The effect of acute intermittent hypoxia on human limb motoneurone output.

NEW FINDINGS: What is the central question of this study? Does a single session of repeated bouts of acute intermittent hypoxic breathing enhance the motoneuronal output of the limb muscles of healthy able-bodied participants? What is the main finding and its importance? Compared to breathing room air, there were some increases in motoneuronal output following acute intermittent hypoxia, but the increases were variable across participants and in time after the intervention and depended on which neurophysiological measure was checked. ABSTRACT: Acute intermittent hypoxia (AIH) induces persistent increases in output from rat phrenic motoneurones. Studies in people with spinal cord injury (SCI) suggest that AIH improves limb performance, perhaps via postsynaptic changes at cortico-motoneuronal synapses. We assessed whether limb motoneurone output in response to reflex and descending synaptic activation is facilitated after one session of AIH in healthy able-bodied volunteers. Fourteen participants completed two experimental days, with either AIH or a sham intervention (randomised crossover design). We measured H-reflex recruitment curves and homosynaptic post-activation depression (HPAD) of the H-reflex in soleus, and motor evoked potentials (MEPs) evoked by transcranial magnetic stimulation (TMS) and their recruitment curves in first dorsal interosseous. All measurements were performed at rest and occurred at baseline, 0, 20, 40 and 60 min post-intervention. The intervention was 30 min of either normoxia (sham, F i O 2 ${F_{{\rm{i}}{{\rm{O}}_{\rm{2}}}}}$  ≈ 0.21) or AIH (alternate 1-min hypoxia [ F i O 2 ${F_{{\rm{i}}{{\rm{O}}_{\rm{2}}}}}$  ≈ 0.09], 1-min normoxia). After AIH, the H-reflex recruitment curve shifted leftward. Lower stimulation intensities were needed to evoke 5%, 50% and 99% of the maximal H-reflex at 40 and 60 min after AIH (P < 0.04). The maximal H-reflex, recruitment slope and HPAD were unchanged after AIH. MEPs evoked by constant intensity TMS were larger 40 min after AIH (P = 0.027). There was no change in MEP recruitment or the maximal MEP. In conclusion, some measures of the evoked responses from limb motoneurones increased after a single AIH session, but only at discrete time points. It is unclear to what extent these changes alter functional performance.

Declines in muscle contractility and activation during isometric contractions of the knee extensors vary with contraction intensity and exercise volume.

NEW FINDINGS: What is the central question of this study? Is there a critical threshold beyond which the loss of muscle contractility is regulated by the level of muscle activation during single-limb exercise of differing intensities and volumes? What is the main finding and its importance? Plateaus in the decline in muscle contractility during single-limb knee extension depended on both exercise volume and contraction intensity.  A plateau was only evident with an increase in exercise volume.  Muscle activation increased and did not decline despite substantial reductions in contractility. The findings indicate that the decrease in muscle contractility exhibited by resistance-trained men during the performance of submaximal isometric contractions with the knee extensors was not regulated by the level of muscle activation. ABSTRACT: Our study examined the influence of contraction intensity and exercise volume on changes in muscle contractility and activation of the knee extensor muscles. Maximal voluntary torque (MVT) and rate of change in torque, surface electromyograms, voluntary activation, V-waves and quadriceps resting twitch measures were assessed in 10 resistance-trained men during two experimental sessions. Each session began with an initial baseline series of contractions at a fixed intensity of 40% or 80% MVT. The 40%-only session continued with five contractions to task failure at 40% MVT. The 80% session continued with five contractions to failure each at 80%, 60% and 40% MVT. Greater reductions in MVT were observed during the baseline contractions of the 40%-only session compared with the 80% session at each matched-volume time point (P < 0.05), with similar changes in twitch values (P < 0.001). MVT and twitch values plateaued at each intensity during the 80% session and were significantly different across intensities: 80% > 60% > 40% (P < 0.001). There were no differences for measures during the five contractions at 40% MVT performed on the different days, despite a greater volume of exercise performed prior to the 40% MVT during the 80% session. At each contraction intensity, a plateau in contractility loss was observed as more contractions were performed. We found that initial increases in muscle activation were maintained in the presence of increases in exercise volume and, in contrast to the critical-threshold hypothesis, did not decline in parallel with reductions in muscle contractility.

