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Neuromechanical Modeling of Postural Responses:Mechanisms of Balance Impairments in Parkinson's Disease

Award Number: R01HD046922
ORGANIZATION: NATIONAL INSTITUTE OF CHILD HEALTH AND HUMAN DEVELOPMENT
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

Group Awards By Issue Date FY or Funding FY:

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Our long-term goal is to advance our scientific knowledge and computational approaches to identify causes of balance impairments leading to falls in Parkinson’s disease (PD) to guide the rational development more effective treatments and rehabilitation for improving balance. Recent insights from our neuromechanical simulation studies in tandem with our ongoing work characterizing changes reactive balance control after rehabilitation in people with PD have implicated our overall hypothesis that the cardinal parkinsonian sign of rigidity is a cause of balance impairments. Rigidity is not typically considered in fall risk, yet our ongoing studies demonstrate a previously-unreported association between leg rigidity and prior falls. We believe that identifying the causes of this association will lead to improved diagnosis and treatment of balance impairments in PD. Our objective is to identify the effects of leg rigidity on postural robustness, defined as the ability to maintain the feet in place in reactive balance. Based on our neuromechanical simulations, we hypothesize that parkinsonian rigidity increases two distinct aspects of postural muscle activity that can each reduce postural robustness: tonic muscle activity, defined as the magnitude of muscle activity in static postures, and dynamic muscle activity is defined as the magnitude and timing of muscle activity generated by sensorimotor feedback in reactive balance. We will use combined experimental and computational approaches to systematically isolate the causal linkages and interactions between rigidity, muscle activity, and postural robustness in PD. In addition to electromyographic (EMG) recordings, we will also establish the reliability of measuring tonic muscle activity during standing using frequency domain near-infrared spectroscopy (FDNIRS) combined with diffuse correlation spectroscopy (DCS). In Aim 1 we will test well-characterized PD participants with confirmed dopamine-responsive rigidity to identify the effects of leg rigidity on tonic muscle activity, dynamic muscle activity, and postural robustness; we will manipulate rigidity using dopamine medication and an activation maneuver. In Aim 2 we will test neurotypical participants to identify causal role of modulating tonic and dynamic muscle activity on postural robustness; we will modulate muscle activity using EMG biofeedback and adaptation. In Aim 3 we will develop neuromechanical simulations to quantitatively demonstrate mechanistic relationships between tonic muscle activity, dynamic muscle activity, and postural robustness. We will augment our neuromechanical models of balance with agonist-antagonist muscle models. If successful, we will 1) identify the causal role of rigidity on impaired balance in PD, 2) validate a novel and clinically-feasible method (NIRS) to measure rigidity in functionally-relevant tasks, and 3) establish a broadly extendable generative neuromechanical model of balance to simulate how multiple mechanisms interact to cause balance impairments. These outcomes will enable us to identify optimal treatment targets for the rational development of rehabilitation and other therapies for balance impairments across many disorders.


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 = -$1,428 )
2024	2021	EMORY UNIVERSITY	201 DOWMAN DR NE	ATLANTA	GA	30322	DEKALB	USA	Child Health and Human Development Extramural Research	000	15	11/8/2023	NON-COMPETING CONTINUATION	-$1,428
														Subtotal = -$1,428

Issue Date FY: 2021 ( Subtotal = $491,750 )
2021	2021	EMORY UNIVERSITY	201 DOWMAN DR	ATLANTA	GA	30322	DEKALB	USA	Child Health and Human Development Extramural Research	000	15	5/5/2021	NON-COMPETING CONTINUATION	$491,750
														Subtotal = $491,750

Issue Date FY: 2020 ( Subtotal = $569,636 )
2020	2020	EMORY UNIVERSITY	201 DOWMAN DR	ATLANTA	GA	30322	DEKALB	USA	Child Health and Human Development Extramural Research	000	14	5/29/2020	NON-COMPETING CONTINUATION	$569,636
														Subtotal = $569,636

Issue Date FY: 2019 ( Subtotal = $569,636 )
2019	2019	EMORY UNIVERSITY	1599 CLIFTON RD.	ATLANTA	GA	30322	DEKALB	USA	Child Health and Human Development Extramural Research	000	13	6/21/2019	NON-COMPETING CONTINUATION	$508,090
2019	2019	EMORY UNIVERSITY	1599 CLIFTON RD.	ATLANTA	GA	30322	DEKALB	USA	Child Health and Human Development Extramural Research	001	13	8/7/2019	SUPPLEMENT FOR EXPANSION	$61,546
														Subtotal = $569,636

Issue Date FY: 2018 ( Subtotal = $509,385 )
2018	2018	EMORY UNIVERSITY	1599 CLIFTON RD.	ATLANTA	GA	30322	DEKALB	USA	Child Health and Human Development Extramural Research	000	12	6/12/2018	NON-COMPETING CONTINUATION	$509,385
														Subtotal = $509,385

