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Dynamics of long range network interactions in focal epilepsy

Award Number: R01NS084142
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: 09/01/2013
PERIOD OF PERFORMANCE END DATE: 06/30/2024

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Dynamics of long range network interactions in focal epilepsy - PROJECT SUMMARY Epilepsy is the world’s most prominent serious brain disorder, affecting nearly 50 million people worldwide. For about 30% of these patients, seizures remain poorly controlled despite optimal medical management, with attendant effects on health and quality of life. In order to enable advances in the therapeutic management of epilepsy, a thorough understanding of how cellular processes that drive seizures are linked to large-scale network effects is needed. While seizures impact large brain areas and often multiple lobes, the driving processes span regions on the scale of millimeters. These have been well characterized in animal models, but the relevance to human seizures, i.e. how seizures are driven by brain signals from small-scale processes remains unclear. Instead, the view that naturally-occurring seizures may be attributable instead to large-scale neural mass effects (i.e., the epileptic network) is a subject of ongoing debate. Previously, we defined a key role for surround inhibition in shaping EEG recordings of seizures at the onset site and on small spatial scales. We now propose that surround inhibition has a dual role. On a millimeter scale, its abrupt failure permits the advance of a seizure. At long distances from the seizure focus, strong local inhibition serves to mask the excitatory effects of seizures and may help to hasten seizure termination, while weakened inhibition may permit emergence of ictal activity at a distant, noncontiguous seizure site. Multiple seizure foci may go unrecognized with standard EEG interpretation methods, and are likely a critical factor in epilepsy surgery failures. We hypothesize that once established, multiple ictal generators behave as delay-coupled oscillators, demonstrating activity that is synchronized or even temporally reversed. This results in complex and at times counterintuitive network behavior that can be challenging to reverse engineer from EEG recordings. Typically, however, even intracranial EEG recordings provide only a limited view of neural activity. In this project, an interdisciplinary research group with combined expertise in epilepsy, clinical neurophysiology, computational modeling, and mathematics will conduct a comprehensive study of the neuronal contributors to epileptic networks utilizing a unique combined dataset of simultaneous microelectrode and macroelectrode recordings of human seizures. Using a machine learning approach, we will apply this information to develop a multivariate EEG biomarker based on the inferred source of EEG discharges, high frequency oscillations, and very low frequency (DC) shifts and assess its predictive value for post-resection surgical outcome. We anticipate that the project will lead to a theoretical framework for rational development of innovative strategies for developing interventions to control seizures.


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 = -$1 )
2025	2022	THE TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK	630 W 168TH ST FL 4	NEW YORK	NY	10032	NEW YORK	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	10	11/12/2024	NON-COMPETING CONTINUATION	-$1
														Subtotal = -$1

Issue Date FY: 2022 ( Subtotal = $609,033 )
2022	2022	TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK, THE	630 W 168TH ST FL 4	NEW YORK	NY	10032	NEW YORK	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	10	6/13/2022	NON-COMPETING CONTINUATION	$609,033
2022	2017	TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK, THE	630 W 168TH ST FL 4	NEW YORK	NY	10032	NEW YORK	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	5	10/1/2021	NON-COMPETING CONTINUATION	$0
														Subtotal = $609,033

Issue Date FY: 2021 ( Subtotal = $612,436 )
2021	2021	TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK, THE	630 W 168TH ST FL 4	NEW YORK	NY	10032	NEW YORK	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	9	7/23/2021	NON-COMPETING CONTINUATION	$612,436
														Subtotal = $612,436

Issue Date FY: 2020 ( Subtotal = $615,913 )
2020	2020	TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK	630 W 168TH ST FL 4	NEW YORK	NY	10032	NEW YORK	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	8	6/18/2020	NON-COMPETING CONTINUATION	$615,913
														Subtotal = $615,913

