Increased H‐reflex excitability is not accompanied by changes in neural drive following 24 days of unilateral lower limb suspension

The purpose of this study was to determine whether the gain in soleus H‐reflex excitability induced by unilateral lower limb suspension (ULLS) is associated with changes in neural drive to the plantar flexor muscles. Six male subjects (23 ± 2 years, 187 ± 7 cm, 79 ± 9 kg) underwent 24 days of ULLS of the dominant limb. Plantar flexor maximal voluntary contraction (MVC) torque, activation capacity (twitch interpolation), soleus maximal electromyographic (EMG) activity, Hoffman (H)‐reflex, and the first volitional (V) wave normalized to the compound muscle action potential (M‐wave) were quantified before and after ULLS. Following ULLS, MVC torque decreased by 15% (P < 0.05). However, neither activation capacity nor EMG activity was significantly altered after the suspension. The V‐wave remained unchanged consistently after ULLS, whereas the H‐reflex increased significantly (+20%). Furthermore, there was no significant relationship between changes in H‐reflex and V‐wave over the ULLS period. These findings indicate that 24 days of ULLS can result in a substantial reduction of muscle strength without any apparent change in voluntary activation capacity. H‐reflex and V‐wave findings suggest that the spinal adaptations that underlie the unloading‐induced increase in resting soleus H‐reflex excitability did not significantly affect the efferent motor output to the plantar flexor muscles. Muscle Nerve, 2009     

Changes in soleus H‐reflex during walking in middle‐aged,healthy subjects

Introduction: To assess the effect of aging on stretch reflex modulation during walking, soleus H‐reflexes obtained in 15 middle‐aged (mean age 56.4 ± 6.9 years) and 15 young (mean age 23.7 ± 3.9 years) subjects were compared. Methods: The H‐reflex amplitude, muscle activity (EMG) of the soleus and tibialis anterior muscles, and EMG/H‐reflex gain were measured during 4‐km/h treadmill walking. Results: The normalized H‐reflex amplitude was lower in the swing phase for the middle‐aged group, and there was no difference in muscle activity. EMG/H‐reflex gain did not differ between groups. Conclusions: H‐reflex amplitude during walking was affected by aging, and changes during the swing phase could be seen in the middle‐aged subjects. Subdividing the 2 age groups into groups of facilitated or suppressed swing‐phase H‐reflex revealed that the H‐reflex amplitude modulation pattern in the group with facilitated swing‐phase H‐reflex may be influenced by aging. Muscle Nerve 51: 419–425, 2015     

H-reflex modulation in the human medial and lateral gastrocnemii during standing and walking

Introduction: The soleus H‐reflex is dynamically modulated during walking. However, modulation of the gastrocnemii H‐reflexes has not been studied systematically. Methods: The medial and lateral gastrocnemii (MG and LG) and soleus H‐reflexes were measured during standing and walking in humans. Results: Maximum H‐reflex amplitude was significantly smaller in MG (mean 1.1 mV) or LG (1.1 mV) than in soleus (3.3 mV). Despite these size differences, the reflex amplitudes of the three muscles were positively correlated. The MG and LG H‐reflexes were phase‐ and task‐dependently modulated in ways similar to the soleus H‐reflex. Conclusions: Although there are anatomical and physiological differences between the soleus and gastrocnemii muscles, the reflexes of the three muscles are similarly modulated during walking and between standing and walking. Our findings support the hypothesis that these reflexes are synergistically modulated during walking to facilitate ongoing movement. Muscle Nerve 45: 116–125, 2012     

