Supraspinal fatigue after normoxic and hypoxic exercise in humans

•  Processes leading to fatigue occur within the exercising muscle (peripheral fatigue) and the nervous system (central fatigue). •  We asked whether central processes of fatigue would be increased after strenuous exercise in environments where oxygen availability is reduced (hypoxia) compared to the same absolute exercise intensity at sea‐level. •  Our main finding was that the contribution of central processes to fatigue was increased after exercise in hypoxia (equivalent to ∼3800 m above sea‐level). •  The greater amount of central fatigue in hypoxia was due to suboptimal neural output from the brain and was associated with reductions in oxygen availability. •  The findings provide a plausible mechanism for why exercise performance is impaired at high altitude, and might help our understanding of exercise limitation in patients with reduced oxygen delivery to the brain.

• Publication year

  2012

• Venue

  Journal of Physiology

• Publication date

  2012-04-02

• Fields of study

  Medicine, Environmental Science

• Identifiers
  DOI 10.1113/jphysiol.2012.228890PMID 22473785PMCID 3424730
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• The anaerobic threshold measurement to evaluate exercise performance.

  2015cited by this paper
• Frontal cerebral cortex blood flow, oxygen delivery and oxygenation during normoxic and hypoxic exercise in athletes

  2011cited by this paper
• Implications of group III and IV muscle afferents for high‐intensity endurance exercise performance in humans

  2011cited by this paper
• Reduced muscle activation during exercise related to brain oxygenation and metabolism in humans

  2010influential reference
• Effect of graded hypoxia on supraspinal contributions to fatigue with unilateral knee-extensor contractions.

  2010influential reference
• Alterations in Central Fatigue by Pharmacological Manipulations of Neurotransmitters in Normal and High Ambient Temperature

  2010cited by this paper
• Last Word on Point:Counterpoint: The interpolated twitch does/does not provide a valid measure of the voluntary activation of muscle

  2009cited by this paper
• Cortical voluntary activation of the human knee extensors can be reliably estimated using transcranial magnetic stimulation

  2009influential reference
• Opioid‐mediated muscle afferents inhibit central motor drive and limit peripheral muscle fatigue development in humans

  2009influential reference
• Locomotor exercise induces long-lasting impairments in the capacity of the human motor cortex to voluntarily activate knee extensor muscles.

  2009influential reference
• Voluntary activation of human knee extensors measured using transcranial magnetic stimulation

  2009cited by this paper
• Acute hypoxia impairs dynamic cerebral autoregulation: results from two independent techniques.

  2009influential reference
• Frontal and motor cortex oxygenation during maximal exercise in normoxia and hypoxia.

  2009influential reference
• Nervous System Function during Exercise in Hypoxia

  2009cited by this paper
• Cerebrovascular responses to incremental exercise during hypobaric hypoxia: effect of oxygenation on maximal performance.

  2008influential reference
• Skeletal muscle fatigue: cellular mechanisms.

  2008cited by this paper
• Severity of arterial hypoxaemia affects the relative contributions of peripheral muscle fatigue to exercise performance in healthy humans

  2007influential reference
• Effect of acute severe hypoxia on peripheral fatigue and endurance capacity in healthy humans.

  2007cited by this paper
• Effects of acute hypoxia on cerebral and muscle oxygenation during incremental exercise.

  2007cited by this paper
• Corticomotor excitability contributes to neuromuscular fatigue following marathon running in man

  2007cited by this paper
• Transcranial Doppler estimation of cerebral blood flow and cerebrovascular conductance during modified rebreathing.

  2007cited by this paper
• Cerebrovascular responses to altitude.

  2007influential reference
• Capillary-Oxygenation-Level-Dependent Near-Infrared Spectrometry in Frontal Lobe of Humans

  2007cited by this paper
• The neurobiology of muscle fatigue: 15 years later.

  2007cited by this paper
• Effect of exercise-induced arterial hypoxemia on quadriceps muscle fatigue in healthy humans.

  2006cited by this paper
• Effects of arterial oxygen content on peripheral locomotor muscle fatigue.

