Excitatory drive to spinal motoneurones is necessary for serotonin to modulate motoneurone excitability via 5-HT2 receptors in humans.

Serotonin modulates corticospinal excitability, motoneurone firing rates and contractile strength via 5-HT2 receptors. However, the effects of these receptors on cortical and motoneurone excitability during voluntary contractions have not been explored in humans. Therefore, the purpose of this study was to investigate how 5-HT2 antagonism affects corticospinal and motoneuronal excitability with and without descending drive to motoneurones. Twelve individuals (aged 24 ± 4 years) participated in a double-blind, placebo-controlled, crossover study, whereby the 5-HT2 antagonist cyproheptadine was administered. Transcranial magnetic stimulation (TMS) was delivered to the motor cortex to produce motor evoked potentials (MEPs), and electrical stimulation at the cervicomedullary junction was used to generate cervicomedullary motor evoked potentials (CMEPs) in the biceps brachii at rest and during a range of submaximal elbow flexions. Evoked potentials were also obtained after a conditioning TMS pulse to produce conditioned MEPs and CMEPs (100 ms inter-stimulus interval). 5-HT2 antagonism reduced maximal torque (p < 0.001), and compared to placebo, reduced unconditioned MEP amplitude at rest (p = 0.003), conditioned MEP amplitude at rest (p = 0.033) and conditioned MEP amplitude during contractions (p = 0.020). 5-HT2 antagonism also increased unconditioned CMEP amplitude during voluntary contractions (p = 0.041) but not at rest. Although 5-HT2 antagonism increased long-interval intracortical inhibition, net corticospinal excitability was unaffected during voluntary contractions. Given that spinal motoneurone excitability was only affected when descending drive to motoneurones was present, the current study indicates that excitatory drive is necessary for 5-HT2 receptors to regulate motoneurone excitability but not intracortical circuits.

Does lower-limb osteoarthritis alter motor cortex descending drive and voluntary activation? A systematic review and meta-analysis.

Purpose: The aim of the study was to quantify motor cortex descending drive and voluntary activation (VA) in people with lower-limb OA compared to controls. Methods: A systematic review and meta-analysis according to the PRISMA guidelines was carried out. Seven databases were searched until 30 December 2022. Studies assessing VA or responses to transcranial magnetic stimulation (TMS; i.e. motor evoked potential, intracortical facilitation, motor threshold, short-interval intracortical inhibition, and silent period) were included. Study quality was assessed using Joanna Briggs Institute criteria and evidence certainty using GRADE. The meta-analysis was performed using RevMan inverse variance, mixed-effect models. Results: Eighteen studies were included, all deemed low-quality. Quadriceps VA was impaired with knee OA compared to healthy controls (standardised mean difference (SMD) = 0.84, 95% CI = -1.12-0.56, low certainty). VA of the more symptomatic limb was impaired (SMD = 0.42, 95% CI = -0.75-0.09, moderate certainty) compared to the other limb in people with hip/knee OA. As only two studies assessed responses to TMS, very low-certainty evidence demonstrated no significant difference between knee OA and healthy controls for motor evoked potential, intracortical facilitation, resting motor threshold or short-interval intracortical inhibition. Conclusions: Low-certainty evidence suggests people with knee OA have substantial impairments in VA of their quadriceps muscle when compared to healthy controls. With moderate certainty we conclude that people with hip and knee OA had larger impairments in VA of the quadriceps in their more painful limb compared to their non-affected/other limb.

Effects of jaw clenching and mental stress on persistent inward currents estimated by two different methods.

Spinal motoneuron firing depends greatly on persistent inward currents (PICs), which in turn are facilitated by the neuromodulators serotonin and noradrenaline. The aim of this study was to determine whether jaw clenching (JC) and mental stress (MS), which may increase neuromodulator release, facilitate PICs in human motoneurons. The paired motor unit (MU) technique was used to estimate PIC contribution to motoneuron firing. Surface electromyograms were collected using a 32-channel matrix on gastrocnemius medialis (GM) during voluntary, ramp, plantar flexor contractions. MU discharges were identified, and delta frequency (ΔF), a measure of recruitment-derecruitment hysteresis, was calculated. Additionally, another technique was used (VibStim) that evokes involuntary contractions that persist after cessation of combined Achilles tendon vibration and triceps surae neuromuscular electrical stimulation. VibStim measures of plantar flexor torque and soleus activity may reflect PIC activation. ΔF was not significantly altered by JC (p = .679, n = 18, 9 females) or MS (p = .147, n = 14, 5 females). However, all VibStim variables quantifying involuntary torque and muscle activity during and after vibration cessation were significantly increased in JC (p < .011, n = 20, 10 females) and some, but not all, increased in MS (p = .017-.05, n = 19, 10 females). JC and MS significantly increased the magnitude of involuntary contractions (VibStim) but had no effect on GM ΔF during voluntary contractions. Effects of increased neuromodulator release on PIC contribution to motoneuron firing might differ between synergists or be context dependent. Based on these data, the background level of voluntary contraction and, hence, both neuromodulation and ionotropic inputs could influence neuromodulatory PIC enhancement.