Muscle activation does not increase after a fatigue plateau is reached during 8 sets of resistance exercise in trained individuals.

The premise of eliciting the greatest acute fatigue is accepted and used for designing programs that include excessive, potentially dangerous volumes of high-intensity resistance exercise. There is no evidence examining acute fatigue and neuromuscular responses throughout multiple sets of moderate-to-high intensity resistance exercise. Fifteen resistance-trained male subjects performed a single exercise session using 8 sets of Bulgarian split squats performed at 75% maximal force output. Maximal force output (N) was measured after every set of repetitions. Electromyographic (EMG) activity of vastus lateralis was monitored during all force trials and exercise repetitions. Repetitions per set decreased from the first to the third set (p < 0.001). Maximal force output decreased from preexercise to set 4 (p < 0.001). Electromyographic amplitudes during exercise did not change. Secondary subgroup analysis was performed based on the presence, or not, of a fatigue plateau (<5% reductions in maximal force output in subsequent sets). Nine participants exhibited a fatigue plateau, and 6 did not. Participants who plateaued performed less first-set repetitions, accrued less total volume, and did not exhibit increases in EMG amplitudes during exercise. Initial strength levels and neuromuscular demand of the exercise was the same between the subgroups. These data suggest that there are individual differences in the training session responses when prescribing based off a percentage of maximal strength. When plateaus in fatigue and repetitions per set are reached, subsequent sets are not likely to induce greater fatigue and muscle activation. High-volume resistance exercise should be carefully prescribed on an individual basis, with intrasession technique and training responsiveness continually monitored.

Motor evoked potentials in the human upper and lower limb do not increase after single 30-minute sessions of acute intermittent hypoxia.

Acute Intermittent Hypoxia (AIH) can induce sustained facilitation of motor output in people with spinal cord injury (SCI). Most studies of corticospinal tract excitability in humans have used 9% FiO2 AIH (AIH-9%), with inconsistent outcomes. We investigated the effect of single sessions of 9% FiO2 and 12% FiO2 AIH (AIH-12%) on corticospinal excitability of a hand and leg muscle in able-bodied adults. Ten naïve participants without SCI completed three sessions comprising 15 cycles of one minute of AIH-9%, AIH-12% or sham (SHAM-21%) followed by one minute of room air (21% FiO2) in a randomised crossover design. Motor evoked potentials (MEPs, n=30, ~1mV) elicited at rest by transcranial magnetic stimulation and maximal M-waves (Mmax) evoked by peripheral nerve stimulation were measured from the first dorsal interosseous (FDI) and tibialis anterior (TA) muscles at baseline and at ~0, 20, 40, and 60 minutes post-intervention. AIH-9% induced the greatest reduction in SpO2 (to 85% vs 93% and 100% in AIH-12% and SHAM-21%, respectively; p < 0.001) and the greatest increase in ventilation (by 22% vs 12% and -3% in AIH-12% and SHAM-21%, respectively (p<0.001)). There was no difference in MEP amplitudes (%Mmax) after any of the three conditions (AIH-9%, AIH-12%, SHAM-21%) for both FDI (p=0.399) and TA (p=0.582). Despite greater cardiorespiratory changes during AIH-9%, there was no evidence of corticospinal facilitation (tested with MEPs) in this study. Further studies could explore variability in response to AIH between individuals and other methods to measure motor facilitation in people with and without spinal cord injuries.

Transcutaneous spinal stimulation in people with and without spinal cord injury: Effect of electrode placement and trains of stimulation on threshold intensity.

