# Multiscale models of proprioceptive encoding to reveal mechanisms of impaired sensorimotor control

> **NIH NIH R01** · EMORY UNIVERSITY · 2022 · $582,364

## Abstract

PROJECT SUMMARY
Our long-term goal is to identify neural mechanisms and the functional roles of sensorimotor signals in health
and disease as needed to guide mechanistically targeted diagnoses, assessments, and treatments for
neurological movement disorders. Here we address the scientific barriers to understanding and treating a
broad class of movement disorder symptoms recently defined as joint hyper-resistance, which encompass
spasticity in stroke, spinal cord injury, or cerebral palsy; parkinsonian rigidity, and hypertonia. The objective of
this collaborative, interdisciplinary proposal is to identify neural mechanisms of hyper-resistance and dissociate
their relative roles in abnormal movement. We will focus on the neural mechanisms underlying two clinically-
defined neural contributions to hyper-resistance: non-velocity dependent involuntary background activation and
velocity-dependent stretch hyper-reflexia. We hypothesize that increased spinal excitability in many
neurological disorders causes involuntary background activation and velocity-dependent stretch hyper-reflexia
via three dissociable neural mechanisms: 1) alpha-drive to extrafusal muscle fibers increasing background
muscle tension, 2) gamma-drive to specialized intrafusal muscle fibers in muscle spindles sensory organs,
increasing their sensitivity to muscle stretch, and 3) sensorimotor gain of the spinal transformation of
monosynaptic sensory input into motor output. Our proposed tests of this hypothesis will advance understanding
of the important, yet still unresolved relative contributions made by these neural mechanisms to hyper-resistance.
Based on our neuromechanical and multiscale modeling advances in the prior funding period, in Aim 1 we will
develop a multiscale in silico neuromuscular circuit model to predict how independent changes in alpha-
drive, gamma-drive, and sensorimotor gain differentially affect clinically-relevant movements such as the tendon
tap and pendulum test. In Aim 2, we will characterize the relative increases in alpha-drive, gamma-drive,
and sensorimotor gain across clinically-relevant spinal excitability levels in a living biological
neuromuscular circuit in vivo using a decerebrate rat preparation. In Aim 3 we will identify clinically-relevant
movement abnormalities across spinal excitability levels in a novel biohybrid robotic system coupling
the living neuromuscular circuit (in vivo) to a virtual biomechanical limb (in silico). A robotic controller will enforce
the physics of dynamically changing inertial and gravitational forces, allowing movement to emerge from the
causal interaction between the in vivo neuromuscular circuit and the virtual limb. Through the close coordination
of these Aims, we will establish a computational and experimental framework to address clinical barriers (1) to
determine how changes in neural mechanisms and the inertial properties of the limb could correct movement
abnormalities, (2) to provide insight into how these m...

## Key facts

- **NIH application ID:** 10436158
- **Project number:** 5R01HD090642-07
- **Recipient organization:** EMORY UNIVERSITY
- **Principal Investigator:** Timothy C Cope
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $582,364
- **Award type:** 5
- **Project period:** 2016-09-16 → 2026-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10436158

## Citation

> US National Institutes of Health, RePORTER application 10436158, Multiscale models of proprioceptive encoding to reveal mechanisms of impaired sensorimotor control (5R01HD090642-07). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10436158. Licensed CC0.

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