Issue Date FY: 2019 ( Subtotal = $613,085 )
2019	2019	TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK	630 W 168TH ST FL 4	NEW YORK	NY	10032	NEW YORK	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	004	7	7/3/2019	NON-COMPETING CONTINUATION	$613,085
2019	2018	TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK	630 W 168TH ST FL 4	NEW YORK	NY	10032	NEW YORK	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	003	6	2/17/2019	COMPETING CONTINUATION	$897,801
2019	2018	TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK	630 W 168TH ST FL 4	NEW YORK	NY	10032	NEW YORK	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	6	12/19/2018	COMPETING CONTINUATION	$0
2019	2017	TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK	630 W 168TH ST FL 4	NEW YORK	NY	10032	NEW YORK	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	002	5	2/17/2019	NON-COMPETING CONTINUATION	-$511,645
2019	2016	TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK	630 W 168TH ST FL 4	NEW YORK	NY	10032	NEW YORK	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	4	2/17/2019	EXTENSION WITH OR WITHOUT FUNDS	-$386,156
														Subtotal = $613,085

Issue Date FY: 2018 ( Subtotal = $689,291 )
2018	2018	TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK	630 W 168TH ST FL 4	NEW YORK	NY	10032	NEW YORK	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	6	9/24/2018	COMPETING CONTINUATION	$689,291
2018	2017	TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK	630 W 168TH ST FL 4	NEW YORK	NY	10032	NEW YORK	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	5	9/24/2018	NON-COMPETING CONTINUATION	$0
														Subtotal = $689,291

Issue Date FY: 2017 ( Subtotal = $511,645 )
2017	2017	TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK	630 W 168TH ST FL 4	NEW YORK	NY	10032	NEW YORK	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	005	5	6/7/2017	NON-COMPETING CONTINUATION	$511,645
2017	2016	TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK	630 W 168TH ST FL 4	NEW YORK	NY	10032	NEW YORK	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	002	4	12/5/2016	EXTENSION WITH OR WITHOUT FUNDS	$600,899
2017	2016	TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK	630 W 168TH ST FL 4	NEW YORK	NY	10032	NEW YORK	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	004	4	3/1/2017	EXTENSION WITH OR WITHOUT FUNDS	$8,320
2017	2015	TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK	630 W 168TH ST FL 4	NEW YORK	NY	10032	NEW YORK	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	3	12/5/2016	NON-COMPETING CONTINUATION	-$581,439
2017	2014	TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK	630 W 168TH ST FL 4	NEW YORK	NY	10032	NEW YORK	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	2	12/5/2016	NON-COMPETING CONTINUATION	-$19,460
2017	2014	TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK	630 W 168TH ST FL 4	NEW YORK	NY	10032	NEW YORK	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	003	2	3/1/2017	NON-COMPETING CONTINUATION	-$8,320
														Subtotal = $511,645

Issue Date FY: 2016 ( Subtotal = $574,409 )
2016	2016	COLUMBIA UNIVERSITY	615 WEST 131ST ST, 4TH FLOOR	NEW YORK	NY	10027	NEW YORK	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	4	6/6/2016	EXTENSION WITH OR WITHOUT FUNDS	$574,409
														Subtotal = $574,409

Issue Date FY: 2015 ( Subtotal = $581,439 )
2015	2015	COLUMBIA UNIVERSITY	615 WEST 131ST ST, 4TH FLOOR	NEW YORK	NY	10027	NEW YORK	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	3	7/2/2015	NON-COMPETING CONTINUATION	$581,439
														Subtotal = $581,439

Issue Date FY: 2014 ( Subtotal = $580,058 )
2014	2014	COLUMBIA UNIVERSITY	615 WEST 131ST ST, 4TH FLOOR	NEW YORK	NY	10027	NEW YORK	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	2	6/25/2014	NON-COMPETING CONTINUATION	$580,058
														Subtotal = $580,058

Issue Date FY: 2013 ( Subtotal = $599,040 )
2013	2013	COLUMBIA UNIVERSITY	615 WEST 131ST ST, 4TH FLOOR	NEW YORK	NY	10027	NEW YORK	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	1	8/5/2013	NEW	$599,040
														Subtotal = $599,040

Grand Total All Awards = $5,986,348

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Dynamics of long range network interactions in focal epilepsy

Award Number: R01NS084142

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: 09/01/2013

PERIOD OF PERFORMANCE END DATE: 06/30/2024

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