StretchfMRI: a new technique to study the brainstem correlates of long-latency responses

Project: Research project

Project Details

Description

Spasticity is a common condition after stroke. Clinically, spasticity can be recognized as a velocity-dependent increase in stretch reflexes and results in significant disability. From a neurophysiological level, it is known that different supraspinal pathways contribute to spasticity by modulating the excitability of spinal circuits that are involved in the short-latency reflex. Spasticity is also associated with abnormal long-latency responses (LLRs), and it is currently recognized that, though often overlooked, abnormal LLRs contribute to functional deficits in individuals with chronic stroke at least as much as abnormal short-latency reflexes.
Unfortunately, limited knowledge is available on the neural pathways that regulate a LLR. While it is known that the LLR follows a transcortical pathway, it has also been advanced that many essential properties of the LLR are processed in the reticular formation (RF), a region in the brainstem composed of a constellation of multiple interconnected nuclei. However, because of the difficulty in measuring in-vivo function of the RF, evidence on the role of the RF in modulating LLR has been only obtained indirectly in humans. Direct evidence has been derived in monkeys, though it is unclear how these results relate to human diseases, as no veridical animal model exists for spasticity.
As such, there is a lack in knowledge about the neural substrates of the long-latency response, which limits our understanding of the neural substrates of spasticity, an understanding that is needed to develop neuroscience-grounded interventions to promote recovery of motor function after stroke.
Our research team has developed unique tools that we propose to combine to study the contribution of nuclei in the RF to LLR for the first time in vivo and in human. Dr. Sergi has developed the MR-StretchWrist, a novel MRI-compatible robot capable of controlled-speed perturbations to the wrist joint to elicit LLRs. Co-PI David Ress has developed functional Magnetic Resonance Imaging (fMRI) sequences to measure function of brainstem nuclei with unprecedented resolution and optimal contrast-to-noise ratio. Also, our team benefits from the collaboration with an expert in stroke neurophysiology, Dr. Jules Dewald. In this project, we will develop a novel tool for studying the neuromuscular system in-vivo, StretchfMRI, a technique that combines robotic perturbations with electromyography (EMG) and with high-resolution brainstem functional imaging. Moreover, we will use StretchfMRI to identify the involvement of brainstem nuclei in LLRs.
Our central hypothesis is that nuclei in the reticular formation contribute to processing long-latency responses. We will test this central hypothesis via two specific aims.
Aim 1: Develop and validate StretchfMRI
Aim 2: Test the double reciprocal model of the reticular formation for long-latency responses
StatusActive
Effective start/end date2/1/201/31/22

Funding

  • University of Delaware (56808//1R21NS111310-01A1)
  • National Institute of Neurological Disorders and Stroke (56808//1R21NS111310-01A1)

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