The effects of electrical stimulation of ventromedial prefrontal cortex on skin sympathetic nerve activity.

Skin sympathetic nerve activity (SSNA) is primarily involved in thermoregulation and emotional expression; however, the brain regions involved in the generation of SSNA are not completely understood. In recent years, our laboratory has shown that blood-oxygen-level-dependent signal intensity in the ventromedial prefrontal cortex (vmPFC) and dorsolateral prefrontal cortex (dlPFC) are positively correlated with bursts of SSNA during emotional arousal and increases in signal intensity in the vmPFC occurring with increases in spontaneous bursts of SSNA even in the resting state. We have recently shown that unilateral transcranial alternating current stimulation (tACS) of the dlPFC causes modulation of SSNA but given that the current was delivered between electrodes over the dlPFC and the nasion, it is possible that the effects were due to current acting on the vmPFC. To test this, we delivered tACS to target the right vmPFC or dlPFC and nasion and recorded SSNA in 11 healthy participants by inserting a tungsten microelectrode into the right common peroneal nerve. The similarity in SSNA modulation between ipsilateral vmPFC and dlPFC suggests that the ipsilateral vmPFC, rather than the dlPFC, may be causing the modulation of SSNA during ipsilateral dlPFC stimulation.

Reference values for nerve conduction studies of the peroneal, tibial, and sural nerve derived from a large population-based cohort: Associations with demographic and anthropometric characteristics-The Maastricht study.

INTRODUCTION/AIMS: Nerve conduction studies (NCSs) are widely used to support the clinical diagnosis of neuromuscular disorders. The aims of this study were to obtain reference values for peroneal, tibial, and sural NCSs and to examine the associations with demographic and anthropometric factors. METHODS: In 5099 participants (aged 40-79 years) without type 2 diabetes of The Maastricht Study, NCSs of peroneal, tibial, and sural nerves were performed. Values for compound muscle action potential (CMAP) and sensory nerve action potential amplitude, nerve conduction velocity (NCV), and distal latency were acquired. The association of age, sex, body mass index (BMI), and height with NCS values was determined using uni- and multivariate linear regression analyses. RESULTS: Detailed reference values are reported per decade for men and women. Significantly lower NCVs and longer distal latencies were observed in all nerves in older and taller individuals as well as in men. In these groups, amplitudes of the tibial and sural nerves were significantly lower, whereas a lower peroneal nerve CMAP was only significantly associated with age. BMI showed a multidirectional association. After correction for anthropometric factors in the multivariate analysis, the association between sex and NCS values was less straightforward. DISCUSSION: These values from a population-based dataset could be used as a reference for generating normative values. Our findings show the association of NCS values with anthropometric factors. In clinical practice, these factors can be considered when interpreting NCS values.

Optimizing the technique for eliciting antidromic sural and superficial fibular sensory nerve action potentials.

INTRODUCTION/AIMS: Lower limb sensory nerve action potentials are an important component of nerve conduction studies. Most testing of the sural and superficial fibular nerves involves antidromic techniques above the ankle, which result in a falsely unobtainable response in 2%-6% of healthy people. Cadaver, surgical, and more recent ultrasound series suggest this may relate to the site of fascia penetration of the nerve, and it is hypothesized that a modified technique may be more likely to produce reliable responses and reduce false-negative errors. METHODS: This article evaluates a variety of recording distances for both nerves in 100 healthy controls, including varying recording electrode positions and techniques, to provide the optimal electrodiagnostic information in healthy control subjects. RESULTS: Shorter stimulation distances produce higher-amplitude responses but become confounded by increasing stimulation artifact at very short distances, with the best balance found at around 10 cm. In both sural and superficial fibular nerves, amplitude increases by approximately 10%/cm compared with the standard 14 cm distance. The Daube superficial fibular technique produced a higher amplitude than the Izzo Intermediate technique (by 22.46%, p < .001). The calculated upper limit of normal for side-to-side variation in amplitude was around 50% in the sural nerve but over 70% in the superficial fibular nerve. DISCUSSION: It is proposed that the 10 cm recording distance for both nerves is optimal, with minimal false-negatives and a higher amplitude elicited than with existing techniques.