Issue Date FY: 2017 ( Subtotal = $537,698 )
2017	2017	EMORY UNIVERSITY	1599 CLIFTON RD.	ATLANTA	GA	30322	DEKALB	USA	Child Health and Human Development Extramural Research	000	11	9/12/2017	COMPETING CONTINUATION	$537,698
														Subtotal = $537,698

Issue Date FY: 2014 ( Subtotal = $269,231 )
2014	2014	EMORY UNIVERSITY	1784 N DECATUR RD,S 530 NDBLDG	ATLANTA	GA	30322	DEKALB	USA	Child Health and Human Development Extramural Research	000	10	6/26/2014	NON-COMPETING CONTINUATION	$269,231
														Subtotal = $269,231

Issue Date FY: 2013 ( Subtotal = $263,203 )
2013	2013	EMORY UNIVERSITY	1784 N DECATUR RD,S 530 NDBLDG	ATLANTA	GA	30322	DEKALB	USA	Child Health and Human Development Extramural Research	000	9	6/7/2013	NON-COMPETING CONTINUATION	$263,203
														Subtotal = $263,203

Issue Date FY: 2012 ( Subtotal = $277,791 )
2012	2012	EMORY UNIVERSITY	1784 N DECATUR RD,S 530 NDBLDG	ATLANTA	GA	30322	DEKALB	USA	Child Health and Human Development Extramural Research	000	8	4/27/2012	NON-COMPETING CONTINUATION	$277,791
														Subtotal = $277,791

Issue Date FY: 2011 ( Subtotal = $278,195 )
2011	2011	EMORY UNIVERSITY	1784 N DECATUR RD,S 530 NDBLDG	ATLANTA	GA	30322	DEKALB	USA	Child Health and Human Development Extramural Research	000	7	6/10/2011	NON-COMPETING CONTINUATION	$278,195
														Subtotal = $278,195

Issue Date FY: 2010 ( Subtotal = $296,522 )
2010	2010	EMORY UNIVERSITY	1784 N DECATUR RD,S 530 NDBLDG	ATLANTA	GA	30322	DEKALB	USA	Child Health and Human Development Extramural Research	000	6	6/24/2010	COMPETING CONTINUATION	$296,522
														Subtotal = $296,522

Issue Date FY: 2008 ( Subtotal = $308,533 )
2008	2008	GEORGIA TECH RESEARCH CORPORATION	HINMAN BUILDING	ATLANTA	GA	30332	FULTON	USA	Child Health and Human Development Extramural Research	000	5	3/14/2008	NON-COMPETING CONTINUATION	$308,533
														Subtotal = $308,533

Issue Date FY: 2007 ( Subtotal = $342,371 )
2007	2007	GEORGIA TECH RESEARCH CORPORATION	HINMAN BUILDING	ATLANTA	GA	30332	FULTON	USA	Child Health and Human Development Extramural Research	000	4	3/28/2007	NON-COMPETING CONTINUATION	$342,371
														Subtotal = $342,371

Issue Date FY: 2006 ( Subtotal = $352,196 )
2006	2006	GEORGIA TECH RESEARCH CORPORATION	HINMAN BUILDING	ATLANTA	GA	30332	FULTON	USA	Child Health and Human Development Extramural Research	000	3	3/28/2006	NON-COMPETING CONTINUATION	$352,196
														Subtotal = $352,196

Issue Date FY: 2005 ( Subtotal = $360,274 )
2005	2005	GEORGIA TECH RESEARCH CORPORATION	HINMAN BUILDING	ATLANTA	GA	30332	FULTON	USA	Child Health and Human Development Extramural Research	000	2	3/8/2005	NON-COMPETING CONTINUATION	$360,274
														Subtotal = $360,274

Issue Date FY: 2004 ( Subtotal = $352,800 )
2004	2004	GEORGIA TECH RESEARCH CORPORATION	HINMAN BUILDING	ATLANTA	GA	30332	FULTON	USA	Child Health and Human Development Extramural Research	000	1	3/19/2004	NEW	$327,382
2004	2004	GEORGIA TECH RESEARCH CORPORATION	HINMAN BUILDING	ATLANTA	GA	30332	FULTON	USA	Child Health and Human Development Extramural Research	001	1	9/24/2004	SUPPLEMENT FOR EXPANSION	$25,418
														Subtotal = $352,800

Grand Total All Awards = $5,777,793

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Neuromechanical Modeling of Postural Responses:Mechanisms of Balance Impairments in Parkinson's Disease

Award Number: R01HD046922

ORGANIZATION: NATIONAL INSTITUTE OF CHILD HEALTH AND HUMAN DEVELOPMENT

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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