Neural correlates of forward and backward walking in MS: insights from myelin water imaging.

Mobility impairments and increased fall risk are common in multiple sclerosis (MS), resulting from myelin degradation in motor pathways. While forward walking is a common mobility assessment, backward walking shows greater sensitivity in distinguishing fallers due to its increased postural and cognitive demands. However, the neurobiological mechanisms underlying backward walking deficits remain unclear. This study examined associations among myelin water imaging (MWI) metrics-myelin water fraction (MWF) and geometric mean of intermediate-T2 relaxation times (geomT_2IEW)-in motor pathways and forward and backward walking performance in MS. Forty-three individuals with relapsing-remitting MS completed forward and backward walking assessments. MWI assessed MWF and geomT_2IEW in four motor tracts: corpus callosum body (CC_body), superior and inferior cerebellar peduncles (SCP, ICP), and corticospinal tract (CST). Multiple regression models examined associations between regional MWF and geomT2IEW and walking velocity in each direction, controlling for age and disease severity, measured via the Patient-Determined Disease Steps (PDDS). Higher MWF in the SCP was significantly associated with faster backward velocity (b = 0.046, p = 0.026), while MWF in the CC_body was the strongest predictor of forward velocity (b = 0.019, p = 0.030). GeomT_2IEW was not significantly associated with walking velocity. PDDS was a significant covariate, with greater impairment linked to slower speeds (p < 0.001). Forward and backward walking involve distinct neural networks, with SCP myelin content linked to backward walking and CC_body myelin to forward walking. Findings highlight the utility of backward walking assessments in identifying MS-related mobility deficits and suggest targeting cerebellar pathways in rehabilitation to improve gait and reduce fall risk.