The mechanisms underlying normal and dysfunctional cortical control of movement is a topic of great neurobiological and clinical importance. Features of cortical organization have been shown to relate directly to normal movement as well as aspects of movement disorders in conditions such as stroke and cerebral palsy. While the cortical control of the arm and hand in primates has been the focus of considerable attention over many years and the subject of a large number of studies, comparatively little is known about the cortical control of the lower extremity despite its obvious importance both clinically and in the motor repertoire of primates including humans. Early work in anesthetized macaques and baboons has established some basic features of the synaptic linkage between hindlimb motoneurons and primary motor cortex (M1), including the existence of monosynaptic connections, suggesting a synaptic linkage similar to that for arm and hand motoneurons. While the work on synaptology has been somewhat limited, it nevertheless forms an essential foundation for additional functional studies in awake primates. The overall objective of this proposal is to answer fundamental questions about the functional properties and organization of hindlimb cortical control toward a larger goal of developing a knowledge base that parallels that for the forelimb. Toward this goal, we propose the following six specific aims: 1) to determine the properties of muscles synergies represented in the output of hindlimb M1 cortex, in comparison to forelimb cortex, 2) to identify basic features of M1 hindlimb muscle representation in comparison with the forelimb muscle representation, 3) to determine the strength and nature of the synaptic linkage from hindlimb M1 cortex in the primate to motoneurons of 20 hindlimb muscles in comparison to that from forelimb M1 cortex, 4) to characterize the properties of the prominent late facilitation peak(s) in stimulus triggered averages (StTAs) of hindlimb muscles from M1 cortex and to determine the neural mechanism underlying these late peaks, 5) to determine the characteristics of M1 output effects on ipsilateral hindlimb muscles in comparison to effects on contralateral muscles, and 6) to determine the nature of output effects from M1 cortex to fast and slow ankle extensor muscles in the monkey using spike and stimulus triggered averaging of EMG activity.
Damage to the cerebral cortex and corticospinal neurons associated with stroke, ALS, traumatic brain injury and spinal cord injury produce severe impairments of the lower extremity that lead to considerable disability and reduction in the patient's quality of life. This proposal focuses on delineating features of normal cortical output organization to lower extremity muscles. The data derived form this work will be applicable to understanding hindlimb motor deficits associated with damage to the cerebral cortex and may suggest new strategies for therapeutic intervention.
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