Differences in Trapezius Muscle H-Reflex between Asymptomatic Subjects and Symptomatic Shoulder Pain Subjects.

In chronic shoulder pain, adaptations in the nervous system such as in motoneuron excitability, could contribute to impairments in scapular muscles, perpetuation and recurrence of pain and reduced improvements during rehabilitation. The present cross-sectional study aims to compare trapezius neural excitability between symptomatic and asymptomatic subjects. In 12 participants with chronic shoulder pain (symptomatic group) and 12 without shoulder pain (asymptomatic group), the H reflex was evoked in all trapezius muscle parts, through C3/4 nerve stimulation, and the M-wave through accessory nerve stimulation. The current intensity to evoke the maximum H reflex, the latency and the maximum peak-to-peak amplitude of both the H reflex and M-wave, as well as the ratio between these two variables, were calculated. The percentage of responses was considered. Overall, M-waves were elicited in most participants, while the H reflex was elicited only in 58-75% or in 42-58% of the asymptomatic and symptomatic participants, respectively. A comparison between groups revealed that the symptomatic group presented a smaller maximum H reflex as a percentage of M-wave from upper trapezius and longer maximal H reflex latency from the lower trapezius (p < 0.05). Subjects with chronic shoulder pain present changes in trapezius H reflex parameters, highlighting the need to consider trapezius neuromuscular control in these individuals' rehabilitation.

Contraction Velocity of the Elbow Flexors Assessed by Tensiomyography: A Comparison Between Formulas.

ABSTRACT: Mesquita, RNO, Latella, C, Ruas, CV, Nosaka, K, and Taylor, JL. Contraction velocity of the elbow flexors assessed by tensiomyography: A comparison between formulas. J Strength Cond Res 37(10): 1969-1977, 2023-Muscle contraction velocity ( Vc ) assessed by tensiomyography is a promising measure for athlete profiling. Multiple formulas are used to estimate Vc , but the most suitable method is yet to be established. Fifteen adults (2 female subjects) underwent tensiomyography assessment of biceps brachii muscle at 10, 45 and 90° of elbow flexion on 2 separate days. Vc was calculated using 6 formulas. Formulas 1 and 2 are measures of the early phase of the twitch; Formulas 3-5 are measures over a wider time-window, with Formula 5 normalizing Vc to maximal displacement ( D m); and we proposed Formula 6 as a measure of peak Vc . Test-retest reliability, the required minimum number of trials, proportional bias, and effects of joint angle were investigated. Higher reliability (coefficient of variation: 2.8-6.9%) was found for Formula 1 (0-2 mm of displacement) and Formula 5 (normalized 10-90% of D m). Overall, a minimum of 6-7 trials was required to obtain reliable estimates. For 10° only, significant positive proportional bias ( r = 0.563-0.670) was found for all formulas except Formula 5. Vc was faster ( p < 0.001) at shorter muscle lengths for all formulas except Formula 5 ( p = 0.06). Vc in the early phase of the twitch was more reliable when calculated using absolute displacement (Formula 1) than a relative threshold (Formula 2). Over a larger time-window, Formulas 3 and 4 were similarly reliable. Because they are derived from different components of the twitch and different parameters, the different formulas should not be used interchangeably. Additionally, more precise nomenclature is required to describe the information obtained from each formula.

Sprint cycling rate of torque development associates with strength measurement in trained cyclists.