Post‐activation potentiation: The neural effects of post—activation depression

Introduction: Our knowledge of the neurophysiology of post‐activation potentiation (PAP) is limited. The purpose of this study was to examine the effect of PAP on twitch torque and H‐reflex amplitude after a 10‐s maximal voluntary contraction (MVC). Methods: PAP measurements were assessed with the plantarflexors in a relaxed state and during a tonic contraction at 10% MVC. Results: The H‐reflex/maximum M‐wave ratio (H/M) decreased significantly (P < 0.05) and returned to baseline levels after 1 min. The decrement in H/M was depressed when the plantarflexors were active at 10% MVC, and the depression was more obvious in the lateral gastrocnemius than in the soleus muscle. Conclusions: The inhibition induced immediately after contraction could be attributed to post‐activation depression. We conclude that PAP after a 10‐s MVC cannot be attributed to increased motor neuron excitability through the reflex pathway as assessed by the H‐reflex technique. Muscle Nerve 52 : 252–259, 2015     

Reproducibility of electromyographic and mechanical parameters of the triceps surae during submaximal and maximal plantar flexions

Introduction: Neuromuscular parameters must be reproducible to examine neuromuscular adaptations in interventional and clinical studies. The reproducibility of neuromuscular parameters for the soleus (SOL), lateral gastrocnemius (LG), and medial gastrocnemius (MG) was assessed over a period of 2 weeks. Methods: Thirteen subjects (27.4 years, 69.5 kg) were tested for numerous electromyographic (e.g., voluntary and electrical evoked EMG) and mechanical (e.g., voluntary activation level) parameters in 3 test sessions. Results: The majority of the data (28 of 34) revealed moderate and substantial reproducibility. H_max20%/M_max20% and V_sup/M_sup were less reproducible in LG than in MG and SOL. Muscle activity and M‐waves did not differ between muscles. The ICC for the mechanical data was >0.79. Conclusions: The H‐reflex during voluntary contraction of the LG should be considered with caution. Mechanical data on muscle activation level are reproducible. The reproducibility of neuromuscular parameters is sufficient for interventional studies. Muscle Nerve 53: 464–470, 2016     

Effects of moderate‐ and high‐intensity chronic exercise on brain‐derived neurotrophic factor expression in fast and slow muscles

Introduction: Brain‐derived neurotrophic factor (BDNF) protein expression is sensitive to cellular activity. In the sedentary state, BDNF expression is affected by the muscle phenotype. Methods: Eighteen Wistar rats were divided into the following 3 groups: sedentary (S); moderate‐intensity training (MIT); and high‐intensity training (HIT). The training protocol lasted 8 weeks. Forty‐eight hours after training, total RNA and protein levels in the soleus and plantaris muscles were obtained. Results: In the plantaris, the BDNF protein level was lower in the HIT than in the S group (P < 0.05). A similar effect was found in the soleus (without significant difference). In the soleus, higher Bdnf mRNA levels were found in the HIT group (P < 0.001 vs. S and MIT groups). In the plantaris muscle, similar Bdnf mRNA levels were found in all groups. Conclusions: These results indicate that high‐intensity chronic exercise reduces BDNF protein level in fast muscles and increases Bdnf mRNA levels in slow muscles. Muscle Nerve 53: 446–451, 2016     

Influence of joint position on synergistic muscle activity after fatigue of a single muscle head

Introduction: We investigated synergistic muscle activity after fatigue of a single muscle in different joint positions. Methods: Two experimental groups (n = 12 each) performed maximal voluntary contractions (MVCs) before and after fatiguing the gastrocnemius lateralis (GL), using neuromuscular electrical stimulation (NMES). Neuromuscular tests, including muscle activity during MVC, H‐reflex, and twitch interpolation, were performed. One group completed the experiment in a knee‐extended position with the second group in a knee‐flexed position. Results: In the knee‐flexed position, the muscle activity increased in non‐stimulated synergistic muscles. In contrast, in the knee‐extended position, muscle activity of the synergistic muscles remained unaltered. The MVC force remained unaltered in the flexed position and decreased in the extended position. Conclusions: Synergistic muscles compensate for the fatigued muscle in the flexed position but not in the extended position. Compensation mechanisms seem to depend on joint position. Muscle Nerve 51 : 259–267, 2015     

