Mapping Corticoreticulospinal Motor Control Using Brainstem and Spinal Cord fMRI in Chronic Hemiparetic Stroke

PROJECT SUMMARY
Approximately 60% of hemiparetic stroke-survivors experience significant chronic motor deficits in their paretic
upper limb, typically caused by damage to the corticospinal tract (CST). Alternative neural pathways, such as
the cortico-reticulospinal tract (CRST), can be recruited to achieve movement of the affected arm and hand, but
may have undesirable consequences. For example, the diffuse, bilateral branching of reticulospinal neurons can
produce abnormal muscle co-activations (synergies) in the paretic limb, and involuntary mirror movements
(associated reactions) between limbs. Together, these effects create stereotypical movement patterns post-
stroke, and there is growing interest in novel "anti-synergy" interventions to enhance usage of residual CST
systems rather than strengthening the CRST. Imaging has the potential to become an invaluable tool for
evaluating whether rehabilitative strategies can preferentially access CST versus CRST pathways. However,
current functional imaging research has focused on cortical activity, and must theoretically infer what pathway is
used. Structural MRI can directly assess changes in white matter pathways, but it is limited to detecting long-
term plasticity. To guide new interventions, there is a critical need to directly evaluate what descending motor
pathways are active during specific movements. Thus, the overall objective of this study is to generate a novel
fMRI dataset in participants with post-stroke hemiparesis, capturing neural activity during unilateral hand-
grasping throughout the CST and CRST, and to evaluate differences when grasping with the paretic versus non-
paretic hand. Our lab has developed advanced strategies to improve fMRI signal quality, but we show that large
datasets per person are still needed to accurately localize and interpret activation patterns; this is challenging in
stroke-survivors, who may fatigue quickly. Our innovative MRI-compatible hand-grip device provides supported,
adjustable arm positioning and real-time force feedback, allowing us to reproduce a motor task across multiple
sessions and generate sufficient data. In Aim 1, we acquire multi-echo fMRI data in the brain and brainstem; we
hypothesize that increased reliance on the CRST will cause increased ipsilateral cortical and brainstem activation
when grasping with the paretic limb, and that this will correlate with functional impairment (Upper-Extremity Fugl-
Meyer Assessment). In Aim 2, we acquire fMRI data in the spinal cord; we hypothesize that grasping with the
paretic hand will be associated with increased activation in more superior cord segments (intra-limb synergies)
and grasping with the non-paretic hand will correspond to increased activation in the contralateral hemi-cord
(associated reactions). We will also explore how neural activity correlates with individual EMG measures of
muscle co-activation. This work is significant because it will provide direct evidence of descending motor pathway
involvement in post-stroke hemiparesis, and demonstrate the utility of neuroimaging for identifying physical and
pharmacological interventions to reduce reliance on CRST and drive more effective rehabilitation.

Grant Number: 1R03HD113915-01
NIH Institute/Center: NIH
Principal Investigator: Molly Bright