11:50 a.m., May 14, 2009----Researchers in the Exercise Neuroscience Laboratory at the University of Delaware are studying the control of muscular force and movement at the most fundamental level of force control: a single motoneuron and the muscle fibers that it innervates, known collectively as a motor unit.

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Chris Knight, assistant professor in the Department of Health, Nutrition and Exercise Sciences, hopes that what he and his research team learn from the recordings of individual motor units will provide valuable new insights into what's going on in the brains of individuals suffering from movement disorders such as stroke, Parkinson's Disease, and tremor.

Using specialized multichannel needle or fine-wire electrodes in humans, Knight and his students record action potentials as they arrive at muscle tissue. “Whereas techniques such as brain imaging or EEG provide information about the function of the central nervous system from a supraspinal perspective, our recordings provide a window to the function of the nervous system at the periphery,” he says.

Knight has been studying motor-control mechanisms in the elderly for the past several years, and he has recently shifted his focus from healthy older adults to patients with movement disorders.

“Our lab is one of just a handful in the country using this technique to collect data from patient populations,” he says. “We can learn a great deal by analyzing data from patients who have movement disorders and comparing it with data from healthy older adults.”

A University of Delaware Research Foundation (UDRF) Strategic Initiative grant has enabled Knight to collaborate with researchers in the UD Department of Physical Therapy, using stroke patients in the Physical Therapy Clinic as subjects.

Knight has worked with Stuart Binder-McLeod, Edward L. Ratledge Professor and chairperson of the Department of Physical Therapy, and Darcy Reisman, assistant professor, who are developing a physiologically based intervention to improve functional ambulation in individuals who have sustained a stroke.

“This has been a great collaboration,” Knight says, “because it fosters leveraging of various aspects of stroke research on campus. Others are investigating function and intervention, while my research team is studying mechanism.”

Knight has also benefited from a close working relationship with Ingrid Pretzer-Aboff, assistant professor in UD's School of Nursing. “Ingrid is immersed in the Parkinson's community,” he says. “She has trained people in their homes to improve function, and she is bringing patients into my lab so we can study mechanism.”

So far, the number of patients that Knight has been able to test is small, but the feedback they have yielded has immeasurable value.

“Every time we test a patient, we get better at it,” he says, “and the more different types of movement disorders we see, the more we can learn to help others. What we've found is that the healthy elderly are much more similar to each other than are those with movement disorders -- a mildly affected stroke patient is vastly different from a severely affected stroke patient. We've had to modify our approach to interpret the data we're getting from these individuals.”

Knight explains that there are two primary mechanisms of control at the motor unit level -- recruitment and rate coding. The central nervous system can increase the strength of muscle contraction by increasing the number of active motor units as well as by increasing the firing rate of individual motor units.

In healthy individuals, both mechanisms are invoked during muscle contraction. However, the data that Knight has collected on one patient, who is several years post-stroke, has indicated an absence of the ability to rate code. “There have been some hints of this in the literature,” he says, “but with the technique we're using here we can actually see evidence of a loss of rate coding ability, and that ability is necessary for strength, quickness, and control.”

Knight is particularly interested in quickness because it's closely tied to fall prevention. “There's lots of research on strength and fatigue,” he says. “But quickness can be overlooked.”

Maria Bellumori, a graduate student in Knight's lab who recently defended her master's thesis, developed and validated a protocol for measuring quickness noninvasively. “The protocol works very well for both stroke and Parkinson's patients,” Knight says. “We were very fortunate recently to have the opportunity to test a Parkinson's patient, first without his medications and then again after he took them. We witnessed changes in his tremor behavior and got great data showing those changes at the neuron level.”

Knight hopes that the tool may be able to help distinguish Parkinson's Disease from other types of tremor, or possibly enable monitoring of patients on different types of drugs to see whether they affect neuronal activity differently.

Bellumori will spend 10 weeks this summer as an intern working with Dr. Mary Kay Floeter at the National Institute of Neurological Disorders and Stroke (NINDS) in Bethesda, Md. Floeter's current research focuses on analyzing changes in motor neurons and spinal circuits in patients with disorders that disrupt the corticospinal motor system.

“This will be a great opportunity for Maria,” Knight says, “while also providing a bridge between our lab and the NINDS.”

“Our main goal,” he adds, “is to bring all of our resources to the patient population. As subjects, they can teach us a great deal, and any new knowledge we can generate to facilitate earlier diagnosis will translate into earlier treatment and management programs, increasing the odds for improved function.”

Article by Diane Kukich
Photo by Ambre Alexander