Precision Sensorimotor Control in Aging Fragile X Mental Retardation 1 Gene Premutation Carriers

Abstract

Individuals with premutation alleles of the FMR1 gene are at risk of developing Fragile X-associated Tremor/Ataxia Syndrome (FXTAS), a neurodegenerative condition affecting sensorimotor, cognitive and psychological function. There is limited information on quantitative symptom traits in aging premutation carriers to assist in identifying neurodegenerative processes and understanding neurodegenerative mechanisms. 26 FMR1 premutation carriers ages 44-77 years and 31 age-matched healthy controls completed a visually guided precision gripping task in which they pressed with their thumb and forefinger against load cells while receiving visual feedback. Individuals maintained a constant force for 2- or 8- seconds. During initial pressing, reaction time, the rate at which individuals increased their force, and force accuracy were measured. During sustained gripping, the complexity of the force time series, force variability, and mean force were examined. At the end of each trial, the rate at which individuals decreased their force was measured. During initial pressing, premutation carriers, relative to controls, showed longer reaction times, particularly at younger ages. They also showed reduced rates of force generation and reduced accuracy relative to controls. During sustained force, premutation carriers demonstrated reduced force complexity, though this effect varied as a function of age and hand; it was reduced across ages for the non-dominant hand but was more severely reduced at younger ages for the dominant hand. Lower sustained force complexity was associated with greater cytosine-guanine-guanine (CGG) repeat length. Increased reaction time, increased sustained force variability, and increased rates of force relaxation each were associated with more severe clinically rated FXTAS symptoms. Findings of increased reaction time in premutation carriers implicate neurodegenerative processes affecting the ability to rapidly prepare the motor system for action. Premutation carriers also showed reduced accuracy of their initial force output indicating impairments precisely planning rapid motor behavior. Reduced complexity of sustained motor output suggests deficits in reactively adjusting motor behavior in response to sensory feedback. Overall, these results indicate that sensorimotor issues in aging premutation carriers affect multiple motor systems, and quantitative tests of precision visuomotor ability may serve as key targets for monitoring FXTAS risk and progression.