Voluntary activation does not differ when using two different methods to determine transcranial magnetic stimulator output.

According to current guidelines, when measuring voluntary activation (VA) using transcranial magnetic stimulation (TMS), stimulator output (SO) should not exceed the intensity that, during a maximal voluntary contraction (MVC), elicits a motor evoked potential (MEP) from the antagonist muscle >15%-20% of its maximal M-wave amplitude. However, VA is based on agonist evoked-torque responses [i.e., superimposed twitch (SIT) and estimated resting twitch (ERT)], which means limiting SO based on electromyographic (EMG) responses will often lead to a submaximal SIT and ERT, possibly underestimating VA. Therefore, the purpose of this study was to compare elbow flexor VA calculated using the original method (i.e., intensity based on MEP size; SOMEP) and a method based solely on eliciting the largest SIT at 50% MVC torque (SOSIT), regardless of triceps brachii MEP size. Fifteen healthy, young participants performed 10 sets of brief contractions at 100%, 75%, and 50% MVC torque, with TMS delivered at SOMEP (73.0 ± 13.5%) or SOSIT (92.0 ± 10.8%) for five sets each. Although the mean ERT torque was greater using SOSIT (15.2 ± 4.8 Nm) compared with SOMEP (13.0 ± 3.7 Nm; P = 0.031), the SIT amplitude at 100% MVC torque was not different (SOMEP: 0.69 ± 0.49 Nm vs. SOSIT: 0.74 ± 0.52 Nm; P = 0.604). Despite the ERT disparity, VA scores were not different between SOMEP (94.6 ± 3.5%) and SOSIT (95.0 ± 3.3%; P = 0.572). Even though SOSIT did not lead to a higher VA score than the SOMEP method, it has the benefit of yielding the same result without the need to record antagonist EMG or perform MVCs when determining SO, which can induce fatigue before measuring VA.NEW & NOTEWORTHY When using transcranial magnetic stimulation (TMS) to determine voluntary activation (VA) of the elbow flexors, we hypothesized that a stimulator output designed to limit antagonist muscle activity would evoke submaximal agonist superimposed twitch amplitudes, thus underestimating VA. Contrary to our hypothesis, VA was not greater with an output based on maximal superimposed twitch amplitude. Nevertheless, our findings advance methodological practices by simplifying the equipment and minimizing the time required to determine VA using TMS.

A violation of Fitts' Law occurs when a target range is presented before and during movement.

According to Fitts' Law, the time to reach a target (movement time, MT) increases with distance. A violation of Fitts' Law occurs when target positions are outlined before and during movement, as MTs are not different when reaching to the farthest and penultimate targets. One hypothesis posits that performers cognitively process the edges of a target array before the center, allowing for corrective movements to be completed more quickly when moving to edge targets compared to middle targets. The objective of this study was to test this hypothesis by displaying a target range rather than outlines of individual targets in an effort to identify the effects of array edges. Using a touch-screen laptop, participants (N = 24) were asked to reach to one of three targets which would appear within a presented range. Separately, targets were also presented without a range to determine if the display protocol could evoke Fitts' Law. Movements were assessed with the touch screen and optical position measurement. A main effect was found for relative position within a range (touch: F2,44 = 15.4, p < 0.001, η2p = 0.412; position: F2,40 = 15.6, p < 0.001, η2p = 0.439). As hypothesised, MT to the farthest target in a range was not significantly different than MT to the middle target (touch: p = 0.638, position: p = 0.449). No violation was found when a target range was not presented (touch: p = 0.003, position: p = 0.001). Thus, a target range reproduces the Fitts' Law violation previously documented with individually outlined targets, which supports and extends the discussed hypothesis.

Normobaric hypoxia does not influence the sural nerve cutaneous reflex during standing.

