Sensorimotor and inhibitory control in aging FMR1 premutation carriers

Area of Science:

• Neuroscience
• Genetics
• Ophthalmology

Background:

• Aging FMR1 premutation carriers are at risk for neurodegenerative disorders like FXTAS.
• FXTAS affects males more frequently, but females can also develop the condition, with potentially different impairment patterns.
• Limited research exists on FXTAS phenotypes in females, hindering risk and progression tracking.

Purpose of the Study:

• To investigate quantitative motor and cognitive traits in aging FMR1 premutation carriers.
• To identify potential oculomotor biomarkers for neurodegeneration in FXTAS.
• To explore sex-specific differences in FXTAS-related impairments.

Main Methods:

• Oculomotor tests assessing visually guided/reactive saccades (motor) and antisaccades (cognitive control) were administered.
• Participants included 22 FMR1 premutation carriers (73% female) and 32 age- and sex-matched healthy controls.
• Neuromotor impairments were clinically rated and correlated with oculomotor performance.

Main Results:

• No significant differences in reactive saccade latency or accuracy were found between carriers and controls.
• FMR1 premutation carriers exhibited increased antisaccade latencies compared to controls, in both combined and female-only analyses.
• Reduced saccade accuracy and increased antisaccade latency were associated with more severe neuromotor impairments.

Conclusions:

• FMR1 premutation carriers demonstrate a diminished capacity for volitional control over responses.
• Quantitative oculomotor measures, including antisaccade performance, may serve as biomarkers for FXTAS-related neurodegeneration in both sexes.
• Further research is needed to fully understand sex-specific disease trajectories and develop targeted interventions.