Ageing reduces persistent inward current contribution to motor neurone firing: Potential mechanisms and the role of exercise.

Nervous system deterioration is a primary driver of age-related motor impairment. The motor neurones, which act as the interface between the central nervous system and the muscles, play a crucial role in amplifying excitatory synaptic input to produce the desired motor neuronal firing output. For this, they utilise their ability to generate persistent (long-lasting) depolarising currents that increase cell excitability, and both amplify and prolong the output activity of motor neurones for a given synaptic input. Modulation of these persistent inward currents (PICs) contributes to the motor neurones' capacities to attain the required firing frequencies and rapidly modulate them to competently complete most tasks. Thus, PICs are crucial for adequate movement generation. Impairments in intrinsic motor neurone properties can impact motor unit firing capacity, with convincing evidence indicating that the PIC contribution to motor neurone firing is reduced in older adults. Indeed, this could be an important mechanism underpinning the age-related reductions in strength and physical function. Furthermore, resistance training has emerged as a promising intervention to counteract age-associated PIC impairments, with changes in PICs being correlated with improvements in muscular strength and physical function after training. In this review, we present the current knowledge of the PIC magnitude decline during ageing and discuss whether reduced serotonergic and noradrenergic input onto the motor neurones, voltage-gated calcium channel dysfunction or inhibitory input impairments are candidates that: (i) explain age-related reductions in the PIC contribution to motor neurone firing and (ii) underpin the enhanced PIC contribution to motor neurone firing following resistance training in older adults.

Longitudinal changes in intrinsic motoneuron excitability in amyotrophic lateral sclerosis are dependent on disease progression.

Increased amplitude of persistent inward currents (PICs) is observed in pre-symptomatic genetically modified SOD1 mice models of amyotrophic lateral sclerosis (ALS). However, at the symptomatic stage this reverses and there is a large reduction in PIC amplitude. It remains unclear whether these changes in PICs can be observed in humans, with cross-sectional studies in humans reporting contradictory findings. In people with ALS, we estimated the PIC contribution to self-sustained firing of motoneurons, using the paired-motor unit analysis to calculate the Δfrequency (ΔF), to compare the weaker and stronger muscles during the course of disease. We hypothesised that, with disease progression, ΔFs would relatively increase in the stronger muscles; and decline in the weaker muscles. Forty-three individuals with ALS were assessed in two occasions on average 17 weeks apart. Tibialis anterior high-density electromyograms were recorded during dorsiflexion (40% of maximal capacity) ramped contractions, followed by clinical tests. ∆F increased from 3.14 (2.57, 3.71) peaks per second (pps) to 3.55 (2.94, 4.17) pps on the stronger muscles (0.41 (0.041, 0.781) pps, standardised difference (d) = 0.287 (0.023, 0.552), P = 0.030). ∆F reduced from 3.38 (95% CI 2.92, 3.84) pps to 2.88 (2.40, 3.36) pps on the weaker muscles (-0.50 (-0.80, -0.21) pps, d = 0.353 (0.138, 0.567), P = 0.001). The ALSFRS-R score reduced 3.9 (2.3, 5.5) points. These data indicate that the contribution of PICs to motoneuron self-sustained firing increases over time in early stages of the disease when there is little weakness before decreasing as the disease progresses and muscle weakness exacerbates, in alignment with the findings from studies using SOD1 mice. KEY POINTS: Research on mouse model of amyotrophic lateral sclerosis (ALS) suggests that the amplitude of persistent inward currents (PICs) is increased in early stages before decreasing as the disease progresses. Cross-sectional studies in humans have reported contradictory findings with both higher and lower PIC contributions to motoneuron self-sustained firing. In this longitudinal (∼17 weeks) study we tracked changes in PIC contribution to motoneuron self-sustained firing, using the ΔF calculation (i.e. onset-offset hysteresis of motor unit pairs), in tibialis anterior muscles with normal strength and with clinical signs of weakness in people with ALS. ΔFs decreased over time in muscles with clinical signs of weakness. The PIC contribution to motoneuron self-sustained firing increases before the onset of muscle weakness, and subsequently decreases when muscle weakness progresses.

