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Temporal Patterns of Deep Brain Stimulation

Award Number: R37NS040894
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: 09/30/2000
PERIOD OF PERFORMANCE END DATE: 08/31/2024

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Temporal Patterns of Deep Brain Stimulation - DESCRIPTION (provided by applicant): Chronic high-frequency electrical stimulation of the brain, called deep brain stimulation (DBS), has emerged as a well-established therapy for the treatment of movement disorders, including essential tremor and Parkinson's disease (PD). Although the clinical benefits of DBS are well documented, fundamental questions remain about the mechanisms of action, and this lack of understanding will limit the full development and optimization of this promising treatment. One of the hallmarks of DBS is the strong dependence of symptom relief on the frequency of stimulation. High frequency DBS (> 100 Hz) relieves the symptoms of movement disorders, while low frequency stimulation (< 50 Hz) is generally not ineffective. During the prior grant period we established that the effects of DBS are also strongly dependent on the temporal pattern of stimulation. Now, we seek to exploit this finding - that the effects of DBS are strongly dependent on the temporal pattern of stimulation - both to understand the relationship between temporal patterns of neural activity and the motor symptoms of PD and to improve the effectiveness and efficiency of DBS through the design of novel optimal temporal patterns of stimulation. We will combine computational modeling, quantitative behavior and single unit neural recording in an animal model of PD, and translational experiments in humans with PD to advance both the understanding and application of DBS. First, we will measure the effects on tremor and bradykinesia of symptogenic temporal patterns of DBS, designed to generate neural typified by either theta-frequency or beta-frequency oscillations, and determine the causality between these temporal patterns of neural activity and the motor symptoms of PD. Second, we will use model-based optimization to design novel temporal patterns of stimulation intended to suppress maximally the abnormal synchronous oscillations in the theta- and beta-frequency bands, and measure the effects of DBS with these patterns on tremor and bradykinesia in a rat model of PD and in persons with PD and STN DBS. Third, we will measure the effects of the frequency and temporal pattern of DBS on neural activity the basal ganglia and cortex. We will use innovative hardware that enables recording of local field potentials during the application of DBS and correlate the changes in neural oscillatory activity with changes in symptoms in persons with PD and STN DBS, as well as in a rat model of PD. The temporal pattern of DBS is a novel and important parameter that we will exploit, both to understand the relationship between the patterns of neural activity and motor symptoms of PD, and as a novel way to improve the efficacy and efficiency of DBS. The outcomes of the proposed research will contribute to understanding the relationship between patterns of neuronal activity and the symptoms of movement disorders, to improving the treatment of Parkinsonian symptoms with DBS, and to uncovering the mechanisms of action of 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: 2025 ( Subtotal = $0 )
2025	2021	DUKE UNIVERSITY	2200 W MAIN ST	DURHAM	NC	27705	DURHAM	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	17	1/15/2025	NON-COMPETING CONTINUATION	$0
2025	2021	DUKE UNIVERSITY	2200 W MAIN ST	DURHAM	NC	27705	DURHAM	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	002	17	1/17/2025	NON-COMPETING CONTINUATION	$0
2025	2018	DUKE UNIVERSITY	2200 W MAIN ST	DURHAM	NC	27705	DURHAM	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	14	1/15/2025	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2024 ( Subtotal = $0 )
2024	2021	DUKE UNIVERSITY	2200 W MAIN ST	DURHAM	NC	27705	DURHAM	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	17	10/27/2023	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2023 ( Subtotal = $0 )
2023	2021	DUKE UNIVERSITY	2200 W MAIN ST	DURHAM	NC	27705	DURHAM	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	17	9/22/2023	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2021 ( Subtotal = $660,715 )
2021	2021	DUKE UNIVERSITY	2200 W MAIN ST STE 710	DURHAM	NC	27708	DURHAM	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	17	8/25/2021	NON-COMPETING CONTINUATION	$660,715
														Subtotal = $660,715

Issue Date FY: 2020 ( Subtotal = $660,715 )
2020	2020	DUKE UNIVERSITY	2200 W MAIN ST STE 710	DURHAM	NC	27708	DURHAM	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	002	16	8/21/2020	NON-COMPETING CONTINUATION	$660,715
2020	2019	DUKE UNIVERSITY	2200 W MAIN ST STE 710	DURHAM	NC	27708	DURHAM	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	15	2/15/2020	EXTENSION WITH OR WITHOUT FUNDS	$231,919
2020	2018	DUKE UNIVERSITY	2200 W MAIN ST STE 710	DURHAM	NC	27708	DURHAM	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	14	2/15/2020	NON-COMPETING CONTINUATION	-$231,919
														Subtotal = $660,715

Issue Date FY: 2019 ( Subtotal = $660,715 )
2019	2019	DUKE UNIVERSITY	2200 W MAIN ST STE 710	DURHAM	NC	27708	DURHAM	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	15	9/18/2019	EXTENSION WITH OR WITHOUT FUNDS	$660,715
2019	2018	DUKE UNIVERSITY	2200 W MAIN ST STE 710	DURHAM	NC	27708	DURHAM	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	14	2/21/2019	NON-COMPETING CONTINUATION	$0
														Subtotal = $660,715

Issue Date FY: 2018 ( Subtotal = $559,063 )
2018	2018	DUKE UNIVERSITY	2200 W MAIN ST STE 710	DURHAM	NC	27708	DURHAM	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	14	8/20/2018	NON-COMPETING CONTINUATION	$559,063
														Subtotal = $559,063

Issue Date FY: 2017 ( Subtotal = $558,636 )
2017	2017	DUKE UNIVERSITY	2200 W MAIN ST STE 710	DURHAM	NC	27708	DURHAM	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	13	8/18/2017	NON-COMPETING CONTINUATION	$558,636
														Subtotal = $558,636

Issue Date FY: 2016 ( Subtotal = $558,226 )
2016	2016	DUKE UNIVERSITY	BOX 104004	DURHAM	NC	27708	DURHAM	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	12	8/12/2016	NON-COMPETING CONTINUATION	$558,226
														Subtotal = $558,226

Issue Date FY: 2015 ( Subtotal = $572,581 )
2015	2015	DUKE UNIVERSITY	BOX 104004	DURHAM	NC	27708	DURHAM	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	11	7/29/2015	COMPETING CONTINUATION	$572,581
														Subtotal = $572,581

Grand Total All Awards = $4,230,651

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Temporal Patterns of Deep Brain Stimulation

Award Number: R37NS040894

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: 09/30/2000

PERIOD OF PERFORMANCE END DATE: 08/31/2024

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