Exercise-induced depression of the diaphragm motor evoked potential is not affected by non-invasive ventilation

https://doi.org/10.1016/j.resp.2006.06.007Get rights and content

Abstract

Whole body exercise is followed by a depression of the diaphragm motor evoked potential (MEP). It is unknown whether the change is due to diaphragm activity or whole body exercise. To test the hypothesis that exercise-induced MEP depression was related to diaphragm activity, we performed two experiments. The first examined the effect of whole body exercise, performed with and without the use of non-invasive ventilation (NIV). NIV resulted in significant unloading of the diaphragm (pressure time product 101 ± 68 cm H2O/s/min versus 278  ±  95 cm H2O/s/min, p < 0.001). Both conditions produced significant MEP depression compared to the control condition (% drop at 5 min, after exercise and exercise with NIV: 29 and 34%, p = 0.77). Study 2 compared exercise with isocapnic hyperventilation. At 20 min the MEP had fallen by 29% in the exercise session versus 5% with hyperventilation (p = 0.098). We conclude that the work of breathing during whole body exercise is not the primary driver of exercise-induced diaphragm MEP depression.

Introduction

The reasons for the development of muscle fatigue after exercise are complex. Fatigue is defined as ‘any exercise-induced reduction in the ability to exert muscle force or power’ (Bigland-Ritchie and Woods, 1984). Depending on the protocol, some contribution is generally considered to arise from the central nervous system, and this has been termed supraspinal or ‘central’ fatigue (Gandevia, 2001). Since the diaphragm is the principle muscle of inspiration, mechanisms of diaphragm fatigue are of clinical and physiological interest.

Transcranial magnetic stimulation has been used to investigate the function of supraspinal structures in humans through its ability to excite the cortico-spinal tract. A single stimulus of sufficient magnitude to the motor cortex produces an electrical response in a muscle (motor evoked potential, MEP), although this response may be influenced by other structures in the cortico-spinal pathway as well as the motor cortex.

During and after significant muscular activity, there is a characteristic pattern of change in the MEP. During the contraction and for a short period of time after (seconds to minutes), the MEP is potentiated (Brasil-Neto et al., 1999, Balbi et al., 2002). Following this, a prolonged decline in the MEP amplitude, without change in peripheral transmission or conduction time, typically reaching a nadir between 5 and 15 min, has been described both after exercise of single muscle groups (Brasil-Neto et al., 1993, McKay et al., 1995, Gandevia, 1996, Samii et al., 1996a, Samii et al., 1996b), and also dynamic whole body exercise (Hollge et al., 1997, Fulton et al., 2002, Verin et al., 2004, Jonville et al., 2005). In those experiments that have focused on single muscle groups, the response is thought to be muscle specific.

Our group has previously demonstrated a persistent significant decline in the diaphragm MEP after exhaustive treadmill exercise (Verin et al., 2004). We hypothesised that exercise-induced MEP depression of the diaphragm was related to whole body exercise itself, rather than to the work done by the diaphragm muscle during exercise. If this hypothesis is correct, then it implies that mechanisms which are not necessarily muscle specific are involved in inducing cortical MEP depression.

Two separate studies were performed. In the first study we used non-invasive ventilation to reduce the work of the diaphragm during exercise (study 1—exercise and non-invasive ventilation). In the second study we compared exercise with hyperventilation (study 2—exercise versus hyperventilation).

Section snippets

Subjects

Subjects, who were without neurological, psychiatric, cardiac, respiratory or locomotor disease and on no medication, were requested to refrain from intense exercise in the 24 h before the study, from significant alcohol consumption on the night before the study, and from caffeine on the day of the study. All gave their written informed consent and the experiment was approved by the Royal Brompton Hospital ethics committee and performed according to the declaration of Helsinki.

Study 1

The mean peak V˙O2 of the subjects was 39.9 ± 8.3 ml/kg/min (range 29.6–55.7 ml/kg/min) which was 113 ± 28% predicted (Fig. 3). The mean anaerobic threshold was 132 ± 18 W.

The work of breathing during the three conditions varied significantly (p < 0.001). The pressure time product during exercise was substantially and significantly reduced by the ventilator (101 ± 68 cm H2O/s/min versus 278 ± 95 cm H2O/s/min, p < 0.001). The end-tidal CO2 was not different between the two exercise conditions (exercise with

Discussion

Our data confirm that the motor evoked potential of the diaphragm and quadriceps elicited by transcranial magnetic stimulation is reduced after moderate whole body exercise. Furthermore, the data suggest that the reduction seen in the diaphragmatic motor evoked potential is not proportional to the work of breathing per se. An equivalent reduction of the MEP was seen when the diaphragm was rested during exercise by using a non-invasive ventilator. Moreover hyperventilation, without exercise did

Acknowledgements

We are grateful to all of the subjects who took part in this particularly demanding experiment, especially those who came back for a second go. We are also grateful to the research fellows who allowed us to use all of the equipment in the muscle laboratory for days at a time, preventing them from doing any physiology experiments for themselves. Mark Dayer was supported by a British Heart Foundation project grant (PG/2001042). Dr. Hopkinson was principally supported by the Wellcome Trust (Grant

References (72)

  • D. Zhang et al.

    Analysis of trace amino acid neurotransmitters in hypothalamus of rats after exhausting exercise using microdialysis

    J. Chromatogr. B Biomed. Sci. Appl.

    (2001)
  • U. Ziemann

    TMS and drugs

    Clin. Neurophysiol.

    (2004)
  • G. Abbruzzese et al.

    The excitability of the human motor cortex increases during execution and mental imagination of sequential but not repetitive finger movements

    Exp. Brain Res.

    (1996)
  • B. Andersen et al.

