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Treadmill walking exercise training effects on processing speed and thalamic resting-state functional connectivity in multiple sclerosis: a pilot study
B.M. Sandroff1, G.R. Wylie1, C.L. Johnson2, B.P. Sutton2, J. Deluca1, R.W. Motl3 1Kessler Foundation, West Orange, NJ, 2Beckman Institute of Advanced Sciences, 3Kinesiology and Community Health, University of Illinois at Urbana-Champaign, Urbana, IL, United States
Background: Cognitive impairment is common and debilitating among persons with multiple sclerosis (MS), and might be managed with exercise training. This is based on a rigorous and systematic line of research that identified progressive (both intensity and duration) treadmill walking exercise (TMWX) as an optimal exercise stimulus for improving cognition in fully-ambulatory persons with MS.
Objective: The present pilot study adopted a single-blind randomized controlled trial (RCT) design and is the first to examine the effect of a TMWX training intervention on cognition and functional MRI (fMRI) outcomes among fully-ambulatory persons with MS.
Methods: Eight fully-ambulatory females with relapsing-remitting MS were randomly assigned into exercise training intervention or waitlist control conditions. The intervention condition involved 12-weeks of supervised, progressive chronic TMWX training that was designed based on pilot work. Participants underwent measures of processing speed (i.e., Symbol Digit Modalities Test; SDMT) and cardiorespiratory fitness (i.e., peak aerobic capacity; VO2peak) before and after the 12-week period. Participants further underwent fMRI scans for measurement of resting-state functional connectivity (RSFC) between the thalamus and frontal cortical regions before and after the 12-week period.
Results: Overall, there were large intervention effects on SDMT performance (d=0.72) and VO2peak (d=0.88). There further were large intervention effects on RSFC between the thalamus and right middle frontal gyrus (MFG; d=1.92) and anterior cingulate cortex (ACC; d=1.70), respectively. The change in VO2peak was moderately associated with change in SDMT performance (r=.60), and change in RSFC between the thalamus and right MFG (r=.48) and ACC (r=.54), respectively. Further, change in SDMT was moderately associated with change in RSFC between the thalamus and right MFG (r=.42) and ACC (r=.53), respectively.
Conclusions: This small pilot RCT provides exciting proof-of-concept data supporting progressive TMWX training for potentially improving processing speed, cardiorespiratory fitness, and thalamocortical RSFC over time in fully-ambulatory persons with MS. This pattern of preliminary results seemingly supports an adaptive compensatory mechanism whereby TMWX training improves cardiorespiratory fitness, which might result in improved processing speed, which may be explained by increased thalamocortical RSFC.
B.M. Sandroff1, G.R. Wylie1, C.L. Johnson2, B.P. Sutton2, J. Deluca1, R.W. Motl3 1Kessler Foundation, West Orange, NJ, 2Beckman Institute of Advanced Sciences, 3Kinesiology and Community Health, University of Illinois at Urbana-Champaign, Urbana, IL, United States
Background: Cognitive impairment is common and debilitating among persons with multiple sclerosis (MS), and might be managed with exercise training. This is based on a rigorous and systematic line of research that identified progressive (both intensity and duration) treadmill walking exercise (TMWX) as an optimal exercise stimulus for improving cognition in fully-ambulatory persons with MS.
Objective: The present pilot study adopted a single-blind randomized controlled trial (RCT) design and is the first to examine the effect of a TMWX training intervention on cognition and functional MRI (fMRI) outcomes among fully-ambulatory persons with MS.
Methods: Eight fully-ambulatory females with relapsing-remitting MS were randomly assigned into exercise training intervention or waitlist control conditions. The intervention condition involved 12-weeks of supervised, progressive chronic TMWX training that was designed based on pilot work. Participants underwent measures of processing speed (i.e., Symbol Digit Modalities Test; SDMT) and cardiorespiratory fitness (i.e., peak aerobic capacity; VO2peak) before and after the 12-week period. Participants further underwent fMRI scans for measurement of resting-state functional connectivity (RSFC) between the thalamus and frontal cortical regions before and after the 12-week period.
Results: Overall, there were large intervention effects on SDMT performance (d=0.72) and VO2peak (d=0.88). There further were large intervention effects on RSFC between the thalamus and right middle frontal gyrus (MFG; d=1.92) and anterior cingulate cortex (ACC; d=1.70), respectively. The change in VO2peak was moderately associated with change in SDMT performance (r=.60), and change in RSFC between the thalamus and right MFG (r=.48) and ACC (r=.54), respectively. Further, change in SDMT was moderately associated with change in RSFC between the thalamus and right MFG (r=.42) and ACC (r=.53), respectively.
Conclusions: This small pilot RCT provides exciting proof-of-concept data supporting progressive TMWX training for potentially improving processing speed, cardiorespiratory fitness, and thalamocortical RSFC over time in fully-ambulatory persons with MS. This pattern of preliminary results seemingly supports an adaptive compensatory mechanism whereby TMWX training improves cardiorespiratory fitness, which might result in improved processing speed, which may be explained by increased thalamocortical RSFC.