Jane A. Kent-Braun

QUANTITATION OF CENTRAL ACTIVATION FAILURE DURING MAXIMAL VOLUNTARY CONTRACTIONS IN HUMANS

Muscle fatigue or neuromuscular disease may result in central activation failure during maximal voluntary contractions (MVCs). Superimposition of an electrically stimulated contraction during an MVC has been used to detect central activation failure. To determine the most sensitive means of quantitating central activation failure using this technique, we compared the increment in isometric force from single‐, double‐, and high‐frequency trains (50 Hz, 500 or 1000 ms) of stimuli of the peroneal nerve imposed during three separate MVCs of the dorsiflexor muscles. Completeness of activation was quantitated with the central activation ratio (CAR) = MVC/(MVC + stimulated force). Comparisons were made of the CARs of three groups of subjects during the three stimulation conditions: 7 healthy subjects, 13 patients with amyotrophic lateral sclerosis, and 5 healthy subjects after fatiguing exercise. For all three groups, the CAR was significantly lower during the train of stimuli condition (means = 0.76–0.89) compared with either the single or double stimuli conditions (means = 0.96–1.00). The results suggest that a superimposed high‐frequency train of stimuli is a more sensitive indicator of central activation failure during isometric MVCs compared with either the superimposed single or double stimuli methods.

Central and peripheral contributions to muscle fatigue in humans during sustained maximal effort

Abstract The purpose of this study was to estimate the relative contributions of central and peripheral factors to the development of human muscle fatigue. Nine healthy subjects [five male, four female; age = 30 (2) years, mean (SE)] sustained a maximum voluntary isometric contraction (MVC) of the ankle dorsiflexor muscles for 4 min. Fatigue was quantitated as the fall in MVC. Three measures of central activation and one measure of peripheral activation (compound muscle action potential, CMAP) were made using electromyography (EMG) and electrical stimulation. Measures of intramuscular metabolism were made using magnetic resonance spectroscopy. After exercise, MVC and electrically stimulated tetanic contraction (50 Hz, 500 ms) forces were 22.2 (3.7)% and 37.3 (7.1)% of pre-exercise values, respectively. The measures of central activation suggested some central fatigue during exercise: (1) the central activation ratio [MVC/(MVC + superimposed tetanic force)] fell from 0.94 (0.03) to 0.78 (0.09), (2) the MVC/tetanic force ratio fell from 2.3 (0.7) to 1.3 (0.7), and (3) the integral of the EMG (iEMG) signal decreased to 72.6 (9.1)% of the initial value, while the CMAP amplitude was unchanged. Intramuscular pH was associated by regression with the decline in MVC force (and therefore fatigue) and iEMG. The results indicate that central factors, which were not associated with altered peripheral excitability, contributed approximately 20% to the muscle fatigue developed, with the remainder being attributable to intramuscular (i.e., metabolic) factors. The association between pH and iEMG is consistent with proton concentration as a feedback mechanism for central motor drive during maximal effort.

Sex differences in human skeletal muscle fatigue.

HICKS, A.L., J. KENT-BRAUN, and D.S. DITOR. Sex differences in human skeletal muscle fatigue. Exerc. Sports Sci. Rev., Vol. 29, No. 3, pp. 109–112, 2001. Research on muscle fatigue suggests that greater fatigue resistance may be evident in females compared with males. The possible mechanisms for this sex difference include factors related to muscle mass, substrate utilization, muscle morphology, and neuromuscular activation.

Quantitation of lower physical activity in persons with multiple sclerosis

Multiple sclerosis (MS) is a demyelinating disease of the central nervous system that often affects the motor system. We tested the hypothesis that physical activity was lower in a group of 17 MS patients (mean +/- SD; age = 46 +/- 6 yr, 11 females, 6 males) compared with 15 healthy sedentary control subjects (age = 44 +/- 7 yr, 9 females, 6 males). Physical activity was measured with a three-dimensional accelerometer and with an activity questionnaire for 7 d. Vector magnitude values from the accelerometer for the MS and sedentary control subjects were 121,027 +/- 59,336 and 185,892 +/- 60,566 arbitrary units/day, respectively (P = 0.01). Estimated energy expenditure values derived from the questionnaire were 35.9 +/- 3.0 and 36.2 +/- 4.1 Kcal.kg-1.d-1 (NS), respectively. Thus, when measured directly with an accelerometer, activity was lower in MS compared with sedentary control subjects. The data also suggest that the accelerometer was more sensitive than the questionnaire for detecting differences in activity between two relatively sedentary populations, including one with neurologic disease.

Central basis of muscle fatigue in chronic fatigue syndrome

We studied whether muscle fatigue, metabolism, or activation are abnormal in the chronic fatigue syndrome (CFS). Subjects performed both an intermittent submaximal and a sustained maximal voluntary isometric exercise protocol of the tibialis anterior muscle. The extent of fatigue, metabolic response, and changes in both M-wave amplitude and twitch tension during exercise were similar in patients and controls. The response to systemic exercise was also normal in the patients. However, voluntary activation of the tibialis was significantly lower in the patients during maximal sustained exercise. The results indicate that patients with CFS have (1) normal fatigability and metabolism at both the intracellular and systemic levels, (2) normal muscle membrane function and excitation-contraction coupling, and (3) an inability to fully activate skeletal muscle during intense, sustained exercise. This failure of activation was well in excess of that found in controls, suggesting an important central component of muscle fatigue in CFS.