Caffeine does not influence persistent inward current contribution to motoneuron firing.

The purpose of this study was to investigate whether caffeine consumption would change persistent inward current (PIC) contribution to motoneuron firing at increased contraction intensities and after repetitive sustained maximal contractions. Before and after the consumption of 6 mg·kg-1 of caffeine or placebo, 16 individuals performed isometric triangular-shaped ramp dorsiflexion contractions (to 20% and 40% of peak torque), followed by four maximal contractions sustained until torque production dropped to 60% of maximum, and consecutive 20% triangular-shaped contractions. Tibialis anterior motor unit firing frequencies were analyzed from high-density surface electromyograms. PIC contribution to motor unit firing was estimated by calculating the delta frequency (ΔF) using the paired motor unit technique. Motoneuron peak firing frequencies at 20% and 40% contractions and total torque-time integral during the repetitive sustained maximal contractions were also assessed. ΔF increased 0.69 peaks per second (pps) (95% CI = -0.98, -0.405; d = -0.87) from 20% to 40% contraction intensities and reduced 0.85 pps (95% CI = 0.66, 1.05; d = 0.99) after the repetitive sustained maximal contractions, regardless of caffeine consumption. Participants produced 337 Nm·s (95% CI = 49.9, 624; d = 0.63) more torque integral during the repetitive sustained maximal contractions after caffeine consumption. A strong repeated-measures correlation (r = 0.61; 95% CI = 0.49, 0.69) was observed between reductions of ΔF and peak firing frequencies after the repetitive sustained maximal contractions. PIC contribution to motoneuron firing increases from 20% to 40% contraction intensities, with no effect of caffeine (on rested tibialis anterior). Repetitive sustained maximal contractions reduced PIC contribution to motoneuron firing, regardless of caffeine or placebo consumption, evidencing that changes in intrinsic motoneuron properties contributed to performance loss. Caffeine-attenuated reduction of torque production capacity was unlikely mediated by PICs.NEW & NOTEWORTHY Persistent inward current (PIC) contribution to motoneuron firing increases with contraction intensities and is reduced after repetitive sustained maximal contractions, regardless of caffeine consumption. Reductions of PIC contribution to motoneuron firing and peak firing frequencies were largely associated, evidencing a novel mechanism underpinning decrements in maximal torque production capacity following repetitive sustained maximal contractions. Caffeine consumption attenuated neuromuscular performance reductions-allowing higher time-torque integral production during repetitive sustained maximal contractions. This was unlikely mediated by PIC.

Intrinsic motor neuron excitability is increased after resistance training in older adults.

This study investigated the effects of high-intensity resistance training on estimates of the motor neuron persistent inward current (PIC) in older adults. Seventeen participants (68.5 ± 2.8 yr) completed a 2-wk nonexercise control period followed by 6 wk of resistance training. Surface electromyographic signals were collected with two 32-channel electrodes placed over soleus to investigate motor unit discharge rates. Paired motor unit analysis was used to calculate delta frequency (ΔF) as an estimate of PIC amplitudes during 1) triangular-shaped contractions to 20% of maximum torque capacity and 2) trapezoidal- and triangular-shaped contractions to 20% and 40% of maximum torque capacity, respectively, to understand their ability to modulate PICs as contraction intensity increases. Maximal strength and functional capacity tests were also assessed. For the 20% triangular-shaped contractions, ΔF [0.58-0.87 peaks per second (pps); P ≤ 0.015] and peak discharge rates (0.78-0.99 pps; P ≤ 0.005) increased after training, indicating increased PIC amplitude. PIC modulation also improved after training. During the control period, mean ΔF differences between 20% trapezoidal-shaped and 40% triangular-shaped contractions were 0.09-0.18 pps (P = 0.448 and 0.109, respectively), which increased to 0.44 pps (P < 0.001) after training. Also, changes in ΔF showed moderate to very large correlations (r = 0.39-0.82) with changes in peak discharge rates and broad measures of motor function. Our findings indicate that increased motor neuron excitability is a potential mechanism underpinning training-induced improvements in motor neuron discharge rate, strength, and motor function in older adults. This increased excitability is likely mediated by enhanced PIC amplitudes, which are larger at higher contraction intensities.NEW & NOTEWORTHY Resistance training elicited important alterations in soleus intrinsic motor neuronal excitability, likely mediated by enhanced persistent inward current (PIC) amplitude, in older adults. Estimates of PICs increased after the training period, accompanied by an enhanced ability to increase PIC amplitudes at higher contraction intensities. Our data also suggest that changes in PIC contribution to self-sustained discharging may contribute to increases in motor neuron discharge rates, maximal strength, and functional capacity in older adults after resistance training.