Hypoxia increases postural sway compared to normoxia, but the underlying sensorimotor factors remain unclear. An important contributor to balance control is cutaneous feedback arising from the feet, which can be partially characterized by electrically evoking a reflex from a purely cutaneous nerve (i.e., sural) and sampling the subsequent motor activity of a muscle. The purpose of the present study was to determine how normobaric hypoxia influences sural nerve reflex parameters during a standing posture. It was hypothesized that normobaric hypoxia would reduce cutaneous reflex area compared to normoxia. Participants (n = 16; 5 females, 11 males) stood with their feet together while receiving two trials of 50 sural nerve stimulations (200-Hz, 5-pulse train, presented randomly every 3-6 s) at baseline (BL; normoxia), and at 2 (H2) and 4 (H4) h of normobaric hypoxia (~ 0.11 fraction of inspired oxygen in a hypoxic chamber). The sural nerve reflex was recorded using surface electromyography from the left medial gastrocnemius, and characterized by area and duration of the initial positive and negative peaks of the response. When normalized to pre-stimulus electromyography, the area of the peak-to-peak cutaneous reflex was not different than BL (p ≥ 0.14) for up to 4 h of normobaric hypoxia (BL: 0.26 ± 0.22, H2: 0.19 ± 0.19, H4: 0.22 ± 0.20 A.U.). Furthermore, the duration of the response was not different during hypoxia (BL: 73.2 ± 42.4; H2: 75.2 ± 47.0; H4: 77.6 ± 54.6 ms; p ≥ 0.13) than BL. Thus, reflexes arising from cutaneous afferents of the lateral border of the foot are resilient to at least 4 h of normobaric hypoxia.

Critical considerations of the contribution of the corticomotoneuronal pathway to central fatigue.

Neural drive originating in higher brain areas reaches exercising limb muscles through the corticospinal-motoneuronal pathway, which links the motor cortex and spinal motoneurones. The properties of this pathway have frequently been observed to change during fatiguing exercise in ways that could influence the development of central fatigue (i.e. the progressive reduction in voluntary muscle activation). However, based on differences in motor cortical and motoneuronal excitability between exercise modalities (e.g. single-joint vs. locomotor exercise), there is no characteristic response that allows for a categorical conclusion about the effect of these changes on functional impairments and performance limitations. Despite the lack of uniformity in findings during fatigue, there is strong evidence for marked 'inhibition' of motoneurones as a direct result of voluntary drive. Endogenous forms of neuromodulation, such as via serotonin released from neurones, can directly affect motoneuronal output and central fatigue. Exogenous forms of neuromodulation, such as brain stimulation, may achieve a similar effect, although the evidence is weak. Non-invasive transcranial direct current stimulation can cause transient or long-lasting changes in cortical excitability; however, variable results across studies cast doubt on its claimed capacity to enhance performance. Furthermore, with these studies, it is difficult to establish a cause-and-effect relationship between brain responsiveness and exercise performance. This review briefly summarizes changes in the corticomotoneuronal pathway during various types of exercise, and considers the relevance of these changes for the development of central fatigue, as well as the potential of non-invasive brain stimulation to enhance motor cortical excitability, motoneuronal output and, ultimately, exercise performance.

Cognition and brain iron deposition in whole grey matter regions and hippocampal subfields.

Regional brain iron accumulation is observed in many neurodegenerative diseases, including Alzheimer's disease and Parkinson's disease, and is associated with cognitive decline. We explored associations between age, cognition and iron content in grey matter regions and hippocampal subfields in 380 participants of the Aberdeen children of the 1950s cohort and their first-generation relatives (aged 26-72 years). Participants underwent cognitive assessment at the time of MRI scanning. Quantitative susceptibility mapping of these MRI data was used to assess iron content in grey matter regions and in hippocampal subfields. Principle component analysis was performed on cognitive test scores to create a general cognition score. Spline analysis was used with the Akaike information criterion to determine if order 1, 2 or 3 natural splines were optimal for assessing non-linear relationships between regional iron and age. Multivariate linear models were used to assess associations between regional iron and cognition. Higher iron correlated with older age in the left putamen across all ages and in the right putamen of only participants over 58. Whereas a decrease in iron with older age was observed in the right thalamus and left pallidum across all ages. Right amygdala iron levels were associated with poorer general cognition scores and poorer immediate recall scores. Iron was not associated with any measures of cognitive performance in other regions of interest. Our results suggest that, whilst iron in some regions was associated with cognitive performance, there is an overall lack of association between regional iron content and cognitive ability in cognitively healthy individuals.

