Monday, June 30, 2025 6/30/2025

Investigating Inhibitory Control Networks in Parkinson's Disease

Award Number: K23NS117735
ORGANIZATION: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP
PERIOD OF PERFORMANCE START DATE: 04/01/2021
PERIOD OF PERFORMANCE END DATE: 03/31/2026

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Investigating Inhibitory Control Networks in Parkinson's Disease - Project Summary: The overall goal of this project is to provide applicant J. Nicole Bentley, MD appropriate resources and mentorship to develop skills allowing a path to research independence in the field of neuromodulation for cognitive disorders. This proposal focuses on the role of dorsolateral prefrontal cortex (DLPFC) in altered cognition in Parkinson’s disease (PD) patients with simultaneous intracranial cortical and subcortical recordings during awake deep brain stimulation (DBS) surgery. Cognitive impairment is a common non-motor symptom of Parkinson’s disease (PD), affecting one-quarter of newly diagnosed patients, and more than 80% of patients over the course of the disease. Despite its prevalence, very few treatment options exist. Unfortunately, mainstay treatments for motor symptoms of PD such as dopaminergic medications and high- frequency deep brain stimulation (DBS) do not improve and in some instances can even worsen cognitive symptoms. Recent evidence in PD patients suggests that reduced prefrontal theta frequency oscillatory activity is associated with impaired cognition, specifically evident in the domain of inhibitory control. Given its dense connections to basal ganglia and pre-motor areas, neuromodulation of the DLPFC-basal ganglia network could enhance elements of cognitive dysfunction in PD. Our novel preliminary data shows DLPFC and subcortical power modulation and phase-amplitude coupling during an intraoperative Simon task measuring inhibitory control, and that bursting theta-frequency DBS modulates DLPFC theta power. Here we propose studies to (1) simultaneously record DLPFC and globus pallidus interna (GPi) local field potentials (LFPs) in awake PD patients during the Simon task, and (2) contrast continuous and intermittent theta stimulation from the DBS electrode at the GPi to determine the effect on behavioral and electrophysiologic measures. Given the increasing prevalence of cognitive impairment and the dearth of available treatments, there is an urgent need to foster the development of clinician-neuroscientists with this interest. As a neurosurgeon with specialization in neuromodulation, Dr. Bentley is an ideal candidate to serve in this role. She has assembled a multi-disciplinary and multi-institutional team of expert mentors who will provide guidance and support towards the scientific and career development aims of this proposal. She and her mentors have designed a career development plan consisting of cognitive neuroscience, computational neuroscience, and signal processing techniques. These training aims will be combined with the high volume of a tertiary movement disorders functional neurosurgery practice at the University of Alabama, Birmingham. With the institution’s robust resources in research computing, biostatistics, engineering, and neurophysiology, this proposal will ensure that Dr. Bentley is well-prepared for progressing to research independence by the completion of this award.


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 = $217,718 )
2025	2025	UNIVERSITY OF ALABAMA AT BIRMINGHAM	701 S 20TH STREET	BIRMINGHAM	AL	35294	JEFFERSON	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	5	6/27/2025	SUPPLEMENT FOR EXPANSION	$53,294
2025	2025	UNIVERSITY OF ALABAMA AT BIRMINGHAM	701 S 20TH STREET	BIRMINGHAM	AL	35294	JEFFERSON	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	5	6/6/2025	NON-COMPETING CONTINUATION	$164,424
														Subtotal = $217,718

Issue Date FY: 2024 ( Subtotal = $188,761 )
2024	2024	UNIVERSITY OF ALABAMA AT BIRMINGHAM	701 S 20TH STREET	BIRMINGHAM	AL	35294	JEFFERSON	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	4	3/8/2024	NON-COMPETING CONTINUATION	$188,761
														Subtotal = $188,761

Issue Date FY: 2023 ( Subtotal = $192,615 )
2023	2023	UNIVERSITY OF ALABAMA AT BIRMINGHAM	701 S 20TH ST	BIRMINGHAM	AL	35294	JEFFERSON	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	3	4/7/2023	NON-COMPETING CONTINUATION	$176,108
2023	2023	UNIVERSITY OF ALABAMA AT BIRMINGHAM	701 S 20TH ST	BIRMINGHAM	AL	35294	JEFFERSON	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	3	7/13/2023	NON-COMPETING CONTINUATION	$16,507
														Subtotal = $192,615

Issue Date FY: 2022 ( Subtotal = $178,268 )
2022	2022	UNIVERSITY OF ALABAMA AT BIRMINGHAM	701 S 20TH ST	BIRMINGHAM	AL	35294	JEFFERSON	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	2	4/18/2022	NON-COMPETING CONTINUATION	$178,268
														Subtotal = $178,268

Issue Date FY: 2021 ( Subtotal = $187,334 )
2021	2021	UNIVERSITY OF ALABAMA AT BIRMINGHAM	701 S 20TH ST	BIRMINGHAM	AL	35294	JEFFERSON	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	1	6/23/2021	NEW	$0
2021	2021	UNIVERSITY OF ALABAMA AT BIRMINGHAM	701 S 20TH ST	BIRMINGHAM	AL	35294	JEFFERSON	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	1	2/11/2021	NEW	$187,334
														Subtotal = $187,334

Grand Total All Awards = $964,696

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Investigating Inhibitory Control Networks in Parkinson's Disease

Award Number: K23NS117735

ORGANIZATION: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP

PERIOD OF PERFORMANCE START DATE: 04/01/2021

PERIOD OF PERFORMANCE END DATE: 03/31/2026

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