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.

The contribution of the tendon electrode to M-wave characteristics in the biceps brachii, vastus lateralis and tibialis anterior.

In some compound muscle action potentials (M waves) recorded using the belly-tendon configuration, the tendon electrode makes a noticeable contribution to the M wave. However, this finding has only been demonstrated in some hand and foot muscles. Here, we assessed the contribution of the tendon potential to the amplitude of the vastus lateralis, biceps brachii and tibialis anterior M waves, and we also examined the role of this tendon potential in the shoulder-like feature appearing in most M waves. M waves were recorded separately at the belly and tendon locations of the vastus lateralis, biceps brachii and tibialis anterior from 38 participants by placing the reference electrode at a distant (contralateral) site. The amplitude of the M waves and the latency of their peaks and shoulders were measured. In the vastus lateralis, the tendon potential was markedly smaller in amplitude (∼75%) compared to the belly M wave (P = 0.001), whereas for the biceps brachii and tibialis anterior, the tendon and belly potentials had comparable amplitudes. In the vastus lateralis, the tendon potential showed a small positive peak coinciding in latency with the shoulder of the belly-tendon M wave, whilst in the biceps brachii and tibialis anterior, the tendon potential showed a clear negative peak which coincided in latency with the shoulder. The tendon potential makes a significant contribution to the belly-tendon M waves of the biceps brachii and tibialis anterior muscles, but little contribution to the vastus lateralis M waves. The shoulder observed in the belly-tendon M wave of the vastus lateralis is caused by the belly potential, the shoulder in the biceps brachii M wave is generated by the tendon potential, whereas the shoulder in the tibialis anterior M wave is caused by both the tendon and belly potentials. NEW FINDINGS: What is the central question of this study? Does a tendon electrode make a noticeable contribution to the belly-tendon M wave in the vastus lateralis, biceps brachii and tibialis anterior muscles? What is the main finding and its importance? Because the patellar tendon potential is small in amplitude, it hardly influences the amplitude and shape of the belly-tendon M wave of the vastus lateralis. However, for the biceps brachii and tibialis anterior muscles, the potentials at the tendon sites show a large amplitude, and thus have a great impact on the corresponding belly-tendon M waves.

Lower motor unit discharge rates in gastrocnemius lateralis, but not in gastrocnemius medialis or soleus, in runners with Achilles tendinopathy: a pilot study.

OBJECTIVES: Deficits in muscle performance could be a consequence of a reduced ability of a motor neuron to increase the rate in which it discharges. This study aimed to investigate motor unit (MU) discharge properties of each triceps surae muscle (TS) and TS torque steadiness during submaximal intensities in runners with Achilles tendinopathy (AT). METHODS: We recruited runners with (n = 12) and without (n = 13) mid-portion AT. MU discharge rate was analysed for each of the TS muscles, using high-density surface electromyography during 10 and 20% isometric plantar flexor contractions. RESULTS: MU mean discharge rate was lower in the gastrocnemius lateralis (GL) in AT compared to controls. In AT, GL MU mean discharge rate did not increase as torque increased from 10% peak torque, 8.24 pps (95% CI 7.08 to 9.41) to 20%, 8.52 pps (7.41 to 9.63, p = 0.540); however, in controls, MU discharge rate increased as torque increased from 10%, 8.39 pps (7.25-9.53) to 20%, 10.07 pps (8.89-11.25, p < 0.001). There were no between-group difference in gastrocnemius medialis (GM) or soleus (SOL) MU discharge rates. We found no between-group differences in coefficient of variation of MU discharge rate in any of the TS muscles nor in TS torque steadiness. CONCLUSION: Our data demonstrate that runners with AT may have a lower neural drive to GL, failing to increase MU discharge rate to adjust for the increase in torque demand. Further research is needed to understand how interventions focussing on increasing neural drive to GL would affect muscle function in runners with AT.

