Global Cortical Thinning Predicts Slower Forward and Backward Walking in Multiple Sclerosis

Gait impairment and falls are common in multiple sclerosis (MS), yet the neural substrates contributing to mobility decline remain poorly understood. While prior studies have linked regional gray matter atrophy to motor outcomes, the role of diffuse cortical changes in complex gait tasks, such as backward walking, is less clear. This study examined whether diffuse cortical thinning is associated with forward and backward walking speed, and whether these relationships differ between fallers and nonfallers in MS. Forty-three individuals with MS (55 ± 10 years; 65% female) completed forward and backward Timed 25-Foot Walk assessments and high-resolution structural MRI. Cortical thickness and gray matter volume were estimated. Region-specific associations with gait speed were examined using regression with false discovery rate (FDR) correction. Principal component analysis revealed a global cortical thinning component that was associated with slower forward (β = -0.065, adjusted R² = 0.14) and backward (β = -0.061, adjusted R² = 0.19) walking speeds. In contrast, volumetric components did not significantly predict gait. Fallers and nonfallers did not differ in gait speed or cortical thinning, but exploratory moderation suggested stronger cortical thinning-gait associations in fallers, although effects did not remain significant after FDR correction. These preliminary findings suggest that diffuse cortical thinning is a consistent neural correlate of gait slowing in MS, with exploratory evidence suggesting that this relationship may be stronger among individuals with recent falls.