Differences in resting state functional connectivity relative to multiple sclerosis and impaired information processing speed.

Background: Fifty-one percent of individuals with multiple sclerosis (MS) develop cognitive impairment (CI) in information processing speed (IPS). Although IPS scores are associated with health and well-being, neural changes that underlie IPS impairments in MS are not understood. Resting state fMRI can provide insight into brain function changes underlying impairment in persons with MS.
Objectives: We aimed to assess functional connectivity (FC) differences in (i) persons with MS compared to healthy controls (HC), (ii) persons with both MS and CI (MS-CI) compared to HC, (iii) persons with MS that are cognitively preserved (MS-CP) compared to HC, (iv) MS-CI compared to MS-CP, and (v) in relation to cognition within the MS group.
Methods: We included 107 participants with MS (age 49.5 ± 12.9, 82% women), and 94 controls (age 37.9 ± 15.4, 66% women). Each participant was administered the Symbol Digit Modalities Test (SDMT) and underwent a resting state fMRI scan. The MS-CI group was created by applying a z -score cut-off of ≤ -1.5 to locally normalized SDMT scores. The MS-CP group was created by applying a z -score of ≥0. Control groups (HC _MS-CI and HC _MS-CP ) were based on the nearest age-matched HC participants. A whole-brain ROI-to-ROI analysis was performed followed by specific contrasts and a regression analysis.
Results: Individuals with MS showed FC differences compared to HC that involved the cerebellum, visual and language-associated brain regions, and the thalamus, hippocampus, and basal ganglia. The MS-CI showed FC differences compared to HC _MS-CI that involved the cerebellum, visual and language-associated areas, thalamus, and caudate. SDMT scores were correlated with FC between the cerebellum and lateral occipital cortex in MS. No differences were observed between the MS-CP and HC _MS-CP or MS-CI and MS-CP groups.
Conclusion: Our findings emphasize FC changes of cerebellar, visual, and language-associated areas in persons with MS. These differences were apparent for (i) all MS participants compared to HC, (ii) MS-CI subgroup and their matched controls, and (iii) the association between FC and SDMT scores within the MS group. Our findings strongly suggest that future work that examines the associations between FC and IPS impairments in MS should focus on the involvement of these regions.
Competing Interests: RM receives research funding from: CIHR, Research Manitoba, Multiple Sclerosis Society of Canada, Multiple Sclerosis Scientific Foundation, Crohn’s and Colitis Canada, National Multiple Sclerosis Society, CMSC, The Arthritis Society, US Department of Defense and UK MS Society. She serves on the Editorial Board of Neurology. She is a co-investigator on studies funded in part by Biogen Idec and Roche (no funds to her or her institution). RP receives research funding from the Workers Compensation Board of Manitoba. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
(Copyright © 2023 Carter, Patel, Fisk, Figley, Marrie, Mazerolle, Uddin, Wong, Graff, Bolton, Marriott, Bernstein, Kornelsen.)