Acute and prolonged competing effects of activation history on human motor unit firing rates during contractile impairment and recovery.

The purpose of this study was to investigate the effect of inducing post-activation potentiation (PAP) during prolonged low-frequency force depression (PLFFD) on motor unit (MU) firing rates. In 10 participants, grouped firing rates of 3027 MUs from the tibialis anterior were recorded with tungsten microelectrodes. Baseline MU firing rates at 25% isometric maximal voluntary contraction (MVC) were ∼14 Hz. A 1 min dorsiflexion MVC reduced torque and maximal MU firing rates (36 Hz) by 49% and 52%, respectively. Following task completion, firing rates at 25% of baseline MVC torque and torque in response to electrically evoked (single twitch, 10 Hz and 50 Hz) stimulation were assessed before and after a 5 s MVC (to induce PAP) every 10 min for 60 min. From 10 to 60 min after task completion, the torque ratios (twitch:50 Hz and 10:50 Hz) were depressed (∼30%) relative to baseline (P < 0.001), indicating PLFFD; and firing rates were higher by ∼15% relative to baseline (P < 0.001). This occurred despite recovery of MVC rates (∼99%) and torque (∼95%) by 10 min (P > 0.3). Inducing PAP during PLFFD increased both low to high torque ratios (twitch and 10:50 Hz) by ∼200% and ∼135%, respectively (P < 0.001) and firing rates were ∼18% lower relative to PLFFD rates (P < 0.001), despite a speeding of evoked contractile properties (P = 0.001). Thus, firing rates appear strongly matched to alterations in torque, rather than contractile speed when modified by contractile history, and lower rates during PAP may be a mechanism to mitigate effects of PLFFD. The effect of activation history on contractile function demonstrates acute compensatory responses of motoneuron output. KEY POINTS: Prolonged low frequency force depression (PLFFD) following a sustained 1 min isometric maximal voluntary contraction causes an increase in submaximal mean motor unit (MU) firing rates. Inducing post-activation potentiation (PAP) during PLFFD, however, causes a reduction in mean submaximal MU firing rates to a level below those at baseline. The mean firing rate reduction during PAP occurs despite a speeding of evoked contractile properties and thus firing rates are more strongly matched to alterations in torque, rather than contractile speed when modified by various contractile histories. The reductions in firing rates during PAP may mitigate the effects of PLFFD during voluntary contractions. These results demonstrate that firing rates are highly responsive to opposing influences on the contractile state and can make rapid compensatory rate adjustments dependent on the active state of the muscle.

Increased corticospinal inhibition following brief maximal and submaximal contractions in humans.

A potentiating conditioning contraction (CC) has been shown to increase silent period duration, an index of corticospinal inhibition; however, it is unknown if the CC must induce potentiation for corticospinal inhibition to increase. Ten healthy, young adults (four females) completed this study to assess potentiation and silent period (SP) duration before and after four types of CCs: voluntary and electrically evoked maximal CCs to optimize potentiation, and voluntary and electrically evoked submaximal CCs (∼40% of maximal voluntary force) that induced minimal potentiation. Stimulation was applied to the ulnar nerve to evoke twitches for the assessment of potentiation and to evoke tetanic CCs of the first dorsal interosseous muscle. The SP was elicited by applying transcranial magnetic stimulation to the motor cortex during brief contractions at 25% of maximal voluntary force. Changes to twitch force and SP duration were not different for voluntary and tetanic contractions, so data were pooled. Twitch force increased by 81.2 ± 35.7% (P < 0.001) and 3.2 ± 6.5% (P = 0.039) following maximal and submaximal CCs, respectively. The SP was prolonged following maximal (12.6 ± 6.3%; P < 0.001) and submaximal (4.8 ± 4.9%; P < 0.001) CCs. Correlations between post-CC twitch force and SP duration were not significant for maximal or submaximal conditions (r = -0.068; r = 0.067; P ≥ 0.780, respectively). Duration of the SP increased not only following maximal-intensity CCs but also after submaximal-intensity CCs that induced virtually no potentiation (∼3%). Thus, we suggest that corticospinal inhibition is not directly related to mechanisms of muscle potentiation per se, but, rather, the level of muscle contraction likely mediates feedback from large diameter afferents that affect the SP.NEW & NOTEWORTHY The transcranial magnetic stimulation-induced silent period reflects a transient state of corticospinal inhibition that is influenced by recent history of muscle activation, which may include an effect of potentiation. We demonstrate that silent period duration increases following both voluntary and electrically evoked maximal and submaximal conditioning contractions, even though the latter intensity produced virtually no muscle potentiation. Feedback from group Ia and Ib muscle afferents is proposed as the cause of the increased corticospinal inhibition.

