Force and effort are important components of a motor task that can impact rehabilitation effectiveness. However, few studies have evaluated the impact of these factors on cortical activation during gait. The purpose of the study was to investigate the relation between cortical activation and effort required during exoskeleton-mediated gait at different levels of physical assistance in healthy individuals. Twenty-four healthy participants walked 10 m with an exoskeleton that provided four levels of assistance: 100%, 50%, 0%, and 25% resistance. Functional near-infrared spectroscopy (fNIRS) was used to measure cerebral flow dynamics with a 20-channel (plus two reference channels) device that covered most cortical motor regions bilaterally. We measured changes in oxyhemoglobin (HbO₂) and deoxyhemoglobin (HbR). According to HbO₂ levels, cortical activation only differed slightly between the assisted conditions and rest. In contrast, bilateral and widespread cortical activation occurred during the two unassisted conditions (somatosensory, somatosensory association, primary motor, premotor, and supplementary motor cortices). A similar pattern was seen for HbR levels, with a smaller number of significant channels than for HbO₂. These results confirmed the hypothesis that there is a relation between cortical activation and level of effort during gait. This finding should help to optimize neurological rehabilitation strategies to drive neuroplasticity.

Serotonin (5-HT) is known as a potent immune cell modulator in autoimmune diseases and should be protective in the pathogenesis of multiple sclerosis (MS). Nevertheless, there is limited knowledge about receptors involved in 5-HT effects as well as induced mechanisms. Among 5-HT receptors, the 5-HT₇ receptor is able to activate naïve T cells and influence the inflammatory response; however, its involvement in the disease has never been studied so far. In this study, we collected blood sample from three groups: acute relapsing MS patients (ARMS), natalizumab-treated MS patients (NTZ), and control subjects. We investigated the 5-HT₇ expression on circulating lymphocytes and evaluated the effects of its activation on cytokine production with peripheral blood mononuclear cell (PBMC) cultures. We found a significant increase in the 5-HT₇ surface expression on T lymphocytes and on the different CD4⁺ T cell subsets exclusively in NTZ-treated patients. We also showed that the selective agonist 5-carboxamidotryptamine (5-CT)-induced 5-HT₇R activation significantly promotes the production of IL-10, a potent immunosuppressive cytokine in PBMCs. This study provides for the first time a dysregulation of 5-HT₇ expression in NTZ-MS patients and its ability to promote IL-10 release, suggesting its protective role. These findings strengthen the evidence that 5-HT₇ may play a role in the immuno-protective mechanisms of NTZ in MS disease and could be considered as an interesting therapeutic target in MS.