Transcutaneous spinal cord stimulation (TSS) is purported to improve motor function in people after spinal cord injury (SCI). However, several methodology aspects are yet to be explored. We investigated whether stimulation configuration affected the intensity needed to elicit spinally evoked motor responses (sEMR) in four lower limb muscles bilaterally. Also, since stimulation intensity for therapeutic TSS (i.e., trains of stimulation, typically delivered at 15-50 Hz) is sometimes based on the single-pulse threshold intensity, we compared these two stimulation types. In non-SCI participants (n = 9) and participants with a SCI (n = 9), three different electrode configurations (cathode-anode); L1-midline (below the umbilicus), T11-midline and L1-ASIS (anterior superior iliac spine; non-SCI only) were compared for the sEMR threshold intensity using single pulses or trains of stimulation which were recorded in the vastus medialis, medial hamstring, tibialis anterior, medial gastrocnemius muscles. In non-SCI participants, the L1-midline configuration showed lower sEMR thresholds compared to T11-midline (p = 0.002) and L1-ASIS (p < 0.001). There was no difference between T11-midline and L1-midline for participants with SCI (p = 0.245). Spinally evoked motor response thresholds were ~13% lower during trains of stimulation compared to single pulses in non-SCI participants (p < 0.001), but not in participants with SCI (p = 0.101). With trains of stimulation, threshold intensities were slightly lower and the incidence of sEMR was considerably lower. Overall, stimulation threshold intensities were generally lower with the L1-midline electrode configuration and is therefore preferred. While single-pulse threshold intensities may overestimate threshold intensities for therapeutic TSS, tolerance to trains of stimulation will be the limiting factor in most cases.

Respiratory-related evoked potentials in chronic obstructive pulmonary disease and healthy aging.

Altered neural processing and increased respiratory sensations have been reported in chronic obstructive pulmonary disease (COPD) as larger respiratory-related evoked potentials (RREPs), but the effect of healthy-aging has not been considered adequately. We tested RREPs evoked by brief airway occlusions in 10 participants with moderate-to-severe COPD, 11 age-matched controls (AMC) and 14 young controls (YC), with similar airway occlusion pressure stimuli across groups. Mean age was 76 years for COPD and AMC groups, and 30 years for the YC group. Occlusion intensity and unpleasantness was rated using the modified Borg scale, and anxiety rated using the Hospital Anxiety and Depression Scale. There was no difference in RREP peak amplitudes across groups, except for the N1 peak, which was significantly greater in the YC group than the COPD and AMC groups (p = 0.011). The latencies of P1, P2 and P3 occurred later in COPD versus YC (p < 0.05). P3 latency occurred later in AMC than YC (p = 0.024). COPD and AMC groups had similar Borg ratings for occlusion intensity (3.0 (0.5, 3.5) [Median (IQR)] and 3.0 (3.0, 3.0), respectively; p = 0.476) and occlusion unpleasantness (1.3 (0.1, 3.4) and 1.0 (0.75, 2.0), respectively; p = 0.702). The COPD group had a higher anxiety score than AMC group (p = 0.013). A higher N1 amplitude suggests the YC group had higher cognitive processing of respiratory inputs than the COPD and AMC groups. Both COPD and AMC groups showed delayed neural responses to the airway occlusion, which may indicate impaired processing of respiratory sensory inputs in COPD and healthy aging.

Voluntary activation of knee extensor muscles with transcranial magnetic stimulation.

We examined if transcranial magnetic stimulation (TMS) is a valid tool for assessment of voluntary activation of the knee extensors in healthy individuals. Maximal M-waves (Mmax) of vastus lateralis (VL) were evoked with electrical stimulation of femoral nerve (FNS); Mmax of medial hamstrings (HS) was evoked with electrical stimulation of sciatic nerve branches; motor evoked potentials (MEPs) of VL and HS were evoked with TMS; superimposed twitches (SIT) of knee extensors were evoked with FNS and TMS. In study 1, TMS intensity [69% output (SD: 5)] was optimized for MEP sizes, but guidelines for test validity could not be met. Agonist VL MEPs were too small [51.4% Mmax (SD: 11.9); guideline ≥70% Mmax] and antagonist HS MEPs were too big [16.5% Mmax (SD: 10.3); guideline <10% Mmax]. Consequently, the TMS estimated resting twitch [99.1 N (SD: 37.2)] and FNS resting twitch [142.4 N (SD: 41.8)] were different. In study 2, SITs at 90% maximal voluntary contraction (MVC) were similar between TMS [16.1 N (SD: 10.3)] and FNS [20.9 N (SD: 16.7)], when TMS intensity was optimized for this purpose, suggesting a procedure that combines TMS SITs with FNS resting twitches could be valid. In study 3, which tested the TMS intensity [56% output (SD: 18)] that evoked the largest SIT at 90% MVC, voluntary activation from TMS [87.3% (SD: 7.1)] and FNS [84.5% (SD: 7.6)] was different. In sum, the contemporary procedure for TMS-based voluntary activation of the knee extensors is invalid. A modified procedure improves validity but only in individuals who meet rigorous inclusion criteria for SITs and MEPs.NEW & NOTEWORTHY We discovered that the contemporary procedure for assessing voluntary activation of the knee extensor muscles with transcranial magnetic stimulation (TMS) is invalid. TMS activates too few agonist quadriceps motoneurons and too many antagonist hamstrings motoneurons to estimate the resting twitch accurately. A modified procedure, in which TMS-evoked superimposed twitches are considered together with the resting twitch from femoral nerve stimulation, is valid but only in select individuals who meet rigorous eligibility criteria.