Motor unit firing rates in young and very old adult males during an isokinetic fatiguing task and short-term recovery in the anconeus muscle.

Understanding motor unit (MU) properties with muscle fatigue in adult aging is limited to isometric tasks. The purpose was to investigate the effect of an isokinetic fatiguing task on MU firing rates between two adult age groups of males. Single MUs were recorded by intramuscular electrodes in the anconeus muscle of eight young (19-33 yr) and 11 very old adults (78-93 yr). Fatigue was induced by repeated isokinetic maximal voluntary contractions at 25% of maximum velocity (Vmax), until elbow extension power decreased by 35%. At baseline, the very old had lower maximal power (135 vs. 214 W, P = 0.002) and slower maximal velocity (177 vs. 196°/s, P < 0.001) compared with young. Despite a similar number of contractions (average 39 young and 44 very old) to task failure (P = 0.33), the older males were less fatigable as time under tension was ∼25% longer (P = 0.04). Maximum firing rates from ∼20 single MUs per age group were tracked continuously throughout the task and during 10 min of recovery. Similar rates were recorded (24.7 and 23.6 Hz, P = 0.18) at baseline 25% Vmax, and during the task (23.3 and 28.7% decrease, P = 0.21) between young and very old, respectively. Power and MU rates were recovered similarly by 2 min of rest in both groups (all P > 0.15). Despite differences in baseline capability, very old males in this relatively slow isokinetic task were more fatigue resistant, but the fatigue-related reduction and recovery in MU rates were similar between groups. Therefore, fatigue in this task between age groups is not differentially affected by alterations in firing rates.NEW & NOTEWORTHY Maximal motor unit firing rates were recorded during an isokinetic fatiguing protocol and short-term recovery in young and very old adult males. Prior studies were limited to isometric fatiguing tasks. Despite the old being ∼37% weaker and less fatigable, anconeus rates during elbow extension declined with fatigue and recovered similarly to young males. Therefore, it is unlikely that greater fatigue resistance of very old males during isokinetic contractions is related to differences in motor unit rates.

Test-retest repeatability of electrically evoked isotonic power and isometric torque in the plantar flexors.

Electrically evoked isometric torque has good to excellent repeatability, but the degree of repeatability for electrically evoked isotonic power is unknown. We evaluated the test-retest repeatability of plantar flexion isometric torque and isotonic power evoked using brief tetanic trains at 10 and 50 Hz. Both torque and power had excellent (intraclass correlation coefficient >0.9) repeatability at low and high frequencies. Similar to isometric torque, electrically evoked isotonic power is a stable measure for studying dynamic muscle function.

Comparison of prolonged low-frequency force depression assessed using isometric torque and isotonic power following a dynamic fatiguing task.

