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Optimizing coordinated reset deep brain stimulation for Parkinson's disease

Award Number: R01NS117822
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: 09/30/2020
PERIOD OF PERFORMANCE END DATE: 06/30/2026

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Optimizing coordinated reset deep brain stimulation for Parkinson's disease - PROJECT SUMMARY/ABSTRACT Parkinson’s disease (PD) is a neurodegenerative disorder affecting 6-7 million people worldwide. Traditional high frequency, isochronal deep brain stimulation (DBS) is an effective treatment for the motor signs associated with PD. Clinical outcomes, however, vary across centers and within centers across patients. Adverse effects can be induced by “current-spread” to unintended brain areas when the DBS lead is sub-optimally placed which limits clinical benefits. Coordinated reset (CR) DBS is a promising novel DBS approach that has the potential to overcome the limitations of traditional DBS. By alternating lower intensity stimulation delivered in a burst pattern across different contacts of the DBS lead, CR DBS is associated with less current spread, thus reducing the incidence of adverse effects, and improvement in motor signs that persist for days to weeks after cessation of stimulation, i.e. carryover effect. Although the effectiveness of CR DBS has been demonstrated in both preclinical and clinical studies, the selection of CR parameters that provide the greatest carryover effect has been challenging. The optimal target for CR DBS must also be identified. The proposed study using a within-subject experimental design will 1) optimize the critical parameter (cycle rate) of CR DBS, (2) compare the effect of CR DBS in the subthalamic nucleus (STN) and internal segment of the globus pallidus (GPi), and (3) characterize the changes in cortical and subcortical neuronal activities associated with its therapeutic effect. The nonhuman primate model of PD will be used with each animal implanted with DBS leads in the STN and GPi and high- density Utah arrays placed over the primary motor, dorsal premotor and dorsolateral prefrontal cortices. Objective and quantitative motor assessments will be performed to measure the acute and carryover effect of CR DBS with different cycle rates and in different targets (STN and GPi). The central hypothesis is that the therapeutic effect of CR DBS is greatest when the cycle rate is based on subject-specific pathophysiological biomarkers associated with the PD state. We further hypothesize that CR DBS in GPi will provide greater acute benefits in motor signs and induce significantly longer carryover effects. We predict that motor improvements induced by CR DBS will correlate with a reduction in synchronized neuronal activity within and across cortical and subcortical nodal points in the basal-ganglia-thalamocortical (BGTC) circuit. The results of this study will provide a time efficient approach for the selection of CR DBS cycle rate based on subject-specific biomarker activity in the BGTC circuit, identify the optimal target for CR DBS and enhance our understanding of the mechanism(s) underlying the therapeutic effect of CR DBS. Results of the study will significantly advance the development of CR DBS for the treatment of PD that will enhance clinical outcomes, prolong battery life and induce fewer side effects leading to higher quality of life for PD patients undergoing DBS.


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 = $590,908 )
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	5	7/26/2024	NON-COMPETING CONTINUATION	$590,908
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	4	6/14/2024	NON-COMPETING CONTINUATION	$0
														Subtotal = $590,908

Issue Date FY: 2023 ( Subtotal = $625,645 )
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	4	6/16/2023	NON-COMPETING CONTINUATION	$625,645
														Subtotal = $625,645

Issue Date FY: 2022 ( Subtotal = $625,645 )
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	3	6/6/2022	NON-COMPETING CONTINUATION	$625,645
														Subtotal = $625,645

Issue Date FY: 2021 ( Subtotal = $620,200 )
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	2	5/27/2021	NON-COMPETING CONTINUATION	$620,200
														Subtotal = $620,200

Issue Date FY: 2020 ( Subtotal = $563,346 )
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	1	9/22/2020	NEW	$563,346
														Subtotal = $563,346

Grand Total All Awards = $3,025,744

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Optimizing coordinated reset deep brain stimulation for Parkinson's disease

Award Number: R01NS117822

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: 09/30/2020

PERIOD OF PERFORMANCE END DATE: 06/30/2026

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