  2006influential reference
• EVIDENCE FOR A SUPRASPINAL CONTRIBUTION TO HUMAN MUSCLE FATIGUE

  2006cited by this paper
• Fatigue-Sensitive Afferents Inhibit Extensor but Not Flexor Motoneurons in Humans

  2006cited by this paper
• A test to establish maximum O2 uptake despite no plateau in the O2 uptake response to ramp incremental exercise.

  2006cited by this paper
• Arterial oxygenation influences central motor output and exercise performance via effects on peripheral locomotor muscle fatigue in humans

  2006cited by this paper
• Effect of exercise on cerebral perfusion in humans at high altitude.

  2005cited by this paper
• Measurement and reproducibility of strength and voluntary activation of lower‐limb muscles

  2004cited by this paper
• Reproducible measurement of voluntary activation of human elbow flexors with motor cortical stimulation.

  2004influential reference
• Demonstration of a second rapidly conducting cortico‐diaphragmatic pathway in humans

  2004cited by this paper
• Brain and central haemodynamics and oxygenation during maximal exercise in humans

  2004cited by this paper
• Measurement of voluntary activation of fresh and fatigued human muscles using transcranial magnetic stimulation

  2003influential reference
• Human neuromuscular fatigue is associated with altered Na+-K+-ATPase activity following isometric exercise.

  2002influential reference
• Spinal and supraspinal factors in human muscle fatigue.

  2001cited by this paper
• Influence of oxygen supply on activation of group IV muscle afferents after low‐frequency muscle stimulation

  2000cited by this paper
• MRI measures of middle cerebral artery diameter in conscious humans during simulated orthostasis.

  2000cited by this paper
• Altered responses of human elbow flexors to peripheral-nerve and cortical stimulation during a sustained maximal voluntary contraction

  1999cited by this paper
• Twitch interpolation of the elbow flexor muscles at high forces

  1998cited by this paper
• Neural control in human muscle fatigue: changes in muscle afferents, motoneurones and motor cortical drive [corrected].

  1998cited by this paper
• Neural control in human muscle fatigue : changes in muscle afferents , moto neurones and moto cortical drive

  1998cited by this paper
• Borg's Perceived Exertion and Pain Scales

  1998cited by this paper
• Myoelectric evidence of peripheral muscle fatigue during exercise in severe hypoxia: some references to m. vastus lateralis myosin heavy chain composition

  1997cited by this paper
• Indexes of flow and cross-sectional area of the middle cerebral artery using doppler ultrasound during hypoxia and hypercapnia in humans.

  1996cited by this paper
• Changes in motor cortical excitability during human muscle fatigue.

  1996influential reference
• Supraspinal factors in human muscle fatigue: evidence for suboptimal output from the motor cortex.

  1996cited by this paper
• Statistics notes: Calculating correlation coefficients with repeated observations: Part 1—correlation within subjects

  1995cited by this paper
• Calculating correlation coefficients with repeated observations: Part 1--Correlation within subjects.

  1995cited by this paper
• Effects of hypoxia on the discharge of group III and IV muscle afferents in cats.

  1992cited by this paper
• Stimulation of the human motor cortex through the scalp

  1991cited by this paper
• Reflex inhibition of human soleus muscle during fatigue.

  1990cited by this paper
• A new method for detecting anaerobic threshold by gas exchange.

  1986cited by this paper
• Noninvasive transcranial Doppler ultrasound recording of flow velocity in basal cerebral arteries.

  1982cited by this paper
• A test to determine parameters of aerobic function during exercise.

  1981cited by this paper
• Voluntary strength and fatigue

  1954cited by this paper
• HIGHLIGHTED TOPIC Fatigue Mechanisms Determining Exercise Performance Convective oxygen transport and fatigue

  year unknowncited by this paper

• Application of Minimum Exercise Model to the Hypoxic Environment.

