Increased resting state functional connectivity after cognitive rehabilitation in progressive MS: CogExStudy results

Abstract

Introduction: It is still unknown whether cognitive rehabilitation (CR) induces changes in structural brain connectivity in people with multiple sclerosis (PwMS). Objectives/Aims: To study the efficacy of the Guttmann, NeuroPersonalTrainer® (GNPT) rehabilitation program on cog-nition and characterise the induced changes in diffusion-based structural networks. Methods: Multi-centre, phase II, double-blinded and ran-domised clinical trial comparing upward intensity training (active treatment) to low intensity static training (static treatment). Patients underwent cognitive assessment using Rao's battery and brain MRI pre and post 12 weeks of online training. An advanced tractography algorithm, based on multishell diffusion MRI data, was used to obtain node-based graph metrics (local efficiency and nodal strength) from microscopic fractional ani-sotropy (uFA) weighted network adjacency matrices. We used mixed-effect models to determine cognitive differences and uFA changes induced by CR. Results: Seventy PwMS completed the study (age 48.9±8.8, disease duration 16.8±9.0 years): active treatment: 36, static treatment: 34. Both groups improved verbal memory after CR: active treatment: β=1.099 (95%CI, 0.80-1.40) and static treatment: β=0.718 (95%CI, 0.41-1.03), p<0.001. At post-CR, patients with active treatment had an increment in both local efficiency and strength in 19 (25%) and 18 (24%) nodes, including the basal ganglia, frontal, temporal, parietal and cingulate cortex. In patients with static treatment, enlargement of local efficiency and strength was observed in 8 (11%) and 7 (9%) nodes, mainly involving the temporal, occipital and cingulate cortex. Increased network efficiency mainly in the parietal cortex (mean β=0.368, 95%CI 0.04-1.10, p=0.032) was associated with cognitive improvement in both groups. Conclusion: The GNPT improves verbal memory and induces changes in diffusion-based structural networks in multimodal regions. These findings reinforce the CR as a valuable tool to enhance cognitive skills and promote neuronal plasticity and show its usefulness as a reliable application for the clinical management of cognitive deficits in PwMS.