PURPOSE: Prolonged low-frequency force depression (PLFFD) occurs following both dynamic and static fatiguing tasks, but it has been assessed predominately using measures of isometric torque. However, it is unknown whether PLFFD induced during dynamic tasks is adequately characterized by isometric torque, which excludes velocity and power. The purpose of this study was to compare PLFFD assessed using isometric torque and isotonic power following a concentric fatiguing task. METHODS: Young (18-31 years) males (n = 9) and females (n = 4) performed isotonic plantar flexion contractions until a ~ 75% reduction in peak power. Isotonic and isometric contractions were electrically evoked at 10 Hz and 50 Hz via tibial nerve stimulation. Isotonic and isometric PLFFD was assessed as the ratio of 10 to 50 Hz for power and torque, respectively. Recovery was assessed immediately, and at 2.5, 5, 10, 20, and 30 min after task termination. RESULTS: Relative to baseline, 10:50 Hz ratio assessed using isotonic power was reduced more than isometric torque (30 min 41 ± 17 vs. 25 ± 12% reduction, p = 0.001); however, both contraction modes displayed similar trajectories throughout recovery (p = 0.906). The larger reduction in isotonic 10:50 Hz ratio was due to greater impairments in 10 Hz power compared to 10 Hz isometric torque (30 min 38 ± 20 vs. 21 ± 11% reduction, p < 0.001). CONCLUSION: The similar trajectories of 10:50 Hz ratios throughout recovery indicate that PLFFD can be adequately characterized using either isometric torque or isotonic power.

Muscle fatigability and post-acute COVID-19 syndrome: A case study.

The acute phase of COVID-19 has been well studied, however with increasing post-acute COVID-19 syndrome, much is unknown about its long-term effects. A common symptom in both the acute and post-acute phases has been fatigue, assessed predominantly qualitatively. Here we present a case study objectively assessing neuromuscular fatiguability in a young male (27 year, 1.85 m, 78 kg) who continues to experience COVID-19 related fatigue and cognitive dysfunction, including other symptoms, 12+ months post-infection. Prior to infection, he was part of a neuromuscular study forming the basis of our pre-COVID-19 results. The study was repeated 12 months post-COVID-19 infection. Muscle strength, endurance, torque steadiness, voluntary activation, twitch properties, electromyography, and compound muscle action potential were obtained and compared pre- and post-COVID-19. All measurements were done using a dorsiflexion dynamometer in which the participant also was asked to produce a one-minute fatiguing maximal voluntary contraction. Muscle strength, voluntary activation, and fatigability (slope of torque) showed no meaningful differences, suggesting intrinsic neuromuscular properties are not affected. However, torque steadiness was impaired three-fold in the post- compared with pre-COVID-19 test. The participant also reported a higher level of perceived exertion subjectively and a continued complaint of fatigue. These findings indicate that muscle fatiguability in post-acute COVID-19 syndrome may not be a limitation of the muscle and its activation, but a perceptual disconnect caused by cognitive impairments relating to physical efforts. This case report suggests the potential value of larger studies designed to assess these features in post-acute COVID-19 syndrome.

Frequency-dependent coexistence of muscle fatigue and potentiation assessed by concentric isotonic contractions in human plantar flexors.

The purpose was to investigate whether postactivation potentiation (PAP) mitigates power (i.e., torque × angular velocity) loss during dynamic fatiguing contractions and subsequent recovery by enhancing either muscle torque or angular velocity in human plantar flexors. In 12 participants, electrically stimulated (1, 10, and 50 Hz) dynamic contractions were done during a voluntary isotonic fatiguing protocol until a 75% loss in voluntary peak power, and throughout 30 min of recovery. At the initial portion of fatigue (20% decrease), power responses of evoked low frequencies (1 and 10 Hz) were enhanced due to PAP (156% and 137%, respectively, P < 0.001), whereas voluntary maximal efforts were depressed due to fatiguing mechanisms. Following the fatiguing task, prolonged low-frequency force depression (PLFFD) was evident by reduced 10:50 Hz peak power ratios (21%-24%) from 3 min onward during the 30-min recovery (P < 0.005). Inducing PAP with maximal voluntary dynamic contractions during PLFFD enhanced the peak power responses of low frequencies (1 and 10 Hz) by 128%-160%, P < 0.01. This PAP response mitigated the effects of PLFFD as the 1:50 (P < 0.05) and 10:50 (P > 0.4) Hz peak power ratios were greater or not different from the prefatigue (baseline) values. In addition, PAP enhanced peak torque more than peak angular velocity during both baseline and fatigue measurements (P < 0.03). These results indicate that PAP can ameliorate PLFFD acutely when evaluated during concentric isotonic contractions and that peak torque is enhanced to a greater degree compared with peak angular velocity at baseline and in a fatigued state.NEW & NOTEWORTHY Postactivation potentiation (PAP) enhanced stimulated low frequencies (1 and 10 Hz) during muscle fatigue development when assessed with power (torque × angular velocity) in a voluntary isotonic fatiguing task. Following the task during 30 min of recovery, prolonged low-frequency force depression (PLFFD) was evident, and inducing PAP with brief maximal contractions during this state ameliorated the effects of PLFFD. PAP enhanced peak torque more than peak angular velocity during both baseline and fatiguing conditions.