Post-fatigue ability to activate muscle is compromised across a wide range of torques during acute hypoxic exposure.

The purpose of this study was to assess how severe acute hypoxia alters the neural mechanisms of muscle activation across a wide range of torque output in a fatigued muscle. Torque and electromyography responses to transcranial and motor nerve stimulation were collected from 10 participants (27 years ± 5 years, 1 female) following repeated performance of a sustained maximal voluntary contraction that reduced torque to 60% of the pre-fatigue peak torque. Contractions were performed after 2 h of hypoxic exposure and during a sham intervention. For hypoxia, peripheral blood oxygen saturation was titrated to 80% over a 15-min period and remained at 80% for 2 h. Maximal voluntary torque, electromyography root mean square, voluntary activation and corticospinal excitability (motor evoked potential area) and inhibition (silent period duration) were then assessed at 100%, 90%, 80%, 70%, 50% and 25% of the target force corresponding to the fatigued maximal voluntary contraction. No hypoxia-related effects were identified for voluntary activation elicited during motor nerve stimulation. However, during measurements elicited at the level of the motor cortex, voluntary activation was reduced at each torque output considered (P = .002, ηp 2  = .829). Hypoxia did not impact the correlative linear relationship between cortical voluntary activation and contraction intensity or the correlative curvilinear relationship between motor nerve voluntary activation and contraction intensity. No other hypoxia-related effects were identified for other neuromuscular variables. Acute severe hypoxia significantly impairs the ability of the motor cortex to voluntarily activate fatigued muscle across a wide range of torque output.

Intrinsic Neuromuscular Fatigability in Humans: The Critical Role of Stimulus Frequency.

Electrically evoked contractions provide insight into intrinsic neuromuscular fatigability and also represent a valuable technique to maintain muscle mass in a clinical setting. To appropriately investigate intrinsic fatigability and design optimal stimulation protocols, it would seem to be crucial to stimulate the muscle at a frequency equivalent to the mean motor unit discharge rate expected at the target force level.

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.

The effects of forearm position and contraction intensity on cortical and spinal excitability during a submaximal force steadiness task of the elbow flexors.

Elbow flexor force steadiness is less with the forearm pronated (PRO) compared with neutral (NEU) or supinated (SUP) and may relate to neural excitability. Although not tested in a force steadiness paradigm, lower spinal and cortical excitability was observed separately for biceps brachii in PRO, possibly dependent on contractile status at the time of assessment. This study aimed to investigate position-dependent changes in force steadiness as well as spinal and cortical excitability at a variety of contraction intensities. Thirteen males (26 ± 7 yr; means ± SD) performed three blocks (PRO, NEU, and SUP) of 24 brief (~6 s) isometric elbow flexor contractions (5, 10, 25 or 50% of maximal force). During each contraction, transcranial magnetic stimulation or transmastoid stimulation was delivered to elicit a motor-evoked potential (MEP) or cervicomedullary motor-evoked potential (CMEP), respectively. Force steadiness was lower in PRO compared with NEU and SUP (P ≤ 0.001), with no difference between NEU and SUP. Similarly, spinal excitability (CMEP/maximal M wave) was lower in PRO than NEU (25 and 50% maximal force; P ≤ 0.010) and SUP (all force levels; P ≤ 0.004), with no difference between NEU and SUP. Cortical excitability (MEP/CMEP) did not change with forearm position (P = 0.055); however, a priori post hoc testing for position showed excitability was 39.8 ± 38.3% lower for PRO than NEU at 25% maximal force (P = 0.006). The data suggest that contraction intensity influences the effect of forearm position on neural excitability and that reduced spinal and, to a lesser extent, cortical excitability could contribute to lower force steadiness in PRO compared with NEU and SUP.NEW & NOTEWORTHY To address conflicting reports about the effect of forearm position on spinal and cortical excitability of the elbow flexors, we examine the influence of contraction intensity. For the first time, excitability data are considered in a force steadiness context. Motoneuronal excitability is lowest in pronation and this disparity increases with contraction intensity. Cortical excitability exhibits a similar pattern from 5 to 25% of maximal force. Lower corticospinal excitability likely contributes to relatively poor force steadiness in pronation.