Inflammatory response during slow‐ and fast‐twitch muscle regeneration

Introduction: Skeletal muscles are characterized by their unique ability to regenerate. Injury of a so‐called fast‐twitch muscle, extensor digitorum longus (EDL), results in efficient regeneration and reconstruction of the functional tissue. In contrast, slow‐twitch muscle (soleus) fails to properly reconstruct and develops fibrosis. This study focuses on soleus and EDL muscle regeneration and associated inflammation. Methods: We determined differences in the activity of neutrophils and M1 and M2 macrophages using flow cytometry and differences in the levels of proinflammatory cytokines using Western blotting and immunolocalization at different times after muscle injury. Results: Soleus muscle repair is accompanied by increased and prolonged inflammation, as compared to EDL. The proinflammatory cytokine profile is different in the soleus and ED muscles. Conclusions: Muscle repair efficiency differs by muscle fiber type. The inflammatory response affects the repair efficiency of slow‐ and fast‐twitch muscles. Muscle Nerve 55 : 400–409, 2017     

Soleus H‐reflex modulation during balance recovery after forward falling

Introduction: Our purpose was to examine the Hoffmann reflex (H‐reflex) during balance recovery after a simulated forward fall from 2 different inclination angles. Methods: The soleus H‐reflex of 15 healthy adults was measured in 2 different leaning positions (exerting a horizontal force at 15% and 30% of body weight, respectively), with no release (Int0) and at 2 different intervals (Int1, Int2) after the release (～45 and ～65 ms, respectively). Results: During Int2, the H‐reflex, which was evoked before the onset of the soleus electromyography, was significantly higher than the H‐reflex induced 20 ms earlier (Int1). No significant difference was observed between Int0 and Int1 and between the 2 leaning positions. Conclusions: These findings indicate that Ia afferent input is facilitated before muscle activation during forward falling. This could be important for the timely activation and increased rate of force development required during this task. Muscle Nerve 54 : 952–958, 2016     

Can neck muscle spindle afferents activate fusimotor neurons of the lower limb?

Introduction: We investigated whether vibratory stimulation of the dorsal neck muscles activates fusimotor neurons of lower limb muscles in relaxed human subjects. Methods: The triceps surae (TS) muscles of seated subjects (n = 15) were conditioned to leave their muscle spindles in either an insensitive (hold‐long) or sensitive (hold‐short) state. A vibrator (80 HZ ) was applied to the dorsal neck muscles for 10 seconds. The tendon jerk was evoked from the right TS immediately before (during) or 5 seconds after (interposed) the offset of vibration. Results: The size of the reflex after hold‐long muscle conditioning and after neck vibration was significantly smaller than the control hold‐short reflex (P < 0.001). However, after hold‐short conditioning, neck vibration significantly increased tendon jerk amplitude, both during (P = 0.001) and interposed (P = 0.026). Conclusion: Dorsal neck vibration increases spinal reflex excitability of the TS in relaxed and seated subjects, but not through fusimotor excitation. Muscle Nerve, 2012     

Tetanus toxin reduces local and descending regulation of the H‐reflex

Introduction: Skeletal muscles that are under the influence of tetanus toxin show an exaggerated reflex response to stretch. We examined which changes in the stretch reflex may underlie the exaggerated response. Methods: H‐reflexes were obtained from the tibialis anterior (TA) and flexor digitorum brevis (FDB) muscles in rats 7 days after intramuscular injection of tetanus toxin into the TA. Results: We found effects of the toxin on the threshold, amplitude, and duration of H‐waves from the TA. The toxin inhibited rate‐dependent depression in the FDB between the stimulation frequencies of 0.5–50 HZ and when a conditioning magnetic stimulus applied to the brain preceded a test electrical stimulus delivered to the plantar nerve. Conclusions: Tetanus toxin increased the amplitude of the H‐wave and reduced the normal depression of H‐wave amplitude that is associated with closely timed stimuli, two phenomena that could contribute to hyperactivity of the stretch reflex. Muscle Nerve 49:495–501, 2014     