A unique variation of the deep fibular nerve: A case report.

Deep fibular nerve is one of the two terminal branches of the common fibular nerve. The deep fibular nerve can be damaged in procedures related the anterior compartment of the leg such as the application of an external fixator to the leg and operations using intramedullary nailing after tibial fracture. Therefore, it is important to know the anatomy and variations of the deep fibular nerve. An anatomical variation concerning the deep fibular nerve was detected in the right lower extremity of the 65-year-old cadaver we dissected. In this case, it was observed that the deep fibular nerve split into two nerve arms in the distal half of the leg and reunited after continuing 9cm apart to form a loop. This loop formation may increase the iatrogenic damage of the deep fibular nerve as a result of surgery and percutaneous interventions to the anterior leg compartment. We described in this case report a hitherto unobserved finding of the branching pattern of the deep fibular nerve. We think that this unique anatomical variation seen in the right lower extremity of the case of academic interest and will also help orthopedicians in anterior leg compartment surgery.

Crossed reflex responses to flexor nerve stimulation in mice.

Motor responses in one leg to sensory stimulation of the contralateral leg have been named "crossed reflexes" and are extensively investigated in cats and humans. Despite this effort, a circuit-level understanding of the crossed reflexes has remained missing. In mice, advances in molecular genetics enabled insights into the "commissural spinal circuitry" that ensures coordinated leg movements during locomotion. Despite some common features between the commissural spinal circuitry and the circuit for the crossed reflexes, the degree to which they overlap has remained obscure. Here, we describe excitatory crossed reflex responses elicited by electrically stimulating the common peroneal nerve that mainly innervates ankle flexor muscles and the skin on anterolateral aspect of the hind leg. Stimulation of the peroneal nerve with low current intensity evoked low-amplitude motor responses in the contralateral flexor and extensor muscles. At higher current strengths, stimulation of the same nerve evoked stronger and more synchronous responses in the same contralateral muscles. In addition to the excitatory crossed reflex pathway indicated by muscle activation, we demonstrate the presence of an inhibitory crossed reflex pathway, which was modulated when the motor pools were active during walking. The results are compared with the crossed reflex responses initiated by stimulating proprioceptors from extensor muscles and cutaneous afferents from the posterior part of the leg. We anticipate that these findings will be essential for future research combining the in vivo experiments presented here with mouse genetics to understand crossed reflex pathways at the network level in vivo.NEW & NOTEWORTHY Insights into the mechanisms of crossed reflexes are essential for understanding coordinated leg movements that maintain stable locomotion. Advances in mouse genetics allow for the selective manipulation of spinal interneurons and provide opportunities to understand crossed reflexes. Crossed reflexes in mice, however, are poorly described. Here, we describe crossed reflex responses in mice initiated by stimulation of the common peroneal nerve, which serves as a starting point for investigating crossed reflexes at the cellular level.

A topographical and physiological exploration of C-tactile afferents and their response to menthol and histamine.