PURPOSE: A cyclist's rate of force/torque development (RFD/RTD) and peak force/torque can be measured during single-joint or whole-body isometric tests, or during cycling. However, there is limited understanding of the relationship between these measures, and of the mechanisms that contribute to each measure. Therefore, we examined the: (i) relationship between quadriceps central and peripheral neuromuscular function with RFD/RTD in isometric knee extension, isometric mid-thigh pull (IMTP), and sprint cycling; and (ii) relationship among RFD/RTD and peak force/torque between protocols. METHODS: Eighteen trained cyclists completed two familiarisation and two experimental sessions. Each session involved an isometric knee extension, IMTP, and sprint cycling protocol, where peak force/torque, average and peak RFD/RTD, and early (0-100 ms) and late (0-200 ms) RFD/RTD were measured. Additionally, measures of quadriceps central and peripheral neuromuscular function were assessed during the knee extension. RESULTS: Strong relationships were observed between quadriceps early EMG activity (EMG50/M) and knee extension RTD (r or ρ = 0.51-0.65) and IMTP late RFD (r = 0.51), and between cycling early or late RTD and peak twitch torque (r or ρ = 0.70-0.75). Strong-to-very strong relationships were observed between knee extension, IMTP, and sprint cycling for peak force/torque, early and late RFD/RTD, and peak RFD/RTD (r or ρ = 0.59-0.80). CONCLUSION: In trained cyclists, knee extension RTD or IMTP late RFD are related to measures of quadriceps central neuromuscular function, while cycling RTD is related to measures of quadriceps peripheral neuromuscular function. Further, the strong associations among force/torque measures between tasks indicate a level of transferability across tasks.

Motor cortical excitability and pre-supplementary motor area neurochemistry in healthy adults with substantia nigra hyperechogenicity.

Substantia nigra (SN) hyperechogenicity, viewed with transcranial ultrasound, is a risk marker for Parkinson's disease. We hypothesized that SN hyperechogenicity in healthy adults aged 50-70 years is associated with reduced short-interval intracortical inhibition in primary motor cortex, and that the reduced intracortical inhibition is associated with neurochemical markers of activity in the pre-supplementary motor area (pre-SMA). Short-interval intracortical inhibition and intracortical facilitation in primary motor cortex was assessed with paired-pulse transcranial magnetic stimulation in 23 healthy adults with normal (n = 14; 61 ± 7 yrs) or abnormally enlarged (hyperechogenic; n = 9; 60 ± 6 yrs) area of SN echogenicity. Thirteen of these participants (7 SN- and 6 SN+) also underwent brain magnetic resonance spectroscopy to investigate pre-SMA neurochemistry. There was no relationship between area of SN echogenicity and short-interval intracortical inhibition in the ipsilateral primary motor cortex. There was a significant positive relationship, however, between area of echogenicity in the right SN and the magnitude of intracortical facilitation in the right (ipsilateral) primary motor cortex (p = .005; multivariate regression), evidenced by the amplitude of the conditioned motor evoked potential (MEP) at the 10-12 ms interstimulus interval. This relationship was not present on the left side. Pre-SMA glutamate did not predict primary motor cortex inhibition or facilitation. The results suggest that SN hyperechogenicity in healthy older adults may be associated with changes in excitability of motor cortical circuitry. The results advance understanding of brain changes in healthy older adults at risk of Parkinson's disease.

Corticospinal and intracortical responses from both motor cortices following unilateral concentric versus eccentric contractions.

Cross-education is the phenomenon where training of one limb can cause neuromuscular adaptations in the opposite untrained limb. This effect has been reported to be greater after eccentric (ECC) than concentric (CON) strength training; however, the underpinning neurophysiological mechanisms remain unclear. Thus, we compared responses to transcranial magnetic stimulation (TMS) in both motor cortices following single sessions of unilateral ECC and CON exercise of the elbow flexors. Fourteen healthy adults performed three sets of 10 ECC and CON right elbow flexor contractions at 75% of respective maximum on separate days. Elbow flexor maximal voluntary isometric contraction (MVIC) torques were measured before and after exercise, and responses to single- and paired-pulse TMS were recorded from the non-exercised left and exercised right biceps brachii. Pre-exercise and post-exercise responses for ECC and CON were compared by repeated measures analyses of variance (ANOVAs). MVIC torque of the exercised arm decreased (p < 0.01) after CON (-30 ± 14%) and ECC (-39 ± 13%) similarly. For the non-exercised left biceps brachii, resting motor threshold (RMT) decreased after CON only (-4.2 ± 3.9% of maximum stimulator output [MSO], p < 0.01), and intracortical facilitation (ICF) decreased (-15.2 ± 20.0%, p = 0.038) after ECC only. For the exercised right biceps, RMT increased after ECC (8.6 ± 6.2% MSO, p = 0.014) but not after CON (6.4 ± 8.1% MSO, p = 0.066). Thus, unilateral ECC and CON elbow flexor exercise modulated excitability differently for the non-exercised hemisphere. These findings suggest that responses after a single bout of exercise may not reflect longer term adaptations.