Firing rate trajectories of human motor units during activity-dependent muscle potentiation.

During activity-dependent potentiation (ADP), motor unit firing rates (MUFRs) are lower; however, the mechanism for this response is not known. During increasing torque isometric contractions at low contraction intensities, MUFR trajectories initially accelerate and saturate demonstrating a nonlinear response due to the activation of persistent inward currents (PICs) at the motoneuron. The purpose was to assess whether PICs are a factor in the reduction of MUFRs during ADP. To assess this, MUFR trajectories were fit with competing functions of linear regression and a rising exponential (i.e., acceleration and saturation). With fine-wire electrodes, discrete MU potential trains were recorded in the tibialis anterior during slowly increasing dorsiflexion contractions to 10% of maximal voluntary contraction following both voluntary [postactivation potentiation (PAP)] and evoked [posttetanic potentiation (PTP)] contractions. In eight participants, 25 MUs were recorded across both ADP conditions and compared with the control with no ADP effect. During PAP and PTP, the average MUFRs were 16.4% and 9.2% lower (both P ≤ 0.001), respectively. More MUFR trajectories were better fit to the rising exponential during control (16/25) compared with PAP (4/25, P < 0.001) and PTP (8/25, P = 0.03). The MU samples that had a rising exponential MUFR trajectory during PAP and PTP displayed an ∼11% lower initial acceleration compared with control (P < 0.05). Thus, presumed synaptic amplification and MUFR saturation due to PIC properties are attenuated during ADP regardless of the type of conditioning contraction. This response may contribute to lower MUFRs and likely occurred because synaptic input is reduced when contractile function is enhanced.NEW & NOTEWORTHY During activity-dependent muscle potentiation (ADP), initial motor unit firing rate (MUFR) acceleration and the occurrence of MUFR trajectory saturation as a function of increasing contraction intensity were assessed. With no ADP (control), trajectories were more likely to accelerate and saturate (16/25 units) compared with voluntary- and stimulated-induced ADP conditions (4/25 and 8/25 units, respectively) that were fit better linearly. Therefore, during ADP, an attenuated intrinsic response to voluntary synaptic inputs occurs.

Length-dependent changes of lower limb muscle morphology in Chronic Inflammatory Demyelinating Polyneuropathy assessed with magnetic resonance imaging.

The objective of the present study was to assess muscle quantity of the thigh and leg in patients with chronic inflammatory demyelinating polyneuropathy (CIDP) compared to age and sex matched controls in exploring length-dependent changes of innervated muscles. In five people with CIDP and seven controls, magnetic resonance imaging was used to assess muscle morphology of the four parts of the quadriceps and medial hamstring muscles. Findings were compared to the triceps surae from a subset of participants. The CIDP group had less contractile tissue in the quadriceps (11.5%, P<0.05), hamstrings (15.6%, P<0.05) and triceps surae (35.9%, P<0.05) compared to controls. Additionally, CIDP had less contractile tissue (18.7%) in the triceps surae compared to the hamstrings (P<0.05). Muscle quantity in the quadriceps and hamstrings in CIDP was less than controls, but differences were greater for the distal triceps surae. These findings support a length-dependent affect of CIDP on limb musculature composition.

Firing rate trajectories of human occipitofrontalis motor units in response to triangular voluntary contraction intensity.