Unmyelinated tactile (C-tactile or CT) afferents are abundant in arm hairy skin and have been suggested to signal features of social affective touch. Here, we recorded from unmyelinated low-threshold mechanosensitive afferents in the peroneal and radial nerves. The most distal receptive fields were located on the proximal phalanx of the third finger for the superficial branch of the radial nerve and near the lateral malleolus for the peroneal nerve. We found that the physiological properties with regard to conduction velocity and mechanical threshold, as well as their tuning to brush velocity, were similar in CT units across the antebrachial (n = 27), radial (n = 8), and peroneal (n = 4) nerves. Moreover, we found that although CT afferents are readily found during microneurography of the arm nerves, they appear to be much more sparse in the lower leg compared with C-nociceptors. We continued to explore CT afferents with regard to their chemical sensitivity and found that they could not be activated by topical application to their receptive field of either the cooling agent menthol or the pruritogen histamine. In light of previous studies showing the combined effects that temperature and mechanical stimuli have on these neurons, these findings add to the growing body of research suggesting that CT afferents constitute a unique class of sensory afferents with highly specialized mechanisms for transducing gentle touch.NEW & NOTEWORHY Unmyelinated tactile (CT) afferents are abundant in arm hairy skin and are thought to signal features of social affective touch. We show that CTs are also present but are relatively sparse in the lower leg compared with C-nociceptors. CTs display similar physiological properties across the arm and leg nerves. Furthermore, CT afferents do not respond to the cooling agent menthol or the pruritogen histamine, and their mechanical response properties are not altered by these chemicals.

Arm cycling increases the short-latency reflex from ankle dorsiflexor afferents to knee extensor muscles.

Low-intensity electrical stimulation of the common peroneal nerve (CPN) evokes a short latency reflex in the heteronymous knee extensor muscles (referred to as the CPN reflex). The CPN reflex is facilitated at a heel strike during walking, contributing to body weight support. However, the origin of the CPN reflex increase during walking remains unclear. We speculate that this increase originates from multiple sources due to a body of evidence suggesting the presence of neural coupling between the arms and legs. Therefore, we investigated the extent to which the CPN reflex is modulated during rhythmic arm cycling. Twenty-eight subjects sat in an armchair and were asked to perform arm cycling at a moderate cadence using a stationary ergometer while performing isometric contraction of the knee extensors, such that the CPN reflex was evoked. The CPN reflex was evoked by stimulating the CPN [0.9-2.0× the motor threshold (MT) in the tibialis anterior muscle] at the level of the neck of the fibula. The CPN-reflex amplitude was measured from the vastus lateralis (VL). The biphasic reflex response in the VL was evoked within 27-45 ms following CPN stimulation. The amplitude of the CPN reflex increased during arm cycling compared with that before cycling. The modulation of the CPN reflex during arm cycling was detected only for CPN stimulation intensity around 1.2× MT. Furthermore, CPN-reflex modulation was not observed during the isometric contraction of the arm or passive arm cycling. Our results suggest the presence of neural coupling between the CPN-reflex pathways and neural systems generating locomotive arm movement.NEW & NOTEWORTHY Whether locomotive arm movements contribute to the control of the reflex pathway from ankle dorsiflexor afferents to knee extensor muscles [common peroneal nerve (CPN)-reflex] is an unresolved issue. The CPN reflex in the stationary leg was facilitated only by arm cycling, and not by passive or isometric motor tasks. Our results suggest that the arm locomotor system modulates the reflex pathway from ankle dorsiflexor afferents to the knee extensor muscles.

Electrical stimulation of the common peroneal nerve and its effects on the relationship between corticomuscular coherence and motor control in healthy adults.

BACKGROUND: Sensory input via neuromuscular electrical stimulation (NMES) may contribute to synchronization between motor cortex and spinal motor neurons and motor performance improvement in healthy adults and stroke patients. However, the optimal NMES parameters used to enhance physiological activity and motor performance remain unclear. In this study, we focused on sensory feedback induced by a beta-band frequency NMES (ß-NMES) based on corticomuscular coherence (CMC) and investigated the effects of ß-NMES on CMC and steady-state of isometric ankle dorsiflexion in healthy volunteers. Twenty-four participants received ß-NMES at the peak beta-band CMC or fixed NMES (f-NMES) at 100 Hz on different days. NMES was applied to the right part of the common peroneal nerve for 20 min. The stimulation intensity was 95% of the motor threshold with a pulse width of 1 ms. The beta-band CMC and the coefficient of variation of force (Force CV) were assessed during isometric ankle dorsiflexion for 2 min. In the complementary experiment, we applied ß-NMES to 14 participants and assessed beta-band CMC and motor evoked potentials (MEPs) with transcranial magnetic stimulation. RESULTS: No significant changes in the means of beta-band CMC, Force CV, and MEPs were observed before and after NMES conditions. Changes in beta-band CMC were correlated to (a) changes in Force CV immediately, at 10 min, and at 20 min after ß-NMES (all cases, p < 0.05) and (b) changes in MEPs immediately after ß-NMES (p = 0.01). No correlations were found after f-NMES. CONCLUSIONS: Our results suggest that the sensory input via NMES was inadequate to change the beta-band CMC, corticospinal excitability, and voluntary motor output. Whereas, the ß-NMES affects the relationship between changes in beta-band CMC, Force CV, and MEPs. These findings may provide the information to develop NMES parameters for neurorehabilitation in patients with motor dysfunction.