Comparison between Eccentric-Only and Coupled Concentric-Eccentric Contractions for Neuromuscular Fatigue and Muscle Damage.

PURPOSE: Eccentric contractions induce muscle damage, but less is known about the effects of preceding concentric contractions to eccentric contractions on muscle damage. We compared eccentric-only (ECC) and coupled concentric and eccentric contractions (CON-ECC) of the knee extensors for parameters of neuromuscular fatigue and muscle damage. METHODS: Twenty participants (age, 19-36 yr) were randomly placed into an ECC or a CON-ECC group (n = 10 per group), without significant (P > 0.06) differences in baseline neuromuscular variables between groups. The ECC group performed six sets of eight ECC at 80% of ECC one-repetition maximum (1-RMecc), whereas the CON-ECC group performed six sets of eight alternating concentric (CON) and ECC (16 contractions per set) at 80% of CON 1-RM and 1-RMecc, respectively. Maximal voluntary isometric contraction force, rate of force development, resting twitch force, maximal M-wave (MMAX), voluntary activation, motor evoked potentials, corticospinal silent period, short interval intracortical inhibition, and muscle soreness were measured before, immediately after, and 1-3 d after exercise. RESULTS: No significant (P ≥ 0.09) differences between ECC and CON-ECC were observed for changes in any variables after exercise. However, maximal voluntary isometric contraction force decreased immediately after exercise (ECC: -20.7% ± 12.8%, CON-ECC: -23.6% ± 23.3%) and was still reduced 3 d after exercise (ECC: -13.6% ± 13.4%, CON-ECC: -3.3% ± 21.2%). Rate of force development at 0-30 ms reduced immediately after exercise (ECC: -38.3% ± 33.9%, CON-ECC: -30.7% ± 38.3%). Voluntary activation, resting twitch force, and motor evoked potential/MMAX decreased and corticospinal silent period increased after exercise (all P ≤ 0.03), but short interval intracortical inhibition and MMAX did not change. Muscle soreness developed (P < 0.001) similarly for both groups (peak, 38.5 ± 29.5 mm). CONCLUSIONS: CON-ECC did not exacerbate neuromuscular fatigue and muscle damage when compared with ECC, despite twice as many contractions performed. Thus, eccentric contractions (n = 48 in both groups) seemed to mainly mediate the neuromuscular responses observed.

Enhanced availability of serotonin limits muscle activation during high-intensity, but not low-intensity, fatiguing contractions.

Serotonin (5-HT) modulates motoneuron excitability during muscle contractions, where the release of 5-HT in the central nervous system (CNS) is linked to the intensity of physical activity. Although there is evidence that enhanced availability of 5-HT can exacerbate fatigue, these effects on the development of fatigue during different contraction intensities are largely unknown. The purpose of this study was to investigate how enhanced 5-HT availability affects voluntary muscle activation and corticospinal excitability during fatigue-inducing contractions. Two experiments were performed. In the first experiment (n = 11), 12 isometric elbow flexions at 20% maximal voluntary contractions (MVCs) were performed for 2 min each with 40-s rest periods. In the second experiment (n = 14), 12 maximal isometric elbow flexions were held for 10 s each with 40-s rest periods. In both experiments, the selective serotonin reuptake inhibitor (20-mg paroxetine), or a placebo, was administered in a two-way crossover design. Muscle responses to transcranial magnetic stimulation (TMS) of the motor cortex (both experiments 1 and 2), as well as motor point stimulation of the elbow flexors (experiment 2) were assessed. Paroxetine reduced both motor cortical (P = 0.018) and motor point voluntary activation (P = 0.036) during the maximal contraction protocol. Paroxetine also reduced exercise-induced lengthening of the TMS silent period during the submaximal (P = 0.037) and maximal (P = 0.002) contraction protocols. Activation of inhibitory 5-HT1A receptors on motoneurons likely exacerbated exercise-induced reductions in voluntary drive to the elbow flexors. However, 5-HT modulation of motor activity also appeared at the supraspinal level.NEW & NOTEWORTHY As serotonin release onto motoneurons may be scaled to the strength of muscle contraction, it may have different effects when neuromuscular fatigue is induced by contractions of different intensities. Enhanced levels of serotonin compromised voluntary activation of muscle when fatigue was induced by strong contractions but not weak contractions. This provides evidence that the serotonergic system has the greatest influence on fatigue that is generated with high neural drive to the target muscle.

