The neural correlates of walking fatigability in people with multiple sclerosis: An fNIRS study

Walking fatigability (WF) is a common and disabling feature of people with multiple sclerosis (pwMS), yet its neural underpinnings are poorly understood. Here, we investigated real-time cortical activity during the 6-min walk test (6MWT) and its relationship with changes in gait speed and quality. PwMS with and without WF (n = 42), and healthy controls (HC, n = 25), completed a 6MWT. Using functional near-infrared spectroscopy, cortical activity was measured in the prefrontal, premotor and motor cortices. Concomitantly, inertial measurement units measured gait speed and quality on a minute-by-minute basis. PwMS with WF (Expanded Disability Status Scale-EDSS = 6 [2.62]) showed marked declines in speed and gait quality, accompanied by altered patterns of cortical activation throughout the 6MWT. While HC and pwMS without WF (EDSS = 3[1.75]) dynamically modulated activity across frontal (p < .004), premotor (p < .043) and motor (p < .032) regions to respond to the task demands, pwMS with WF exhibited sustained reliance on frontal cortical regions and limited engagement of the broader walking network. Across all groups and cortical regions, an overall cortical activity pattern was observed. Specifically, cortical activity peaked during the first minute, stabilised during minutes 2-4, and increased during minutes 5-6. In both HC and pwMS, correlation analyses (rho:324-597) indicate that greater increases in cortical activity were associated with better gait speed/quality. Nevertheless, while these associations suggest that HC can recruit a broader walking control network, pwMS demonstrated an executive-driven pattern of brain-gait control. These findings suggest that walking fatigability can be partly driven by impaired ability to flexibly recruit cortical resources during prolonged walking.