Conditioning Electrical Stimulation Accelerates Regeneration in Nerve Transfers.

OBJECTIVE: Compared to the upper limb, lower limb distal nerve transfer (DNT) outcomes are poor, likely due to the longer length of regeneration required. DNT surgery to treat foot drop entails rerouting a tibial nerve branch to the denervated common fibular nerve stump to reinnervate the tibialis anterior muscle for ankle dorsiflexion. Conditioning electrical stimulation (CES) prior to nerve repair surgery accelerates nerve regeneration and promotes sensorimotor recovery. We hypothesize that CES prior to DNT will promote nerve regeneration to restore ankle dorsiflexion. METHODS: One week following common fibular nerve crush, CES was delivered to the tibial nerve in half the animals, and at 2 weeks, all animals received a DNT. To investigate the effects of CES on nerve regeneration, a series of kinetic, kinematic, skilled locomotion, electrophysiologic, and immunohistochemical outcomes were assessed. The effects of CES on the nerve were investigated. RESULTS: CES-treated animals had significantly accelerated nerve regeneration (p < 0.001), increased walking speed, and improved skilled locomotion. The injured limb had greater vertical peak forces, with improved duty factor, near-complete recovery of braking, propulsive forces, and dorsiflexion (p < 0.01). Reinnervation of the tibialis anterior muscle was confirmed with nerve conduction studies and immunohistochemical analysis of the neuromuscular junction. Immunohistochemistry demonstrated that CES does not induce Wallerian degeneration, nor does it cause macrophage infiltration of the distal tibial nerve. INTERPRETATION: Tibial nerve CES prior to DNT significantly improved functional recovery of the common fibular nerve and its muscle targets without inducing injury to the donor nerve. ANN NEUROL 2020;88:363-374.

Revising nerve conduction reference limits.

INTRODUCTION/AIMS: Our electrodiagnostic laboratory uses reference limits (RL) that have been handed down for four decades. With changes in instrumentation and technique, we wish to know if our RL should be modified. It is also useful to have RL based on patient demographics. METHODS: Latency and velocity data from motor nerve conduction studies of 740 adult patients studied over an 8 mo period were tabulated. RL were derived using both extrapolated reference value (ERef) and multi-variable extrapolated reference value (MeRef) methods. RESULTS: Distal latency values showed a significant but weak correlation with age and/or height. ERef limits for the median and ulnar nerve latency (3.96 and 3.45 ms, respectively) were very similar to current laboratory limits (3.9 and 3.3 ms, respectively). ERef limits for the tibial and fibular nerve latency (5.1 and 4.95 ms, respectively) were slightly shorter. Ulnar velocity did not depend on age or height. The ERef limit was the same as our present laboratory limit (50 m/s). Median and tibial velocity limits decreased with age (R2  > 0.25). Fibular motor nerve conduction limits decreased with age and height (R2  = 0.39). DISCUSSION: ERef and MeRef were useful to validate and revise our latency and velocity RL. We will use ERef limits for tibial and fibular latency. MeRef generated linear regression equations based on age and/or height will be used for conduction velocity analysis of median, fibular, and tibial nerves. This will increase the specificity of our values.

