SBIR-STTR Award

This project is directed towards the development of computerized, noninvasive measurement system designed to evaluate motor disorders in a clinical neurologic setting. A method has been developed that operationally defines two human motor subsystems, referred to as the feed-forward-based volitional motor system and the feedback-based reflexive motor system. The measurement system records and identifies abnormalities in each motor subsystem and in the coordination of the subsystems. While previous methods measure either the volitional or reflexive system, the current method evaluates both and measures the coordination between the two systems. Substantial previous development has resulted in a simple and robust procedure allowing measurement of reflex gain and volitional output during visually guided tracking. Measurement of motor subsystem coordination by this method has identified significant differences between age-matched normal and bradykinetic parkinsonian subjects (p<0.001, Student's t-test, N=30). Thus, one example of defective central coordination of the volitional and reflexive motor systems has been described and mechanism of bradykinesia provided (Johnson et al, 1990). This grant will fund the extension of the described methodology, first by expanding the utility of parkinsonian testing to the evaluation of therapeutic response, and secondly by documenting motor control pathophysiology for a range of motor disorder diagnostic categories. Development of the potential for therapeutic evaluation and diagnosis of motor disorders will justify the clinical utility for quantitative motor evaluation. These extensions will expand the physiologic database, drive software development, and define the market for this methodology.

Public Health Relevance Statement:
Terms:

We will develop a computerized, non-invasive measurement system designed to evaluate motor disorders in a clinical neurological setting. A method was developed that operationally defines two human motor systems: the feed-forward based volitional motor system and the feed back based reflexive motor system. The measurement system records and identifies abnormalities in each motor subsystem and in the coordination of the subsystems. While older methods measure either the volitional or reflexive system, the current method attempts to evaluate both as well as the coordination between the two systems. The Phase 11 proposal focuses on the development of a safe and automated testing platform to quantify motor control abnormalities. One goal is to complete the development of the platform to a stage ready for commercialization, and the second goal is the continued quantitative evaluation of Parkinson's disease and other movement disorders. The main finding in this effort is that when sinusoidal visually guided wrist tracking movements are performed, which are perturbed by torque transients out of phase throughout the movement, both the long latency stretch reflex and volitional EMG can be assessed at different phases in the tracking. Reflex modulation during tracking differed significantly between Parkinson's patients and normal subjects in both wrist flexor and extensor muscles. In the Parkinson's group there was an increased reflexivity during tracking phases in which the muscle was stretched. As a consequence, this increased reflex activity interfered with the volitional activity. No differences in unperturbed volitional EMG modulation were observed between the two groups, demonstrating that the changes in reflex modulation are due to disordered volitional modulation and changes alpha motorneuronal excitability.Awardee's statement of the potential commercial applications of the research: Quantitative measurement of bradykinesia is necessary to test efficacy of existing and experimental pharmacologic treatments. Over 100 companies are developing new drugs and therapies to treat Parkinson's disease in a market expected to reach $900 million by 1998. To improve current diagnosis of Parkinson's patients and aid in this drug research, the system will provide accurate registration of symptomatic progression, test efficacy of drug therapy and individualize drug dosage schedules.National Institute of Neurological Disorders and Stroke (NINDS)