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Optimized Intracranial EEG Targeting in Focal Epilepsy based upon Neuroimaging Connectomics

Award Number: R01NS116504
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: 03/01/2021
PERIOD OF PERFORMANCE END DATE: 02/28/2026

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Optimized Intracranial EEG Targeting in Focal Epilepsy based upon Neuroimaging Connectomics - Despite recent advances in neuroimaging, approximately 2/3 of intractable epilepsy patients that undergo surgical evaluation continue to require intracranial EEG (IEEG), arguably the most invasive diagnostic test in medicine. We currently lack methods to quantitatively map noninvasive imaging measures of structure and function to IEEG. Specifically, there is a critical need to validate whole-brain noninvasive neuroimaging network- based biomarkers to guide precise placement of electrodes and translate noninvasive network neuroimaging to change the paradigms of clinical care. The long-term goal of this proposal is to predict IEEG functional dynamics and surgical outcomes using noninvasive MRI-based measures of structure and function. Our overall objective, which is the next step toward attaining our long-term goal, is to develop open-source noninvasive imaging tools that map epileptic networks by integrating MRI and IEEG data. Our central hypothesis is that noninvasive measures of structure and function relate to and can predict the intricate functional dynamics captured on IEEG. The central hypothesis will be tested in patients undergoing IEEG targeting the temporal lobe network by pursuing three specific aims: 1) To map the patient specific structural connectome to IEEG seizure onset and propagation, 2) To correlate seizure onset and propagation on IEEG with network measures derived from resting state functional MRI (rsfMRI), and 3) To integrate the structural (Aim 1) and functional (Aim 2) connectome with standard qualitative clinical data to predict IEEG network dynamics and surgical outcomes. Under the first aim patients will undergo diffusion tensor imaging (DTI) prior to stereotactic IEEG, an IEEG method that inherently samples long range networks. The functional IEEG network will be mapped to DTI thus defining how seizures are constrained by the underlying structural connectome as they propagate. Under the second aim patients with temporal lobe epilepsy will undergo rsfMRI on 7T MRI prior to stereotactic IEEG. Functional network measures from rsfMRI and IEEG will be coregistered and rsfMRI will be used to predict functional EEG ictal and interictal networks. In the third aim two models predicting IEEG network dynamics and epilepsy surgical outcomes will be created building off of methods developed in Aims 1 and 2. The proposed research is innovative because it represents a substantive departure from the status quo by directly connecting noninvasive multimodal imaging with measures of functional network dynamics in IEEG. The proposed research is significant because it is expected that successful completion of these aims will yield personalized strategies for IEEG targeting based on noninvasive neuroimaging.


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: 2025 ( Subtotal = $558,449 )
2025	2025	TRUSTEES OF THE UNIVERSITY OF PENNSYLVANIA, THE	3451 WALNUT ST STE 440A	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	5	3/10/2025	NON-COMPETING CONTINUATION	$558,449
														Subtotal = $558,449

Issue Date FY: 2024 ( Subtotal = $695,130 )
2024	2024	TRUSTEES OF THE UNIVERSITY OF PENNSYLVANIA, THE	3451 WALNUT ST STE 440A	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	002	4	4/25/2024	NON-COMPETING CONTINUATION	$43,986
2024	2024	TRUSTEES OF THE UNIVERSITY OF PENNSYLVANIA, THE	3451 WALNUT ST STE 440A	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	4	2/23/2024	NON-COMPETING CONTINUATION	$565,579
2024	2024	TRUSTEES OF THE UNIVERSITY OF PENNSYLVANIA, THE	3451 WALNUT ST STE 440A	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	4	2/29/2024	SUPPLEMENT FOR EXPANSION	$85,565
														Subtotal = $695,130

Issue Date FY: 2023 ( Subtotal = $721,572 )
2023	2023	TRUSTEES OF THE UNIVERSITY OF PENNSYLVANIA, THE	3451 WALNUT ST STE 440A	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	3	3/6/2023	SUPPLEMENT FOR EXPANSION	$85,565
2023	2023	TRUSTEES OF THE UNIVERSITY OF PENNSYLVANIA, THE	3451 WALNUT ST STE 440A	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	3	2/27/2023	NON-COMPETING CONTINUATION	$636,007
														Subtotal = $721,572

Issue Date FY: 2022 ( Subtotal = $639,344 )
2022	2022	TRUSTEES OF THE UNIVERSITY OF PENNSYLVANIA, THE	3451 WALNUT ST STE 440A	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	2	5/3/2022	NON-COMPETING CONTINUATION	$639,344
														Subtotal = $639,344

Issue Date FY: 2021 ( Subtotal = $660,904 )
2021	2021	TRUSTEES OF THE UNIVERSITY OF PENNSYLVANIA, THE	3451 WALNUT ST STE 440A	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	1	2/25/2021	NEW	$660,904
														Subtotal = $660,904

Grand Total All Awards = $3,275,399

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Optimized Intracranial EEG Targeting in Focal Epilepsy based upon Neuroimaging Connectomics

Award Number: R01NS116504

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: 03/01/2021

PERIOD OF PERFORMANCE END DATE: 02/28/2026

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