Corticomotor excitability and perception of effort during sustained exercise in the chronic fatigue syndrome

doi:10.1016/S1388-2457(99)00144-3

Clinical Neurophysiology

Volume 110, Issue 11, 1 November 1999, Pages 1883-1891

https://doi.org/10.1016/S1388-2457(99)00144-3 Get rights and content

Abstract

Objective: We have investigated the possibility of a central basis for the complaints of fatigue and poor exercise tolerance in subjects with chronic fatigue syndrome (CFS).

Methods: Transcranial magnetic stimulation of the motor cortex was used to measure sequential changes in motor evoked potential (MEP) amplitude, post-excitatory silent period (SP) duration and twitch force of the biceps brachii muscle during a 20% maximum isometric elbow flexor contraction maintained to the point of exhaustion. Ten patients with post-infectious CFS and 10 age- and sex-matched control subjects were studied. Results were analysed using non-parametric repeated measures analysis of variance (Friedman's test) and Mann–Whitney U-tests for intra- and inter-group comparisons respectively.

Results: Mean endurance time for the CFS group was lower (13.1±3.2 min, mean±SEM) than controls (18.6±2.6 min, P<0.05) and CFS subjects reported higher ratings of perceived exertion. During the exercise period MEP amplitude and SP duration increased in both groups but to a lesser extent in CFS subjects. Interpolated twitch force amplitude also increased during exercise, being more pronounced in CFS subjects.

Conclusion: The findings are in keeping with an exercise-related diminution in central motor drive in association with an increased perception of effort in CFS.

Introduction

Chronic fatigue syndrome (CFS) is characterised by persisting or relapsing unexplained fatigue, poor exercise tolerance, and exhaustion after physical exertion. Other common symptoms include myalgia, disturbed sleep patterns and impairments in concentration and short-term memory (Holmes et al., 1988). In some cases the condition develops after an acute viral infection, in particular influenza or infectious mononucleosis, whilst in others there is no identifiable initiating illness or other causative factor. To date there are no confirmatory laboratory tests for the diagnosis of CFS, which is generally made by a process of exclusion (Sharpe, 1991), although a set of diagnostic criteria for the condition has been agreed (Fukuda et al., 1994).

Despite numerous investigations, the pathophysiology of CFS remains obscure. There have been no consistent abnormalities reported in muscle histology (Peters and Preedy, 1991) or biochemistry (Edwards et al., 1991). Conventional neurophysiological studies have failed to demonstrate consistent abnormalities, apart from the non-specific finding of abnormal muscle fibre ‘jitter’ in some subjects with single fibre EMG studies (Jamal and Miller, 1991) and an increased fibre density in a sub-group of patients with myalgia (Roberts and Byrne, 1994). Previous studies of neuromuscular performance have shown that most individuals with CFS have a normal maximal voluntary force generating capacity and display normal muscle fatiguability when subjected to brief sustained maximal, or intermittent submaximal voluntary contractions (Lloyd et al., 1988, Lloyd et al., 1991, Rutherford and White, 1991, Kent-Braun et al., 1993).

The responses of CFS sufferers to sustained submaximal voluntary contractions have not been investigated. In the absence of demonstrable abnormalities in neuromuscular function, previous workers have suggested the possibility of a ‘central’ basis for the symptoms of CFS, but there have been no reported investigations into the relationship between corticomotor excitability and perceived effort during exercise in this condition.

The technique of transcranial magnetic stimulation (TMS) has allowed investigation of the changes in excitability and inhibitory properties of the human corticomotor pathway during fatiguing exercise (Taylor et al., 1996, Gandevia et al., 1996, Sacco et al., 1997). We have utilised this technique to investigate changes in corticomotor function in a group of CFS sufferers during a sustained submaximal isometric voluntary contraction of the elbow flexors and have also evaluated the subjective perception of effort during this task.

