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Randomized Controlled Trial
. 2025 Oct:189:106349.
doi: 10.1016/j.bandc.2025.106349. Epub 2025 Aug 9.

Aerobic walking exercise training boosts thalamic connectivity in MS patients with cognitive processing speed impairment

Brian M Sandroff  1 , Robert W Motl  2 , Glenn R Wylie  3 , Grace E Wells  4 , Carly L A Wender  3 , Mary Ann Picone  5 , Krupa Pandey  6 , John DeLuca  3 , Gary R Cutter  7
Affiliations
Randomized Controlled Trial

Aerobic walking exercise training boosts thalamic connectivity in MS patients with cognitive processing speed impairment

Brian M Sandroff et al. Brain Cogn. 2025 Oct.

Abstract

Purpose: The current study involved a single-blind, randomized controlled trial on the effects of aerobic treadmill walking exercise training compared with an active control condition as an approach to modify thalamocortical resting-state functional connectivity (RSFC) as a neurobiological correlate of cognitive processing speed (CPS) impairment in 28 fully-ambulatory persons with multiple sclerosis (MS) who were pre-screened for impaired CPS.

Methods: Participants completed baseline assessments of CPS and underwent resting-state fMRI to measure thalamocortical RSFC. Following baseline, participants were randomly assigned into either 12-weeks of supervised, aerobic treadmill walking exercise training or 12-weeks of stretching and range-of-motion activities (active control condition). After the 12-week study period, participants underwent follow-up assessments of CPS and thalamocortical RSFC using a treatment-blinded assessor.

Results: Aerobic treadmill walking exercise training was associated with significantly increased RSFC between the thalamus and frontal/parietal regions relative to the active control condition. By comparison, the active control condition was associated with significantly increased RSFC between the thalamus and occipital regions relative to the treadmill condition.

Conclusions: The current RCT provides critical information on underlying neurophysiological mechanisms of aerobic treadmill walking exercise training and stretching and range-of-motion activities among fully-ambulatory, but CPS impaired persons with MS. This is important for informing the design of aerobic exercise programs that selectively target thalamocortical RSFC as an approach to improve CPS in persons with MS. Such programs may be ripe for inclusion in a future mechanistic trial focusing on thalamocortical RSFC as a mediator of exercise effects on CPS in MS.

Keywords: Brain; Cognition; Exercise; Multiple sclerosis; Neuroimaging.

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Conflict of interest statement

Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

References

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