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Our Brains and Fatigue
Guillaume MilletProfessor, Faculty of Kinesiology
October 4, 2016
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Welcome
Webinar series by University of Calgary scholars Information presented is a summary of the
scholars’ research Please submit questions throughout the duration of
the webinar Keep the conversation live on Twitter during the
webinar using #exploreUCalgary
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Welcome
Professor at the University of Calgary’s Faculty of Kinesiology
Head of the Neuromuscular Fatigue Lab within the faculty’s Human Performance Laboratory
Research interests are in the areas of exercise physiology, neuromuscular function and fatigue
Guillaume Millet
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Physiological, neurophysiological and biomechanical factors associated with fatigue in both:
Patients (neuromuscular diseases, cancer) Extreme exercise
www.ucalgary.ca/nmfl
Neuromuscular Fatigue Laboratory
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Origin of acute fatigue: central vs peripheral
Central fatigue in ultramarathon and at altitude
Limits of current tools to measure fatigue
Acute fatigue resistance: does it play a role in subjective chronic cancer-related fatigue?
Outline
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…leading to an increase of psychological/energy cost to perform an exercise
and/or to a decrease of maximal strength/power
Changes in (physical, mental) capabilities…
…whether or not the task can be sustained.
Definition of fatigue
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Inte
nsity
Maximal strength
Fatigue
Time
100
75
50
25
0
target
Neuromuscular Fatigue Laboratory
Fatigue vs exhaustion
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Inte
nsity
Maximal strength
Fatigue
Time
100
75
50
25
0
Task-Failure
target
Neuromuscular Fatigue Laboratory
Fatigue vs exhaustion
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DurationIntensity
Mode of contractionTem
peratureMuscle typology
Continuous vs intermittent
Fitness level
Local vs global
SexAge
Nut
rition
Altitude
Task dependency
Etc.Neuromuscular Fatigue Laboratory
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Definition of fatigue
Time
Func
tiona
l cap
acity
Workload Fatigue
Neuromuscular Fatigue Laboratory
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Etiology of neuromuscular fatigue: central vs peripheral
Neuromuscular Fatigue Laboratory
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Central fatigue
Motor planning
Motor output
Motoneuron pool output
Motor axon conduction
Neuromuscular junctionPeripheral
fatigueMuscle
Feed
back
Interaction central/peripheral
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Tools to evaluate NM function
Adapted from Millet et al. Eur J Appl Physiol 2011
Sensory Ia afferent axone
a-Mn axoneEMG
Force/Movement
Motor Cortex
Spinal level
Muscle
Transcranial Magnetic Stimulation
Peripheral Nerve Stimulation
Muscle Stimulation
Cervicomedullary Stimulation
Central
Peripheral
Neuromuscular Fatigue Laboratory
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Different types of central fatigue
Fatigue = maximal strength
Cognitive Function
Subjective Fatigue (RPE)
Intermuscular Coordination
Decrease of %VA
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force
stimulus
MVC
Merton J Physiol 1954
superimposed twitch
restingtwitch
Maximal voluntary activation(nerve stimulation)
From Janet Taylor, Neuroscience Research Australia
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force
stimulus
MVC
Merton J Physiol 1954
superimposed twitch
restingtwitch
Maximal voluntary activation(nerve stimulation)
From Janet Taylor, Neuroscience Research Australia
restingtwitch
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Transcranial Magnetic Stimulation (TMS)
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Exercise duration and central fatigue
DurationIntensity
Mode of contraction
Temperature
Muscle typology
Continuous vs intermittent
Fitness level
Local vs global
GenderAge
Nut
rition
Altitude
Neuromuscular Fatigue Laboratory
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Central fatigue in ultra-marathon
165 km
D+/-: 9000m
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Central fatigue in ultra-marathon
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Change in voluntary activation?
PRE
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Change in voluntary activation?
PRE
POST
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Origin of fatigue
peripheral fatigue
(muscular)
central fatigue (neural)
Not as simple as that…
Neuromuscular Fatigue Laboratory
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Causes of central fatigue
Adapted from Janet Taylor, Neuroscience Research Australia
2.