Physical exercise during muscle regeneration improves recovery of the slow/oxidative phenotype

Introduction: As skeletal muscle mass recovery after extensive injury is improved by contractile activity, we explored whether concomitant exercise accelerates recovery of the contractile and metabolic phenotypes after muscle injury. Methods: After notexin‐induced degeneration of a soleus muscle, Wistar rats were assigned to active (running exercise) or sedentary groups. Myosin heavy chains (MHC), metabolic enzymes, and calcineurin were studied during muscle regeneration at different time points. Results: The mature MHC profile recovered earlier in active rats (21 days after injury) than in sedentary rats (42 days). Calcineurin was higher in the active degenerated than in the sedentary degenerated muscles at day 14. Citrate synthase and total lactate dehydrogenase (LDH) activity decreased after injury and were similarly recovered in both active and sedentary groups at 14 or 42 days, respectively. H‐LDH isozyme activity recovered earlier in the active rats. Conclusions: Exercise improved recovery of the slow/oxidative phenotype after soleus muscle injury. Muscle Nerve 55 : 91–100, 2017     

Chemogenetic enhancement of functional recovery after a sciatic nerve injury

Designer receptors exclusively activated by designer drugs (DREADDs) are chemogenetic tools used to modulate neuronal excitability. We hypothesized that activation of excitatory (Gq) DREADD by its designer ligand, clozapine‐N‐oxide (CNO), would increase the excitability of neurons whose axons have been transected following peripheral nerve injury, and that this increase will lead to an enhanced functional recovery. The lateral gastrocnemius (LG) muscle of adult female Lewis rats was injected unilaterally with AAV9‐ hsyn‐ hM3Dq‐mCherry (7.6 × 10⁹ viral genomes/μL) to transduce Gq‐DREADD expression in LG neurons. The contralateral LG muscle served as an uninjected control. No significant changes in either spontaneous EMG activity or electrically evoked direct muscle (M) responses were found in either muscle after injection of CNO (1 mg/kg, i.p.). The amplitude of monosynaptic H‐reflexes in LG was increased after CNO treatment exclusively in muscles previously injected with virus, suggesting that Gq‐DREADD activation increased neuronal excitability. After bilateral sciatic nerve transection and repair, additional rats were treated similarly with CNO for up to three days after injury. Electrophysiological data were collected at 2, 4 and 6 weeks after injury. Evoked EMG responses were observed as early as 2 weeks after injury only in Gq‐DREADD expressing virus injected LG muscle. By 4 weeks after injury, both M‐response and H‐reflex amplitudes were significantly greater in muscles previously injected with viral vector than contralateral, uninjected muscles. Increases in the excitability of injured neurons produced by this novel use of Gq‐DREADD were sufficient to promote an enhancement in functional recovery after a sciatic nerve injury.     

Crossed spinal soleus muscle communication demonstrated by H-reflex conditioning

Introduction: A conditioning volley to the ipsilateral tibial nerve (iTN) inhibits contralateral soleus (cSOL) electromyographic activity at latencies of 37–41 ms. This is evidence for spinal muscular communication in opposing limbs. The aim of our study was to determine whether the cSOL H‐reflex would be inhibited in a similar manner. Methods: Thirteen subjects participated in two experiments: (1) stimuli delivered to the iTN at 85% of the maximal peak‐to‐peak M‐wave (85% M‐max) with a pre‐contracted cSOL; (2) 510 stimuli delivered at 85% M‐max to the iTN with a test volley delivered to the contralateral tibial nerve at interstimulus intervals of ?6 to 100 ms. Results: Significant inhibition was observed in the cSOL H‐reflex when conditioning stimuli were delivered 3–33 ms before the test H‐reflex. Conclusions: The activity of this spinal pathway can be quantified using H‐reflex conditioning to provide a controlled model for further studies of this response. Muscle Nerve, 2011     

