Reduced Cerebellar Activation With Eyes Closed Is Associated With Delayed Peroneal Reaction Time in Patients With...

Chronic ankle instability (CAI) is a common consequence of lateral ankle sprain and is characterized by recurrent episodes of giving way and impaired neuromuscular control. Neuromuscular control impairments (such as decreased postural stability and delayed muscle responses) are dominant during reduced vision. However, the neural mechanisms underlying impaired sensorimotor integration under reduced vision remain unclear. As a key structure involved in sensorimotor processing, the role of the cerebellum during vision-related neuromuscular control impairments has not been well defined.

(1) Are there any differences in cerebellar activation across different visual conditions in patients with CAI compared with a control group? (2) Are there any associations between vision-related cortical activation changes and static and dynamic neuromuscular control deficits in patients with CAI?

This cross-sectional study enrolled physically active adults with unilateral CAI and control participants matched for age, sex, and activity level. Between May and September 2025, a total of 55 individuals were screened. Of these, 64% (35 of 55) were considered eligible based on the inclusion criteria, consisting of 57% (20 of 35) in the CAI group (nine females, mean ± SD age 28 ± 7 years) and 43% (15 of 35) in the control group (eight females, mean age 25 ± 4 years). To assess cerebellar activation and its relation to neuromuscular control, all participants underwent task-based functional MRI (fMRI) and laboratory-based neuromuscular assessments. During fMRI, participants performed repetitive ankle dorsiflexion and plantarflexion movements using an MRI-compatible device under alternating eyes-open and eyes-closed conditions in a block design. Neuromuscular control was assessed during single-leg stance and a sudden ankle inversion (trapdoor) task. Postural stability was quantified using the Romberg ratio derived from center-of-pressure measures. Dynamic neuromuscular response was evaluated by peroneal reaction time using surface EMG synchronized with motion capture. Ankle function and perceived instability were assessed using questionnaires (Cumberland Ankle Instability Tool [CAIT], Foot and Ankle Ability Measure [FAAM], and Ankle Ligament Reconstruction-Return to Sport After Injury [ALR-RSI] tool). Whole-brain analyses were conducted to identify between-group differences in vision-related activation (eyes closed minus eyes open) using a general linear model with Gaussian random field correction. Clusters greater than 50 voxels were considered to be the minimum clinically important difference. Correlation analyses were performed to examine associations between neural activation patterns, neuromuscular outcomes, and clinical measures, with age and sex included as covariates.

Compared with controls, individuals with CAI demonstrated reduced activation when eyes changed from open to closed in bilateral cerebellar regions including lobule VI (left hemisphere: cluster size 156 voxels, group mean difference -25.1 [95% confidence interval (CI) -40.1 to -10.1]; p < 0.001; right hemisphere: cluster size 153 voxels, group mean difference -21.7 [95% CI -36.3 to -7.6]), vermis VI (cluster size 51, group mean difference -26.6 voxels [95% CI -44.8 to -8.4]), and crus I (cluster size 112 voxels, group mean difference -21.9 [95% CI -35.8 to -8.1]), as well as in the left fusiform gyrus (cluster size 54 voxels, group mean difference -18.1 [95% CI -29.3 to -6.8]). Correlation analyses revealed that reduced activation in cerebellar and fusiform gyrus in both eyes-open and eyes-closed states was moderately associated with delayed peroneal reaction time in both visual conditions (eyes open: r = -0.38; p = 0.03; eyes closed: r = -0.40; p = 0.02) and worse self-reported ankle stability and function, as measured by the CAIT (r = 0.34; p = 0.046) and ALR-RSI (r = 0.38; p = 0.02). No correlations were observed between cerebellar activation and Romberg ratio.

Patients with CAI demonstrated reduced cerebellar activation across visual conditions, which was associated with delayed dynamic muscle responses and worse perceived ankle stability.

These findings suggest that patients with CAI had vision-related central activation strategies, such as reduced cerebellar activation when eyes were closed compared with controls. Such neural alterations were associated with decreased neuromuscular control and diminished ankle function. These vision-specific central alterations may be important in designing future interventions aimed at enhancing central sensorimotor integration.