BACKGROUND 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 function. Information on quantitative symptom traits associated with aging in premutation carriers is needed to clarify neurodegenerative processes contributing to FXTAS. MATERIALS AND METHODS 26 FMR1 premutation carriers ages 44-77 years and 31 age-matched healthy controls completed rapid (2 s) and sustained (8 s) visually guided precision gripping tasks. Individuals pressed at multiple force levels to determine the impact of increasing the difficulty of sensorimotor actions on precision behavior. During initial pressing, reaction time, the rate at which individuals increased their force, the duration of pressing, and force accuracy were measured. During sustained gripping, the complexity of the force time series, force variability, and mean force were examined. During relaxation, the rate at which individuals decreased their force was measured. We also examined the relationships between visuomotor behavior and cytosine-guanine-guanine (CGG) repeat length and clinically rated FXTAS symptoms. RESULTS Relative to controls, premutation carriers showed reduced rates of initial force generation during rapid motor actions and longer durations of their initial pressing with their dominant hand. During sustained force, premutation carriers demonstrated reduced force complexity, though this effect was specific to younger premutation carries during dominant hand pressing and was more severe for younger relative to older premutation carriers at low and medium force levels. Increased reaction time and lower sustained force complexity each were associated with greater CGG repeat length for premutation carriers. Increased reaction time and increased sustained force variability were associated with more severe clinically rated FXTAS symptoms. CONCLUSION Overall our findings suggest multiple sensorimotor processes are disrupted in aging premutation carriers, including initial force control guided by feedforward mechanisms and sustained sensorimotor behaviors guided by sensory feedback control processes. Results indicating that sensorimotor issues in aging premutation carriers relate to both greater CGG repeat length and clinically rated FXTAS symptoms suggest that quantitative tests of precision sensorimotor ability may serve as key targets for monitoring FXTAS risk and progression.

中文翻译：

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衰老 FMR1 基因预突变携带者的精确感觉运动控制。

背景技术具有 FMR1 基因前突变等位基因的个体有患脆性 X 相关震颤/共济失调综合征 (FXTAS) 的风险，这是一种影响感觉运动功能的神经退行性疾病。需要有关前突变携带者衰老相关的定量症状特征的信息来阐明导致 FXTAS 的神经退行性过程。材料和方法 26 名年龄为 44-77 岁的 FMR1 前突变携带者和 31 名年龄匹配的健康对照者完成了快速（2 秒）和持续（8 秒）视觉引导的精确抓取任务。个体以多种力量水平按压，以确定增加感觉运动动作难度对精确行为的影响。在初始按压期间，测量了反应时间、个体增加力量的速率、按压的持续时间和力量准确性。在持续抓握期间，检查了力时间序列的复杂性、力的变化性和平均力。在放松期间，测量了个体减少力量的速率。我们还检查了视觉运动行为与胞嘧啶-鸟嘌呤-鸟嘌呤 (CGG) 重复长度和临床评定的 FXTAS 症状之间的关系。结果 相对于对照组，前突变携带者在快速运动动作期间表现出初始力产生率降低，并且用惯用手初始按压的持续时间更长。在持续用力过程中，前突变携带者表现出力量复杂性降低，尽管这种效应是在优势手按压期间特定于年轻前突变携带者的，并且在低和中等力量水平下，相对于年长前突变携带者，年轻人的影响更为严重。增加的反应时间和较低的持续力复杂性均与前突变携带者的较大 CGG 重复长度相关。反应时间的增加和持续力变异性的增加与更严重的临床评级 FXTAS 症状相关。结论总的来说，我们的研究结果表明，衰老前突变携带者的多种感觉运动过程被破坏，包括前馈机制引导的初始力控制和感觉反馈控制过程引导的持续感觉运动行为。结果表明，衰老前突变携带者的感觉运动问题与较长的 CGG 重复长度和临床评定的 FXTAS 症状有关，表明精确感觉运动能力的定量测试可以作为监测 FXTAS 风险和进展的关键目标。