Functional relationships of central and peripheral muscle alterations in multiple sclerosis

The functional implications of central motor impairment and peripheral muscle alterations in multiple sclerosis are unclear. Muscle strength, central and peripheral activation, and symptomatic fatigue were investigated in 16 patients with multiple sclerosis (MS) and 18 control subjects. Voluntary and electrically stimulated isometric contractions were obtained from the ankle dorsiflexor muscles. Maximal voluntary contraction (MVC) was 27% lower in MS patients than controls, although electrically stimulated force was similar. Muscle fat‐free cross‐sectional area (CSA) was similar in both groups. These data indicate central activation impairment in MS. Such impairment in MS was further demonstrated by decreased foot‐tap speed, rate of voluntary force development, and central activation ratio. Peripheral activation changes in MS patients were modest. Although stimulated tetanic force was similar, force relaxation was slower in MS patients compared to controls, resulting in a left‐shifted force–frequency relationship in MS. Motor function changes were not associated with fatigue but were associated with impaired ambulation. Thus, weakness and walking impairment, but not fatigue, were related to impaired central activation in MS. These findings may help optimize rehabilitation strategies designed to improve function in persons with MS. Muscle Nerve 29: 843–852, 2004

Leg power asymmetry and postural control in women with multiple sclerosis.

UNLABELLED The extent of and the interactions between muscle strength, walking speed, postural control, and symptomatic fatigue in multiple sclerosis (MS) are not known, nor are the effects of bilateral strength asymmetries on these variables. PURPOSE To quantify the magnitude of and the associations between bilateral strength and limb-loading asymmetries, postural control, and symptomatic fatigue in women with MS. METHODS Peak knee extensor (KE) and dorsiflexor (DF) isometric torque and isotonic power were assessed bilaterally in 12 women with MS (Expanded Disability Status Scale = 4 +/- 1) and 12 age-matched female controls using a Biodex dynamometer (Biodex Medical, Shirley, NY). Center of pressure (CoP) variability during 20 s of quiet stance was measured in the anteroposterior (AP) and the mediolateral (ML) directions using adjacent force plates. Bilateral asymmetry scores were calculated for power and torque. Normal and brisk walk times (25 ft) and symptomatic fatigue (Visual Analog Fatigue Scale and Fatigue Severity Scale) were measured before strength and balance testing. RESULTS Fatigue was greater and walk times (normal and brisk) were longer in MS (P < or = 0.01). Dorsiflexor (DF) isometric torque and power and knee extensor (KE) isometric strength were similar between groups. KE power was lower (mean +/- SD = 21.5 +/- 16.2%; P < or = 0.05) and KE power asymmetry was greater in MS than in controls (9.2 +/- 6.9%; P = 0.02). Postural variability of the CoP was greater in the AP direction in MS than in controls (7.52 +/- 3.02 and 4.33 +/- 1.79 mm, respectively; P = 0.005). KE power asymmetry was associated with fatigue and walk times (P < or = 0.02), and AP CoP variability was correlated with fatigue, walk times, and power asymmetries (P < or = 0.05). CONCLUSIONS These data provide new evidence of a potential role for KE strength asymmetries in the symptomatic fatigue and physical dysfunction of persons with MS, possibly through an effect on postural stability.

Skeletal Muscle Fatigue in Old Age: Whose Advantage?

The results of recent studies indicate that in healthy men and women aged beyond approximately 65 years, the energy-producing pathways in skeletal muscle may combine with changes in motor unit behavior and muscle contractile properties to provide a unique environment for resisting muscle fatigue under some conditions.

Functional significance of upper and lower motor neuron impairment in amyotrophic lateral sclerosis

The objective of this study was to examine the contribution of lower motor neuron (LMN) and upper motor neuron (UMN) dysfunction to weakness and impaired motor control in 27 patients with amyotrophic lateral sclerosis (ALS). Isometric strength was measured by dorsiflexor maximum voluntary contraction force (MVC). LMN function was measured by tetanic force, twitch force, and the amplitude of the compound muscle action potential. UMN function was measured by the speed of rapid foot taps, the maximum rate of rise of voluntary force, and the central activation ratio [CAR = MVC/(MVC + superimposed tetanic force)]. The results suggest that (1) LMN loss appears to be the primary cause of progressive weakness in ALS; while (2) UMN impairment in ALS leads to slowing of contraction speed and rapid movements, and modest decreases in central activation; and (3) during 6 months of progression, LMN changes were greater than UMN changes.

Postural control in women with multiple sclerosis: effects of task, vision and symptomatic fatigue.

People with multiple sclerosis (MS) often report problems with balance, which may be most apparent during challenging postural tasks such as leaning or reaching, and when relying on non-visual sensory systems. An additional obstacle facing people with MS is a high incidence of symptomatic fatigue (>70%). The purpose of this study was to investigate the changes in balance during upright stance in individuals with mild-to-moderate disability due to MS under normal and restricted vision and different levels of self-reported fatigue. Limb loading asymmetry, sway and magnitude of postural shift in center of pressure, and time-to-contact the stability boundary of the center of mass and center of pressure were assessed during quiet standing and maximal lean and reach tasks. Compared to controls, people with MS displayed greater postural sway, greater loading asymmetry, and shorter time-to-contact during quiet standing. In the postural perturbation tasks the MS group had smaller postural shifts and reduced stability compared to controls in the direction perpendicular to the lean and reach. Limiting vision increased loading asymmetry during quiet standing and postural instability during backward lean in the MS group. Inducing additional fatigue in the MS group did affect postural control in the more challenging balance conditions but had no impact during quiet upright standing. The results of this study indicate subtle changes in postural control during standing in people with mild-to-moderate impairments due to MS.