Section snippets

Subjects

With the approval of the Human Rights Committee of the University of Western Australia, and after informed consent, studies were performed on 10 subjects suffering from post-infection CFS (6 female, 19–46 years of age) and 10 age-matched control subjects (6 female) who were not engaged in any form of physical training. All CFS subjects were carefully screened prior to participation to ensure that they fulfilled the diagnostic criteria of Fukuda et al. (1994) involving full neurological and

Subject characteristics

The two groups were of similar age, sex and body weight (Table 1). The control subjects had slightly greater isometric maximal voluntary forces than the CFS group (180.5±15.5 N compared to 159.5±23.0 N, respectively), although this difference was not statistically significant (Table 2).

Endurance time and ratings of perceived exertion

Control subjects sustained a 20% maximum force contraction (endurance time) for a mean duration of 18.6±2.6 min (range 9–31 min), which was significantly longer than that of the CFS subjects (13.1±3.2 min, range

Discussion

Maximal voluntary isometric elbow flexor strength was not significantly different in the CFS subjects studied compared to a group of age and sex-matched controls, a finding consistent with previous reports (Lloyd et al., 1988, Stokes et al., 1988, Rutherford and White, 1991). Responses to TMS were also similar, with CFS subjects displaying normal threshold intensities for MEP responses and comparable MEP amplitudes. Brouwer and Packer (1994), reported that TMS-induced cortically evoked

Acknowledgements

The authors gratefully acknowledge the financial support of the Neuromuscular Foundation of Western Australia and the assistance provided by the ME/CFS Society of WA.

References (34)

J.P. Hales et al.
Assessment of maximal voluntary contraction with twitch interpolation: an instrument to measure twitch responses
J Neurosci Methods
(1988)
L.A. Jones et al.
Effect of fatigue on force sensation
Exp Neurol
(1983)
L. Kiers et al.
Assessment of cortical motor output: compound muscle action potential versus twitch force recording
Electroenceph clin Neurophysiol
(1995)
W.J. Triggs et al.
Cortical and spinal motor excitability during the transcranial stimulation silent period in humans
Brain Res
(1993)
S.A. Wilson et al.
The muscle silent period following transcranial magnetic cortical stimulation
J Neurol Sci
(1993)
V.E. Amassian et al.
Physiological basis of motor effects of a transient stimulation to cerebral cortex
Neurosurgery
(1987)
G.A.V. Borg
Psychophysical basis of perceived exertion
Med Sci Sports Exerc
(1982)
B. Brouwer et al.
Corticospinal excitability in patients diagnosed with chronic fatigue syndrome
Muscle Nerve
(1994)
D. Burke et al.
Direct comparison of corticospinal volleys in human subjects to transcranial magnetic and electrical stimulation
J Physiol (Lond)
(1993)
B.L. Day et al.
Electrical and magnetic stimulation of the human motor cortex: surface EMG and single motor unit responses
J Physiol (Lond)
(1989)

R.H.T. Edwards et al.

Muscle biochemistry and pathophysiology in chronic fatigue syndrome

Br Med Bull

(1991)

A.J. Fuglevand et al.

Impairment of neuromuscular propagation during human fatiguing contractions at submaximal forces

J Physiol (Lond)

(1993)

K. Fukuda et al.

The chronic fatigue syndrome: a comprehensive approach to its definition and study

Ann Intern Med

(1994)

S.C. Gandevia et al.

Sensations of heaviness

Brain

(1977)

S.C. Gandevia et al.

Supraspinal factors in human muscle fatigue: evidence for suboptimal output from the motor cortex

J Physiol (Lond)

(1996)

G.P. Holmes et al.

Chronic fatigue syndrome: a working case definition

Ann Intern Med

(1988)

M. Inghilleri et al.

Silent period evoked by transcranial stimulation of the human motor cortex and cervicomedullary junction

J Physiol (Lond)

(1993)

Cited by (45)