During voluntary contractions, limb muscle motor unit (MU) firing rates accelerate over a small force range and saturate in response to increasing contraction intensity. In comparison, facial muscles are cranially innervated, and some function without crossing joints. Therefore, the MU firing rate behaviour and characteristics of saturation were explored in a facial muscle that moves skin and facia during voluntary contractions. We evaluated the firing rate trajectory in response to triangular voluntary contraction ramps in the occipitofrontalis muscle of 11 adult participants. Intramuscular electromyography of the frontalis aspect was used to record single MU trains followed up to maximal voluntary contraction intensities. Firing rates were measured from each MU sample, with the firing rate trajectory fit as both exponential (i.e., saturation) and linear models that were compared statistically. The rate coding behaviour of frontalis MUs was broad, as the peak firing rate (mean 76 Hz) was ninefold greater than the firing rate at recruitment threshold (mean 8 Hz). Across 20 MU samples, only 40% (8 MU samples) were determined to have a firing rate trajectory that saturated and had slow acceleration in response to increasing voluntary drive until maximum. The exponential curve of the firing rate trajectory had ~ tenfold lower acceleration as compared to prior reports in limb muscles. These results across all MU samples indicated that voluntary control of the frontalis muscle requires relatively slower accelerating or linear MU firing rate trajectories, suggesting that movements of facial muscles may be directly representative of extrinsic synaptic inputs.

Post-activation potentiation induced by concentric contractions at three speeds in humans.

NEW FINDINGS: What is the central question of this study? Is the degree of in human muscle affected by different shortening velocities, or contraction type? What are the main findings and their importance? The PAP response following maximal concentric contractions was independent of velocity. Slow and moderate velocity maximal contractions produced PAP responses like those from maximal isometric contractions when matched for contraction duration. Despite contraction type differences in cross-bridge and Ca2+ kinetics, maximal contractions, regardless of contraction modality, likely generate sufficient Ca2+ to induce maximal PAP. ABSTRACT: Post-activation potentiation (PAP) is the acute enhancement of contractile properties following a brief (<10 s) high-intensity contraction. Compared with isometric contractions, little is known about the PAP response induced by concentric conditioning contractions (CCs) and the effect of velocity. In the dorsiflexors of 11 participants, twitch responses were measured following 5 s of maximal effort concentric CCs at each of 10, 20 and 50°/s. Concentric PAP responses were compared to a maximal isometric voluntary contraction (MVC) matched for contraction time. Additionally, concentric CCs were compared to isometric CCs matched for mean torque, contraction area and time. The PAP response following maximal concentric CCs was independent of velocity and there was no difference in the PAP response between concentric CCs and an isometric MVC. During maximal contractions, regardless of contraction modality, there is likely sufficient Ca2+ to induce a similar full PAP response, and thus there was no difference between speeds or contraction type. Following concentric CCs there was a significantly larger peak twitch torque than following their isometric torque matches (49-58%), and faster maximal rates of torque development at the three speeds (62-77%). However, these responses are likely related to greater EMG in concentric contractions, 125-129% of isometric maximum compared to 38-54%, and not to contraction modality per se. Thus, PAP responses following maximal concentric CCs are not affected by velocity and responses are not different from an isometric MVC. This indicates maximal CCs of 5 s produce a maximal PAP response independent of contraction type (isometric vs. concentric) or shortening velocity.

Firing rate trajectories of human motor units during isometric ramp contractions to 10, 25 and 50% of maximal voluntary contraction.