Location-specific cutaneous electrical stimulation of the footsole modulates corticospinal excitability to the plantarflexors and dorsiflexors during standing.

Non-noxious electrical stimulation to distinct locations of the foot sole evokes location-specific cutaneous reflex responses in lower limb muscles. These reflexes occur at latencies that may enable them to be mediated via a transcortical pathway. Corticospinal excitability to the plantarflexors and dorsiflexors was measured in 16 participants using motor evoked potentials (MEPs). Spinal excitability was measured in eight of the original participants using cervicomedullary motor evoked potentials (CMEPs). Measurements were collected with and without preceding cutaneous stimulus to either the heel (HEEL) or metatarsal (MET) locations of the foot sole, and evoked potentials were elicited to coincide with the arrival of the cutaneous volley at either the motor cortex or spinal cord. Plantarflexor MEPs and CMEPs were facilitated with cutaneous stimulation to the HEEL for MEPs (soleus p = 0.04, medial gastrocnemius (MG) p = 0.017) and CMEPs (soleus p = 0.047 and MG p = 0.015), but they were unchanged following MET stimulation for MEPs or CMEPs. Dorsiflexor MEPs were unchanged with cutaneous stimulation at either location, but dorsiflexor CMEPs increased with cutaneous stimulation (p = 0.05). In general, the increase in CMEP amplitudes was larger than the increase in MEP amplitudes, indicating that an increase in spinal excitability likely explains most of the increase in corticospinal excitability. The larger change observed in the CMEP also indicates that excitability from supraspinal sources likely decreased, which could be due to a net change in the excitability of intracortical circuits. This study provides evidence that cutaneous reflexes from foot sole skin are likely influenced by a transcortical pathway.

Voluntary activation of muscle in humans: does serotonergic neuromodulation matter?

Ionotropic inputs to motoneurones have the capacity to depolarise and hyperpolarise the motoneurone, whereas neuromodulatory inputs control the state of excitability of the motoneurone. Intracellular recordings of motoneurones from in vitro and in situ animal preparations have provided extraordinary insight into the mechanisms that underpin how neuromodulators regulate neuronal excitability. However, far fewer studies have attempted to translate the findings from cellular and molecular studies into a human model. In this review, we focus on the role that serotonin (5-HT) plays in muscle activation in humans. 5-HT is a potent regulator of neuronal firing rates, which can influence the force that can be generated by muscles during voluntary contractions. We firstly outline structural and functional characteristics of the serotonergic system, and then describe how motoneurone discharge can be facilitated and suppressed depending on the 5-HT receptor subtype that is activated. We then provide a narrative on how 5-HT effects can influence voluntary activation during muscle contractions in humans, and detail how 5-HT may be a mediator of exercise-induced fatigue that arises from the central nervous system.

5-HT2 receptor antagonism reduces human motoneuron output to antidromic activation but not to stimulation of corticospinal axons.

The intrinsic electrical properties of motoneurons strongly affect motoneuron excitability to fast-acting excitatory ionotropic inputs. Serotonin (5-HT) is a neurochemical that alters the intrinsic properties of motoneurons, whereby animal models and in vitro experiments indicate that 5-HT increases motoneuron excitability by activating 5-HT2 receptors on the somato-dendritic compartment. In the current study, we examined how antagonism of the 5-HT2 receptor affects motoneuron excitability in humans. We hypothesised that motoneuron excitability would be reduced. The 5-HT2 antagonist cyproheptadine was administered to 10 healthy participants in a double-blinded, placebo-controlled, crossover trial. Electrical cervicomedullary stimulation was used to deliver a synchronised excitatory volley to motoneurons to elicit cervicomedullary motor evoked potentials (CMEPs) in the surface electromyography (EMG) signal of the resting biceps brachii. Likewise, electrical peripheral nerve stimulation was used to generate antidromic spikes in motoneurons and cause recurrent discharges, which were recorded with surface EMG as F-waves in a resting hand muscle. Compared with placebo, we found that 5-HT2 antagonism reduced the amplitude and persistence of F-waves but did not affect CMEP amplitude. 5-HT2 antagonism also reduced maximal contraction strength. The reduced recurrent discharge of motoneurons with 5-HT2 antagonism suggests that 5-HT2 receptors modulate the electrical properties of the initial segment or soma to promote excitability. Conversely, as cyproheptadine did not affect motoneuron excitability to brief synaptic input, but affected maximal contractions requiring sustained input, it seems likely that the 5-HT2 -mediated amplification of synaptic input at motoneuron dendrites is functionally significant only when excitatory input activates persistent inward currents.