Fatigue-related Feedback from Calf Muscles Impairs Knee Extensor Voluntary Activation.

INTRODUCTION: Fatigue-related group III/IV muscle afferent firing from agonist, antagonist or distal muscles impairs the ability to drive the elbow flexors maximally, that is, reduces voluntary activation. In the lower limb, the effect of feedback from distal muscles on the proximal knee extensors is unknown. Here, we test whether maintained group III/IV afferent feedback from the plantarflexor muscles reduces voluntary activation of the knee extensors. METHODS: On 2 d, voluntary activation of the knee extensors during maximal voluntary contractions (MVCs) was assessed in 12 participants before and after a 3-min fatiguing task of the plantarflexors. On 1 d, an inflatable cuff around the calf occluded blood flow for 2 min immediately postexercise (cuff day). The other day had no occlusion (no-cuff day). Supramaximal stimulation of the femoral nerve elicited superimposed twitches during MVC of the knee extensors and resting twitches 2 to 3 s after relaxation. Pain (0-10 point scale) was reported throughout. RESULTS: In the 2 min after the 3-min fatiguing plantarflexor task, voluntary activation was 5.3% (SD, 7%) lower on the cuff day than on the no-cuff day (P = 0.045), and MVC force was reduced by 13% (SD, 16%) (P = 0.021). The resting twitch was similar on both days (P = 0.98). Pain rated 4.9 points higher with the cuff inflated (P = 0.001). CONCLUSIONS: Maintained group III/IV afferent feedback from the fatigued plantarflexor muscles reduced maximal force and voluntary activation of the unfatigued knee extensors, suggesting that afferents from the calf act centrally to inhibit the ability to drive the motoneurones of the knee extensors.

Causal Mediation Analysis Could Resolve Whether Training-Induced Increases in Muscle Strength are Mediated by Muscle Hypertrophy.

Resistance training increases muscle size (i.e., causes hypertrophy) and muscle strength, particularly in untrained individuals. Hypertrophy is widely believed to be one of the mechanisms (i.e., a mediator) by which resistance training increases strength. However, some researchers have questioned whether training-induced hypertrophy causes increases in strength. One approach to resolving this issue has been to use correlations between training-induced changes in muscle size and strength to infer the effect of hypertrophy on strength. This is problematic because correlations between changes in muscle size and strength may be confounded (i.e., correlation is not causation). Another approach has involved randomizing participants to different volumes of exercise to create different levels of hypertrophy and then comparing the strength increases associated with different levels of hypertrophy. This approach is also problematic because the unit of randomization is exercise volume rather than hypertrophy, and the potential for confounding remains. Thus, a new approach is needed to determine the extent to which hypertrophy increases muscle strength. Here, we introduce resistance training researchers to causal mediation analysis and recommend that it be used to resolve the current debate. Causal mediation analysis potentially provides an unconfounded estimate of the effect of a mediating variable (hypertrophy) on an outcome (strength). This analysis is supplemented by causal maps that help conceptualize research questions and identify potential confounders. In addition to resolving the debate on hypertrophy, causal mediation analysis can be used to answer a host of other questions about mechanisms in the health sciences.

Motoneuron excitability of the quadriceps decreases during a fatiguing submaximal isometric contraction.

