Abstract
Friedreich’s ataxia (FA) is a hereditary system degeneration, which progressively affects sensory functions such as proprioceptive feedback, which causes progressive ataxia in FA patients. While major clinical features of movement disorders in FA patients have been identified, the underlying impaired neural control is not sufficiently understood. To elucidate the underlying control mechanism, we investigated single-joint movements of the upper limb in FA patients. Small, tolerable force perturbations were induced during voluntary single-joint arm movements to examine the compensatory reaction of the FA patient’s motor system. Movement kinematics were measured, and muscle torques were quantified. We first found that as in healthy subjects, unperturbed single-joint movements in FA patients preserved similar temporal profiles of hand velocity and muscle torques, however, scaled in duration and amplitude. In addition, the small perturbations were compensated for efficiently in both groups, with the endpoint error < 0.5° (maximum displacement of 5–15°). We further quantified the differences in movement time, torque response, and displacement between patients and controls. To distinguish whether these differences were caused by a malfunction of top-down control or a malfunction of feedback control, the responses were fitted with a detailed model of the stretch reflex. The model simulations revealed that the feedback delay, but not the feedback gain was affected in FA patients. They also showed that the descending control signal was scaled in time and amplitude and co-contraction was smaller in FA patients. Thus, our study explains how the motor deficits of FA patients result from pathological alterations of both top-down and feedback control.
Highlights
Friedreich’s ataxia (FA) is an autosomal recessive inherited disease that causes severe progressive movement disorders
We focus on the function of shortlatency peripheral mechanisms in movement generation and in coping with unexpected mechanical perturbations, which challenge the motor system’s stability in FA patients
Our study shows that elbow–joint movements in FA patients preserved similar temporal profiles, such as bell-shaped velocity and bi-phasic muscle torque, as those in healthy subjects, FA patients had significantly lower speed patients have a prolonged descending control signal and a lower co-contraction
Summary
Friedreich’s ataxia (FA) is an autosomal recessive inherited disease that causes severe progressive movement disorders. The characteristic clinical features of this disease include gait and limb ataxia, dysarthria, and absent lower limb reflexes (Harding 1981; Cook and Giunti 2017). Loss of large primary sensory neurons in the dorsal root ganglia leads to axonal sensory peripheral neuropathy, as well as atrophy of the posterior columns of the spinal cord, which causes loss of position and vibration sense. Atrophy of the spinocerebellar tracts, loss of proprioceptive input to the cerebellum, and the severe atrophy of the dentate nucleus are the cerebellar components of ataxia, leading to coordination disorders. Motor function is affected by progressive degeneration of the corticospinal tracts affects. The resulting motor deficits of FA patients usually worsen over time and the patients become wheelchair-bound in their early twenties
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