People with Long COVID and ME/CFS Exhibit Similarly Impaired Dexterity and Bimanual Coordination: A Case-Case-Control Study
2024, American Journal of Medicine
Dexterity and bimanual coordination had not previously been compared between people with long COVID and people with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Therefore, this study determined dexterity and bimanual coordination in people with long COVID (∼16-month illness duration; n = 21) and ME/CFS (∼16-year illness duration; n = 20), vs age-matched healthy controls (n = 20).
Dexterity and bimanual coordination was determined using the Purdue pegboard test.
The main findings of the present investigation were that people with ME/CFS and people with long COVID were generally comparable for Purdue pegboard tests (P > .556 and d < 0.36 for pairwise comparisons). It is worth noting however, that both these patient groups performed poorer in the Perdue pegboard test than healthy controls (P < .169 and d > 0.40 for pairwise comparisons).
These data suggest that both people with long COVID and people with ME/CFS have similarly impaired dexterity and bimanual coordination. Therefore, there is an urgent need for interventions to target dexterity and bimanual coordination in people with ME/CFS, and given the current pandemic, people with long COVID.
Functional muscle group- and sex-specific parameters for a three-compartment controller muscle fatigue model applied to isometric contractions
2021, Journal of Biomechanics
The three-compartment controller with enhanced recovery (3CC-r) model of muscle fatigue has previously been validated separately for both sustained (SIC) and intermittent isometric contractions (IIC) using different objective functions, but its performance has not yet been tested against both contraction types simultaneously using a common objective function. Additionally, prior validation has been performed using common parameters at the joint level, whereas applications to many real-world tasks will require the model to be applied to agonistic and synergistic muscle groups. Lastly, parameters for the model have previously been derived for a mixed-sex cohort not considering the differece in fatigabilities between the sexes. In this work we validate the 3CC-r model using a comprehensive isometric contraction database drawn from 172 publications segregated by functional muscle group (FMG) and sex. We find that prediction errors are reduced by 19% on average when segregating the dataset by FMG alone, and by 34% when segregating by both sex and FMG. However, minimum prediction errors are found to be higher when validated against both SIC and IIC data together using torque decline as the outcome variable than when validated sequentially against hypothesized SIC intensity-endurance time curves with endurance time as the outcome variable and against raw IIC data with torque decline as the outcome variable.
Neurophysiological abnormalities in individuals with persistent post-concussion symptoms
2019, Neuroscience
Citation Excerpt :
Conversely, significant correlations were observed with intracortical inhibition measures for cSP, SICI and LICI when compared to self-reported fatigue, and somatosensory measures for reaction time, reaction time variability, amplitude and duration discrimination. Altered MEP waveforms have previously been demonstrated in those with other persistent fatigue conditions (e.g. myalgic encephalomyelitis or major depressive disorder) where studies have demonstrated abnormal intracortical inhibition, and/or reduced motor cortex excitability, which are posited to GABAergic receptor activity (Brouwer and Packer, 1994; Sacco et al., 1999; Starr et al., 2000; Steele et al., 2000). While we screened all participants for other neurological and psychiatric disorders, such as myalgic encephalomyelitis (ME) or major depressive disorder (MDD), we relied on self-report that participants in the PCS group were only diagnosed with PCS without comorbidities such as MDD or ME.
Concussion injury results in a rapid onset of transient neurological impairment that can resolve quickly, or sometimes evolve over time, but usually resolve within seven to 10 days. However, a small but noticeable cohort (~ 10%) of individuals continues to experience persistent lingering effects, particularly fatigue, recognized as post-concussion symptoms (PCS). This study explored neurophysiological mechanisms in people with persistent PCS. Studies involved using self-report post-concussion fatigue scale, transcranial magnetic stimulation (TMS) and somatosensory stimulation in those with diagnosed PCS (n = 20; 36.1 ± 14.0 yr., 4 female; mean time post-concussion 15.4 ± 7.6 months) to fully recovered individuals (n = 20; 33.8 ± 6.6 yr., 2 female; post-concussion 12.9 ± 6.6 months) and healthy controls (n = 20; 37.7 ± 8.0 yr., 3 female). PCS participants demonstrated a significantly higher self-report fatigue (score: PCS 20.2 [95% CI 17.4–22.9], Recovered 6.2 [3.1–9.3], Control 2.75 [0.6–4.8]). PCS participants showed a worsening of reaction time (F_2,57 = 4.214; p = 0.020) and increased reaction time variability (F_2,57 = 5.505; p = 0.007). Somatosensory differences were observed for amplitude discrimination (F_2,57 = 5.166; p = 0.009), temporal order judgment (F_2,57 = 4.606; p = 0.014) and duration discrimination (F_2,57 = 6.081; p = 0.004). Increased intracortical inhibition in TMS single pulse suprathreshold stimulation (110%: F_2,57 = 6.842; p = 0.002; 130%: F_2,57 = 4.900; p = 0.011; 150%: F_2,57 = 4.638; p = 0.014; 170%: F_2,57 = 9.845; p < 0.001) and paired pulse protocols was also seen (SICI: F_2,57 = 23.390; p < 0.001, and LICI: F_2,57 = 21.603; p < 0.001). Using non-invasive stimulation techniques, this novel study showed increased cortical inhibition and compromised central information processing, suggesting neural mechanisms underpinning ongoing fatigue, allowing for potential clinical rehabilitation strategies.
Stimulation of the motor cortex and corticospinal tract to assess human muscle fatigue
2013, Neuroscience
Citation Excerpt :
Transcranial magnetic stimulation (TMS) is a non-invasive, pain-less and safe technique to investigate the human motor cortex (Ridding and Rothwell, 2007). TMS is often used to characterize alterations in central motor pathways in neurological diseases (e.g. multiple sclerosis, stroke, chronic fatigue syndrome) and to attempt to link self-reported fatigue to neuromuscular deficiencies in these pathologies (Sacco et al., 1999; Liepert et al., 2005; Knorr et al., 2011). During brief contractions, TMS over the motor cortex can elicit additional force production, i.e. SIT, despite maximal volitional effort (Gandevia et al., 1996).