Motor unit contributions to activation reduction and torque steadiness following active lengthening: a study of residual torque enhancement.

Following active lengthening, steady-state isometric (ISO) torque is greater than a purely ISO contraction at the same muscle length, this is referred to as residual torque enhancement (rTE). A phenomenon of rTE is activation reduction, characterized by reduced electromyography (EMG) amplitude for a given torque output. We hypothesized that lower motor unit discharge rates would contribute to activation reduction and lessening torque steadiness. Ten young male subjects performed ISO dorsiflexion contractions at 10 and 20% of maximal voluntary contraction (MVC) torque. During rTE trials, the muscle was activated at 10° of plantar flexion, then the ankle was rotated to the ISO position at 40°. Fine wire electrodes recorded motor unit (MU)-discharge rates and variability from the tibialis anterior. Surface EMG quantified activation reduction, and steadiness was determined as the coefficient of variation of torque. The activation reduction was 44 and 24% at 10 and 20% MVC, respectively (P < 0.05). Fewer MUs were recorded in the rTE than ISO condition at 10% (~47%) and 20% (~36%) MVC (P < 0.05). Discharge rates were 19 and 26% lower in the rTE compared with the ISO condition for 10 and 20% MVC, respectively (P < 0.05), with no difference in variability between conditions (P > 0.05). Steadiness was ~22 and 18% lower for the rTE than ISO condition at 10 and 20% MVC (P < 0.05). Our findings indicate that activation reduction may be attributed to lower MU discharge rate and fewer detectable MUs and that this theoretically contributes to a reduction in steadiness in the rTE condition.NEW & NOTEWORTHY Our findings indicate that lower electromyographic activity during the torque enhanced condition following active lengthening compared with a purely isometric contraction arises from fewer active motor units and a lower discharge rate of those that are active. We used an acute condition of increased torque capacity to induce a decrease in net output of the motor neuron pool during a submaximal task to demonstrate, in humans, the impact of motor unit activity on torque steadiness.

Time course of neuromuscular responses to acute hypoxia during voluntary contractions.

NEW FINDINGS: What is the central question of this study? How does acute hypoxia alter central and peripheral fatigue during brief and sustained maximal voluntary muscle contractions? What is the main finding and its importance? Perception of fatigue during muscle contractions was increased progressively for 2 h after hypoxic exposure. However, an increase in motor cortex excitability and a decrease in voluntary activation of skeletal muscle were observed across the entire protocol when performing brief (3 s) maximal contractions. These adaptations were abolished if the brief contraction was held for a duration of 20 s, which was presumably attributable to a successful redistribution of blood to overcome the reduced oxygen content. ABSTRACT: Few studies have examined the time course of changes in the motor system after acute exposure to hypoxia. Thus, the purpose of this study was to examine how acute hypoxia affects corticospinal excitability, voluntary activation (VA) and the perception of fatigue during brief (3 s) and sustained (20 s) maximal voluntary contractions (MVCs). Fourteen healthy individuals (23 ± 2.2 years of age; four female) were exposed to hypoxia and sham conditions. During hypoxia, peripheral blood oxygen saturation was titrated over a 15 min period and remained at 80% during testing. Corticospinal excitability and VA were assessed before titration (Pre), 0, 1 and 2 h after. At each time point, the brief and sustained elbow flexion MVCs were performed. Motor evoked potentials (MEPs) were obtained using transcranial magnetic stimulation. Superimposed and resting twitches were obtained from motor point stimulation of biceps brachii to calculate the level of VA, and ratings of perceived fatigue were obtained with a modified CR-10 Borg scale. A condition-by-time interaction was detected for the CR-10 Borg scale, whereby perception of fatigue increased progressively throughout the hypoxia protocol. However, main effects of MEP area and VA indicated that corticospinal excitability increased, and VA of the biceps brachii decreased, throughout the hypoxia protocol. Given that these changes in MEP area and VA were seen only when performing the brief MVCs (and not during the sustained MVCs), performing longer contractions might overcome reduced oxygen content by redirecting blood flow to active areas of the motor system.

