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 utilization of spared corticofugal resources in the lesioned hemisphere thus largely avoiding structural and functional changes to indirect contralesional motor pathways and minimizing the devastating effects of the flexion synergy.

Public Health Relevance

The proposed study seeks to quantify the link between structural and functional changes in the brain and abnormal arm/wrist and finger bending when lifting the arm at the shoulder in individuals with chronic hemiparetic stroke and during the first year of recovery from a stroke. Understanding the neural mechanisms underlying shoulder activation-induced arm/hand impairments in this population and predicting upper limb impairment from early changes at the brain represents a crucial step toward the development of more timely and targeted interventions. These early interventions are anticipated to decrease arm/hand dysfunction when lifting the arm and should thus improve the quality of life of stroke survivors.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
1R01NS105759-01A1
Application #
9662457
Study Section
Musculoskeletal Rehabilitation Sciences Study Section (MRS)
Program Officer
Chen, Daofen
Project Start
2019-05-01
Project End
2024-04-30
Budget Start
2019-05-01
Budget End
2020-04-30
Support Year
1
Fiscal Year
2019
Total Cost
Indirect Cost
Name
Northwestern University at Chicago
Department
Physical Medicine & Rehab
Type
Schools of Medicine
DUNS #
005436803
City
Chicago
State
IL
Country
United States
Zip Code
60611