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Using deep brain stimulation of the parietal cortex to investigate the electrophysiology of human episodic memory

Award Number: R01NS107357
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: 09/01/2018
PERIOD OF PERFORMANCE END DATE: 06/30/2028

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Using deep brain stimulation of the parietal cortex to investigate the electrophysiology of human episodic memory - Parietal regions, including the posterior cingulate cortex, participate in brain networks critical for recollection, order memory, autobiographical retrieval, and episodic simulation. The importance of regions such as the posterior cingulate to episodic processing has been highlighted by data from animal models, non—invasive imaging studies, brain stimulation experiments, and rare reports that use directly recorded brain activity in humans. However, significant knowledge gaps remain related to the specific neurophysiological processes that occur within the posterior cingulate and how this region integrates with hippocampal memory networks. We propose three highly innovative experiments to address these knowledge gaps. First, we will obtain microelectrode recordings from the posterior cingulate cortex during episodic encoding and retrieval. We will identify time cells, a population of neurons that provide direct representation of temporal contextual information. We will also identify episodic boundary cells, which represent a complementary population of neurons critical for episodic construction. We will identify neuronal assemblies in the MTL and concomitant ripple activity in the PCC. Second, we will use the novel experimental manipulation of administering the anticholinergic agent scopolamine to human intracranial EEG subjects performing an episodic memory task and record simultaneous hippocampal and parietal activity (from the posterior cingulate cortex). Based on our preliminary data using this manipulation in this patient population, we predict that we will observe a decrease in activity in the 2-5 Hz `slow theta’ frequency range, as well as commensurate changes in hippocampal—parietal connectivity in the 5-9 Hz `fast theta’ frequency band. The use of scopolamine has direct relevance for understanding cholinergic modulation in hippocampal memory circuits and implications for understanding how degenerative conditions such as Alzheimer’s Disease impact these circuits. Finally, we will use direct brain stimulation applied to the posterior cingulate cortex and angular gyrus in the same experimental subjects to understand how these regions may differentially modulate hippocampal theta oscillations, building on our published work using this experimental approach. These experiments will take advantage of our unique opportunity to obtain direct brain recordings from hippocampal networks in surgical epilepsy patients. Our expertise in this area, demonstrated in our published findings from the previous funded period, supports our ability to collect these proposed data and generative novel, high value datasets that will allow us to address the knowledge gaps outlined above.


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 = $408,208 )
2025	2025	THE UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CENTER	5323 HARRY HINES BLVD	DALLAS	TX	75390	DALLAS	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	003	8	6/27/2025	NON-COMPETING CONTINUATION	$408,208
2025	2023	THE UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CENTER	5323 HARRY HINES BLVD	DALLAS	TX	75390	DALLAS	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	002	6	2/14/2025	COMPETING CONTINUATION	$135,547
2025	2022	THE UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CENTER	5323 HARRY HINES BLVD	DALLAS	TX	75390	DALLAS	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	5	2/14/2025	SUPPLEMENT FOR EXPANSION	-$13,341
2025	2022	THE UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CENTER	5323 HARRY HINES BLVD	DALLAS	TX	75390	DALLAS	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	5	2/14/2025	NON-COMPETING CONTINUATION	-$122,206
														Subtotal = $408,208

Issue Date FY: 2024 ( Subtotal = $395,962 )
2024	2024	THE UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CENTER	5323 HARRY HINES BLVD	DALLAS	TX	75390	DALLAS	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	7	6/28/2024	NON-COMPETING CONTINUATION	$395,962
														Subtotal = $395,962

Issue Date FY: 2023 ( Subtotal = $424,208 )
2023	2023	UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CENTER, THE	5323 HARRY HINES BLVD	DALLAS	TX	75390	DALLAS	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	6	8/1/2023	COMPETING CONTINUATION	$424,208
2023	2022	UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CENTER, THE	5323 HARRY HINES BLVD	DALLAS	TX	75390	DALLAS	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	5	7/31/2023	NON-COMPETING CONTINUATION	$0
														Subtotal = $424,208

Issue Date FY: 2022 ( Subtotal = $392,398 )
2022	2022	UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CENTER, THE	5323 HARRY HINES BLVD	DALLAS	TX	75390	DALLAS	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	5	6/20/2022	SUPPLEMENT FOR EXPANSION	$38,620
2022	2022	UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CENTER, THE	5323 HARRY HINES BLVD	DALLAS	TX	75390	DALLAS	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	5	6/12/2022	NON-COMPETING CONTINUATION	$353,778
														Subtotal = $392,398

Issue Date FY: 2021 ( Subtotal = $513,592 )
2021	2021	UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CENTER, THE	5323 HARRY HINES BLVD	DALLAS	TX	75390	DALLAS	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	3	2/16/2021	SUPPLEMENT FOR EXPANSION	$79,818
2021	2021	UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CENTER, THE	5323 HARRY HINES BLVD	DALLAS	TX	75390	DALLAS	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	002	4	7/19/2021	SUPPLEMENT FOR EXPANSION	$79,977
2021	2021	UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CENTER, THE	5323 HARRY HINES BLVD	DALLAS	TX	75390	DALLAS	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	4	7/14/2021	NON-COMPETING CONTINUATION	$353,797
														Subtotal = $513,592

Issue Date FY: 2020 ( Subtotal = $356,032 )
2020	2020	UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CENTER, THE	5323 HARRY HINES BLVD	DALLAS	TX	75390	DALLAS	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	3	6/24/2020	NON-COMPETING CONTINUATION	$356,032
														Subtotal = $356,032

Issue Date FY: 2019 ( Subtotal = $359,585 )
2019	2019	UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CENTER, THE	5323 HARRY HINES BLVD	DALLAS	TX	75390	DALLAS	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	2	7/18/2019	NON-COMPETING CONTINUATION	$359,585
														Subtotal = $359,585

Issue Date FY: 2018 ( Subtotal = $359,433 )
2018	2018	UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CENTER, THE	5323 HARRY HINES BLVD	DALLAS	TX	75390	DALLAS	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	1	8/21/2018	NEW	$359,433
														Subtotal = $359,433

Grand Total All Awards = $3,209,418

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Using deep brain stimulation of the parietal cortex to investigate the electrophysiology of human episodic memory

Award Number: R01NS107357

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: 09/01/2018

PERIOD OF PERFORMANCE END DATE: 06/30/2028

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