Spinal And Peripheral Mechanisms Of Human Motor Control

Neurological Disorders And Stroke

Investigators

Linked publications, trials & patents

Abstract

The goals of this project are to first, understand the role of spinal cord circuits in coordinating simple movements in humans and, secondly, to evaluate whether changes in the functioning of motor circuits contribute to abnormalities of movement. In FY2003 our clinical studies have focused on two neurological disorders, primary lateral sclerosis and spastic paraplegia, in which degeneration of the corticospinal tract produces progressive spasticity. In these disorders, spinal neurons remain intact, but do not receive input from the motor cortex. Two questions are being explored. First, to investigate the functioning of spinal circuits, we are assessing the excitability and firing behavior of motor neurons innervating spastic muscles in patients with PLS. A goal of this study is to determine whether abnormalities of firing can be modified by peripheral sensory inputs. Sensory inputs to motor neurons are relayed through spinal interneuron circuits. In the last year, in healthy control subjects, we showed that repetitive sensory stimulation was able to transiently strengthen one of the spinal interneuron circuits, disynaptic reciprocal inhibition, that is known to function abnormally in spasticity. A second line of investigation is directed at understanding the likely underlying pathophysiologic processes in PLS and spastic paraplegia. We have hypothesized that , in a subset of PLS patients, corticospinal axons selectively undergo a dying-back degeneration that produces a characteristic "ascending" clinical pattern. A similar hypothesis has been proposed for uncomplicated hereditary spastic paraparesis, in which long sensory as well motor tracts degenerate. To test this hypothesis we are documenting the serial functioning of the long tracts in a cohort of patients, and are planning studies to assess the physiological function short-axon intrinsic connections of the motor cortex.