Our brains and fatigue

Our Brains and Fatigue

Guillaume MilletProfessor, Faculty of Kinesiology

October 4, 2016

Welcome

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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

Physiological, neurophysiological and biomechanical factors associated with fatigue in both:

Patients (neuromuscular diseases, cancer) Extreme exercise

www.ucalgary.ca/nmfl

Neuromuscular Fatigue Laboratory

http://www.ucalgary.ca/nmfl

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

…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

Inte

nsity

Maximal strength

Fatigue

Time

100

75

50

25

0

target


Fatigue vs exhaustion

Inte

nsity

Maximal strength

Fatigue

Time

100

75

50

25

0

Task-Failure

target


Fatigue vs exhaustion

DurationIntensity

Mode of contractionTem

peratureMuscle typology

Continuous vs intermittent

Fitness level

Local vs global

SexAge

Nut

rition

Altitude

Task dependency

Etc.Neuromuscular Fatigue Laboratory


Time

Func

tiona

l cap

acity

Workload Fatigue


Etiology of neuromuscular fatigue: central vs peripheral


Central fatigue

Motor planning

Motor output

Motoneuron pool output

Motor axon conduction

Neuromuscular junctionPeripheral

fatigueMuscle

Feed

back

Interaction central/peripheral

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


Different types of central fatigue

Fatigue = maximal strength

Cognitive Function

Subjective Fatigue (RPE)

Intermuscular Coordination

Decrease of %VA

force

stimulus

MVC

Merton J Physiol 1954

superimposed twitch

restingtwitch

Maximal voluntary activation(nerve stimulation)

From Janet Taylor, Neuroscience Research Australia

force

stimulus

MVC

Merton J Physiol 1954

superimposed twitch

restingtwitch

Maximal voluntary activation(nerve stimulation)

From Janet Taylor, Neuroscience Research Australia

restingtwitch

Transcranial Magnetic Stimulation (TMS)

Exercise duration and central fatigue

DurationIntensity

Mode of contraction

Temperature

Muscle typology


Fitness level

Local vs global

GenderAge

Nut

rition

Altitude


Central fatigue in ultra-marathon

165 km

D+/-: 9000m

Central fatigue in ultra-marathon

Change in voluntary activation?

PRE

Change in voluntary activation?

PRE

POST

Origin of fatigue

peripheral fatigue

(muscular)

central fatigue (neural)

Not as simple as that…


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

Altitude (hypoxia)

DurationIntensity

Mode of contraction

Temperature

Muscle typology


Fitness level

Local vs global

GenderAge

Nut

rition

Altitude


Vergès et al. 2012 Am J Physiol Regul Integr Comp Physiol

Altitude (hypoxia)

4 simulated altitudes

oxygenation

Cuff (total ischemia)

Direct effect of hypoxia on central drive

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


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



hyperNorm

ModHyp

SevHyp

101214161820 *

# Re

petiti

ons



hyperNorm

ModHyp

SevHyp

101214161820 *

# Re

petiti

ons



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

Fatigue induced by 45 s sustained MVC of adductor pollicis

Sheean et al. Brain, 1997, 120: 299-315

Volu

ntar

y ac

tivati

on (%

)

Move the subject

from the bike to

the testing chair

Other option


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

Problem of

recovery (delay)

Other option

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

Testing NMF during and immediately after whole-body exercise


exercise

Neuromuscular function before

and after exercise

Fatigue assessment

Innovative ergometer

VO2

TMS

FNES

CMEP

EMG

Innovative ergometer

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)

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

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


Time

Func

tiona

l cap

acity

Workload Fatigue


Effect of workload on fatigue

Time

Workload

Fatigue and recovery light exerciseHeavy exercise


Func

tiona

l cap

acity

Deteriorated fatigue resistance

Time

Func

tiona

l cap

acity

Workload

Normal fatigue resistanceDeteriorated fatigue resistance


Time

Func

tiona

l cap

acity

Fatigue accumulation

Daily workloads Normal fatigue resistance Deteriorated fatigue resistance

Chronic vs acute fatigue


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

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?

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


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


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)


Tailoring training to fatigue causes

Testing Intervention

Tailoring training to fatigue causes

Testing Intervention

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

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

Acknowledgements

[email protected]

www.ucalgary.ca/nmfl

Merci

Guillaume Millet

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

Thank you

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Our brains and fatigue