Effects of reciprocal inhibition and whole-body relaxation on persistent inward currents estimated by two different methods.

Persistent inward currents (PICs) are crucial for initiation, acceleration, and maintenance of motoneuron firing. As PICs are highly sensitive to synaptic inhibition and facilitated by serotonin and noradrenaline, we hypothesised that both reciprocal inhibition (RI) induced by antagonist nerve stimulation and whole-body relaxation (WBR) would reduce PICs in humans. To test this, we estimated PICs using the well-established paired motor unit (MU) technique. High-density surface electromyograms were recorded from gastrocnemius medialis during voluntary, isometric 20-s ramp, plantarflexor contractions and decomposed into MU discharges to calculate delta frequency (ΔF). Moreover, another technique (VibStim), which evokes involuntary contractions proposed to result from PIC activation, was used. Plantarflexion torque and soleus activity were recorded during 33-s Achilles tendon vibration and simultaneous 20-Hz bouts of neuromuscular electrical stimulation (NMES) of triceps surae. ΔF was decreased by RI (n = 15, 5 females) and WBR (n = 15, 7 females). In VibStim, torque during vibration at the end of NMES and sustained post-vibration torque were reduced by WBR (n = 19, 10 females), while other variables remained unchanged. All VibStim variables remained unaltered in RI (n = 20, 10 females). Analysis of multiple human MUs in this study demonstrates the ability of local, focused inhibition to attenuate the effects of PICs on motoneuron output during voluntary motor control. Moreover, it shows the potential to reduce PICs through non-pharmacological, neuromodulatory interventions such as WBR. The absence of a consistent effect in VibStim might be explained by a floor effect resulting from low-magnitude involuntary torque combined with the negative effects of the interventions. KEY POINTS: Spinal motoneurons transmit signals to skeletal muscles to regulate their contraction. Motoneuron firing partly depends on their intrinsic properties such as the strength of persistent (long-lasting) inward currents (PICs) that make motoneurons more responsive to excitatory input. In this study, we demonstrate that both reciprocal inhibition onto motoneurons and whole-body relaxation reduce the contribution of PICs to human motoneuron firing. This was observed through analysis of the firing of single motor units during voluntary contractions. However, an alternative technique that involves tendon vibration and neuromuscular electrical stimulation to evoke involuntary contractions showed less effect. Thus, it remains unclear whether this alternative technique can be used to estimate PICs under all physiological conditions. These results improve our understanding of the mechanisms of PIC depression in human motoneurons. Potentially, non-pharmacological interventions such as electrical stimulation or relaxation could attenuate unwanted PIC-induced muscle contractions in conditions characterised by motoneuron hyperexcitability.

Effects of different modalities of afferent stimuli of the lumbo-sacral area on control of lumbar paravertebral muscles.

Somatosensory feedback to the central nervous system is essential to plan, perform and refine spine motor control. However, the influence of somatosensory afferent input from the trunk on the motor output to trunk muscles has received little attention. The objective was to compare the effects of distinct modalities of afferent stimulation on the net motoneuron and corticomotor excitability of paravertebral muscles. Fourteen individuals were recruited. Modulation of corticospinal excitability (motor-evoked potential [MEP]) of paravertebral muscles was measured when afferent stimuli (cutaneous noxious and non-noxious, muscle contraction) were delivered to the trunk at 10 intervals prior to transcranial magnetic stimulation. Each peripheral stimulation was applied alone, and subsequent electromyography (EMG) modulation was measured to control for net motoneuron excitability. MEP modulation and MEP/EMG ratio were used as measures of corticospinal excitability with and without control of net motoneuron excitability, respectively. MEP and EMG modulation were smaller after evoked muscle contraction than after cutaneous noxious and non-noxious stimuli. MEP/EMG ratio was not different between stimulation types. Both MEP and EMG amplitudes were reduced after evoked muscle contraction, but not when expressed as MEP/EMG ratio. Noxious and non-noxious stimulation had limited impact on all variables. Distinct modalities of peripheral afferent stimulation of the lumbo-sacral area differently modulated responses of paravertebral muscles, but without an influence on corticospinal excitability with control of net motoneuron excitability. Muscle stimulation reduced paravertebral activity and was best explained by spinal mechanisms. The impact of afferent stimulation on back muscles differs from the effects reported for limb muscles.

