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A Fine Motor Task to Study Joint Kinematics in a Preclinical Model of Neurodegenerative Disease
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Precision Sensorimotor Control in Aging FMR1 Gene Premutation Carriers.

Walker S McKinney1, Zheng Wang2, Shannon Kelly1

  • 1Clinical Child Psychology Program, Life Span Institute and Kansas Center for Autism Research and Training (K-CART), University of Kansas, Lawrence, KS, United States.

Frontiers in Integrative Neuroscience
|October 22, 2019
PubMed
Summary

Aging individuals with FMR1 premutation show sensorimotor deficits, including impaired force control and reduced precision gripping. These deficits correlate with CGG repeat length and fragile X-associated tremor/ataxia syndrome (FXTAS) severity, suggesting potential monitoring tools.

Keywords:
FMR1 premutationbradykinesiadysmetriafragile X-associated tremor/ataxia syndromeneurodegenerationprecision gripsensorimotor

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Area of Science:

  • Neuroscience
  • Genetics
  • Human Physiology

Background:

  • Fragile X-associated tremor/ataxia syndrome (FXTAS) is a neurodegenerative disorder affecting sensorimotor function in individuals with FMR1 gene premutation alleles.
  • Understanding age-related quantitative symptom traits in premutation carriers is crucial for elucidating FXTAS pathogenesis.

Purpose of the Study:

  • To investigate sensorimotor control deficits in FMR1 premutation carriers.
  • To examine the relationship between visuomotor behavior, CGG repeat length, and FXTAS symptom severity.

Main Methods:

  • 26 FMR1 premutation carriers and 31 controls performed visually guided precision gripping tasks at rapid and sustained durations.
  • Measurements included reaction time, force generation rate, pressing duration, force accuracy, force complexity, and force variability.
  • Correlation analyses were performed between sensorimotor measures, CGG repeat length, and FXTAS clinical ratings.

Main Results:

  • Premutation carriers exhibited slower initial force generation and longer pressing durations compared to controls.
  • Reduced force complexity was observed in carriers during sustained gripping, particularly in younger individuals and at lower force levels.
  • Increased reaction time and decreased force complexity were associated with longer CGG repeat lengths.
  • Elevated reaction time and increased force variability correlated with more severe FXTAS symptoms.

Conclusions:

  • Aging FMR1 premutation carriers display disruptions in both feedforward and feedback sensorimotor control mechanisms.
  • Quantitative sensorimotor assessments may serve as valuable tools for monitoring FXTAS risk and disease progression.
  • Findings highlight the link between genetic factors (CGG repeat length) and clinical manifestation of FXTAS through sensorimotor impairments.