Axial perturbations evoke increased postural reflexes in Parkinson’s disease with postural instability

ObjectiveTo measure axially-evoked postural reflexes in 11 Parkinson’s disease (PD) subjects, both stable and unstable, and to compare these with 13 age-matched controls. Methods: We measured the short-latency electromyography (EMG) reflex effects of brief impulsive displacements applied to the upper sternum or C7 for tibialis anterior (TA) and soleus. Our subjects were studied standing normally and when leaning both forwards and backwards.ResultsThe initial mechanical effects of the stimuli were similar but the reflex responses for the unstable PD group were increased, even after allowing for the increased levels of tonic activation. For TA, unstable PD subjects had significantly larger responses than the stable PD group whose responses were in turn significantly larger than controls. For soleus, unstable PD subjects had significantly greater responses than controls.ConclusionsThese findings are consistent with previous evidence that exaggerated postural responses are characteristic of unstable PD subjects.SignificanceIncreased postural reflexes are characteristic of unstable PD subjects and may contribute to the instability seen for these patients in response to larger perturbations.     

Subthalamic nucleus stimulation restores corticospinal facilitation in Parkinson's disease

We have previously shown that in patients with Parkinson's disease (PD), high‐frequency stimulation (HFS) of the subthalamic nucleus (STN) modifies spinal excitability via subcortical reticulospinal routes. To investigate whether STN‐HFS also modifies spinal excitability via transcortical routes in PD, 10 patients with PD (9 men, 1 woman; 58.3 ± 8.3 years) were investigated in the medical OFF‐state with or without STN‐HFS. The H‐reflex of the right soleus muscle was recorded during slight plantar flexion at 20% of maximum force. A conditioning transcranial stimulus was applied at 95% of active motor threshold to the contralateral primary motor leg area (M1) 0–5 ms after eliciting the H‐reflex. The same paradigm was applied to 8 healthy individuals (5 men, 3 women; 50.8 ± 3.0 years). Transcranial magnetic stimulation (TMS) facilitated the H‐reflex amplitude in healthy controls. A facilitatory effect of the corticospinal input on the H‐reflex was also found in patients with PD, but only with STN‐HFS switched on. When STN‐HFS was discontinued, the H‐reflex was no longer facilitated by the TMS pulse. Accordingly, analysis of variance showed a main effect of stimulation (F = 11.15; P = 0.005), ISI (F = 6.1; P = 0.003), and an interaction between stimulation and group (PD vs. control) (F = 8.9; P = 0.01). STN‐HFS restores the normal facilitatory drive of a transcranially evoked motor cortical response to the spinal motoneuron pool. In addition to subcortical routes, STN‐DBS also alters spinal excitability via transcortical pathways. © 2008 Movement Disorder Society.     

Depression of involuntary activity in muscles paralyzed by spinal cord injury

Involuntary muscle contractions are common after spinal cord injury (SCI). Increased sensitivity to Ia muscle afferent input may contribute to the development of these spasms. Since tendon vibration results in a period of postactivation depression of the Ia synapse, we sought to determine whether Achilles tendon vibration (80 HZ for 2 s) altered involuntary contractions evoked by superficial peroneal nerve (SPN) stimulation (5 pulses at 300 HZ) in paralyzed leg muscles of subjects with chronic (>1 year) SCI. Responses to SPN stimulation that were conditioned by vibration were reduced in 66% of trials (by 33+/-12% in tibialis anterior and 40+/-16% in soleus). These reductions in electromyographic activity are unlikely to be mediated by changes at the Ia synapse or motoneuron because vibration did not alter the magnitude of the soleus H reflex. The electromyographic reductions may involve long-lasting neuromodulatory effects on spinal inhibitory interneurons or synapses involved in the flexor reflex pathway. Vibration-evoked depression of electromyographic activity may be clinically useful in controlling involuntary muscle contractions after SCI.     

