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Original Research|Articles in Press

Cerebellar contributions to motor and cognitive control in Multiple Sclerosis

Published:January 05, 2022DOI:https://doi.org/10.1016/j.apmr.2021.12.010
Cerebellar contributions to motor and cognitive control in Multiple Sclerosis
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      Highlights

      • •
        The cerebellum is a common site for Multiple Sclerosis (MS)-related disability.
      • •
        Greater SCP, MCP and lobule volume is associated with better motor and cognitive function
      • •
        Greater diffusivity of SCP is related to better motor and cognitive function
      • •
        Understanding structure-function relationships is key for targeted therapeutics in MS

      Abstract

      Objective: To evaluate relationships between specific cerebellar regions and common clinical measures of motor and cognitive function in persons with multiple sclerosis.
      Design: Cross-sectional
      Setting: Laboratory
      Participants: Twenty-nine PwMS and 28 age and sex-matched healthy controls.
      Interventions: Not Applicable
      Main Outcome Measures: Both diffusion and lobule MRI analyses and common clinical measures of motor and cognitive function were used to examine structure-function relationships in the cerebellum.
      Results: PwMS demonstrate significantly worse motor and cognitive function compared to controls: weaker strength, slower walking, and poorer performance on the Symbol Digit Modalities Test, but demonstrate no differences in cerebellar volume. However, PwMS demonstrate significantly worse diffusivity (Mean Diffusivity: p=0.0003; Axial Diffusivity: p=0.0015; Radial Diffusivity: p=0.0005; Fractional Anisotropy: p=0.016) of the superior cerebellar peduncle (SCP), the primary output of the cerebellum. Increased volume of the motor lobules (I-V, VIII) was significantly related to better motor (p<0.022) and cognitive (p=0.046) performance, and increased volume of the cognitive lobules (VI-VII) was also related to better motor (p<0.032) and cognitive (p=0.008) performance, supporting the role of the cerebellum in both motor and cognitive functioning.
      Conclusion: These data highlight the contributions of the cerebellum to both motor and cognitive function in PwMS. Using novel neuroimaging techniques to examine structure-function relationships in PwMS improves our understanding of individualized differences in this heterogeneous group and may provide an avenue for targeted, individualized rehabilitation aimed at improving cerebellar dysfunction in MS.

      Keywords

      Abbreviations:

      2MWT (Two minute walk test), AD (axial diffusivity), DTI (Diffusion tensor imaging), FA (Fractional anisotropy), ICP (Inferior cerebellar peduncle), MCP (Middle cerebellar peduncle), MD (Mean diffusivity), MRI (Magnetic resonance imaging), MS (Multiple Sclerosis), PwMS (Person(s) with Multiple Sclerosis), RD (Radial diffusivity), RRMS (Relapsing remitting Multiple Sclerosis), SCP (Superior cerebellar peduncle), SDMT (Symbol digit modalities test), SSST (Six spot step test), T25FW (Timed 25 foot walk), TUG (Timed up and go)
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      Article Info

      Publication History

      Accepted: December 13, 2021
      Received in revised form: October 25, 2021
      Received: July 2, 2021

      Publication stage

      In Press Journal Pre-Proof

      Footnotes

      This work was previously presented at the Consortium of Multiple Sclerosis Centers Annual Meeting in 2015.

      Funding Acknowledgement: National Multiple Sclerosis Society Research Grant (KMZ)

      Author Disclosures: Dr. Fritz serves on the MS scientific advisory board for Helius Medical.

      Ms. Edwards has no disclosures.

      Dr. Ye has no disclosures.

      Dr. Prince is a founder of Sonovex, Inc. and serves on its Board of Directors. He has received consulting fees from JuneBrain LLC and is PI on a grant from Biogen and a coinvestigator on research grants from JuneBrain LLC and Genentech.

      Dr. Yang has no disclosures.

      Mr. Gressett has no disclosures.

      Ms. Keller has no disclosures.

      Ms. Myers has no disclosures.

      Dr. Calabresi has received consulting fees from Disarm, Nervgen, and Biogen for serving on scientific advisory boards, and is PI on a grant from Genentech to Johns Hopkins University.

      Dr. Zackowski has no disclosures.

      Identification

      DOI: https://doi.org/10.1016/j.apmr.2021.12.010

      Copyright

      © 2022 Published by Elsevier Inc. on behalf of The American Congress of Rehabilitation Medicine.

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