  2025cites this paper
• Cerebral cortical activation and muscle performance during blood flow restriction training after ischemic stroke: A randomised functional near-infrared spectroscopy study

  2025cites this paper
• Cross-Sectional Study on Functional Characteristics of Elbow Joints in Stroke Patients with Hemiplegia in Plateau Environments

  2025cites this paper
• Neuromuscular Fatigue Induced by Cycling at a Fixed Level of Perceived Effort: Effects of Different Purported Hypoxic Methods

  2025cites this paper
• Hypoxia and Cognitive Ability in Humans: A Systematic Review and Meta-Analysis

  2025cites this paper
• Cardiorespiratory and oxygenation responses in iron-deficient anemic women during whole-body exercise under moderate hypoxia.

  2025cites this paper
• Arterial desaturation rate does not influence self‐selected knee extension force but alters ventilatory response to progressive hypoxia: A pilot study

  2024cites this paper
• Effects of acute simulated altitude on the maximal lactate steady state in humans.

  2024cites this paper
• The effects of exercise, heat-induced hypo-hydration and rehydration on blood–brain-barrier permeability, corticospinal and peripheral excitability

  2024cites this paper
• The Effect of Acute Physical Fatigue on Information Processing, Pain Threshold and Muscular Performance

  2024cites this paper
• Electrical stimulation for investigating and improving neuromuscular function in vivo: Historical perspective and major advances.

  2023cites this paper
• Altitude-induced effects on neuromuscular, metabolic and perceptual responses before, during and after a high-intensity resistance training session

  2023cites this paper
• The severity of acute hypoxaemia determines distinct changes in intracortical and spinal neural circuits

  2023cites this paper
• Quadriceps fatigue during hypoxic and ischemic knee-extension exercise is similar in males and females.

  2023cites this paper
• Electromyographic signature of isometric squat in the highest refuge in Europe

  2023cites this paper
• Cerebral blood flow and immediate and sustained executive function benefits following single bouts of passive and active exercise.

  2023cites this paper
• Post‐fatigue ability to activate muscle is compromised across a wide range of torques during acute hypoxic exposure

  2022influential citation
• Fatigue and Human Performance: An Updated Framework

  2022cites this paper
• General Neural Process in Cycling Exercise

  2022cites this paper
• Cognitive fatigue due to exercise under normobaric hypoxia is related to hypoxemia during exercise

  2022cites this paper
• Time course recovery of cerebral blood velocity metrics post aerobic exercise: A systematic review.

  2022cites this paper
• Physiological Function during Exercise and Environmental Stress in Humans—An Integrative View of Body Systems and Homeostasis

  2022cites this paper
• Repeated Ischemic Preconditioning Effects on Physiological Responses to Hypoxic Exercise.

  2022cites this paper
• The Exercising Brain: An Overlooked Factor Limiting the Tolerance to Physical Exertion in Major Cardiorespiratory Diseases?

  2022cites this paper
• The Reliability of Transcranial Magnetic Stimulation-Derived Corticomotor Inhibition as a Brain Health Evaluation Tool in Soccer Players

  2022influential citation
• Neuromuscular fatigability at high altitude: Lowlanders with acute and chronic exposure, and native highlanders

  2022cites this paper
• Effect of Paprika Xanthophyll Supplementation on Cognitive Improvement in a Multitasking Exercise: A Pilot Study for Middle-Aged and Older Adults

  2022cites this paper
• Plyometric Training in Normobaric Hypoxia improves Jump Performance

  2021cites this paper
• Self-Selected Motivational Music Enhances Physical Performance in Normoxia and Hypoxia in Young Healthy Males

  2021cites this paper
• Is a verification phase useful for confirming maximal oxygen uptake in apparently healthy adults? A systematic review and meta-analysis.

  2021cites this paper
• Declines in muscle contractility and activation during isometric contractions of the knee extensors vary with contraction intensity and exercise volume

  2021cites this paper
• Severe acute hypoxia impairs recovery of voluntary muscle activation after sustained submaximal elbow flexion

  2021cites this paper
• Effects of graded hypoxia during exhaustive intermittent cycling on subsequent exercise performance and neuromuscular responses

  2021cites this paper
• Effects of induced local ischemia during a 4-km cycling time trial on neuromuscular fatigue development.