Regenerative peripheral nerve interface free muscle graft mass and function.

BACKGROUND: Regenerative peripheral nerve interfaces (RPNIs) transduce neural signals to provide high-fidelity control of neuroprosthetic devices. Traditionally, rat RPNIs are constructed with ~150 mg of free skeletal muscle grafts. It is unknown whether larger free muscle grafts allow RPNIs to transduce greater signal. METHODS: RPNIs were constructed by securing skeletal muscle grafts of various masses (150, 300, 600, or 1200 mg) to the divided peroneal nerve. In the control group, the peroneal nerve was transected without repair. Endpoint assessments were conducted 3 mo postoperatively. RESULTS: Compound muscle action potentials (CMAPs), maximum tetanic isometric force, and specific muscle force were significantly higher for both the 150 and 300 mg RPNI groups compared to the 600 and 1200 mg RPNIs. Larger RPNI muscle groups contained central areas lacking regenerated muscle fibers. CONCLUSIONS: Electrical signaling and tissue viability are optimal in smaller as opposed to larger RPNI constructs in a rat model.

Presynaptic inhibition in restless legs syndrome.

Introduction: Restless legs syndrome (RLS) is a condition that particularly urges at night in resting and causes the need to move the legs. Although the pathophysiology has not yet been clarified, dopamine and iron metabolism and spinal cord pathologies are blamed for causing the condition. There are few studies on spinal reflex mechanisms on RLS. In the present study, we aimed to investigate the role of presynaptic inhibition (PreI) in the spinal cord in RLS.Methods: Fourteen patients with RLS and 14 controls with similar demographic characteristics were included in the study. Soleus muscle H-reflex (Ht) investigation was performed for subjects whose electrophysiologic investigation was normal. The Ht response was conditioned to the stimulation of the common peroneal nerve (CPN) (Hc). The test and conditioned stimulation intervals were kept between 10 ms, 20 ms, 30 ms, 40 ms, 50 ms, 75 ms, 100 ms, 150 ms and 200 ms. In each inter-stimulus interval, nonparametric repeat measurement evaluations were conducted with the percentage value of Hc/Ht. The Hc/Ht values of the study and control groups in the same intervals were compared separately.Results: A significant decrease was detected in Hc values in the control group in the repeat measurement values at 20 ms and 100 ms inter-stimulus intervals; however, there was not decrease in any intervals in the patient's group.Conclusion: The absence of any decrease in Hc reflexes for 20-100 ms intervals revealed that discernible PreI was vanished in RLS patients.

Sympathetic arterial baroreflex hysteresis in humans: different patterns during low- and high-pressure levels.

Fluctuations in diastolic pressure modulate muscle sympathetic nerve activity (MSNA) through the arterial baroreflex. A higher sympathetic baroreflex sensitivity (sBRS) to pressure falls compared with rises has been reported; however, the underlying mechanisms are unclear. We assessed whether beat-to-beat falling and rising diastolic pressures operate on two distinct baroreflex response curves. Twenty-two men (32 ± 8 yr) underwent sequential bolus injections of nitroprusside and phenylephrine (modified Oxford test) with continuous recording of heart rate, blood pressure, and MSNA. The weighted negative linear regression slope between falling or rising diastolic pressure and MSNA burst incidence quantified sBRSfall and sBRSrise, respectively. The diastolic pressure evoking a MSNA burst incidence of 50 (T50) was calculated. sBRSfall was greater than sBRSrise (-6.24 ± 2.80 vs. -4.34 ± 2.16 bursts·100 heartbeats-1·mmHg-1, P = 0.01) and had a narrower operating range (14 ± 8 vs. 20 ± 10 mmHg, P = 0.01) that was shifted rightward (T50, 75 ± 9 and 70 ± 11 mmHg, P < 0.001). At diastolic pressures below baseline, sBRSfall was less than sBRSrise (-1.81 ± 1.31 vs. -3.59 ± 1.70 bursts·100 heartbeats-1·mmHg-1, P = 0.003) as low absolute pressures operated closer to the saturation plateau on the falling, compared with the rising pressure curve. At pressures above baseline, sBRSfall was greater than sBRSrise (-5.23 ± 1.94 and -3.79 ± 1.67 bursts·100 heartbeats-1·mmHg-1, P = 0.03). These findings demonstrate that the sympathetic arterial baroreflex possesses two response curves for processing beat-to-beat diastolic pressure falls and rises. The falling pressure curve is rightward shifted, which reduces sensitivity to falling pressure at low absolute pressures. This demonstrates that the direction of the hysteresis is influenced by the prevailing pressure level relative to each baroreflex response curve.NEW & NOTEWORTHY The findings show that the arterial baroreflex processes diastolic pressure dependent on the direction of pressure change from the previous beat, yielding two distinct baroreflex response curves to falling and rising pressure. Overall, the falling pressure curve is rightward shifted and more sensitive. The rightward shift caused a hysteresis reversal at hypotensive pressures as the falling pressure saturation plateau of the sigmoid response curve occurred at higher pressures than the rising pressure curve.

