pHFOs) HFOs using unsupervised machine learning; (iii) localize noninvasively the HFO-onset generator and compare it with the clinical gold standard for resection tailoring, i.e. the iEEG-defined SOZ; and (iv) assess the predictive value of the HFO- onset generator in terms of surgical outcome. To pursue these aims, we will record HD-EEG and MEG data from 50 children (0-18 years old) with MRE and 50 typically developing (TD) children. This application combines the use of cutting-edge pediatric neuroimaging instruments, 3D printing technology, and innovative signal processing tools together with extensive neuroimaging experience with children. Our research will have a direct impact on the life of children with MRE since it will provide a new noninvasive biomarker of the EZ that would limit invasive long-term monitoring, augment presurgical planning, and improve the surgical outcome.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2024 ( Subtotal = $418,311 )
2024	2024	COOK CHILDREN'S MEDICAL CENTER	801 7TH AVE	FORT WORTH	TX	76104	TARRANT	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	6	5/3/2024	NON-COMPETING CONTINUATION	$30,185
2024	2024	COOK CHILDREN'S MEDICAL CENTER	801 7TH AVE	FORT WORTH	TX	76104	TARRANT	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	6	3/21/2024	NON-COMPETING CONTINUATION	$388,126
														Subtotal = $418,311

Issue Date FY: 2023 ( Subtotal = $455,691 )
2023	2023	COOK CHILDREN'S MEDICAL CENTER	801 7TH AVE	FORT WORTH	TX	76104	TARRANT	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	5	4/19/2023	NON-COMPETING CONTINUATION	$455,691
														Subtotal = $455,691

Issue Date FY: 2022 ( Subtotal = $473,553 )
2022	2022	COOK CHILDREN'S MEDICAL CENTER	801 7TH AVE	FORT WORTH	TX	76104	TARRANT	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	4	6/24/2022	NON-COMPETING CONTINUATION	$47,358
2022	2022	COOK CHILDREN'S MEDICAL CENTER	801 7TH AVE	FORT WORTH	TX	76104	TARRANT	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	4	3/14/2022	NON-COMPETING CONTINUATION	$426,195
														Subtotal = $473,553

Issue Date FY: 2021 ( Subtotal = $428,636 )
2021	2021	COOK CHILDREN'S MEDICAL CENTER	801 7TH AVE	FORT WORTH	TX	76104	TARRANT	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	3	3/30/2021	NON-COMPETING CONTINUATION	$428,636
2021	2019	COOK CHILDREN'S MEDICAL CENTER	801 7TH AVE	FORT WORTH	TX	76104	TARRANT	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	2	12/1/2020	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$0
														Subtotal = $428,636

Issue Date FY: 2020 ( Subtotal = $0 )
2020	2019	COOK CHILDREN'S MEDICAL CENTER	801 7TH AVE	FORT WORTH	TX	76104	TARRANT	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	002	2	5/8/2020	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$0
2020	2019	COOK CHILDREN'S MEDICAL CENTER	801 7TH AVE	FORT WORTH	TX	76104	TARRANT	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	2	3/31/2020	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$636,637
2020	2019	CHILDREN'S HOSPITAL CORPORATION, THE	300 LONGWOOD AVE	BOSTON	MA	02115	SUFFOLK	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	003	1	6/22/2020	NEW	$0
2020	2019	CHILDREN'S HOSPITAL CORPORATION, THE	300 LONGWOOD AVE	BOSTON	MA	02115	SUFFOLK	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	1	3/28/2020	NEW	-$636,637
														Subtotal = $0

Issue Date FY: 2019 ( Subtotal = $640,021 )
2019	2019	CHILDREN'S HOSPITAL CORPORATION, THE	300 LONGWOOD AVE	BOSTON	MA	02115	SUFFOLK	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	1	6/5/2019	NEW	$640,021
														Subtotal = $640,021

Grand Total All Awards = $2,416,212

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Interictal High Frequency Oscillations of Epileptogenecity in Pediatric Patients

Award Number: R01NS104116

ORGANIZATION: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 07/01/2019

PERIOD OF PERFORMANCE END DATE: 03/31/2025

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