Gender‐specific neuromuscular adaptations to unloading in isolated rat soleus muscles

Introduction: The potential of gender to affect unloading‐induced neuromuscular adaptations was investigated. Methods: Twenty male and 20 female rats were assigned to control (CTL), or unloaded (UL) conditions. After 2 weeks of unloading, soleus muscles were removed, and neuromuscular function was assessed during a train of alternating indirect (neural) and direct (muscle) stimuli. Results: In rested muscle, strength showed significant (P ≤ 0.05) main effects for gender (male > female) and treatment (CTL > UL). By the end of the testing protocol, when muscles showed fatigue, gender‐related and treatment‐related differences in strength had disappeared. Neuromuscular transmission efficiency and strength suffered a greater decline during the testing protocol in males than females. Unloaded male muscles displayed greater contractile velocity than female muscles both when rested and fatigued. Conclusions: Gender affected unloading‐induced neuromuscular adaptations. The greater strength of rested male muscles was due to greater muscle mass and neuromuscular transmission efficiency. Muscle Nerve 54 : 300–307, 2016     

Contraction history produces task-specific variations in spinal excitability in healthy human soleus muscle

Introduction: In human movements muscles lengthen and then shorten, or occasionally shorten and then lengthen, but it is unclear whether the nature of neural activation of the initial phase influences the neural state of the subsequent phase. We examined whether contraction history modulates spinal excitability in the healthy human soleus muscle. Methods: Subjects performed six blocks of 10 repetitions of four muscle actions consisting of specific combinations of passive shortening (PAS), and passive lengthening (PAL), shortening contraction (SHO), and lengthening contraction (LEN); that is: (1) SHO+PAL; (2) PAS+LEN; (3) PAS+PAL; and (4) SHO+LEN. Results: Compared with baseline, the H‐reflex increased in the block of 300–400 s after SHO+PAL and decreased in the block of 0–100 s after PAS+LEN and SHO+LEN. Conclusions: Our results suggest that spinal excitability is potentiated during a muscle action preceded by muscle shortening, but it becomes depressed during a muscle action preceded by muscle lengthening. Muscle Nerve, 2010.     

Muscle proteins during 60‐day bedrest in women: Impact of exercise or nutrition

Almost no data exist regarding skeletal muscle responses to real or simulated spaceflight in women. We determined the impact of 60‐day bedrest (BR, n = 8), 60‐day bedrest with exercise‐training (BRE, n = 8), and 60‐day bedrest with a leucine‐enriched, high‐protein diet (BRN, n = 8) on muscle protein composition. Vastus lateralis and soleus muscle biopsies were analyzed for global protein fractions (mixed, sarcoplasmic, myofibrillar) and force‐specific proteins (myosin, actin, collagen). Concentrations (micrograms per milligram muscle wet weight) of these proteins were maintained (P > 0.05) in BR, despite large changes in quadriceps (?21%) and triceps surae (?29%) volume. Neither countermeasure influenced muscle protein content in either muscle (P > 0.05), despite exacerbation (BRN) or prevention (BRE) of atrophy. Pre‐bedrest comparisons showed less myofibrillar protein in the soleus (?16%, P < 0.05), primarily due to less myosin (?12%, P < 0.05) and more collagen (234%, P < 0.05) than the vastus lateralis. Muscle protein composition is tightly regulated in lower limb muscles of women, despite the most extreme weightlessness‐induced atrophy reported in humans. In contrast, men who underwent prolonged unloading were unable to proportionally regulate atrophy of the soleus. These findings have implications for astronauts and clinical conditions of sarcopenia regarding the maintenance of muscle function and prevention of frailty. Muscle Nerve, 2008