Effects of α-lactalbumin on strength, fatigue and psychological parameters: a randomised double-blind cross-over study.

PURPOSE: The neurotransmitter serotonin has a strong effect on behaviour and motor control. Regarding motor control, serotonin contributes to the development of fatigue and is also involved in the ability of motor neurones to operate across a large range of forces (gain control). The consumption of tryptophan-rich supplements (such as α-lactalbumin) is of interest because this amino acid is the only precursor for brain serotonin synthesis. Therefore, the purpose of this study was to determine the effects of α-lactalbumin supplementation on neuromuscular performance. METHODS: Using a randomised double-blind cross-over design, 16 healthy participants performed plantar flexor and handgrip maximal voluntary contractions, a 30-s submaximal handgrip contraction, and a plantar flexor fatigue protocol before and 90 min after consuming either 40 g of α-lactalbumin, an isonitrogenous beverage (Zein) or an isocaloric beverage (corn-starch). Sleepiness, mood, and cognition were assessed to evaluate any psychological effects. RESULTS: α-Lactalbumin decreased force steadiness by 25% during the sustained submaximal handgrip contraction (p < 0.01) and induced greater fatigue (15% reduction in total torque-time integral, p = 0.01) during the fatigue protocol. These effects were not observed for the other control beverages. No effects were found for maximal or explosive strength, or psychological measurements. CONCLUSIONS: 40 g of α-lactalbumin increased handgrip force variability and reduced performance during fatiguing muscle contractions but did not influence brief maximal contractions or psychological parameters in healthy individuals. These findings support the hypothesis that the consumption of α-lactalbumin can increase motor neurone input-output gain and exacerbate central fatigue during sustained maximal exercise.

The effects of α-lactalbumin supplementation and handgrip contraction on soleus motoneuron excitability.

INTRODUCTION: We tested two strategies that hypothetically increase serotonin availability (α-lactalbumin consumption and a remote submaximal handgrip contraction) on estimates of persistent inward currents (PICs) amplitude of soleus muscle in healthy participants. METHODS: With a randomised, double-blind, and cross-over design, 13 healthy participants performed triangular-shaped ramp contractions with their plantar flexors (20% of maximal torque), followed by a 30-s handgrip sustained contraction (40% of maximal force) and consecutive repeated triangular-shaped contractions. This was performed before and after the consumption of either 40 g of α-lactalbumin, an isonitrogenous beverage (Zein) or an isocaloric beverage (Corn-starch). Soleus motor units discharge rates were analysed from high-density surface electromyography signals. PICs were estimated by calculating the delta frequency (ΔF) of motor unit train spikes using the paired motor unit technique. RESULTS: ΔF (0.19 pps; p = 0.001; d = 0.30) and peak discharge rate (0.20 pps; p < 0.001; d = 0.37) increased after the handgrip contraction, irrespective of the consumed supplement. No effects of α-lactalbumin were observed. CONCLUSIONS: Our results indicate that 40 g of α-lactalbumin was unable to modify intrinsic motoneuron excitability. However, performing a submaximal handgrip contraction before the plantar flexion triangular contraction was capable of increasing ΔF and discharge rates on soleus motor units. These findings highlight the diffused effects of serotonergic input, its effects on motoneuron discharge behaviour, and suggest a cross-effector effect within human motoneurons.