This review aims to characterize fatigue-related changes in corticospinal excitability and inhibition in healthy subjects. Transcranial magnetic stimulation (TMS) has been extensively used in recent years to investigate modifications within the brain during and after fatiguing exercise. Single-pulse TMS reveals reduction in motor-evoked potentials (MEP) when measured in relaxed muscle following sustained fatiguing contractions. This modulation of corticospinal excitability observed in relaxed muscle is probably not specific to the fatigue induced by the motor task. During maximal and submaximal fatiguing contractions, voluntary activation measured by TMS decreases, suggesting the presence of supraspinal fatigue. The demonstration of supraspinal fatigue does not eliminate the possibility of spinal contribution to central fatigue. Concomitant measurement of TMS-induced MEP and cervicomedullary MEP in the contracting muscle, appropriately normalized to maximal muscle compound action potential, is necessary to determine the relative contribution of cortical and spinal mechanisms in the development of central fatigue. Recent studies comparing electromyographic (EMG) responses to paired-pulse stimuli at the cortical and subcortical levels suggest that impaired motoneuron responsiveness rather than intracortical inhibition may contribute to the development of central fatigue. This review examines the mechanical and EMG responses elicited by TMS (single- and paired-pulse) and cervicomedullary stimulation both during and after a fatiguing exercise. Particular attention is given to the muscle state and the type of fatiguing exercise when assessing and interpreting fatigue-induced changes in these parameters. Methodological concerns and future research interests are also considered.
The relationship between muscle pain and fatigue
2012, Neuromuscular Disorders
Citation Excerpt :
Little is known about the changes in CMD in neuromuscular disorders and few studies have investigated the physiological adaptations that occur in the central motor pathway in response to peripheral weakness and pain. Our studies with transcranial magnetic stimulation in patients with chronic fatigue syndrome have shown that CMD during fatiguing exercise is reduced and that the excitability of the motor cortex and central motor pathway does not increase to the same degree as in normal subjects [6]. In a twitch interpolation study of patients with fibromyalgia Miller et al. [4] found that most subjects were able to maintain an appropriate level of voluntary muscle activation during an intermittent fatiguing exercise protocol of the elbow flexors, but central motor drive was not investigated during sustained submaximal contractions or in other muscle groups.
Pain and fatigue may occur together during sustained exhausting muscle contractions, particularly as the limit of endurance is approached, and both can restrict muscle performance. Patients with neuromuscular disorders may have chronic myofascial pain (e.g. fibromyalgia) or contraction-induced pain (e.g. in metabolic myopathies). In some patients these two types of pain may coexist and both may inhibit central motor drive during exercise. Little is known about the central motor adaptations that occur in patients with neuromuscular disorders and how the effects of pain are mediated. Transcranial magnetic brain stimulation has made it possible to investigate the changes in excitability of the central motor pathway during fatiguing muscle activity and have thrown light on the mechanisms of fatigue in normal subjects and individuals with chronic fatigue syndrome and multiple sclerosis, but there have been few studies in patients with neuromuscular disorders. Repetitive magnetic brain stimulation protocols can now be used to modulate the excitability of the motor system during exercise to delay the onset of peripheral fatigue, and to reduce chronic pain. The possible application of these techniques in patients with neuromuscular disorders warrants further investigation.
Cancer-Related Fatigue: Central or Peripheral?
2009, Journal of Pain and Symptom Management
Citation Excerpt :
Reduced central drive in healthy individuals normally contributes approximately 20% to fatigue, as measured by reductions in muscle maximum voluntary contraction force and TF.11 CRF resembles chronic fatigue syndrome (CFS), in which central drive is also reduced.35–38 However, in CFS, muscle performance, voluntary activation, and twitch properties are normal.39
To evaluate cancer-related fatigue (CRF) by objective measurements to determine if CRF is a more centrally or peripherally mediated disorder, cancer patients and matched noncancer controls completed a Brief Fatigue Inventory (BFI) and underwent neuromuscular testing. Cancer patients had fatigue measured by the BFI, were off chemotherapy and radiation (for more than four weeks), had a hemoglobin level higher than 10 g/dL, and were neither receiving antidepressants nor were depressed on a screening question. The controls were screened for depression and matched by age, gender, and body mass index. Neuromuscular testing involved a sustained submaximal elbow flexion contraction (SC) at 30% maximal level (30% maximum elbow flexion force). Endurance time (ET) was measured from the beginning of the SC to the time when participants could not maintain the SC. Evoked twitch force (TF), a measure of muscle fatigue, and compound action potential (M-wave), an assessment of neuromuscular-junction transmission were performed during the SC. Compared with controls, the CRF group had a higher BFI score (P < 0.001), a shorter ET (P < 0.001), and a greater TF with the SC (CRF > controls, P < 0.05). This indicated less muscle fatigue. There was a greater TF (P < 0.05) at the end of the SC, indicating greater central fatigue, in the CRF group, which failed to recruit muscle (to continue the SC), as well as the controls. M-Wave amplitude was lower in the CRF group than in the controls (P < 0.01), indicating impaired neuromuscular junction conduction with CRF unrelated to central fatigue (M-wave amplitude did not change with SC). These data demonstrate that CRF patients exhibited greater central fatigue, indicated by shorter ET and less voluntary muscle recruitment during an SC relative to controls.

