Acute Effects of Treadmill Walking
Exercise on Inhibitory Control in MS:
Do Exercise Intensity and Thermosensitivity Matter?
Brian M. Sandroff1 & Robert W. Motl2
1Kessler
Foundation, West Orange, NJ
2University of Illinois at Urbana-Champaign, Urbana, IL
EXERCISE NEUROSCIENCE
LABORATORY
Disclosures
• The authors report no conflicts of interests
• The work presented in this presentation was not funded
by an external grant, but was completed in partial
fulfillment of the first author’s graduate degree under
the supervision of second author.
Cognitive Impairment in MS
• Cognitive impairment is prevalent, disabling, and poorlymanaged in multiple sclerosis (MS)
– Upwards of 50% demonstrate
cognitive impairment1
– Impairment in domains of CPS,
executive function, etc.2
– Associated with negative health
outcomes3
– No FDA-approved treatment for
cognitive impairment in MS (e.g.,
symptomatic or DMTs)4
– Studies involving cognitive
rehabilitation have been conflicting4
1
Chiaravalloti & DeLuca, 2008; 2 Prakash et al., 2008; 3 Benedict et al., 2005;
4
Amato et al., 2013;
Exercise Training and Cognition in MS
• Inconsistent evidence from 3 RCTs
of exercise training and cognition
in MS:5-7
• Not in-line with literature from the
general population on exercise and
cognitive function8
• Discrepancy might be due to
exercise stimuli
• Not well-studied in MS
5
Oken et al., 2004; 6 Romberg et al., 2005; 7 Briken et al., 2014; 8 Voss et al., 2011
Optimal Exercise Stimulus?
• For optimally improving cognition in MS, recent
evidence suggests:
• Domain of exercise training?
• Aerobic exercise9,10
• Which domains of cognitive functioning?
• CPS/inhibitory control9-11
• What about disability status?
• Fully-ambulatory persons with MS10,12,13
• What type (modality) of exercise?
• Treadmill walking exercise14
9
Motl & Sandroff, 2012; 10 Sandroff et al., 2015, Neurorehabil Neural Repair; 11 Sandroff et al., 2015, Arch Clin Neuropsychol; 12 Sandroff
et al., 2013; 13 Sandroff et al., 2014; 14 Sandroff et al., 2015, J Clin Exp Neuropsychol;
What Next?
• Prior to initiating RCT, necessary to examine the dosedependent effects of varying intensities of treadmill
walking exercise on inhibitory control
• Critical for better delineating the optimal exercise
stimulus for improving cognition in MS
Acute Exercise and Cognition
• One potential starting point is by examining the effects
of acute aerobic exercise on cognitive function
• Assumption: acute effects of single bouts of exercise on
cognition will be additive and cumulative during
longitudinal interventions15
• This approach is in parallel with approach for physiological
adaptations to exercise training15
• Importance: increases the potential for meaningful
improvements in cognition
15
Haskell, 1994;
Objective/Hypothesis
• Compare acute effects of light, moderate, and vigorous
intensity treadmill walking exercise on inhibitory control
in 24 persons with MS using a within-subjects, repeatedmeasures design
• Hypothesis: moderate intensity treadmill walking
exercise would exert the largest beneficial effects on
inhibitory control relative to quiet rest16
16
McMorris & Hale, 2012;
Experimental Setup
• N=24 persons with MS
– EDSS ≤ 4.0
– Experimental conditions: 20 minutes of light, moderate,
and vigorous intensity treadmill walking exercise, quiet
rest control
– Cognitive domain: Inhibitory control (modified flanker
task)
– Administered modified flanker task immediately before and
after exercise bouts and quiet rest
Modified Flanker Task
• Computerized measure of inhibitory
control (i.e., interference control)17
– Included in NIH Toolbox for Cognition18
• Particularly sensitive to acute
aerobic exercise14,16,19
• Requires participants to inhibit
task-irrelevant information in order
to correctly respond to centrally
presented target stimulus
• Target stimulus presented amid
congruent or incongruent flanking
stimuli
17 Eriksen
& Eriksen, 1974; 18 Weintraub et al., 2013; 19 Hillman et al., 2009;
Modified Flanker Task—Outcomes
• Mean reaction time (RT) in ms
• Interference control score:
– Provides a measure of the cost of
interfering stimuli on inhibitory
control
– Incongruent RT minus congruent RT
Procedure
1.
2.
3.
4.
5.
1.
2.
3.
4.
Session 1 (Baseline):
Informed Consent
Flanker Task
EDSS
Incremental Exercise Test (Important for precise prescription of exercise intensity)
Flanker Task
Sessions 2-5:
Light Intensity
Sessions 2-5:
Moderate Intensity
Sessions 2-5:
Vigorous Intensity
Quiet Rest
Flanker Task
Treadmill Walking
Flanker Task
1.
2.
3.
4.
1.