Facilitation-inhibition control of motor neuronal persistent inward currents in young and older adults.

A well-coordinated facilitation-inhibition control of motor neuronal persistent inward currents (PICs) via diffuse neuromodulation and local inhibition is essential to ensure motor units discharge at required times and frequencies. Present best estimates indicate that PICs are reduced in older adults; however, it is not yet known whether PIC facilitation-inhibition control is also altered with ageing. We investigated the responses of PICs to (i) a remote handgrip contraction, which is believed to diffusely increase serotonergic input onto motor neurones, and (ii) tendon vibration of the antagonist muscle, which elicits reciprocal inhibition, in young and older adults. High-density surface electromyograms were collected from soleus and tibialis anterior of 18 young and 26 older adults during triangular-shaped plantar and dorsiflexion contractions to 20% (handgrip experiments) and 30% (vibration experiments) of maximum torque (rise-decline rate of 2%/s). A paired-motor-unit analysis was used to calculate ∆F, which is assumed to be proportional to PIC strength. ΔF increased in both soleus (0.55 peaks per second (pps), 16.0%) and tibialis anterior (0.42 pps, 11.4%) after the handgrip contraction independent of age. Although antagonist tendon vibration reduced ΔF in soleus (0.28 pps, 12.6%) independent of age, less reduction was observed in older (0.42 pps, 10.7%) than young adults (0.72 pps, 17.8%) in tibialis anterior. Our data indicate a preserved ability of older adults to amplify PICs following a remote handgrip contraction, during which increased serotonergic input onto the motor neurones is expected, in both lower leg muscles. However, PIC deactivation in response to reciprocal inhibition was impaired with ageing in tibialis anterior despite being preserved in soleus. KEY POINTS: Motor neuronal persistent inward currents (PICs) are facilitated via diffuse neuromodulation and deactivated by local inhibition to ensure motor units discharge at required times and frequencies, allowing normal motor behaviour. PIC amplitudes appear to be reduced with ageing; however, it is not known whether PIC facilitation-inhibition control is also altered. Remote handgrip contraction, which should diffusely increase serotonergic input onto motor neurones, facilitated PICs similarly in both soleus and tibialis anterior of young and older adults. Antagonist tendon vibration, which induces reciprocal inhibition, reduced PICs in soleus in both young and older adults but had less effect in tibialis anterior in older adults. Data from lower-threshold motor units during low-force contractions suggest that PIC facilitation is preserved with ageing in soleus and tibialis anterior. However, the effect of reciprocal inhibition on the contribution of PICs to motor neurone discharge seems reduced in tibialis anterior but preserved in soleus.

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.

Runners with mid-portion Achilles tendinopathy have greater triceps surae intracortical inhibition than healthy controls.

OBJECTIVES: This study aimed to investigate short-interval intracortical inhibition (SICI) and muscle function in the triceps surae of runners with mid-portion Achilles tendinopathy (AT). METHODS: Runners with (n = 11) and without (n = 13) AT were recruited. Plantar flexor isometric peak torque and rate of torque development (RTD) were measured using an isokinetic dynamometer. Triceps surae endurance was measured as single-leg heel raise (SLHR) to failure test. SICI was assessed using paired-pulse transcranial magnetic stimulation during a sustained contraction at 10% of plantar flexor isometric peak torque. RESULTS: Triceps surae SICI was 14.3% (95% CI: -2.1 to 26.4) higher in AT than in the control group (57.9%, 95% CI: 36.2 to 79.6; and 43.6% 95% CI: 16.2 to 71.1, p = 0.032) irrespective of the tested muscle. AT performed 16 (95% CI: 7.9 to 23.3, p < 0.001) fewer SLHR repetitions on the symptomatic side compared with controls, and 14 (95% CI: 5.8 to 22.0, p = 0.004), fewer SLHR repetitions on the non-symptomatic compared with controls. We found no between-groups differences in isometric peak torque (p = 0.971) or RTD (p = 0.815). PERSPECTIVE: Our data suggest greater intracortical inhibition for the triceps surae muscles for the AT group accompanied by reduced SLHR endurance, without deficits in isometric peak torque or RTD. The increased SICI observed in the AT group could be negatively influencing triceps surae endurance; thus, rehabilitation aiming to reduce intracortical inhibition should be considered to improve patient outcomes. Furthermore, SLHR is a useful clinical tool to assess plantar flexor function in AT patients.