Motoneurone
properties
3. Afferent input
1. Corticospinal
drive(Supraspinal
fatigue)
muscle spindlesexcitation
tendon organsinhibition
recurrentinhibitiongroup III & IV
fatigue-sensitive muscle afferents
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Altitude (hypoxia)
DurationIntensity
Mode of contraction
Temperature
Muscle typology
Continuous vs intermittent
Fitness level
Local vs global
GenderAge
Nut
rition
Altitude
Neuromuscular Fatigue Laboratory
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Vergès et al. 2012 Am J Physiol Regul Integr Comp Physiol
Altitude (hypoxia)
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4 simulated altitudes
oxygenation
Cuff (total ischemia)
Direct effect of hypoxia on central drive
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50
55
60
65
70
Befcuff
1min
2min
3min
4min
5min
#1 #2 #3 #4 #5 #6 #7 #8 #9 #10 #11 Last
cere
bral
TO
I (%
)
30% 21% 14% 9%
Cerebral oxygenation
Millet et al. J Appl Physiol, 2012
Direct effect of hypoxia on central drive
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0
10
20
30
40
50
60
70
Befcuff
1min
2min
3min
4min
5min
#1 #2 #3 #4 #5 #6 #7 #8 #9 #10 #11 Last
mus
cle
TOI (
%)
30% 21% 14% 9%
Muscle oxygenation
Millet et al. J Appl Physiol, 2012
Direct effect of hypoxia on central drive
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hyperNorm
ModHyp
SevHyp
101214161820 *
# Re
petiti
ons
Millet et al. J Appl Physiol, 2012
Direct effect of hypoxia on central drive
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hyperNorm
ModHyp
SevHyp
101214161820 *
# Re
petiti
ons
Millet et al. J Appl Physiol, 2012
Direct effect of hypoxia on central drive
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Neuromuscular function during
exerciseTy
pica
l ex
erci
sePr
oble
ms
Adva
ntag
esSingle joint, isometric
contraction
• Measurements during exercise
• Mostly upper body and/or single-limb exercise
• Isometric• Does not represent exercise performed
in sports/rehabilitation.
Fatigue assessment
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Fatigue induced by 45 s sustained MVC of adductor pollicis
Sheean et al. Brain, 1997, 120: 299-315
Volu
ntar
y ac
tivati
on (%
)
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Move the subject
from the bike to
the testing chair
Other option
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Neuromuscular function during
exercise
Neuromuscular function before
and after exercise
Typi
cal
exer
cise
Prob
lem
sAd
vant
ages
Single joint, isometric contraction
Human locomotion : walking, cycling
• Measurements during exercise • Ecological situation• Represents the reality of daily
life/rehabilitation in patients.
• Mostly upper body and/or single-limb exercise
• Isometric• Does not represent exercise performed
in sports/rehabilitation.
• Installation time required to test subjects
• Depending on the type of exercise, determining factors of fatigue and exhaustion (exercise cessation) might be completely misinterpreted.
Fatigue assessment
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Problem of
recovery (delay)
Other option
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Effect of short recovery on muscle fatigue
38
PRE 20 40 60 80 100 1 2 4 8% fatiguing exercise Recovery (min)
100
90
80
70
60
50
40
30
Torq
ue (%
initi
al v
alue
)High frequency tetanusHigh frequency doubletSingle twitch
Froyd et al. J Physiol 2013
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Testing NMF during and immediately after whole-body exercise
Neuromuscular function during
exercise
Neuromuscular function before
and after exercise
Fatigue assessment
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Innovative ergometer
VO2
TMS
FNES
CMEP
EMG
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Innovative ergometer
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Chronic fatigue
Chronic Fatigue: even more complicated
e.g. Cancer-Related Fatigue Severe, unrelenting feeling of fatigue, that is not
improved by rest or sleep
CRF affects 70-100% of individuals with cancer
Last up to months/years post cancer (up to 30% of survivors)
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Cancer-related fatigue
Physical activity is important in fatigue managementCramp & Daniel, 2008, Cochrane Reviews
VICIOUS CYCLE OF FATIGUE
Fatigue is the #1 reported side effect by cancer patients and has been found to be the most distressing treatment-related symptom.
• 94% of oncologists treat pain, only 5% treat fatigue
-National Cancer Institute, 2007
From Nicole Culos-Reed
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Acute neuromuscular fatigue and chronic fatigue in cancer?