View all citing articles on Scopus

View full text

Corticomotor excitability and perception of effort during sustained exercise in the chronic fatigue syndrome

Abstract

Introduction

Section snippets

Subjects

Subject characteristics

Endurance time and ratings of perceived exertion

Discussion

Acknowledgements

J Neurosci Methods

Exp Neurol

Electroenceph clin Neurophysiol

Brain Res

J Neurol Sci

Physiological basis of motor effects of a transient stimulation to cerebral cortex

Neurosurgery

Psychophysical basis of perceived exertion

Med Sci Sports Exerc

Corticospinal excitability in patients diagnosed with chronic fatigue syndrome

Muscle Nerve

Direct comparison of corticospinal volleys in human subjects to transcranial magnetic and electrical stimulation

J Physiol (Lond)

Electrical and magnetic stimulation of the human motor cortex: surface EMG and single motor unit responses

J Physiol (Lond)

Muscle biochemistry and pathophysiology in chronic fatigue syndrome

Br Med Bull

Impairment of neuromuscular propagation during human fatiguing contractions at submaximal forces

J Physiol (Lond)

The chronic fatigue syndrome: a comprehensive approach to its definition and study

Ann Intern Med

Sensations of heaviness

Brain

Supraspinal factors in human muscle fatigue: evidence for suboptimal output from the motor cortex

J Physiol (Lond)

Chronic fatigue syndrome: a working case definition

Ann Intern Med

Silent period evoked by transcranial stimulation of the human motor cortex and cervicomedullary junction

J Physiol (Lond)