# Effect of Neural Constraints on Movement in Stroke

> **NIH NIH R01** · NORTHWESTERN UNIVERSITY · 2024 · $645,633

## Abstract

Project Summary
Post-stroke impairments, including muscle weakness, hyperactive muscle (hypertonia) and associated stretch
reflexes (spasticity), and loss of independent joint control (flexion synergy), pose significant challenges to routine
daily activities, making stroke a leading contributor to motor dysfunction in the United States.
Our extensive research has identified abnormally increased motor neuron excitability post-stroke, hinting at
elevated spinal norepinephrine (NE) levels. NE, a potent neuromodulator, not only intensifies and prolongs inputs
to motoneurons but also increases reliance on indirect contralesional cortico-reticular tracts, as shown in the
previous cycle of this R01 grant. Our central hypothesis suggests that reducing NE levels will diminish spinal
motoneuron excitability, encourage the use of direct motor pathways from the lesional hemisphere, and improve
motor performance in individuals post hemiparetic stroke.
To validate this hypothesis, we will evaluate the impact of the drug Tizanidine (Zanaflex®, TIZ) on spinal
motoneuron excitability, motor cortical activity, descending pathways utilization, and motor behavior of the paretic
arm and hand in chronic hemiparetic stroke across various aims. More specifically, in Aim 1 we propose to
evaluate Tizanidine's effect on spinal motoneuron excitability using high-density surface EMG during isometric
tasks. Aim 2 will explore NE's role in amplifying the use of indirect motor pathways through EEG/EMG signals
and kinetics during isometric shoulder abduction and hand-opening tasks. Aim 3 will examine NE's modulation
of flexion synergy and spasticity, assessing spasticity expression before and during movement, as well as
reaching distance and hand-opening ability as a function of shoulder abduction loading using a novel robotic
paradigm.
Anticipated results are expected to illustrate how NE-driven pathophysiological adaptations contribute to motor
impairments in chronic stroke. This understanding will inform more effective rehabilitative strategies, integrating
pharmacology with targeted physical interventions, aiming to enhance upper limb motor function and improve
the quality of life for individuals post-hemiparetic stroke.

## Key facts

- **NIH application ID:** 10995048
- **Project number:** 2R01HD039343-16
- **Recipient organization:** NORTHWESTERN UNIVERSITY
- **Principal Investigator:** JULIUS P DEWALD
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $645,633
- **Award type:** 2
- **Project period:** 2000-09-15 → 2029-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10995048

## Citation

> US National Institutes of Health, RePORTER application 10995048, Effect of Neural Constraints on Movement in Stroke (2R01HD039343-16). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10995048. Licensed CC0.

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