Examine longitudinal changes in cortical gyrification in multiple sclerosis (MS) and the link between cortical reshaping, lesion load, and disability.

Across the cohort, LGI decreased over time in the cingulate, superior frontal, and medial orbitofrontal gyri (P_FWE<0.05, adjusted for age and sex). Within individual cortical regions, correlation between change in LGI and change in cortical thickness and volume was weak to moderate. The number of cortical areas with ≥5% LGI reduction was associated with worsening timed 25-foot walk (ρ=0.302, P=0.039) and 9-hole peg test (ρ=0.361, P=0.013). Global gyrification decrease was associated with higher cortical (ρ=-0.296, P=0.043) and white matter lesion burden (ρ=-0.303, P=0.039). An age-adjusted backward regression model used to determine the influence of baseline cortical and white matter lesion load on LGI changes predicted 16.2% of LGI variance (P=0.001), and higher cortical lesion burden predicted gyrification loss (β=-0.403, P=0.005).

Loss of gyrification is associated with worsening disability and lesion burden, especially in the cortex. Further investigation of LGI in MS may elucidate the factors influencing cortical remodeling and how cortical remodeling contributes to disability.