Andrews et al. Fatigue in Cancer 2004
Anemia – cachexia – reduction of specific force
Cancer and cancer treatment
Altered muscle
metabolism
Peripheral (muscular)
mechanisms
Central (brain)
mechanisms
physical performance and fatigue
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Definition of fatigue
Time
Func
tiona
l cap
acity
Workload Fatigue
Neuromuscular Fatigue Laboratory
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Effect of workload on fatigue
Time
Workload
Fatigue and recovery light exerciseHeavy exercise
Neuromuscular Fatigue Laboratory
Func
tiona
l cap
acity
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Deteriorated fatigue resistance
Time
Func
tiona
l cap
acity
Workload
Normal fatigue resistanceDeteriorated fatigue resistance
Neuromuscular Fatigue Laboratory
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Time
Func
tiona
l cap
acity
Fatigue accumulation
Daily workloads Normal fatigue resistance Deteriorated fatigue resistance
Chronic vs acute fatigue
Neuromuscular Fatigue Laboratory
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Chronic fatigue
Chronic Fatigue: even more complicated
e.g. Cancer-Related Fatigue Severe, unrelenting feeling of fatigue, that is not
improved by rest or sleep
CRF affects 70-100% of individuals with cancer
Last up to months/years post cancer (up to 30% of survivors)
Subjective
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PNS
CNS
Muscle
1. Sensory pathway from periphery
2. Copy of efferent signal to sensory
cortex
May contribute to chronic fatigue
Neuromuscular vs subjective fatigue?
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Hypothesized mechanisms
Direct
Physiologic• Voluntary activation• Muscle strength• Muscle endurance• Cardiopulmonary fitness• Body composition• Fatiguability• Muscle efficiency
Biologic/hematologic• Inflammatory response• Muscle damage• Metabolic function
(insulin resistance)• Endocrine function• Immune function• Anemia (brain and
muscle oxygenation)
Indirect
Psychological• Anxiety• Depression• Distress• Cognition
Social• Social
interaction• Positive • reinforcement
Behavioral• Sleep quantity and quality• Appetite
Adapted from McNeely et al. 2010
Cancer-related fatigue
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Hypothesized mechanisms
Direct
Physiologic• Voluntary activation• Muscle strength• Muscle endurance• Cardiopulmonary fitness• Body composition• Fatiguability• Muscle efficiency
Biologic/hematologic• Inflammatory response• Muscle damage• Metabolic function
(insulin resistance)• Endocrine function• Immune function• Anemia (brain and
muscle oxygenation)
Indirect
Psychological• Anxiety• Depression• Distress• Cognition
Social• Social
interaction• Positive • reinforcement
Behavioral• Sleep quantity and quality• Appetite
Adapted from McNeely et al. 2010
Cancer-related fatigue
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Makes no sense if not considering… the Big Picture
Anemia
Pain
Activity Level
Mal-nutrition
Sleep Disorders
Co-Morbidities
Neuro-muscular Function
Cachexia
Inflamm. & oxidative
stress
Psycho-social environment
Low acute fatigue resistance cannot fully explain directly chronic fatigue… but can contribute (provided it is appropriately measured)
Cancer-related fatigue
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Tailoring training to fatigue causes
Testing Intervention
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Tailoring training to fatigue causes
Testing Intervention
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Examples
• Social interaction
• Sleep quality and quality
• Inflammatory response
• Muscle damage• Metabolic function• Immune function
• Voluntary activation
• Cardiopulmonary fitness
Outdoor endurance training
late afternoon
Strength training high volume
Electromyostimulation
• Cachexia
Strength training low volume
Supervised group training
Low intensity endurance training
High intensity endurance training
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Take home message
Goal: better understand Chronic Fatigue (e.g. CRF) to better treat it!
Tailor training interventions
Testing tools Training tools Tested on athletes
Ultimately enhance the quality of life of patients
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Acknowledgements
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Upcoming webinars
No Pain No Gain? The Sociology of Sports, October 6, 12-1 p.m. MST
The Race to Prevent Running Injuries, October 11, 12-1 p.m. MST
Inside the Mind of an Olympian, October 13, 12-1 p.m. MST
Knocking Out Concussions in Sports, October 20, 10-11 a.m. MST
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Thank you
Sign up for other UCalgary webinars,download our eBooks,
and watch videos on the outcomes of our scholars’ research at
ucalgary.ca/explore/collections
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