2.
3.
4.
Quiet Rest
Flanker Task
Treadmill Walking
Flanker Task
Quiet Rest
Flanker Task
Treadmill Walking
Flanker Task
Sessions 2-5:
Quiet Rest
1.
2.
3.
4.
Quiet Rest
Flanker Task
Quiet Rest
Flanker Task
Within-subjects design; order of conditions
randomized and counterbalanced
Primary Results
• 4 × 2 × 2 ANOVA: Statistically significant 3-way
condition × time × congruency interaction on RT
(F(3,69)=4.27, p=.01, ηp2=.16)
– Overall pre-to-post reductions in the cost of interfering stimuli on
RT for light (d=-0.63), moderate (d=-0.45), and vigorous (d=0.63) intensity treadmill walking exercise compared with quiet
rest
• 3 × 2 × 2 follow-up ANOVA: Non-statistically significant
condition × time × congruency interaction on RT
(F(2,46)=0.88, p=.42, ηp2=.04)
– Similar pre-to-post reductions in cost of interfering stimuli on RT
for light, moderate, and vigorous intensity treadmill walking
exercise
Interference Control of RT
Interference Control-RT (ms)
65
60
55
Light
Moderate
50
Vigorous
Rest
45
40
Pre
Post
Time
What Might This Mean?
• General effects of varying intensities of treadmill
walking exercise relative to quiet rest on speed-related
measures of inhibitory control
• Light, moderate, and vigorous intensity treadmill
walking exercise might be exercise stimuli for
optimally improving interference control of RT in fullyambulatory persons with MS
What About Thermosensitivity?
• Growing concern that increases in core body
temperature (as little as 0.5°C)20 result in worsening
of cognitive and motor symptoms in thermosensitive
persons with MS21,22
• Do increases in core body temperature negate the
potentially beneficial effects of treadmill walking
exercise on inhibitory control in thermosensitive
persons with MS?
20
Rasminsky, 1973; 21 Romberg et al., 2012; 22 Hamalainen et al., 2012;
Follow-Up Study: Thermosensitivity
• N=14 thermosensitive persons with MS
– EDSS ≤ 4.0
– Within-subjects, repeated-measures design
– Experimental conditions: 20 minutes of vigorous intensity
treadmill walking exercise, quiet rest control
– Cognitive domain: Inhibitory control (modified flanker task)
– Measured core body temperature using ingestible sensor
capsules and wireless data recorder
• Measured every 10-seconds; computed minute-by-minute averages
– Administered flanker task immediately before and after
exercise bout and quiet rest
Primary Results
• Core Body Temperature: Statistically significant 2-way
condition × time interaction on core body temperature
(F(1,13)=83.13, p<.01, ηp2=.87)
– Vigorous intensity treadmill walking exercise was associated with
increased core body temperature over time (+0.6°C), whereas
there was minimal change with quiet rest (-0.1°C)
• Inhibitory Control: Statistically significant 3-way
condition × time × congruency interaction on RT
(F(1,13)=5.25, p=.04, ηp2=.29)
– Overall pre-to-post reductions in the cost of interfering stimuli on
RT for vigorous intensity treadmill walking exercise compared
with quiet rest
What Might This Mean?
• Exercise-related increases in core body temperature
over the ‘critical threshold’ of 0.5°C did not negate
improvements in cognitive performance in
thermosensitive persons with MS
Implications for RCT
• Throughout exercise training intervention, persons with
MS might accumulate cognitive benefits at all intensities
– Seemingly independent of exercise-related increases in core
body temperature
• Exercise prescription
– Increasing exercise intensity for improving cardiorespiratory
fitness (i.e., exercise progression)23
• Participant compliance
– Low-fit participants can start slow and progress gradually,
while continually accruing small acute improvements in
cognitive performance
23
American College of Sports Medicine, 2013;
Implications for Progressive MS
• Severe ambulatory impairment  barrier to exercise
participation24
• Preliminary RCT evidence of aerobic exercise on verbal
memory and alertness outcomes in progressive MS7
• No systematically developed exercise stimuli in
progressive MS25
– Acute exercise approach may be advantageous starting point
– Effects of adaptive modalities of aerobic exercise on
cognition?
24
Motl, 2010; 25 Sandroff, 2015;
Strengths and Limitations
• Strengths:
– Within-subjects, repeated-measures designs
– Systematic approach for developing better RCTs of exercise
and cognition in MS
• Limitations:
– Relatively small sample sizes
– Did not control for possible influences of age, sex, disability
status on acute exercise effects on inhibitory control
• Within-subjects design accounts for this26
26 Stevens,
1996;
Acknowledgements
Everyone in attendance
ACTRIMS
ENRL Director: Prof. Rob Motl
Senior VP for Research and Training at KF: Dr. John
DeLuca
• Research staff of post-docs, grads, URAs, and project
coordinators
• Research participants
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