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The effects of parkinsonism and deep brain stimulation on basal ganglia-thalamocortical circuitry during sleep-wake behavior

Award Number: R01NS110613
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: 07/01/2024
PERIOD OF PERFORMANCE END DATE: 03/31/2029

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The effects of parkinsonism and deep brain stimulation on basal ganglia-thalamocortical circuitry during sleep-wake behavior - PROJECT SUMMARY/ABSTRACT Over 75% of people with Parkinson's disease (PD) have significant sleep-wake disturbances that are major contributors to decreased quality of life and can be more disabling and resistant to treatment than the motor symptoms of PD. Currently, the mechanisms contributing to disordered sleep in people with PD are poorly understood and there is a critical need for therapeutic inventions to improve sleep quality. This project will provide new insight into the pathophysiology of sleep-wake disturbances in PD by characterizing the changes in sleep- related neuronal activity and physiological interactions that occur between subcortical and cortical structures in the basal ganglia thalamocortical (BGTC) circuit during progressively more severe parkinsonian states. We will expand our previous work to include the pedunculopontine nucleus (PPN) given its critical role regulating sleep- wake states and extensive connectivity to the BGTC, exploring the changes in coupling and connectivity that occur within and across the BGTC-PPN network that underlie disordered sleep in PD secondary to dopaminergic loss in the substantia nigra (Aim 1). It will compare how deep brain stimulation (DBS) in the STN, GPi, and GPe modifies subcortical-cortical interactions in the BGTC-PPN circuit to influence sleep-wake behavior and elucidate the fiber pathway activations underlying these changes (Aims 2 and 3). This study will provide data with immediate translational value by identifying whether DBS in one target is more effective than another in normalizing sleep-related neuronal activity and improving sleep-wake behavior. Furthermore, knowledge about how changes in neuronal activity across the BGTC-PPN network correlates with altered sleep from normal, parkinsonian, and parkinsonian+DBS conditions will provide the basis to develop more effective stimulation strategies that utilize target-specific physiological biomarkers and closed-loop DBS control paradigms tailored to individual patient's sleep disturbances. These data will also provide the basis to target specific pathways with DBS to optimize sleep-related outcomes in PD.


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: 2026 ( Subtotal = $611,842 )
2026	2026	REGENTS OF THE UNIVERSITY OF MINNESOTA	2221 UNIVERSITY AVE SE STE 100	MINNEAPOLIS	MN	55414	HENNEPIN	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	8	4/6/2026	NON-COMPETING CONTINUATION	$611,842
														Subtotal = $611,842

Issue Date FY: 2025 ( Subtotal = $609,311 )
2025	2025	REGENTS OF THE UNIVERSITY OF MINNESOTA	2221 UNIVERSITY AVE SE STE 100	MINNEAPOLIS	MN	55414	HENNEPIN	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	7	4/16/2025	NON-COMPETING CONTINUATION	$609,311
2025	2023	REGENTS OF THE UNIVERSITY OF MINNESOTA	2221 UNIVERSITY AVE SE STE 100	MINNEAPOLIS	MN	55414	HENNEPIN	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	5	3/4/2025	NON-COMPETING CONTINUATION	$0
														Subtotal = $609,311

Issue Date FY: 2024 ( Subtotal = $577,227 )
2024	2024	REGENTS OF THE UNIVERSITY OF MINNESOTA	200 OAK ST SE	MINNEAPOLIS	MN	55455	HENNEPIN	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	6	6/28/2024	COMPETING CONTINUATION	$577,227
2024	2023	REGENTS OF THE UNIVERSITY OF MINNESOTA	200 OAK ST SE	MINNEAPOLIS	MN	55455	HENNEPIN	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	5	6/21/2024	NON-COMPETING CONTINUATION	$0
														Subtotal = $577,227

Issue Date FY: 2023 ( Subtotal = $552,395 )
2023	2023	REGENTS OF THE UNIVERSITY OF MINNESOTA	200 OAK ST SE # 224	MINNEAPOLIS	MN	55455	HENNEPIN	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	5	3/16/2023	NON-COMPETING CONTINUATION	$552,395
														Subtotal = $552,395

Issue Date FY: 2022 ( Subtotal = $602,777 )
2022	2022	REGENTS OF THE UNIVERSITY OF MINNESOTA	200 OAK ST SE # 224	MINNEAPOLIS	MN	55455	HENNEPIN	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	4	4/4/2022	NON-COMPETING CONTINUATION	$602,777
														Subtotal = $602,777

Issue Date FY: 2021 ( Subtotal = $608,494 )
2021	2021	REGENTS OF THE UNIVERSITY OF MINNESOTA	200 OAK ST SE # 224	MINNEAPOLIS	MN	55455	HENNEPIN	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	3	3/17/2021	NON-COMPETING CONTINUATION	$608,494
														Subtotal = $608,494

Issue Date FY: 2020 ( Subtotal = $590,469 )
2020	2020	REGENTS OF THE UNIVERSITY OF MINNESOTA	200 OAK ST SE # 224	MINNEAPOLIS	MN	55455	HENNEPIN	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	2	4/14/2020	NON-COMPETING CONTINUATION	$590,469
														Subtotal = $590,469

Issue Date FY: 2019 ( Subtotal = $571,692 )
2019	2019	REGENTS OF THE UNIVERSITY OF MINNESOTA	200 OAK ST SE # 224	MINNEAPOLIS	MN	55455	HENNEPIN	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	1	2/27/2019	NEW	$571,692
														Subtotal = $571,692

Grand Total All Awards = $4,724,207

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The effects of parkinsonism and deep brain stimulation on basal ganglia-thalamocortical circuitry during sleep-wake behavior

Award Number: R01NS110613

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: 07/01/2024

PERIOD OF PERFORMANCE END DATE: 03/31/2029

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