# Generation of Motor Cortical Dynamics Controlling Skilled Locomotion

> **NIH NIH R01** · CASE WESTERN RESERVE UNIVERSITY · 2024 · $390,425

## Abstract

PROJECT SUMMARY
Walking over natural terrain with skill and flexibility requires the nervous system to adapt limb movements to
environmental demands on each step. To drive the limbs over an obstacle without stumbling, the brain must
generate commands to modulate the appropriate muscle synergies at a specific phase of the ongoing
locomotor rhythm. The loss or impairment of these commands in disease can result in falls, which are common
in older adults and impose a significant burden on the healthcare system. While previous studies have
demonstrated that the motor cortex is critical for skilled locomotion, two key gaps currently impede progress in
developing models of cortical control. First, because gait modification is controlled by coordinated patterns of
activity across the motor cortical population, it is necessary to measure these population-level patterns in
behaving animals, and to identify how these patterns relate to specific aspects of movement. Second, because
motor cortex generates descending commands by integrating multiple sources of input from other brain
regions, it is critical to determine how these inputs influence motor cortical dynamics along specific,
behaviorally-relevant dimensions. Our long-term goal is to identify the dynamical principles governing the
interactions across distributed neural populations, and to determine how these principles enable the adaptation
of the locomotor pattern in a complex environment. The overall objective of this proposal is to determine how
neural population dynamics in motor cortex are generated during skilled locomotion by identifying the impact of
cerebellar and posterior parietal inputs on specific motor cortical dimensions. Our central hypothesis is that the
cerebellum selectively drives step-entrained dimensions of motor cortical population activity that are
synchronized with the rhythm of lower motor centers, while the posterior parietal cortex selectively drives motor
commands for gait modification in obstacle-modulated dimensions. To directly test this hypothesis, we will first
record from motor cortical ensembles in unrestrained mice performing skilled locomotion and use
computational techniques to isolate step-entrained and obstacle-modulated dimensions of neural population
activity (Aim 1). Next, we will use optogenetic perturbations to identify the effect of disrupting inputs from the
cerebellum (Aim 2) and posterior parietal cortex (Aim 3) on activity in these dimensions. The proposed
research is significant because the identification of how inputs to motor cortex generate its dynamics in healthy
animals is expected to provide a foundation for future studies of how these dynamics degrade in
neurodegenerative disease and aging, and to support the improvement of closed-loop deep brain stimulation
strategies for movement disorders. The proposed research is innovative because it integrates the dynamical
systems framework for the analysis and interpretation of data with the optogeneti...

## Key facts

- **NIH application ID:** 10846821
- **Project number:** 5R01NS129576-02
- **Recipient organization:** CASE WESTERN RESERVE UNIVERSITY
- **Principal Investigator:** Britton Alan Sauerbrei
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $390,425
- **Award type:** 5
- **Project period:** 2023-06-01 → 2028-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10846821

## Citation

> US National Institutes of Health, RePORTER application 10846821, Generation of Motor Cortical Dynamics Controlling Skilled Locomotion (5R01NS129576-02). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/10846821. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*