Effects of three neuromuscular electrical stimulation methods on muscle force production and neuromuscular fatigue.

This study compared the acute responses of three neuromuscular electrical stimulation (NMES) methods on muscle torque-time integral (TTI) and neuromuscular fatigue. Narrow-pulse (0.2 ms; NP), wide-pulse (1 ms; WP), and tendon vibration superimposed onto wide-pulse (WP + VIB)-NMES conditions were applied to sixteen healthy individuals (n = 16) in three separate sessions in a randomized order. Stimulation intensity was set to elicit 20% of maximal voluntary contraction (MVC); the stimulus pattern comprised four sets of 20 repetitions (5 s On and 5 s Off) with a one-minute inter-set interval. TTI was measured for each NMES condition and MVC, voluntary activation (VA), peak twitch torque (Peaktwitch ), and peak soleus (EMGSOL ), medial (EMGMG ), and lateral gastrocnemius (EMGLG ) electromyography were measured before and immediately after each NMES condition. TTI was higher during WP + VIB (19.63 ± 6.34 MVC.s, mean difference = 3.66, p < 0.001, Cohen's d = 0.501) than during WP (15.97 ± 4.79 MVC.s) condition. TTI was higher during WP + VIB (mean difference = 3.79, p < 0.001, Cohen's d = 0.626) than during NP (15.84 ± 3.73 MVC.s) condition. MVC and Peaktwitch forces decreased (p ≤ 0.001) immediately after all conditions. No changes were observed for VA (p = 0.365). EMGSOL amplitude reduced (p = 0.040) only after NP, yet EMGLG and EMGMG amplitudes decreased immediately after all conditions (p = 0.003 and p = 0.013, respectively). WP + VIB produced a higher TTI than WP and NP-NMES, with similar amounts of neuromuscular fatigue across protocols. All NMES protocols induced similar amounts of peripheral fatigue and reduced EMG amplitudes.

Potential role of passively increased muscle temperature on contractile function.

Declines in muscle force, power, and contractile function can be observed in older adults, clinical populations, inactive individuals, and injured athletes. Passive heating exposure (e.g., hot baths, sauna, or heated garments) has been used for health purposes, including skeletal muscle treatment. An acute increase in muscle temperature by passive heating can increase the voluntary rate of force development and electrically evoked contraction properties (i.e., time to peak twitch torque, half-relation time, and electromechanical delay). The improvements in the rate of force development and evoked contraction assessments with increased muscle temperature after passive heating reveal peripheral mechanisms' potential role in enhancing muscle contraction. This review aimed to summarise, discuss, and highlight the potential role of an acute passive heating stimulus on skeletal muscle cells to improve contractile function. These mechanisms include increased calcium kinetics (release/reuptake), calcium sensitivity, and increased intramuscular fluid.

Lower knee flexion and hip extension rate of torque development in athletes with previous hamstring strain injury.

Persistent deficits in strength and voluntary activation have been observed in athletes with a history of hamstring strain injury. The mechanisms contributing to these deficits are poorly understood and consequently may not be appropriately addressed during rehabilitation. This study aimed to investigate the impact of intended knee flexor contraction mode (concentric, eccentric or isometric) on the rate of torque development and surface electromyography (sEMG) rise in athletes with and without a history of unilateral hamstring strain injury. The impact of the previous injury on hip extensor rate of torque development was also investigated. Previously injured limbs exhibited a slower rate of torque development (mean difference = -31%, p = 0.02, Cohen's d = 0.62) and biceps femoris rate of sEMG rise (mean difference = -181% · s-1, p = 0.003, Cohen's d = 1.10) during intended eccentric knee flexor contractions compared with control limbs. Previously injured (mean difference = -29%, p = 0.01, Cohen's d = 0.85) and contralateral uninjured limbs (mean difference = -31%, p = 0.007, Cohen's d = 0.73) exhibited a slower rate of torque development during isometric hip extensor contractions compared with control limbs. These findings may highlight lower levels of descending input to hamstring motoneurons in previously injured athletes.

