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Dissecting the Cognitive Roles of Hippocampus and Other Temporal Lobe Structures in Patients Undergoing Epilepsy Surgery

Award Number: R01NS088748
ORGANIZATION: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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Project Summary: We have conducted the largest prospective comparative study of laser amygdalohippocampotomy (SLAH), a minimally invasive procedure ablating the amygdalo-hippocampal complex (AHC) versus selective and standard open resection (OR) epilepsy surgery (N=425+). We demonstrated that SLAH is superior to OR in 1-year cognitive outcomes in adults (including episodic verbal memory & perceptual (semantic) recognition or name retrieval of objects/faces), while achieving comparable seizure control. We will extend our analysis longitudinally in an unprecedented manner (5-10 year outcome) leveraging this unique cohort of well-studied patients including neuropsychological (NP), structural and functional neuroimaging and seizure outcomes. We have also amassed a large sample of cases involving stereotactic laser ablation [SLA] of non-AHC structures. The heterogeneity of these SLA cases and the focal nature of the laser ablation surgical zones create an amazing opportunity for lesion-behavioral analyses. We will expand our neuroimaging analyses to include rigorous voxel lesion symptom mapping (VLSM) and novel methods of connectivity modeling with diffusion tensor imaging and resting state fMRI. We will focus on the neural circuitry responsible for declarative memory and language, while determining the optimal surgical zones to produce the best long-term cognitive and seizure outcomes. VLSM allows us to determine which temporal lobe regions are critical for specific cognitive functions, while connectivity analyses will reveal the interconnectedness of these regions in the individual patient (allowing us to determine the relative risk of decline at the patient level). Our preliminary findings indicate that: 1) SLAH patients exhibit unexpected improvement in multiple cognitive functions, which is unparalleled in their OR counterparts, and 2) SLA procedures sparing the AHC and broader medial TL regions frequently lead to severe decline in verbal memory/naming, particularly in cases of focal ablations of the language dominant temporal pole or fusiform gyrus. This suggests that verbal declarative memory depends upon a broad network extending beyond the AHC, which is a paradigm shift for surgical planning (i.e., regions thought to be expendable during surgical approach are actually critical to function). This knowledge is fundamentally important from mechanistic and clinical translational points of view, and our data and planned analyses provide a unique and feasible way to draw robust conclusions on these long-standing knowledge gaps. Our data raise pivotal questions about existing declarative memory models and the mechanism of recovery underlying the superior cognitive outcomes in many SLAH/SLA cases (e.g., functional sparing vs. reorganization), which we will address in this renewal by following our patients over time. Finally, while more epilepsy centers are employing SLA due to its improved cognitive outcomes, ultimate clinical adoption rests on seizure control, making it critical to determine SLAH efficacy over a longer time span.


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 = $563,717 )
2024	2024	EMORY UNIVERSITY	201 DOWMAN DR NE	ATLANTA	GA	30322	DEKALB	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	10	6/26/2024	NON-COMPETING CONTINUATION	$563,717
														Subtotal = $563,717

Issue Date FY: 2023 ( Subtotal = $629,245 )
2023	2023	EMORY UNIVERSITY	201 DOWMAN DR	ATLANTA	GA	30322	DEKALB	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	9	6/13/2023	NON-COMPETING CONTINUATION	$601,964
2023	2023	EMORY UNIVERSITY	201 DOWMAN DR	ATLANTA	GA	30322	DEKALB	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	9	6/20/2023	SUPPLEMENT FOR EXPANSION	$27,281
														Subtotal = $629,245

Issue Date FY: 2022 ( Subtotal = $804,229 )
2022	2022	EMORY UNIVERSITY	201 DOWMAN DR	ATLANTA	GA	30322	DEKALB	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	003	8	4/25/2022	SUPPLEMENT FOR EXPANSION	$118,513
2022	2022	EMORY UNIVERSITY	201 DOWMAN DR	ATLANTA	GA	30322	DEKALB	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	002	8	4/6/2022	NON-COMPETING CONTINUATION	$615,019
2022	2022	EMORY UNIVERSITY	201 DOWMAN DR	ATLANTA	GA	30322	DEKALB	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	7	2/11/2022	SUPPLEMENT FOR EXPANSION	$70,697
2022	2021	EMORY UNIVERSITY	201 DOWMAN DR	ATLANTA	GA	30322	DEKALB	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	7	2/11/2022	SUPPLEMENT FOR EXPANSION	$0
														Subtotal = $804,229

Issue Date FY: 2021 ( Subtotal = $681,366 )
2021	2021	EMORY UNIVERSITY	201 DOWMAN DR	ATLANTA	GA	30322	DEKALB	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	002	7	8/3/2021	SUPPLEMENT FOR EXPANSION	$47,816
2021	2021	EMORY UNIVERSITY	201 DOWMAN DR	ATLANTA	GA	30322	DEKALB	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	7	4/8/2021	NON-COMPETING CONTINUATION	$633,550
2021	2018	EMORY UNIVERSITY	201 DOWMAN DR	ATLANTA	GA	30322	DEKALB	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	5	3/8/2021	NON-COMPETING CONTINUATION	$0
														Subtotal = $681,366

Issue Date FY: 2020 ( Subtotal = $703,745 )
2020	2020	EMORY UNIVERSITY	201 DOWMAN DR	ATLANTA	GA	30322	DEKALB	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	6	6/30/2020	COMPETING CONTINUATION	$703,745
														Subtotal = $703,745

Issue Date FY: 2018 ( Subtotal = $588,093 )
2018	2018	EMORY UNIVERSITY	1599 CLIFTON RD.	ATLANTA	GA	30322	DEKALB	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	5	4/25/2018	NON-COMPETING CONTINUATION	$588,093
														Subtotal = $588,093

Issue Date FY: 2017 ( Subtotal = $588,735 )
2017	2017	EMORY UNIVERSITY	1599 CLIFTON RD.	ATLANTA	GA	30322	DEKALB	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	4	5/31/2017	NON-COMPETING CONTINUATION	$58,873
2017	2017	EMORY UNIVERSITY	1599 CLIFTON RD.	ATLANTA	GA	30322	DEKALB	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	4	4/10/2017	NON-COMPETING CONTINUATION	$529,862
														Subtotal = $588,735

Issue Date FY: 2016 ( Subtotal = $591,309 )
2016	2016	EMORY UNIVERSITY	1784 N DECATUR RD,S 530 NDBLDG	ATLANTA	GA	30322	DEKALB	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	3	4/7/2016	NON-COMPETING CONTINUATION	$591,309
														Subtotal = $591,309

Issue Date FY: 2015 ( Subtotal = $592,535 )
2015	2015	EMORY UNIVERSITY	1784 N DECATUR RD,S 530 NDBLDG	ATLANTA	GA	30322	DEKALB	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	2	5/1/2015	NON-COMPETING CONTINUATION	$592,535
														Subtotal = $592,535

Issue Date FY: 2014 ( Subtotal = $634,658 )
2014	2014	EMORY UNIVERSITY	1784 N DECATUR RD,S 530 NDBLDG	ATLANTA	GA	30322	DEKALB	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	1	6/24/2014	NEW	$634,658
														Subtotal = $634,658

Grand Total All Awards = $6,377,632

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Dissecting the Cognitive Roles of Hippocampus and Other Temporal Lobe Structures in Patients Undergoing Epilepsy Surgery

Award Number: R01NS088748

ORGANIZATION: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

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