Modulation of vestibular-evoked responses prior to simple and complex arm movements.

During destabilizing, voluntary arm movements, the vestibular system provides sensory cues related to head motion that are necessary to preserve upright balance. Although sensorimotor processing increases in accordance with task complexity during the preparation phase of reaching, it is unclear whether vestibular signals are also enhanced when maintaining postural control prior to the execution of a voluntary movement. To probe whether vestibular cues are a component of complexity-related increases in sensorimotor processing during movement preparation, vestibular-evoked responses to stochastic (0-25 Hz; root mean square = 1 mA) binaural, bipolar electrical vestibular stimulation (EVS) were examined. These responses were assessed using cumulant density function estimates in the upper and lower limbs prior to ballistic arm movements of varying complexity in both standing (experiment 1) and seated (experiment 2) conditions. In experiment 1, EVS-electromyography (EMG) cumulant density estimates surpassed 95% confidence intervals for biceps and triceps brachii, as well as the left and right medial gastrocnemius. For the latter two muscles, the responses were enhanced 10-18% with increased movement complexity. In experiment 2, the EVS-EMG cumulant density estimates also surpassed 95% confidence intervals in the upper limb, confirming the presence of vestibular-evoked responses while seated; however, the amplitude was significantly less than standing. This study demonstrates the vestibular system contributes to postural stability during the preparation phase of reaching. As such, vestibular-driven signals may be used to update an internal model for upcoming reaching tasks or to prepare for imminent postural disturbances.

The inclusion of interstimulus interval variability does not mitigate electrically-evoked fatigue of the knee extensors.

PURPOSE: Transcutaneous electrical stimulation (TES) is used to activate muscles when volitional capacity is impaired but potential benefits are limited by rapid force loss (fatigue). Most TES fatigue protocols employ constant-frequency trains, with stimuli at a fixed interstimulus interval (ISI); however, a brief ISI between the first two pulses (variable-frequency train, VFT) to maximize the catchlike property of muscle can attenuate fatigue development. The purpose of this study was to investigate if a VFT that simulates intrinsic variability of voluntary motor unit discharge rates would also mitigate fatigue, owing to the sensitivity of muscle to acute activation history. METHODS: On two visits, 24 healthy adults (25.3 ± 3.7 years; 12 females) received 3 min of intermittent TES to the quadriceps of the dominant leg. Trains of eight pulses at 10 Hz were delivered with a constant (100 ms) or variable ISI (80-120 ms). Contractile impulse, rate of force development (RFD), and rate of relaxation (RFR) were determined for each tetanus RESULTS: During fatigue and recovery, contractile impulse did not differ between protocols (p ≥ 0.796) and sexes (p ≥ 0.493), with values of 77 ± 17% control at task end and 125 ± 19% control 2 min later. RFD and RFR also showed no effect of the protocol (p ≥ 0.310) or participant sex (p ≥ 0.119). Both measures slowed (38 ± 23% and 33 ± 22%, respectively) but dissociated during recovery as RFD remained 16 ± 18% below control at 5 min, whereas RFR recovered to control by 30 s (101 ± 22%). CONCLUSION: Contrary to expectations, the VFT protocol did not attenuate fatigue development, which suggests no benefit to mimicking the inherent variability of motor unit discharge rates.

The Time Course of Motoneuronal Excitability during the Preparation of Complex Movements.