Estimates of persistent inward currents increase with the level of voluntary drive in low-threshold motor units of plantar flexor muscles.

This study tested whether estimates of persistent inward currents (PICs) in the human plantar flexors would increase with the level of voluntary drive. High-density surface electromyograms were collected from soleus and gastrocnemius medialis of 21 participants (29.2 ± 2.6 yr) during ramp-shaped isometric contractions to 10%, 20%, and 30% (torque rise and decline of 2%/s and 30-s duration) of each participant's maximal torque. Motor units identified in all the contraction intensities were included in the paired-motor unit analysis to calculate delta frequency (ΔF) and estimate the PICs. ΔF is the difference in discharge rate of the control unit at the time of recruitment and derecruitment of the test unit. Increases in PICs were observed from 10% to 20% [Δ = 0.6 pulse per second (pps); P < 0.001] and from 20% to 30% (Δ = 0.5 pps; P < 0.001) in soleus and from 10% to 20% (Δ = 1.2 pps; P < 0.001) but not from 20% to 30% (Δ = 0.09 pps; P = 0.724) in gastrocnemius medialis. Maximal discharge rate increased for soleus and gastrocnemius medialis from 10% to 20% [Δ = 1.75 pps (P < 0.001) and Δ = 2.43 pps (P < 0.001), respectively] and from 20% to 30% [Δ = 0.80 pps (P < 0.017) and Δ = 0.92 pps (P = 0.002), respectively]. The repeated-measures correlation identified associations between ΔF and increases in maximal discharge rate for soleus (r = 0.64; P < 0.001) and gastrocnemius medialis (r = 0.77; P < 0.001). An increase in voluntary drive tends to increase PIC strength, which has key implications for the control of force but also for comparisons between muscles or studies when relative force levels might be different. Increases in voluntary descending drive amplify PICs in humans and provide an important spinal mechanism for motor unit discharging, and thus force output modulation.NEW & NOTEWORTHY Animal experiments and computational models have shown that motor neurons can amplify the synaptic input they receive via persistent inward currents. Here we show in humans that this amplification varies proportionally to the magnitude of the voluntary drive to the muscle.

Plantar flexor muscle stretching depresses the soleus late response but not tendon tap reflexes.

The purpose of this study was to investigate changes in muscle spindle sensitivity with early and late soleus reflex responses via tendon taps and transcranial magnetic stimulation, respectively, after an acute bout of prolonged static plantar flexor muscle stretching. Seventeen healthy males were tested before and after 5 min (5 × 60-s stretches) of passive static stretching of the plantar flexor muscles. Maximal voluntary isometric torque and M wave-normalized triceps surae muscle surface electromyographic activity were recorded. Both soleus tendon reflexes, evoked by percussion of the Achilles tendon during rest and transcranial magnetic stimulation-evoked soleus late responses during submaximal isometric dorsiflexion were also quantified. Significant decreases in maximal voluntary isometric plantar flexion torque (-19.2 ± 13.6%, p = .002) and soleus electromyographic activity (-20.1 ± 11.4%, p < .001) were observed immediately after stretching, and these changes were highly correlated (r = 0.76, p < .001). No changes were observed in tendon reflex amplitude or latency or peak muscle twitch torque (p > .05). Significant reductions in soleus late response amplitudes (-46.9 ± 36.0%, p = .002) were detected, although these changes were not correlated with changes in maximal electromyographic activity, torque or tendon reflex amplitudes. No changes in soleus late response latency were detected. In conclusion, impaired neural drive was implicated in the stretch-induced force loss; however, no evidence was found that this loss was related to changes in muscle spindle sensitivity. We hypothesize that the decrease in soleus late response indicates a stretch-induced reduction in a polysynaptic postural reflex rather than spindle reflex sensitivity.

