Limitation of physical performance in a muscle fatiguing handgrip exercise is mediated by thalamo‐insular activity

In this study, we investigated central/supraspinal processes mediating cessation of a muscle fatiguing exercise. Fifteen male subjects performed 39 intermittent, isometric handgrip contractions (13 s on, 5–6 s off) with the dominant right hand while brain activation was assessed by means of functional magnetic resonance imaging (fMRI). An adaptive, partly stochastic protocol was designed such that in approximately 50% of the contraction trials the required force could not be held until the end of the trial (task failure trial). Trials performed in compliance with the force requirements (succeeded trial) were compared with task failure trials concerning neural activity during a small time window before task failure occurred. The data revealed significantly increased activation contralaterally in both the mid/anterior insular cortex and the thalamus during the investigated time window in the case of subsequent task failure. In accordance with other studies investigating sensations that alert the organism to urgent homeostatic imbalance such as air hunger, hunger for food, and pain, we assume that an increased thalamo‐insular activation in the context of a fatigue‐induced handgrip exercise could reflect increased homeostatic disturbance in the exercising muscle and may be of essential importance by mediating task failure to maintain the integrity of the organism. Hum Brain Mapp, 2011. © 2010 Wiley Periodicals, Inc.

[1]  R. Treede,et al.  Human brain mechanisms of pain perception and regulation in health and disease , 2005, European journal of pain.

[2]  Stuart D. Rosen,et al.  Breathlessness in humans activates insular cortex , 2000, Neuroreport.

[3]  P Hassmén,et al.  Effect of branched-chain amino acid supplementation on mental performance. , 1991, Acta physiologica Scandinavica.

[4]  S C Gandevia,et al.  Group III and IV muscle afferents differentially affect the motor cortex and motoneurones in humans , 2008, The Journal of physiology.

[5]  E. Ravussin,et al.  Neuroanatomical correlates of hunger and satiation in humans using positron emission tomography. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[6]  W. Penfield,et al.  The insula; further observations on its function. , 1955, Brain : a journal of neurology.

[7]  Inge Zijdewind,et al.  Voluntary activation and cortical activity during a sustained maximal contraction: An fMRI study , 2009, Human brain mapping.

[8]  R Bandler,et al.  Lateralized and widespread brain activation during transient blood pressure elevation revealed by magnetic resonance imaging , 2000, The Journal of comparative neurology.

[9]  K H PRIBRAM,et al.  Respiratory and vascular responses in monkeys from temporal pole, insula, orbital surface and cingulate gyrus; a preliminary report. , 1949, Journal of neurophysiology.

[10]  M Liotti,et al.  Brain responses associated with consciousness of breathlessness (air hunger). , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[11]  J M Davis,et al.  Central and peripheral factors in fatigue. , 1995, Journal of sports sciences.

[12]  N. Secher,et al.  Cerebral perturbations provoked by prolonged exercise , 2004, Progress in Neurobiology.

[13]  J. Mitchell,et al.  New insights into central cardiovascular control during exercise in humans: a central command update , 2006, Experimental physiology.

[14]  K L Casey,et al.  Forebrain mechanisms of nociception and pain: analysis through imaging. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[15]  T D Noakes,et al.  A signalling role for muscle glycogen in the regulation of pace during prolonged exercise , 2004, British Journal of Sports Medicine.

[16]  R. Wurtman,et al.  Exercise and Neuromodulators , 1992, International journal of sports medicine.

[17]  R. Peyron,et al.  Functional imaging of brain responses to pain. A review and meta-analysis (2000) , 2000, Neurophysiologie Clinique/Clinical Neurophysiology.

[18]  Jing Z. Liu,et al.  Human brain activation during sustained and intermittent submaximal fatigue muscle contractions: an FMRI study. , 2003, Journal of neurophysiology.

[19]  R. Harper,et al.  Hyperoxic Brain Effects Are Normalized by Addition of CO2 , 2007, PLoS medicine.

[20]  Natasha M. Maurits,et al.  Effects of motor fatigue on human brain activity, an fMRI study , 2007, NeuroImage.