For a simple RT task, movement complexity increases RT and also corticospinal excitability, as measured by the motor evoked potential (MEP) elicited by TMS of the motor cortex. However, it is unknown if complexity-related increases in corticospinal excitability during the preparation of movement are mediated at the cortical or spinal level. The purposes of this study were to establish a time course of motoneuronal excitability before prime mover activation and to assess task-dependent effects of complex movements on motoneuronal and cortical excitability in a simple RT paradigm. It was hypothesized that motoneuronal and cortical excitability would increase before prime mover activation and in response to movement complexity. In a seated position, participants completed ballistic elbow extension/flexion movements with their dominant arm to one, two, or three targets. TMS and transmastoid stimulation (TS) were delivered at 0%, 70%, 80% or 90% of mean premotor RT for each complexity level. Stimulus intensities were set to elicit MEPs and cervicomedullary MEPs (CMEPs) of ∼10% of the maximal M-wave in the triceps brachii. Compared with 0% RT, motoneuronal excitability (CMEP amplitude) was already 10% greater at 70% RT. CMEP amplitude also increased with movement complexity as both the two- and three-movement conditions had greater motoneuronal excitability than the one-movement condition (p < .038). Importantly, when normalized to the CMEP, there was no increase in MEP amplitude. This suggests that complexity-related increases in corticospinal excitability are likely to be mediated more by increased excitability at a motoneuronal than cortical level.

Corticospinal excitability is enhanced while preparing for complex movements.

Movement complexity is known to increase reaction time (RT). More recently, transcranial magnetic stimulation (TMS) of the motor cortex has revealed that movement complexity can alter corticospinal excitability. However, the impact of a sequential addition of movement components on corticospinal excitability during the preparatory phase of a simple RT task is unknown. Thus, the purpose of this study was to examine how motor evoked potentials (MEPs) in the premotor period were affected by the complexity of a movement in a simple RT paradigm. Participants (n = 12) completed ballistic movements with their dominant arm, in which they directed a robotic handle to one, two or three targets (32 trials per condition). TMS was delivered prior to movement at 0, 70, 80 or 90% of each participant's mean premotor RT, at the stimulator intensity which yielded a triceps brachii MEP of ~ 10% the maximal M-wave. As expected, premotor RT slowed with increasing task complexity. Although background electromyographic activity (EMG) of the triceps brachii during the preparation phase did not differ among conditions, MEP amplitude increased with movement complexity (i.e., MEPs were greater for the 2- and 3-movement conditions, compared to the 1-movement condition at 80% of premotor RT). We propose the lengthened RTs could be due in part to less suppression of particular motor circuits, while other circuitry is responsible for the increased MEPs. This study demonstrates that, prior to movement, corticospinal excitability increases as a consequence of movement complexity.

Central contributions to torque depression: an antagonist perspective.

Torque depression (TD) is the reduction in steady-state isometric torque following active muscle shortening when compared to an isometric reference contraction at the same muscle length and activation level. Central nervous system excitability differs in the TD state. While torque production about a joint is influenced by both agonist and antagonist muscle activation, investigations of corticospinal excitability have focused on agonist muscle groups. Hence, it is unknown how the TD state affects spinal and supraspinal excitability of an antagonist muscle. Eight participants (~ 24y, three female) performed 14 submaximal dorsiflexion contractions at the intensity needed to maintain a level of integrated electromyographic activity in the soleus equivalent to 15% of that recorded during a maximum plantar flexion contraction. The seven contractions of the TD protocol included a 2 s isometric phase at an ankle angle of 140°, a 1 s shortening phase at 40°/s, and a 7 s isometric phase at an angle of 100°. The seven isometric reference contractions were performed at an ankle angle of 100° for 10 s. Motor evoked potentials (MEPs), cervicomedullary motor evoked potentials (CMEPs), and maximal M-waves (Mmax) were recorded from the soleus in both conditions. In the TD compared to isometric reference state, a 13% reduction in dorsiflexor torque was accompanied by 10% lower spinal excitability (normalized CMEP amplitude; CMEP/Mmax), and 17% greater supraspinal excitability (normalized MEP amplitude; MEP/CMEP) for the soleus muscle. These findings demonstrate a neuromechanical coupling following active muscle shortening and indicate that the underlying mechanisms of TD influence antagonist activation during voluntary force production.