Static Stretching Reduces Motoneuron Excitability: The Potential Role of Neuromodulation.

Prolonged static muscle stretching transiently reduces maximal muscle force, and this force loss has a strong neural component. In this review, we discuss the evidence suggesting that stretching reduces the motoneuron's ability to amplify excitatory drive. We propose a hypothetical model in which stretching causes physiological relaxation, reducing the brainstem-derived neuromodulatory drive necessary to maximize motoneuron discharge rates.

Mechanisms underlying performance impairments following prolonged static stretching without a comprehensive warm-up.

Whereas a variety of pre-exercise activities have been incorporated as part of a "warm-up" prior to work, combat, and athletic activities for millennia, the inclusion of static stretching (SS) within a warm-up has lost favor in the last 25 years. Research emphasized the possibility of SS-induced impairments in subsequent performance following prolonged stretching without proper dynamic warm-up activities. Proposed mechanisms underlying stretch-induced deficits include both neural (i.e., decreased voluntary activation, persistent inward current effects on motoneuron excitability) and morphological (i.e., changes in the force-length relationship, decreased Ca2+ sensitivity, alterations in parallel elastic component) factors. Psychological influences such as a mental energy deficit and nocebo effects could also adversely affect performance. However, significant practical limitations exist within published studies, e.g., long-stretching durations, stretching exercises with little task specificity, lack of warm-up before/after stretching, testing performed immediately after stretch completion, and risk of investigator and participant bias. Recent research indicates that appropriate durations of static stretching performed within a full warm-up (i.e., aerobic activities before and task-specific dynamic stretching and intense physical activities after SS) have trivial effects on subsequent performance with some evidence of improved force output at longer muscle lengths. For conditions in which muscular force production is compromised by stretching, knowledge of the underlying mechanisms would aid development of mitigation strategies. However, these mechanisms are yet to be perfectly defined. More information is needed to better understand both the warm-up components and mechanisms that contribute to performance enhancements or impairments when SS is incorporated within a pre-activity warm-up.

Lack of cortical or Ia-afferent spinal pathway involvement in muscle force loss after passive static stretching.

This study investigated whether modulation of corticospinal-motoneuronal excitability and/or synaptic transmission of the Ia afferent spinal reflex contributes to decreases in voluntary activation and muscular force after an acute bout of prolonged static muscle stretching. Fifteen men performed five 60-s constant-torque stretches (15-s rest intervals; total duration 5 min) of the plantar flexors on an isokinetic dynamometer and a nonstretching control condition in random order on 2 separate days. Maximum isometric plantar flexor torque and triceps surae muscle electromyographic activity (normalized to M wave; EMG/M) were simultaneously recorded immediately before and after each condition. Motor-evoked potentials (using transcranial magnetic stimulation) and H-reflexes were recorded from soleus during EMG-controlled submaximal contractions (23.4 ± 6.9% EMG maximum). No changes were detected in the control condition. After stretching, however, peak torque (mean ± SD; -14.3 ± 7.0%) and soleus EMG/M (-17.8 ± 6.2%) decreased, and these changes were highly correlated (r = 0.83). No changes were observed after stretching in soleus MEP or H-reflex amplitudes measured during submaximal contractions, and interindividual variability of changes was not correlated with changes in EMG activity or maximum torque. During EMG-controlled submaximal contractions, torque production was significantly decreased after stretching (-22.7 ± 15.0%), indicating a compromised muscular output. These data provide support that changes in the excitability of the corticospinal-motoneuronal and Ia afferent spinal reflex pathways do not contribute to poststretch neural impairment.NEW & NOTEWORTHY This study is the first to specifically examine potential sites underlying the decreases in neural activation of muscle and force production after a bout of muscle stretching. However, no changes were found in either the H-reflex or motor-evoked potential amplitude during submaximal contractions.