Differential Effects of Gait Rehabilitation Exercises on Cortical Haemodynamics in Multiple Sclerosis

Multiple sclerosis (MS) is a chronic neurodegenerative disease characterized by progressive motor impairment, in which gait dysfunction significantly contributes to disability and reduced quality of life. Although gait rehabilitation improves functional outcomes, the neural mechanisms underlying recovery remain poorly understood, particularly across different training modalities. In this context, identifying how rehabilitation modulates cortical haemodynamics is crucial to better understand recovery processes and optimize treatment strategies. Here, we investigate the cortical haemodynamic changes induced by different gait training exercises within the context of the PROGR-EX clinical study. Twenty-four MS patients underwent distinct gait interventions: robot-assisted gait training (RAGT) with progressively increasing walking speed at low intensity (low-RAGT), RAGT at constant walking speed (conventional-RAGT), or overground gait training (OGT). Functional near-infrared spectroscopy (fNIRS) signals were recorded during an upper-limb motor task before treatment (T0), at the end of treatment (T1), and at follow-up (T2). A cross-sectional comparison with healthy controls was also performed. At baseline, MS patients showed altered cortical lateralization in a frontal-dominant brain network, with increased ipsilateral and reduced contralateral oxygenation compared to healthy controls. Longitudinal analyses revealed intervention-specific effects. Low-RAGT promoted a shift toward a more lateralized pattern, with increased contralateral and reduced ipsilateral activity at T1, and sustained reduction of ipsilateral involvement at T2. OGT induced a reduction of ipsilateral activity at both T1 and T2, while conventional-RAGT showed no clear shift toward a physiological oxygenation pattern. Gait rehabilitation modulates cortical haemodynamics in an exercise-dependent manner, with low-RAGT appearing to be the most effective in promoting a shift toward physiological motor lateralization.