[21]  R. Enoka,et al.  Men are more fatigable than strength-matched women when performing intermittent submaximal contractions. , 2004, Journal of applied physiology.

[22]  Karleyton C Evans,et al.  BOLD fMRI identifies limbic, paralimbic, and cerebellar activation during air hunger. , 2002, Journal of neurophysiology.

[23]  Roger M Enoka,et al.  Task failure during fatiguing contractions performed by humans. , 2005, Journal of applied physiology.

[24]  A Schnitzler,et al.  Somatic and limbic cortex activation in esophageal distention: a functional magnetic resonance imaging study. , 1998, Annals of neurology.

[25]  E. Reiman,et al.  Thermosensory activation of insular cortex , 2000, Nature Neuroscience.

[26]  R. Johansson,et al.  Contractile speed and EMG changes during fatigue of sustained maximal voluntary contractions. , 1983, Journal of neurophysiology.

[27]  J B Poline,et al.  Neural substrates for the perception of acutely induced dyspnea. , 2001, American journal of respiratory and critical care medicine.

[28]  T D Noakes,et al.  Evidence for complex system integration and dynamic neural regulation of skeletal muscle recruitment during exercise in humans , 2004, British Journal of Sports Medicine.

[29]  L M Parsons,et al.  Neuroimaging evidence implicating cerebellum in the experience of hypercapnia and hunger for air. , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[30]  T. Noakes,et al.  Linear relationship between the perception of effort and the duration of constant load exercise that remains. , 2004, Journal of applied physiology.

[31]  R. Passingham,et al.  Relation between cerebral activity and force in the motor areas of the human brain. , 1995, Journal of neurophysiology.

[32]  Synaptic responses of lumbar α-motoneurones to chemical algesic stimulation of skeletal muscle in spinal cats , 1979, Brain Research.

[33]  Markus Amann,et al.  Opioid‐mediated muscle afferents inhibit central motor drive and limit peripheral muscle fatigue development in humans , 2009, The Journal of physiology.

[34]  A. Paintal,et al.  Functional analysis of Group III afferent fibres of mammalian muscles , 1960, The Journal of physiology.

[35]  R. Turner,et al.  Characterizing Evoked Hemodynamics with fMRI , 1995, NeuroImage.

[36]  Anthony K. P. Jones,et al.  Pain processing during three levels of noxious stimulation produces differential patterns of central activity , 1997, Pain.

[37]  J. Girvin,et al.  Cardiovascular effects of human insular cortex stimulation , 1992, Neurology.

[38]  J. L. Taylor,et al.  Changes in motor cortical excitability during human muscle fatigue. , 1996, The Journal of physiology.

[39]  M. Kaufman,et al.  Effect of metabolic products of muscular contraction on discharge of group III and IV afferents. , 1988, Journal of applied physiology.

[40]  E. Reiman,et al.  The application of positron emission tomography to the study of normal and pathologic emotions. , 1997, The Journal of clinical psychiatry.

[41]  R. Hoffman,et al.  Effect of naloxone on perceived exertion and exercise capacity during maximal cycle ergometry. , 2002, Journal of applied physiology.

[42]  R. Fitts,et al.  Lactate and contractile force in frog muscle during development of fatigue and recovery. , 1976, The American journal of physiology.

[43]  J. Williamson,et al.  Evidence for central command activation of the human insular cortex during exercise. , 2003, Journal of applied physiology.

[44]  Karl J. Friston,et al.  Dynamic causal modelling , 2003, NeuroImage.

[45]  A. Grad,et al.  Cardiac Arrhythmia Associated With Reversible Damage to Insula in a Patient With Subarachnoid Hemorrhage , 1994, Stroke.

[46]  S. Gandevia Spinal and supraspinal factors in human muscle fatigue. , 2001, Physiological reviews.

[47]  M. Bushnell,et al.  A thalamic nucleus specific for pain and temperature sensation , 1994, Nature.

[48]  Dirk Sander,et al.  Changes of circadian blood pressure patterns and cardiovascular parameters indicate lateralization of sympathetic activation following hemispheric brain infarction , 1995, Journal of Neurology.