    Failure of activation of spinal motoneurones after muscle fatigue in healthy subjects studied by transcranial magnetic stimulation

    J. Physiol. (Lond.)

    (2003)
  • P. Balbi et al.

    Postexercise facilitation of motor evoked potentials following transcranial magnetic stimulation: a study in normal subjects

    Muscle Nerve

    (2002)
  • W.A. Banks et al.

    Passage of cytokines across the blood–brain barrier

    Neuroimmunomodulation

    (1995)
  • T. Baumer et al.

    Fatigue suppresses ipsilateral intracortical facilitation

    Exp. Brain Res.

    (2002)
  • A. Baydur et al.

    A simple method for assessing the validity of the esophageal balloon technique

    Am. Rev. Respir. Dis.

    (1982)
  • B. Bigland-Ritchie et al.

    Changes in muscle contractile properties and neural control during human muscular fatigue

    Muscle Nerve

    (1984)
  • G. Borg

    Simple rating methods for estimation of perceived exertion

  • G.A. Borg

    Psychophysical bases of perceived exertion

    Med. Sci. Sports Exerc.

    (1982)
  • J.P. Brasil-Neto et al.

    Postexercise depression of motor evoked potentials: a measure of central nervous system fatigue

    Exp. Brain Res.

    (1993)
  • J.P. Brasil-Neto et al.

    Postexercise facilitation of motor evoked potentials elicited by ipsilateral voluntary contraction

    Muscle Nerve

    (1999)
  • A. Demoule et al.

    Validation of surface recordings of the diaphragm response to transcranial magnetic stimulation in humans

    J. Appl. Physiol.

    (2003)
  • R. Fulton et al.

    Fatigue-induced change in corticospinal drive to back muscles in elite rowers

    Exp. Physiol.

    (2002)
  • S.C. Gandevia

    Insights into motor performance and muscle fatigue based on transcranial stimulation of the human motor cortex

    Clin. Exp. Pharmacol. Physiol.

    (1996)
  • S.C. Gandevia et al.

    Impaired response of human motoneurones to corticospinal stimulation after voluntary exercise

    J. Physiol. (Lond.)

    (1999)
  • S.C. Gandevia

    Spinal and supraspinal factors in human muscle fatigue

    Physiol. Rev.

    (2001)
  • R. Guleria et al.

    Central fatigue of the diaphragm and quadriceps during incremental loading

    Lung

    (2002)
  • M.L. Harris et al.

    Quadriceps muscle weakness following acute hemiplegic stroke

    Clin. Rehabil.

    (2001)
  • Y. Hochberg

    A sharper Bonferroni procedure for multiple tests of significance

    Biometrika

    (1988)
  • P.W. Hodges et al.

    Contraction of the human diaphragm during rapid postural adjustments

    J. Physiol. (Lond.)

    (1997)
  • P.W. Hodges et al.

    Activation of the human diaphragm during a repetitive postural task

    J. Physiol. (Lond.)

    (2000)
  • P.W. Hodges et al.

    Postural activity of the diaphragm is reduced in humans when respiratory demand increases

    J. Physiol. (Lond.)

    (2001)
  • J. Hollge et al.

    Central fatigue in sports and daily exercises A magnetic stimulation study

    Int. J. Sports Med.

    (1997)
  • T.V. Ilic et al.

    Short-interval paired-pulse inhibition and facilitation of human motor cortex: the dimension of stimulus intensity

    J. Physiol. (Lond.)

    (2002)
  • Cited by (9)

    • The role of the TMS parameters for activation of the corticospinal pathway to the diaphragm

      2022, Clinical Neurophysiology
      Citation Excerpt :

      Transcranial magnetic stimulation (TMS) of the cortical representation of the breathing muscles and corresponding registration of motor-evoked potentials (MEPs) allows noninvasive inspection of the integrity of the cortico-diaphragmatic pathway (Maskill et al., 1991) for both clinical (e.g. multiple sclerosis (Lagueny et al., 1998), amyotrophic lateral sclerosis (Miscio et al., 2006; Similowski et al., 2000), tetraplegia (Lissens and Vanderstraeten, 1996), stroke (Khedr et al., 2000; Similowski et al., 1996a), chronic obstructive pulmonary disease (Hopkinson et al., 2012), featuring patients for phrenic nerve pacing (Similowski et al., 1996c)) and research applications (Dayer et al., 2007; Demoule et al., 2003; Sharshar et al., 2003, 2004b; Verin et al., 2004).

    • Respiratory motor output during an inspiratory capacity maneuver is preserved despite submaximal exercise

      2013, Respiratory Physiology and Neurobiology
      Citation Excerpt :

      Other approaches such as P0.1, or esophageal pressure (whether amplitude or rate of change) may be influenced by inspiratory airflow (Luo et al., 2009), lung volume change (Hamnegård et al., 1998; Polkey et al., 1998) or recruitment of abdominal muscles (Ninane et al., 1992; Xiao et al., 2012). Other approaches which we have used in the past, such as the motor evoked potential (Verin et al., 2004; Dayer et al., 2007; Hopkinson et al., 2012) are technically difficult during exercise. A second issue with all techniques which assess output is that measuring the absence of a quantity is experimentally unsatisfactory.

    • Efficiency of neural drive during exercise in patients with COPD and healthy subjects

      2010, Chest
      Citation Excerpt :

      Alternatively, there may be neural inhibition that protects the diaphragm from low-frequency fatigue. This possibility is supported, at least in healthy subjects, by data showing that the motor-evoked potential of the diaphragm is reduced following exhaustive treadmill exercise.27 We have previously shown that it was difficult to generate severe diaphragm fatigue because of central inhibition.11

    View all citing articles on Scopus
    View full text