We examine the hypothesis that in persons with multiple sclerosis, fatigue — measured with a questionnaire — is attributable to interactions between the central nervous system and the immune system, which exacerbate both perceived fatigability and performance fatigability. Performance fatigability is represented by the decline in voluntary force during sustained contractions as a consequence of the inability to maintain high levels of voluntary activation.

In able-bodied (AB) individuals, voluntary muscle activation progressively declines during sustained contractions. However, few data are available on voluntary muscle activation during sustained contractions in muscles weakened by spinal cord injury (SCI), where greater force declines may limit task performance. SCI-related impairment of muscle activation complicates interpretation of the interpolated twitch technique commonly used to assess muscle activation. We attempted to estimate and correct for the SCI-related-superimposed twitch. Seventeen participants, both AB and with SCI (American Spinal Injury Association Impairment Scale C/D) produced brief and sustained (2-min) maximal voluntary contractions (MVCs) with the first dorsal interosseous. Force and electromyography were recorded together with superimposed (doublet) twitches. MVCs of participants with SCI were weaker than those of AB participants (20.3 N, SD 7.1 vs. 37.9 N, SD 9.5; P < 0.001); MVC-superimposed twitches were larger in participants with SCI (SCI median 10.1%, range 2.0-63.2%; AB median 4.7%, range 0.0-18.4% rest twitch; P = 0.007). No difference was found after correction for the SCI-related-superimposed twitch (median 6.7%, 0.0-17.5% rest twitch, P = 0.402). Thus during brief contractions, the maximal corticofugal output that participants with SCI could exert was similar to that of AB participants. During the sustained contraction, force decline (SCI, 58.0%, SD 15.1; AB, 57.2% SD 13.3) was similar (P = 0.887) because participants with SCI developed less peripheral (P = 0.048) but more central fatigue than AB participants. The largest change occurred at the start of the sustained contraction when the (corrected) superimposed twitches increased more in participants with SCI (SCI, 16.3% rest twitch, SD 20.8; AB, 2.7%, SD 4.7; P = 0.01). The greater reduction in muscle activation after SCI may relate to a reduced capacity to overcome fast fatigue-related excitability changes at the spinal level.

Age and sex affect the neuromuscular system including performance fatigability. Data on performance fatigability and underlying mechanisms in hand muscles are scarce. Therefore, we determined the effects of age and sex on force decline, and the mechanisms contributing to force decline, during a sustained isometric maximal voluntary contraction (MVC) with the index finger abductor (first dorsal interosseous, FDI). Subjects (n = 51, age range: 19–77 years, 25 females) performed brief and a 2-min sustained MVC with the right FDI. Abduction force and root mean squared electromyographic activity (rms-EMG) were recorded in both hands. Double-pulse stimulation was applied to the ulnar nerve during (superimposed twitch) and after (doublet-force) the brief and sustained MVCs. Compared to females, males were stronger (134%, p < 0.001) and exhibited a greater decline in voluntary (difference: 8%, p = 0.010) and evoked (doublet) force (difference: 12%, p = 0.010) during and after the sustained MVC. Age did not affect MVC, force decline and superimposed twitch. The ratio between the doublet- and MVC-force was greater in females (0.33, p = 0.007) and in older (0.38, p = 0.06) individuals than in males (0.30) and younger (0.30) individuals; after the sustained MVC this ratio increased with age and the increase was larger for females compared to males (p = 0.04). The inadvertent contralateral, left force and rms-EMG activity increased over time (2.7–13.6% MVC and 5.4–17.7% MVC, respectively). Males had higher contralateral forces than females (p = 0.012) and contralateral force was higher at the start of the contralateral contraction in older compared with young subjects (difference: 29%, p = 0.008). In conclusion, our results suggest that the observed sex-differences in performance fatigability were mainly due to differences in peripheral muscle properties. Yet the reduced amount of contralateral activity and the larger difference in evoked versus voluntary force in female subjects indicate that sex-differences in voluntary activation should not be overlooked. These data obtained in neurological healthy adults provides a framework and help the interpretation and referencing of neurophysiological measures in patients suffering from neuromuscular diseases, who often present with symptoms of performance fatigability.