During fatiguing voluntary contractions, the excitability of motoneurons innervating arm muscles decreases. However, the behavior of motoneurons innervating quadriceps muscles is unclear. Findings may be inconsistent because descending cortical input influences motoneuron excitability and confounds measures during exercise. To overcome this limitation, we examined effects of fatigue on quadriceps motoneuron excitability tested during brief pauses in descending cortical drive after transcranial magnetic stimulation (TMS). Participants ( n = 14) performed brief (~5-s) isometric knee extension contractions before and after a 10-min sustained contraction at ~25% maximal electromyogram (EMG) of vastus medialis (VM) on one ( n = 5) or two ( n = 9) days. Electrical stimulation over thoracic spine elicited thoracic motor evoked potentials (TMEP) in quadriceps muscles during ongoing voluntary drive and 100 ms into the silent period following TMS (TMS-TMEP). Femoral nerve stimulation elicited maximal M-waves (Mmax). On the 2 days, either large (~50% Mmax) or small (~15% Mmax) TMS-TMEPs were elicited. During the 10-min contraction, VM EMG was maintained ( P = 0.39), whereas force decreased by 52% (SD 13%) ( P < 0.001). TMEP area remained unchanged ( P = 0.9), whereas large TMS-TMEPs decreased by 49% (SD 28%) ( P = 0.001) and small TMS-TMEPs by 71% (SD 22%) ( P < 0.001). This decline was greater for small TMS-TMEPs ( P = 0.019; n = 9). Therefore, without the influence of descending drive, quadriceps TMS-TMEPs decreased during fatigue. The greater reduction for smaller responses, which tested motoneurons that were most active during the contraction, suggests a mechanism related to repetitive activity contributes to reduced quadriceps motoneuron excitability during fatigue. By contrast, the unchanged TMEP suggests that ongoing drive compensates for altered motoneuron excitability. NEW & NOTEWORTHY We provide evidence that the excitability of quadriceps motoneurons decreases with fatigue. Our results suggest that altered intrinsic properties brought about by repetitive activation of the motoneurons underlie their decreased excitability. Furthermore, we note that testing during voluntary contraction may not reflect the underlying depression of motoneuron excitability because of compensatory changes in ongoing voluntary drive. Thus, this study provides evidence that processes intrinsic to the motoneuron contribute to muscle fatigue of the knee extensors.

The Magnitude of Peripheral Muscle Fatigue Induced by High and Low Intensity Single-Joint Exercise Does Not Lead to Central Motor Output Reductions in Resistance Trained Men.

PURPOSE: To examine quadriceps muscle fatigue and central motor output during fatiguing single joint exercise at 40% and 80% maximal torque output in resistance trained men. METHOD: Ten resistance trained men performed fatiguing isometric knee extensor exercise at 40% and 80% of maximal torque output. Maximal torque, rate of torque development, and measures of central motor output and peripheral muscle fatigue were recorded at two matched volumes of exercise, and after a final contraction performed to exhaustion. Central motor output was quantified from changes in voluntary activation, normalized surface electromyograms (EMG), and V-waves. Quadriceps muscle fatigue was assessed from changes in the size and shape of the resting potentiated twitch (Q.(pot.tw)). Central motor output during the exercise protocols was estimated from EMG and interpolated twitches applied during the task (VA(sub)). RESULTS: Greater reductions in maximal torque and rate of torque development were observed during the 40% protocol (p<0.05). Maximal central motor output did not change for either protocol. For the 40% protocol reductions from pre-exercise in rate and amplitude variables calculated from the Q.(pot.tw) between 66.2 to 70.8% (p<0.001) exceeded those observed during the 80% protocol (p<0.01). V-waves only declined during the 80% protocol between 56.8 ± 35.8% to 53.6 ± 37.4% (p<0.05). At the end of the final 80% contraction VA(sub) had increased from 91.2 ± 6.2% to 94.9 ± 4.7% (p = 0.005), but a greater increase was observed during the 40% contraction where VA(sub) had increased from 67.1 ± 6.1% to 88.9 ± 9.6% (p<0.001). CONCLUSION: Maximal central motor output in resistance trained men is well preserved despite varying levels of peripheral muscle fatigue. Upregulated central motor output during the 40% contraction protocol appeared to elicit greater peripheral fatigue. V-waves declines during the 80% protocol suggest intensity dependent modulation of the Ia afferent pathway.