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.

Early Detection of Prolonged Decreases in Maximal Voluntary Contraction Force after Eccentric Exercise of the Knee Extensors.

PURPOSE: We examined whether the magnitude of muscle damage indicated by changes in maximal voluntary isometric contraction (MVIC) strength 1 to 3 d after unaccustomed eccentric exercise (ECC) was correlated with changes in central and peripheral neuromuscular parameters immediately post-ECC. METHODS: Twenty participants (19-36 yr) performed six sets of eight eccentric contractions of the knee extensors. Rate of force development (RFD) during knee extensor MVIC, twitch force, rate of force development (RFDRT) and rate of relaxation (RRRT) of the resting twitch, maximal M-wave (MMAX), voluntary activation, silent period duration, motor-evoked potentials (MEP) and short-interval intracortical inhibition were assessed before, immediately after, and 1 to 3 d post-ECC. Relationships between changes in these variables immediately post-ECC and changes in MVIC strength at 1 to 3 d post-ECC were examined by Pearson product-moment (r) or Spearman correlations. RESULTS: Maximal voluntary isometric contraction strength decreased (-22.2% ± 18.4%) immediately postexercise, and remained below baseline at 1 (-16.3% ± 15.2%), 2 (-14.7% ± 13.2%) and 3 d post-ECC (-8.6% ± 15.7%). Immediately post-ECC, RFD (0-30-ms: -38.3% ± 31.4%), twitch force (-45.9% ± 22.4%), RFDRT (-32.5% ± 40.7%), RRRT (-38.0% ± 39.7%), voluntary activation (-21.4% ± 16.5%) and MEP/MMAX at rest (-42.5% ± 23.3%) also decreased, whereas the silent period duration at 10%-MVIC increased by 26.0% ± 12.2% (P < 0.05). Decreases in RFD at 0 to 30 ms, 0 to 50 ms, and 0 to 100 ms immediately post-ECC were correlated (P < 0.05) with changes in MVIC strength at 1 d (r = 0.56-0.60) and 2 d post-ECC (r = 0.53-0.63). Changes in MEP/MMAX at 10%-MVIC immediately post-ECC were correlated with changes in MVIC strength at 1 d (r = -0.53) and 2 d (r = -0.54) post-ECC (P < 0.05). CONCLUSIONS: The magnitude of decrease in MVIC strength at 1 to 3 d after ECC was associated with the magnitude of changes in RFD and MEP/MMAX immediately post-ECC. However, based on individual data, these markers were not sensitive for the practical detection of muscle damage.

Human corticospinal-motoneuronal output is reduced with 5-HT2 receptor antagonism.

Animal models indicate that serotonin (5-HT) release onto motoneurons facilitates motor output, particularly during strong motor activities. However, evidence for 5-HT effects during human movement are limited. This study examined how antagonism of the 5-HT2 receptor, which is a 5-HT receptor that promotes motoneuron excitability, affects human movement. Ten healthy participants (24.2 ± 1.9 yr) ingested 8 mg of cyproheptadine (competitive 5-HT2 antagonist) in a double-blinded, placebo-controlled, repeated-measures design. Transcranial magnetic stimulation (TMS) of the motor cortex was used to elicit motor evoked potentials (MEPs) from biceps brachii. First, stimulus-response curves (90%-160% active motor threshold) were obtained during very weak elbow flexions (10% of maximal). Second, to determine if 5-HT effects are scaled to the intensity of muscle contraction, TMS at a fixed intensity was applied during elbow flexions of 20%, 40%, 60%, 80%, and 100% of maximal. Cyproheptadine reduced the size of MEPs across the stimulus-response curves (P = 0.045). Notably, MEP amplitude was 22.3% smaller for the cyproheptadine condition for the strongest TMS intensity. In addition, cyproheptadine reduced maximal torque (P = 0.045), lengthened the biceps silent period during maximal elbow flexions (P = 0.037), and reduced superimposed twitch amplitude during moderate-intensity elbow flexions (P = 0.035). This study presents novel evidence that 5-HT2 receptors influence corticospinal-motoneuronal output, which was particularly evident when a large number of descending inputs to motoneurons were active. Although it is likely that antagonism of 5-HT2 receptors reduces motoneuron gain to ionotropic inputs, supraspinal mechanisms may have also contributed to the study findings.NEW & NOTEWORTHY Voluntary contractions and responses to magnetic stimulation of the motor cortex are dependent on serotonin activity in the central nervous system. 5-HT2 antagonism decreased evoked potential size to high-intensity stimulation, and reduced torque and lengthened inhibitory silent periods during maximal contractions. We provide novel evidence that 5-HT2 receptors are involved in muscle activation, where 5-HT effects are strongest when a large number of descending inputs activate motoneurons.