[49]  L. Sinoway,et al.  Effects of contraction and lactic acid on the discharge of group III muscle afferents in cats. , 1993, Journal of neurophysiology.

[50]  B. Vogt Pain and emotion interactions in subregions of the cingulate gyrus , 2005, Nature Reviews Neuroscience.

[51]  J. Davis,et al.  Neuroendocrine and substrate responses to altered brain 5-HT activity during prolonged exercise to fatigue. , 1993, Journal of applied physiology.

[52]  L. Sinoway,et al.  ATP stimulates chemically sensitive and sensitizes mechanically sensitive afferents. , 2002, American journal of physiology. Heart and circulatory physiology.

[53]  E. Blomstrand,et al.  Amino acids and central fatigue , 2001, Amino Acids.

[54]  J. Le Bas,et al.  Central processing of rectal pain: a functional MR imaging study. , 1999, AJNR. American journal of neuroradiology.

[55]  R. J. Seitz,et al.  Somatic and limbic cortex activation in esophageal distention: A functional imaging study , 1998, Annals of neurology.

[56]  J. L. Taylor,et al.  Supraspinal factors in human muscle fatigue: evidence for suboptimal output from the motor cortex. , 1996, The Journal of physiology.

[57]  R. Djaldetti,et al.  Enhanced fatigue during motor performance in patients with Parkinson's disease , 1998, Neurology.

[58]  Vladimir Hachinski,et al.  Human forebrain activation by visceral stimuli , 1999, The Journal of comparative neurology.

[59]  Gary W. Thickbroom,et al.  Changes in the functional MR signal in motor and non-motor areas during intermittent fatiguing hand exercise , 2007, Experimental Brain Research.

[60]  T. Noakes,et al.  From catastrophe to complexity: a novel model of integrative central neural regulation of effort and fatigue during exercise in humans: summary and conclusions , 2005, British Journal of Sports Medicine.

[61]  K. Berman,et al.  Neural activation during acute capsaicin-evoked pain and allodynia assessed with PET. , 1998, Brain : a journal of neurology.

[62]  W. Cannon,et al.  STRESSES AND STRAINS OF HOMEOSTASIS , 1935 .

[63]  Jing Z. Liu,et al.  Relationship between muscle output and functional MRI-measured brain activation , 2001, Experimental Brain Research.

[64]  C Y Guezennec,et al.  Effects of Prolonged Exercise on Brain Ammonia and Amino Acids , 1998, International journal of sports medicine.

[65]  A. Craig A new view of pain as a homeostatic emotion , 2003, Trends in Neurosciences.

[66]  S. Gandevia,et al.  Distinct forebrain activity patterns during deep versus superficial pain , 2006, Pain.

[67]  A. Craig,et al.  Activation of spinobulbar lamina I neurons by static muscle contraction. , 2002, Journal of neurophysiology.

[68]  Jing Z. Liu,et al.  Nonlinear cortical modulation of muscle fatigue: a functional MRI study , 2002, Brain Research.

[69]  Peter Svensson,et al.  Central representation of muscle pain and mechanical hyperesthesia in the orofacial region: a positron emission tomography study , 2004, Pain.

[70]  S. Mense Nervous outflow from skeletal muscle following chemical noxious stimulation , 1977, The Journal of physiology.

[71]  S C Gandevia,et al.  Ischaemia after exercise does not reduce responses of human motoneurones to cortical or corticospinal tract stimulation , 2000, The Journal of physiology.

[72]  M Liotti,et al.  Neuroimaging of cerebral activations and deactivations associated with hypercapnia and hunger for air. , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[73]  B. Renault,et al.  A dynamic network involving M1‐S1, SII‐insular, medial insular, and cingulate cortices controls muscular activity during an isometric contraction reaction time task , 2009, Human brain mapping.

[74]  G. Egan,et al.  Correlation of regional cerebral blood flow and change of plasma sodium concentration during genesis and satiation of thirst. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[75]  Davis Jm,et al.  Central and peripheral factors in fatigue , 1995 .