UBC-Nepal expedition: acclimatization to high-altitude increases spinal motoneurone excitability during fatigue in humans.

KEY POINTS: Acute exposure and acclimatization to hypoxia are associated with an impairment and partial recovery, respectively, of the capability of the central nervous system to drive muscles during prolonged efforts. Motoneurones play a vital role in muscle contraction and in fatigue, although the effect of hypoxia on motoneurone excitability during exercise has not been assessed in humans. We studied the impact of fatigue on motoneurone excitability in normoxia, acute and chronic exposure (5050 m) to hypoxia. Performance was worse in acute hypoxia but recovered to the normoxic standard in chronic hypoxia, in parallel with an increased excitability of the motoneurones compared to acute exposure to hypoxia. These findings reveal that prolonged hypoxia causes a heightened motoneurone responsiveness during fatiguing exercise; such an adaptation might favour the restoration of performance where low pressures of oxygen are chronically present. ABSTRACT: The fatigue-induced failure of the motor cortex to drive muscles maximally increases in acute hypoxia (AH) compared to normoxia (N) but improves with acclimatization (chronic hypoxia; CH). Despite their importance to muscle output, it is unknown how locomotor motoneurones in humans are affected by hypoxia and acclimatization. Eleven participants performed 16 min of submaximal [25% maximal torque (maximal voluntary contraction, MVC)] intermittent isometric elbow flexions in N, AH (environmental chamber) and CH (7-14 days at 5050 m) (PI O2  = 140, 74 and 76 mmHg, respectively). For each minute of the fatigue protocol, motoneurone responsiveness was measured with cervicomedullary stimulation delivered 100 ms after transcranial magnetic stimulation (TMS) used to transiently silence voluntary drive. Every 2 min, cortical voluntary activation (cVA) was measured with TMS. After the task, MVC torque declined more in AH (∼20%) than N and CH (∼11% and 14%, respectively, P < 0.05), with no differences between N and CH. cVA was lower in AH than N and CH at baseline (∼92%, 95% and 95%, respectively) and at the end of the protocol (∼82%, 90% and 90%, P < 0.05). During the fatiguing task, motoneurone excitability in N and AH declined to ∼65% and 40% of the baseline value (P < 0.05). In CH, motoneurone excitability did not decline and, late in the protocol, was ∼40% higher compared to AH (P < 0.05). These novel data reveal that acclimatization to hypoxia leads to a heightened motoneurone responsiveness during fatiguing exercise. Positive spinal and supraspinal adaptations during extended periods at altitude might therefore play a vital role for the restoration of performance after acclimatization to hypoxia.

UBC-Nepal expedition: peripheral fatigue recovers faster in Sherpa than lowlanders at high altitude.

