# Determination of the Recruitment of Indirect Motor Pathways in Chronic Hemiparetic Stroke

> **NIH NIH R21** · NORTHWESTERN UNIVERSITY · 2020 · $227,565

## Abstract

Abstract. Motor impairments post-stroke, such as the upper limb flexion synergy and abnormal stretch reflexes,
greatly affect an individual’s ability to implement activities of daily living. Despite the development of various
clinical interventions for motor recovery after stroke, rehabilitation treatments, especially in more impaired
individuals, are only minimally effective. This is due to: 1) many remaining gaps in our understanding of specific
mechanisms underlying motor impairments post stroke that inform clinical practice, and 2) lack of sensitive
biomarkers to determine the neuroplasticity resulting from interruptions of neural pathways caused by the stroke
and during recovery. Our long-term goal is to develop a sensitive way to quantitatively assess the lesion-induced
utilization of remaining motor pathways post stroke, which would allow better examination of stroke recovery and
evaluation of rehabilitation interventions. Our previous studies indicate that motor impairments post hemiparetic
stroke are likely caused by an increased reliance on contralesional indirect motor pathways via the brainstem,
following stroke-induced losses of ipsilesional corticospinal projections. Thus, the objective of this proposal is to
quantitatively determine the usage of indirect motor pathways and its link to the expression of the flexion synergy
and abnormal stretch reflexes, by examining changes in neural connectivity of motor pathways as a function of
shoulder abduction (SABD) load. In contrast to the direct corticospinal tract, these indirect pathways contain
more synapses, which thus may cause an enhanced nonlinear neural connectivity via the motor pathways due
to the nonlinear sigmoid shape of synaptic behavior and its cumulative effect across synapses. Thus, our central
hypotheses are that: 1) an increased usage of indirect motor pathways while lifting the paretic arm, requiring
SABD and causing the flexion synergy, will lead to enhanced nonlinear connectivity between brain and muscle
activity; 2) the recruitment of indirect motor pathways will also affect the stretch reflex, in particular, its
transcortical reflex component, resulting in increased nonlinear connectivity between stretch perturbations and
muscle activity. Finally, these indirect pathways may prolong the neural transmission delay in the transcortical
reflex loop, resulting in an increased time lag between perturbations and muscle activity. Using our recently
developed nonlinear connectivity method and mechanically well-controlled experimental paradigms, we aim to
test these hypotheses by: 1) comparing linear vs. nonlinear connectivity between brain and muscle activity during
the generation of different levels of SABD torque in individuals post hemiparetic stroke; 2) quantifying changes
of nonlinear connectivity and time delay of the stretch reflex post-stroke as a function of SABD torque level. As
such, this project will provide new sensitive biomarkers that determine the recruitment ...

## Key facts

- **NIH application ID:** 9978864
- **Project number:** 5R21HD099710-02
- **Recipient organization:** NORTHWESTERN UNIVERSITY
- **Principal Investigator:** JULIUS P DEWALD
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $227,565
- **Award type:** 5
- **Project period:** 2019-07-16 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9978864

## Citation

> US National Institutes of Health, RePORTER application 9978864, Determination of the Recruitment of Indirect Motor Pathways in Chronic Hemiparetic Stroke (5R21HD099710-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9978864. Licensed CC0.

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