Short-latency afferent inhibition is reduced in people with multiple sclerosis during fatiguing muscle contractions.

Understanding how inhibitory pathways influence motor cortical activity during fatiguing contractions may provide valuable insight into mechanisms associated with multiple sclerosis (MS) muscle activation. Short-latency afferent inhibition (SAI) reflects inhibitory interactions between the somatosensory cortex and the motor cortex, and although SAI is typically reduced with MS, it is unknown how SAI is regulated during exercise-induced fatigue. The current study examined how SAI modulates motor evoked potentials (MEPs) during fatiguing contractions. Fourteen people with relapsing-remitting MS (39 ± 6 years, nine female) and 10 healthy individuals (36 ± 6 years, six female) participated. SAI was induced by stimulation of the median nerve that was paired with TMS over the motor representation of the abductor pollicis brevis. A contraction protocol was employed that depressed force generating capacity using a sustained 3-min 15% MVC, immediately followed by a low-intensity (15% MVC) intermittent contraction protocol so that MEP and SAI could be measured during the rest phases of each duty cycle. Similar force, electromyography and MEP responses were observed between groups. However, the MS group had significantly reduced SAI during the contraction protocol compared to the healthy control group (p < .001). Despite the MS group reporting greater scores on the Fatigue Severity Scale and Modified Fatigue Impact Scale, these scales did not correlate with inhibitory measures. As there were no between-group differences in SSEPs, MS-related SAI differences during the fatiguing contractions were most likely associated with disease-related changes in central integration.

Voluntary muscle activation in people with multiple sclerosis is reduced across a wide range of forces following maximal effort-fatiguing contractions.

Although multiple sclerosis (MS) is frequently associated with motor impairment, little is known about how muscle activation is affected with MS. The aim of this study was to use transcranial magnetic stimulation (TMS) and motor nerve stimulation to investigate voluntary muscle activation in people with MS across a range of contraction forces. Ten people with MS (39 ± 7 yr) and 10 healthy controls (40 ± 5 yr) performed elbow flexions at target contraction forces of 25%, 50%, 75%, 90%, and 100% maximal voluntary contraction (MVC) while electromyography (EMG) of the biceps brachii was recorded. Sustained elbow flexion MVCs were then performed until force declined to 60% of baseline MVC, where the target contraction forces were again examined but after the sustained MVC. Following the sustained MVC, there was a reduction in biceps EMG amplitude (P < 0.01) and motor cortical voluntary activation (P < 0.01) for the MS group across all contraction intensities. There was also an increase in the rate of torque development for motor nerve-resting twitches in the MS group following the sustained MVC (P = 0.03). Despite the MS group reporting higher fatigue severity scale scores (P < 0.01), disease duration was a better predictor of muscle activation for the MS group (r = -0.757, P = 0.01). These findings indicate that voluntary muscle activation is compromised in people with MS following maximal effort contractions, which may be associated with disease duration rather than self-reports of fatigue.NEW & NOTEWORTHY We use transcranial magnetic stimulation to demonstrate that people with relapsing-remitting multiple sclerosis (MS) have a reduced ability to activate muscles following maximal effort-fatiguing contractions. A reduced ability to activate the elbow flexor muscles after a fatiguing contraction was associated with disease duration and not self-reported levels of fatigue.

People with multiple sclerosis have reduced TMS-evoked motor cortical output compared with healthy individuals during fatiguing submaximal contractions.

People with multiple sclerosis (PwMS) typically experience greater levels of exercise-induced fatigue compared with healthy individuals. Therefore, this study examined performance fatigability in PwMS when executing a prolonged submaximal contraction. Nine PwMS (38 ± 7 yr, 6 females) and nine healthy controls (35 ± 6 yr, 4 females) performed an elbow flexion at 15% maximal voluntary contraction (MVC) for 26 min. MVCs were performed every 2 min during, and following, the contraction to determine if maximal force was impaired by the low-intensity contraction. Single-pulse transcranial magnetic stimulation (TMS) was delivered to the primary motor cortex with a circular coil during each MVC and during the submaximal contraction. Superimposed and resting twitches were calculated from elbow flexion torque, whereas motor-evoked potentials were calculated from biceps brachii electromyography. Ratings of perceived exertion (RPE) were obtained before each MVC. During the fatiguing contraction protocol, the MS group exhibited a reduced MVC torque compared with the healthy control group (P = 0.044), which aligned with group differences in biceps brachii EMG activity (P = 0.022) and superimposed twitch amplitude (P = 0.016). Fatigue-related decrements in MVC torque (P = 0.044) and biceps brachii EMG activity (P = 0.043) demonstrated in the MS group persisted throughout recovery. However, MS did not affect the RPE during the fatigue task. These findings suggest that PwMS may have greater levels of performance fatigability due to decreased voluntary drive from the motor cortex, which is not associated with greater ratings of perceived exertion.NEW & NOTEWORTHY By combining TMS and motor nerve stimulation during a low-intensity exercise task, we were able to uncover the contribution that different levels of the CNS have during fatiguing exercise in PwMS. Our findings are novel and revealed that PwMS experienced decreased voluntary drive from the motor cortex during a low-intensity sustained fatiguing task that was associated with heightened levels of performance fatigability.

Severe acute hypoxia impairs recovery of voluntary muscle activation after sustained submaximal elbow flexion.

The purpose of this study was to determine how severe acute hypoxia alters neural mechanisms during, and following, a sustained fatiguing contraction. Fifteen participants (25 ± 3.2 years, six female) were exposed to a sham condition and a hypoxia condition where they performed a 10 min elbow flexor contraction at 20% of maximal torque. For hypoxia, peripheral blood oxygen saturation ( SpO2 ) was titrated to 80% over a 15 min period and maintained for 2 h. Maximal voluntary contraction torque, EMG root mean square, voluntary activation, rating of perceived muscle fatigue, and corticospinal excitability (motor-evoked potential) and inhibition (silent period duration) were then assessed before, during and for 6 min after the fatiguing contraction. No hypoxia-related effects were identified for neuromuscular variables during the fatigue task. However, for recovery, voluntary activation assessed by motor point stimulation of biceps brachii was lower for hypoxia than sham at 4 min (sham: 89% ± 7%; hypoxia: 80% ± 12%; P = 0.023) and 6 min (sham: 90% ± 7%; hypoxia: 78% ± 11%; P = 0.040). Similarly, voluntary activation (P = 0.01) and motor-evoked potential area (P = 0.002) in response to transcranial magnetic stimulation of the motor cortex were 10% and 11% lower during recovery for hypoxia compared to sham, respectively. Although an SpO2 of 80% did not affect neural activity during the fatiguing task, motor cortical output and corticospinal excitability were reduced during recovery in the hypoxic environment. This was probably due to hypoxia-related mechanisms involving supraspinal motor circuits. KEY POINTS: Acute hypoxia has been shown to impair voluntary activation of muscle and alter the excitability of the corticospinal motor pathway during exercise. However, little is known about how hypoxia alters the recovery of the motor system after performing fatiguing exercise. Here we assessed hypoxia-related responses of motor pathways both during active contractions and during recovery from active contractions, with transcranial magnetic stimulation and motor point stimulation of the biceps brachii. Fatiguing exercise caused reductions in voluntary activation, which was exacerbated during recovery from a 10 min sustained elbow flexion in a hypoxic environment. These results suggest that reductions in blood oxygen concentration impair the ability of motor pathways in the CNS to recover from fatiguing exercise, which is probably due to hypoxia-induced mechanisms that reduce output from the motor cortex.