  2021cites this paper
• Short-term hypoxic resistance training improves muscular performance in untrained males

  2021cites this paper
• Effects of Repeated Sprint Training in Hypoxia on Physical Performance Among Athletes: A Systematic Review

  2021cites this paper
• Neuromuscular responses to fatiguing locomotor exercise

  2020cites this paper
• Oxygen availability affects exercise capacity, but not neuromuscular fatigue characteristics of knee extensors, during exhaustive intermittent cycling

  2020influential citation
• Central and peripheral muscle fatigue following repeated‐sprint running in moderate and severe hypoxia

  2020cites this paper
• Influence of exertional hypoxemia on cerebral oxygenation in fibrotic interstitial lung disease.

  2020cites this paper
• Neuromuscular and perceptual responses during repeated cycling sprints—usefulness of a “hypoxic to normoxic” recovery approach

  2020cites this paper
• Specific motor cortex hypoexcitability and hypoactivation in COPD patients with peripheral muscle weakness

  2020cites this paper
• Neuromuscular Fatigue of Cycling Exercise in Hypoxia

  2020cites this paper
• Use of transcranial magnetic stimulation to assess relaxation rates in unfatigued and fatigued knee-extensor muscles

  2020cites this paper
• Time course of neuromuscular responses to acute hypoxia during voluntary contractions

  2020cites this paper
• Cerebral haemodynamics and oxygenation during whole‐body exercise over 5 days at high altitude

  2020cites this paper
• Oxygen availability affects exercise capacity, but not neuromuscular fatigue characteristics of knee extensors, during exhaustive intermittent cycling

  2020cites this paper
• The effects of hyperoxia on repeated sprint cycling performance & muscle fatigue.

  2019cites this paper
• Cycling Performed on an Innovative Ergometer at Different Intensities-Durations in Men: Neuromuscular Fatigue and Recovery Kinetics.

  2019cites this paper
• A Systematic Review of Integrated Functional Near-Infrared Spectroscopy (fNIRS) and Transcranial Magnetic Stimulation (TMS) Studies

  2019influential citation
• The effect of severe and moderate hypoxia on exercise at a fixed level of perceived exertion

  2019cites this paper
• Mental fatigue independent of boredom and sleepiness does not impact self-paced physical or cognitive performance in normoxia or hypoxia

  2019influential citation
• The effect of acute consumption of non-specific COX-inhibitors on neuromuscular fatigue and exercise performance

  2019cites this paper
• Liver CEBPβ Modulates the Kynurenine Metabolism and Mediates the Motility for Hypoxia-Induced Central Fatigue in Mice

  2019cites this paper
• Protective inhibition and workability during extreme human activity

  2019cites this paper
• Corticospinal excitability changes following downhill and uphill walking

  2019cites this paper
• Regulation of Cerebral Blood Flow with Emphasis on Age and Environment

  2019influential citation
• Effects of endurance cycling training on neuromuscular fatigue in healthy active men. Part II: Corticospinal excitability and voluntary activation

  2018cites this paper
• Electrophysiological and SCAT 5 characteristics of contact vs non-contact sport athletes

  2018cites this paper
• Neural basis for reduced executive performance with hypoxic exercise

  2018cites this paper
• Influence des modalités de contraction musculaire sur les effets neuroplastiques de l'exercice

  2018cites this paper
• Sodium bicarbonate as an ergogenic aid in acute moderate hypoxic conditions : the effect on severe intensity exercise

  2018cites this paper
• The ‘sensory tolerance limit’: A hypothetical construct determining exercise performance?

  2018cites this paper
• Short-term effects of non-invasive ventilation on cerebral blood flow and cognitive function in COPD.