During low torque graded isometric contractions, motor units (MU) exhibit initial firing rate acceleration followed by saturation demonstrating a non-linear response attributed to persistent inward currents (PICs) which contribute to the net excitatory input. Firing rate saturation studies have been done exclusively at recruitment thresholds of low firing threshold MUs below 10% of isometric maximal voluntary contraction(MVC). It remains unclear whether later recruited (i.e. higher-threshold) MUs follow a similar firing rate trajectory as low-threshold units. Thus, MU firing rate trajectories were explored in relation to MU recruitment threshold (RT) at contraction levels between 10 and 50% of MVC. During graded isometric contractions to 10, 25 and 50% of MVC, single MU potentials were recorded from the tibialis anterior from 5 participants using tungsten microelectrodes. To characterize the firing rate trajectory, each MU train was fit by competing functions of torque as an exponential (i.e. saturated) and simple linear regression, using previous analysis methods (Fuglevand et al. 2015). Throughout a RT range of 0.02-41% of MVC, 261 MUs were compared. In 87% of MUs the better fit was by a linear function, whereas the remaining MUs (13%) were fit better with an exponential (saturated) firing rate trajectory. There was no statistical difference in the number of MUs better fit by the exponential function between low (<10% MVC) and relatively higher threshold MUs (>10% MVC; both p < 0.05). Increasing RT and rate of torque development (RTD) of the ramps were correlated with increased firing rate variability (larger error) in both fits (r = 0.3 and r = 0.4, both p < 0.01). Additionally, there was a 4-fold increase in peak antagonist surface electromyography (EMG) from 10 to 50% MVC contraction ramps. When all MUs were plotted with a normalized firing onset (i.e. 0% MVC) the data visually displayed an initial firing rate acceleration followed by a linear response (biphasic trajectory). Increased synaptic drive and greater antagonist surface EMG during moderate torque outputs may dampen PIC activity as compared with MUs during lower torque (<10% MVC) recruitment levels.

State-of-the-art review: spinal and supraspinal responses to muscle potentiation in humans.

Post-activation potentiation (PAP), described as a muscular phenomenon, refers to the enhancement of contractile properties following a voluntary or electrically stimulated short duration (< 10 s) high-intensity contraction. Mechanistic factors and subsequent effects on voluntary performance have been well documented. Associations between neural activation and PAP, however, are less understood and systematically have not been explored. Thus, the aim is to critically summarize the current understanding of PAP regarding the motor pathway from the corticospinal tract to spinal level factors including the H-reflex and motor unit activation. This review highlights aspects for further investigation by providing an integrative summary of the relationship between PAP and neural control. Contractile history affects neural control in subsequent contractions, (e.g. fatiguing tasks), however, by contrast acute contractile enhancement due to PAP in relation to neural responses are not well-studied. From the limited number of investigations, motor unit discharge rates are reduced subsequent to PAP and, although less consistently reported, generally H-reflexes are depressed. Additionally, corticomedullary evoked potentials are depressed and the cortical silent period is elongated. Thus, overall there is a depression of spinal and supraspinal responses following PAP. Although specific factors responsible and their pathways are unclear, this down-regulation may occur to conserve neural activation when muscle contraction is more responsive, and concurrently a strategy used to delay neuromuscular fatigue. Indeed, the co-existence of PAP and fatigue is not a novel concept, but the interactions between PAP and neural responses are not understood and likely are more than coincidental.

Effect of ankle joint position on triceps surae contractile properties and motor unit discharge rates.

The triceps surae (TS) length-tension relationship can be altered by changing the knee joint position, ankle joint position or both. However, studies exploring the effect of muscle length on neuromuscular properties have focused only on knee joint position changes affecting two of the three muscle components of the TS. Thus, the purpose of this study is to compare the neuromuscular properties of the three TS muscles during plantar flexion contractions at two ankle joint positions, 20° dorsiflexed (DF) and 20° plantar flexed (PF). Maximal isometric voluntary strength (MVC), voluntary activation, and evoked contractile properties of the ankle plantar flexors were compared between both ankle joint positions. Additionally, soleus, medial (MG), and lateral (LG) gastrocnemii motor unit discharge rates (MUDRs) were sampled during plantar flexion contractions at 25%, 50%, 75%, and 100% MVC using indwelling tungsten electrodes. MVC and peak twitch torque were lower by ~61% and 70%, respectively, whereas the maximal rate of torque relaxation was 39% faster in the PF compared with the DF position. Voluntary activation (~95%) was unaffected by changes in ankle joint position. LG MUDRs showed no differences between ankle joint positions, regardless of contraction intensity. Submaximal MG and soleus MUDRs showed no differences between the two ankle joint positions, however both muscles had 9% and 20% higher MUDRs in the DF position, respectively. These results provide further evidence for the differential activation among the three components of the TS with the greatest increases in soleus MUDRs compared with the gastrocnemii when the muscles are lengthened.