KEY POINTS: The reduced oxygen tension of high altitude compromises performance in lowlanders. In this environment, Sherpa display superior performance, but little is known on this issue. Sherpa present unique genotypic and phenotypic characteristics at the muscular level, which may enhance resistance to peripheral fatigue at high altitude compared to lowlanders. We studied the impact of gradual ascent and exposure to high altitude (5050 m) on peripheral fatigue in age-matched lowlanders and Sherpa, using intermittent electrically-evoked contractions of the knee extensors. Peripheral fatigue (force loss) was lower in Sherpa during the first part of the protocol. Post-protocol, the rate of force development and contractile impulse recovered faster in Sherpa than in lowlanders. At any time, indices of muscle oxygenation were not different between groups. Muscle contractile properties in Sherpa, independent of muscle oxygenation, were less perturbed by non-volitional fatigue. Hence, elements within the contractile machinery contribute to the superior physical performance of Sherpa at high altitude. ABSTRACT: Altitude-related acclimatisation is characterised by marked muscular adaptations. Lowlanders and Sherpa differ in their muscular genotypic and phenotypic characteristics, which may influence peripheral fatigability at altitude. After gradual ascent to 5050 m, 12 lowlanders and 10 age-matched Sherpa (32 ± 10 vs. 31 ± 11 years, respectively) underwent three bouts (separated by 15 s rest) of 75 intermittent electrically-evoked contractions (12 pulses at 15 Hz, 1.6 s between train onsets) of the dominant leg quadriceps, at the intensity which initially evoked 30% of maximal voluntary force. Trains were also delivered at minutes 1, 2 and 3 after the protocol to measure recovery. Tissue oxygenation index (TOI) and total haemoglobin (tHb) were quantified by a near-infrared spectroscopy probe secured over rectus femoris. Superficial femoral artery blood flow was recorded using ultrasonography, and delivery of oxygen was estimated (eDO2 ). At the end of bout 1, peak force was greater in Sherpa than in lowlanders (91.5% vs. 84.5% baseline, respectively; P < 0.05). Peak rate of force development (pRFD), the first 200 ms of the contractile impulse (CI200 ), and half-relaxation time (HRT) recovered faster in Sherpa than in lowlanders (percentage of baseline at 1 min: pRFD: 89% vs. 74%; CI200 : 91% vs. 80%; HRT: 113% vs. 123%, respectively; P < 0.05). Vascular measures were pooled for lowlanders and Sherpa as they did not differ during fatigue or recovery (P < 0.05). Mid bout 3, TOI was decreased (90% baseline) whereas tHb was increased (109% baseline). After bout 3, eDO2 was markedly increased (1266% baseline). The skeletal muscle of Sherpa seemingly favours repeated force production at altitude for similar oxygen delivery compared to lowlanders.

Fatigue-related group III/IV muscle afferent feedback facilitates intracortical inhibition during locomotor exercise.

KEY POINTS: This study investigated the influence of group III/IV muscle afferents on corticospinal excitability during cycling exercise and focused on GABAB neuron-mediated inhibition as a potential underlying mechanism. The study provides novel evidence to demonstrate that group III/IV muscle afferent feedback facilitates inhibitory intracortical neurons during whole body exercise. Firing of these interneurons probably contributes to the development of central fatigue during physical activity. ABSTRACT: We investigated the influence of group III/IV muscle afferents in determining corticospinal excitability during cycling exercise and focused on GABAB neuron-mediated inhibition as a potential underlying mechanism. Both under control conditions (CTRL) and with lumbar intrathecal fentanyl (FENT) impairing feedback from group III/IV leg muscle afferents, subjects (n = 11) cycled at a comparable vastus-lateralis EMG signal (∼0.26 mV) before (PRE; 100 W) and immediately after (POST; 90 ± 2 W) fatiguing constant-load cycling exercise (80% Wpeak; 221 ± 10 W; ∼8 min). During, PRE and POST cycling, single and paired-pulse (100 ms interstimulus interval) transcranial magnetic stimulations (TMS) were applied to elicit unconditioned and conditioned motor-evoked potentials (MEPs), respectively. To distinguish between cortical and spinal contributions to the MEPs, cervicomedullary stimulations (CMS) were used to elicit unconditioned (CMS only) and conditioned (TMS+CMS, 100 ms interval) cervicomedullary motor-evoked potentials (CMEPs). While unconditioned MEPs were unchanged from PRE to POST in CTRL, unconditioned CMEPs increased significantly, resulting in a decrease in unconditioned MEP/CMEP (P < 0.05). This paralleled a reduction in conditioned MEP (P < 0.05) and no change in conditioned CMEP. During FENT, unconditioned and conditioned MEPs and CMEPs were similar and comparable during PRE and POST (P > 0.2). These findings reveal that feedback from group III/IV muscle afferents innervating locomotor muscle decreases the excitability of the motor cortex during fatiguing cycling exercise. This impairment is, at least in part, determined by the facilitating effect of these sensory neurons on inhibitory GABAB intracortical interneurons.