# Contralesional Corticobulbospinal Structural and Functional Changes Post Stroke: Biomarkers for the upper limb flexion synergy

> **NIH NIH R01** · NORTHWESTERN UNIVERSITY · 2021 · $509,108

## Abstract

Project Summary Impaired arm and hand function is a major cause of chronic disability among stroke
survivors. In addition to weakness or paralysis, the arm/hand is also affected by the abnormal flexion synergy –
involuntary elbow, wrist, and finger flexion when an individual attempts to lift the arm. The flexion synergy
compromises the ability to reach and open the hand and reduces the control of grasp strength during functional
tasks, thus compounding the stroke survivor’s functional deficits. Most current treatments in mild to moderately
impaired individuals focus on reversing weakness at the elbow/hand without regard to proximal joints which can
have a detrimental effect on reaching and grasping based on the progressive expression of the flexion synergy.
The fine motor control required for normal arm/hand function is largely driven by the contralateral corticospinal
tract. After corticospinal and corticobulbar (i.e., corticofugal) pathways are damaged by a stroke, there is
increased reliance on contralesional cortico-bulbo-spinal tracts. Based on primate research, an increased
reliance on these “lower-resolution” systems causes joint coupling patterns consistent with the flexion synergy
pattern seen in humans post-stroke. Greater reliance on contralesional motor cortices over time is also expected
to result in progressive increases in structural tract integrity in the contralesional- while reducing corticofugal tract
integrity in the lesioned- hemisphere. Our central hypothesis therefore is that ischemic damage to the
corticofugal tracts causes a greater reliance on contralesional indirect corticobulbospinal tract resulting in
increased functional connectivity between contralesional cortex and brainstem nuclei and enhanced structural
morphology of bulbospinal projections that are predictive of the expression of the flexion synergy and recovery
of reaching and hand function. To test this hypothesis, we propose to quantify whether there is greater use of
contralesional sensorimotor cortices as a function of abduction loading and motor impairment severity and its
impact on reaching and grasping (Aim 1). We then propose to quantify the structural morphology and functional
connectivity of corticospinal and contralesional corticobulbospinal projections to motor nuclei in the brain stem
in chronic stroke participants (Aim 2). Lastly, we plan to conduct a longitudinal analysis of the relationship
between structural morphology of contralesional bulbospinal projections and motor recovery, and specifically,
evaluate early morphological change as a predictive biomarker for chronic motor recovery outcome (Aim 3). This
is the first-time longitudinal change in brain function and structure will be linked to synergy induced motor
impairments in the paretic upper limb of individuals with stroke. These structural and functional biomarkers of
motor pathways changes will guide the timely application of anti-synergy interventions that will promote the
maximal utili...

## Key facts

- **NIH application ID:** 10142547
- **Project number:** 5R01NS105759-03
- **Recipient organization:** NORTHWESTERN UNIVERSITY
- **Principal Investigator:** JULIUS P DEWALD
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $509,108
- **Award type:** 5
- **Project period:** 2019-05-01 → 2024-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10142547

## Citation

> US National Institutes of Health, RePORTER application 10142547, Contralesional Corticobulbospinal Structural and Functional Changes Post Stroke: Biomarkers for the upper limb flexion synergy (5R01NS105759-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10142547. Licensed CC0.

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