  2018cites this paper
• Neural Adaptations to Endurance Training

  2018cites this paper
• Hypoxia and Fatigue Impair Rapid Torque Development of Knee Extensors in Elite Alpine Skiers

  2018cites this paper
• Effect of environmental feedbacks on pacing strategy and affective load during a self-paced 30 min cycling time trial

  2018cites this paper
• Effect of acute exposure to toluene on cortical excitability, neuroplasticity, and motor learning in healthy humans

  2018cites this paper
• Caffeine and Placebo Improved Maximal Exercise Performance Despite Unchanged Motor Cortex Activation and Greater Prefrontal Cortex Deoxygenation

  2018cites this paper
• Effects of endurance training on neuromuscular fatigue in healthy active men. Part I: Strength loss and muscle fatigue

  2018cites this paper
• High-intensity exhaustive exercise reduces long-interval intracortical inhibition

  2018cites this paper
• Corticospinal excitability during fatiguing whole body exercise.

  2018influential citation
• On the head: the true impact of routine head strikes in sport

  2018cites this paper
• Performance Fatigability: Mechanisms and Task Specificity.

  2018cites this paper
• Intensity-dependent effects of cycling exercise on corticospinal excitability in healthy humans: a pilot study

  2017cites this paper
• Exercise-induced Fatigue in Severe Hypoxia after an Intermittent Hypoxic Protocol

  2017influential citation
• Effects of high-altitude exposure on supraspinal fatigue and corticospinal excitability and inhibition

  2017cites this paper
• Cortical voluntary activation testing methodology impacts central fatigue

  2017cites this paper
• Recovery of central and peripheral neuromuscular fatigue after exercise.

  2017cites this paper
• Central Factors Contribute to Knee Extensor Strength Loss after 2000-m Rowing in Elite Male and Female Rowers

  2017cites this paper
• Endurance capacity and neuromuscular fatigue following high‐ vs moderate‐intensity endurance training: A randomized trial

  2017cites this paper
• Modulation of specific inhibitory networks in fatigued locomotor muscles of healthy males

  2017cites this paper
• Neuromuscular Fatigue during Prolonged Exercise in Hypoxia

  2017influential citation
• Maximal Voluntary Activation of the Elbow Flexors Is under Predicted by Transcranial Magnetic Stimulation Compared to Motor Point Stimulation Prior to and Following Muscle Fatigue

  2017cites this paper
• Rate dependent influence of arterial desaturation on self-selected exercise intensity during cycling

  2017cites this paper
• Influence des mécanismes de régulation de la fatigue neuromusculaire sur la performance motrice

  2017influential citation
• UBC‐Nepal expedition: acclimatization to high‐altitude increases spinal motoneurone excitability during fatigue in humans

  2017cites this paper
• Compromised Cerebrovascular Regulation and Cerebral Oxygenation in Pulmonary Arterial Hypertension

  2017cites this paper
• Clamping end-tidal carbon dioxide during graded exercise with control of inspired oxygen.

  2016cites this paper
• Intensity-Dependent Contribution of Neuromuscular Fatigue after Constant-Load Cycling.

  2016cites this paper
• Severe hypoxia during incremental exercise to exhaustion provokes negative post-exercise affects.

  2016cites this paper
• Modeling Intermittent Cycling Performance in Hypoxia Using the Critical Power Concept.

  2016cites this paper
• Effects of caffeine on neuromuscular fatigue and performance during high-intensity cycling exercise in moderate hypoxia

  2016cites this paper
• Bilateral Knee Extensor Fatigue Modulates Force and Responsiveness of the Corticospinal Pathway in the Non-fatigued, Dominant Elbow Flexors

  2016influential citation
• Increased PIO2 at Exhaustion in Hypoxia Enhances Muscle Activation and Swiftly Relieves Fatigue: A Placebo or a PIO2 Dependent Effect?

  2016cites this paper
• Are There Critical Fatigue Thresholds? Aggregated vs. Individual Data

  2016cites this paper
• Movement-Related Cortical Potential Amplitude Reduction after Cycling Exercise Relates to the Extent of Neuromuscular Fatigue

  2016cites this paper
• Central and peripheral fatigue following non‐exhaustive and exhaustive exercise of disparate metabolic demands

  2016influential citation
• Does cerebral hypoxia facilitate central fatigue?

  2016cites this paper
• Measurement of voluntary activation based on transcranial magnetic stimulation over the motor cortex.

  2016cites this paper