Neuromechanical modeling of postural responses: Cortical mechanisms of balance impairments in Parkinson's disease

NIH RePORTER · NIH · R01 · $642,210 · view on reporter.nih.gov ↗

Abstract

Our long-term goal is to advance our neuromechanical understanding of balance impairments in Parkinson’s disease (PD) to enable mechanistic, personalized treatments to improve balance and reduce falls. In this renewal, we seek to identify cortical activity metrics related to perceptual, cognitive, and muscle activity impairments in PD, all of which we showed in the prior funding period to be associated with balance impairments and/or fall history. Here we seek to understand neural circuit dysfunction underlying interactions between non-motor and motor symptoms of PD that lead to balance impairments. We build on MPI Ting’s expertise in the neuromechanics of reactive balance control, adding MPI Borich’s expertise in high-density electroencephalography (HD-EEG) and neuroimaging. An innovation of the proposal is the use of a series of support-surface perturbations during standing as a balance probe to identify potential electrophysiological biomarkers of neural circuit dysfunction relevant to balance and mobility impairments in PD. Our recent and preliminary studies demonstrate that the balance probe elicits large, wide-spread cortical activity patterns time- locked to the loss and recovery of balance responses that can be compared within and across individuals on a millisecond time scale. We hypothesize that increased cortical contributions to balance underlie perceptual- motor and cognitive-motor interactions that impair mobility. Our objective is to identify precise spatiotemporal cortical activity patterns underlying perceptual-motor (Aim 1) and cognitive-motor (Aim 2) interactions in PD cortical contributions to muscle activity during balance control (Aim 3). We will use a whole-body perceptual paradigm that enables us to concurrently assess cortical activity related to whole-body motion perception, cognitive and motor set-shifting, as well as cortical drive to balance-correcting muscle activity. We predict greater pre-perturbation beta (13-30 Hz) power during a perceptual task will be correlated with worse perception in PD but not older adults OA without PD (Aim 1), less attenuation of cortical responses will be associated with worse cognitive set-shifting in OA and PD (Aim 2), and that OA and PD will have different cortically-driven antagonist muscle activity (Aim 3). Across Aims, we predict that these poorer functional outcomes will also be associated with increased engagement of cortical areas during the balance probe and lower clinical balance scores. Based on preliminary data, we predict dopamine medications in PD will increase cortical engagement during the balance probe, and in support of our hypothesis, will further impair perceptual- motor, cognitive-motor, and muscle activity outcomes. Finally, we will perform exploratory analyses of electrophysiological outcomes with respect to fall history, prospective falls, and structural and functional neuroimaging data. If successful, we will significantly advance the scientific framework and el...

Key facts

NIH application ID
10981551
Project number
2R01HD046922-16
Recipient
EMORY UNIVERSITY
Principal Investigator
Michael Robert Borich
Activity code
R01
Funding institute
NIH
Fiscal year
2024
Award amount
$642,210
Award type
2
Project period
2004-04-01 → 2029-08-31