# Human network plasticity caused by disuse

> **NIH NIH F31** · WASHINGTON UNIVERSITY · 2020 · $31,438

## Abstract

Project Summary
Prolonged disuse of limbs—and corresponding brain systems—leads to detrimental plasticity that
worsens clinical outcomes after stroke and brain injury. There is currently little understanding of the
neurophysiology of disuse and, as a result, tools for assessment and therapy after neurological
damage are severely limited. Prior work studying related models of plasticity in mice and nonhuman
primates leads us to ask two questions about the neurophysiology of disuse: 1) Does disuse cause
focal disinhibition of motor and control regions? 2) Can disuse account for reduced functional
connectivity observed in stroke patients?
To address these questions, we will use fiberglass casts to constrain use of the dominant upper
extremity for two weeks in healthy participants. Casting causes a dramatic reduction in strength.
Previous studies have shown that reduced strength following disuse likely involves a deficit of
activating upper motor neurons in the primary motor cortex, rather than muscle atrophy or changes in
the peripheral nervous system. To examine changes in the central nervous system, we will acquire 30
minutes of resting-state functional magnetic resonance imaging (fMRI) data every day for nearly two
months before, during and after casting.
Sensory deafferentation, a plasticity model showing some neurophysiological overlap with disuse,
has been extensively studied in animal models. One key mechanism leading to plasticity in
deafferentation is a focal disinhibition of the deafferented cortex. We hypothesize that similar
disinhibition drives plasticity in disuse. Work in mice has shown that disinhibition of the barrel cortex
causes increased fluctuations in resting-state activity, detectable with blood oxygen level-dependent
(BOLD) measurements. Therefore, if disuse leads to disinhibition of motor and control structures, as
we hypothesize, then we should be able to measure larger fluctuations in these structures in our
resting-state fMRI data.
Resting-state functional connectivity (RSFC) is a phenomenon in which functionally related regions
show tight correlations in their resting-state activity. Studies of patients suffering strokes of the
internal capsule, which contains motor axons of the corticospinal tract, found weakened RSFC
between the left and right primary motor cortex. Further, the degree to which this functional
connection was weakened predicted individual differences in motor impairment. We hypothesize that
reduced RSFC in stroke patients may be driven by disuse of the impaired upper extremity. If this is
correct, we should find similar changes in our model of disuse.

## Key facts

- **NIH application ID:** 9930443
- **Project number:** 5F31NS110332-02
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** Dillan Jacob Newbold
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $31,438
- **Award type:** 5
- **Project period:** 2019-04-01 → 2022-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9930443

## Citation

> US National Institutes of Health, RePORTER application 9930443, Human network plasticity caused by disuse (5F31NS110332-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9930443. Licensed CC0.

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