Effects of postexercise blood flow occlusion on quadriceps responses to transcranial magnetic stimulation.

For a fatigued hand muscle, group III/IV afferent firing maintains intracortical facilitation (ICF) without influencing corticospinal excitability. Exercise of larger muscles produces greater afferent firing. Thus, this study investigated if fatigue-related firing of group III/IV afferents from a large muscle group (quadriceps) modulates intracortical and corticospinal networks. In two sessions, participants (n = 18) completed a 2-min maximal voluntary isometric contraction (MVIC) of knee extensors with (OCC) or without (CON) postexercise blood flow occlusion to maintain afferent firing. Pre- and postexercise, single- and paired-pulse transcranial magnetic stimulation (TMS) elicited motor evoked potentials (MEPs) from vastus lateralis (VL), vastus medialis, and rectus femoris. Test pulse intensities evoked VL MEPs of ∼0.5 mV and were adjusted postexercise. The conditioning stimulus for ICF and short-interval intracortical inhibition (SICI) was constant and set to evoke ∼50% of maximum ICF. Muscle pain was also assessed (0-10 scale). Postexercise, muscle pain was greater for OCC than CON (Median = 8.6 vs. 2.3; P < 0.001). MEPs were depressed for CON (all muscles: Δ -24.3 to -34.1%; P ≤ 0.018) despite increased stimulus intensity (∼10%, P < 0.001), but both MEPs and intensity remained unchanged for OCC. ICF was depressed postexercise in OCC (VL and RF: Δ -59.8% and -28.8%, respectively P = 0.016-0.018) but not in CON (all muscles: Δ -3.8 to -44.3%, P = 0.726-1.0), but was not different between conditions (interactions: P = 0.143-0.252). No interactions were observed for SICI (all muscles: P ≥ 0.266). Group III/IV afferent firing counteracts the postcontraction depression of MEPs in quadriceps. However, intracortical inhibitory and facilitatory networks are not implicated in this response.NEW & NOTEWORTHY Maintained exercise-induced firing of group III/IV quadriceps muscle afferents counteracts known reductions in corticospinal excitability that occur with fatigue. However, the results suggest that this increased excitability is not underpinned by changes in intracortical facilitatory or inhibitory networks. These findings are not consistent with previous findings for hand muscle, which reported preserved intracortical facilitation with fatigue-related sustained group III/IV muscle afferent firing.

Involuntary sustained firing of plantar flexor motor neurones: effect of electrical stimulation parameters during tendon vibration.

PURPOSE: Simultaneous application of tendon vibration and neuromuscular electrical stimulation (NMES) induces an involuntary sustained torque. We examined the effect of different NMES parameters (intensity, pattern of stimulation and pulse width) on the magnitude of the evoked involuntary torque. METHODS: Plantar flexor torque was recorded during 33-s Achilles tendon vibration with simultaneous 20-Hz NMES bouts on triceps surae (n = 20; 13 women). Intensity was set to elicit 10, 20 or 30% of maximal voluntary contraction torque (MVC), pulse width was narrow (0.2 ms) or wide (1 ms), and the stimulus pattern varied (5 × 2-s or 10 × 1-s). Up to 12 different trials were performed in a randomized order, and then repeated in those who produced a sustained involuntary torque after the cessation of vibration. RESULTS: Six of 7 men and 5 of 13 women produced a post-vibration sustained torque. Eight of 20 participants did not complete the 30% trials, as they were perceived as painful. Torque during vibration at the end of NMES and the increase in torque throughout the trial were significantly higher in 20 than 10% trials (n = 11; 9.7 ± 9.0 vs 7.1 ± 6.1% MVC and 4.3 ± 4.5 vs 3.6 ± 3.5% MVC, respectively). Post-vibration sustained torque was higher in wide pulse-width trials (5.4 ± 5.9 vs 4.1 ± 4.3% MVC). Measures of involuntary torque were not different between 20 and 30% trials (n = 8). CONCLUSION: Bouts of 5 × 2-s NMES with wide pulse width eliciting 20% MVC provides the most robust responses and could be used to maximise the production of involuntary torque in triceps surae.