Visual Feedback Control of a Rat Ankle Angle Using a Wirelessly Powered Two-Channel Neurostimulator.

Peripheral nerve disconnections cause severe muscle atrophy and consequently, paralysis of limbs. Reinnervation of denervated muscle by transplanting motor neurons and applying Functional Electrical Stimulation (FES) onto peripheral nerves is an important procedure for preventing irreversible degeneration of muscle tissues. After the reinnervation of denervated muscles, multiple peripheral nerves should be stimulated independently to control joint motion and reconstruct functional movements of limbs by the FES. In this study, a wirelessly powered two-channel neurostimulator was developed with the purpose of applying selective FES to two peripheral nerves-the peroneal nerve and the tibial nerve in a rat. The neurostimulator was designed in such a way that power could be supplied wirelessly, from a transmitter coil to a receiver coil. The receiver coil was connected, in turn, to the peroneal and tibial nerves in the rat. The receiver circuit had a low pass filter to allow detection of the frequency of the transmitter signal. The stimulation of the nerves was switched according to the frequency of the transmitter signal. Dorsal/plantar flexion of the rat ankle joint was selectively induced by the developed neurostimulator. The rat ankle joint angle was controlled by changing the stimulation electrode and the stimulation current, based on the Proportional Integral (PI) control method using a visual feedback control system. This study was aimed at controlling the leg motion by stimulating the peripheral nerves using the neurostimulator.

Spinal plasticity with motor imagery practice.

KEY POINTS: While a consensus has now been reached on the effect of motor imagery (MI) - the mental simulation of an action - on motor cortical areas, less is known about its impact on spinal structures. The current study, using H-reflex conditioning paradigms, examined the effect of a 20 min MI practice on several spinal mechanisms of the plantar flexor muscles. We observed modulations of spinal presynaptic circuitry while imagining, which was even more pronounced following an acute session of MI practice. We suggested that the small cortical output generated during MI may reach specific spinal circuits and that repeating MI may increase the sensitivity of the spinal cord to its effects. The short-term plasticity induced by MI practice may include spinal network modulation in addition to cortical reorganization. ABSTRACT: Kinesthetic motor imagery (MI) is the mental simulation of a movement with its sensory consequences but without its concomitant execution. While the effect of MI practice on cortical areas is well known, its influence on spinal circuitry remains unclear. Here, we assessed plastic changes in spinal structures following an acute MI practice. Thirteen young healthy participants accomplished two experimental sessions: a 20 min MI training consisting of four blocks of 25 imagined maximal isometric plantar flexions, and a 20 min rest (control session). The level of spinal presynaptic inhibition was assessed by conditioning the triceps surae spinal H-reflex with two methods: (i) the stimulation of the common peroneal nerve that induced D1 presynaptic inhibition (HPSI response), and (ii) the stimulation of the femoral nerve that induced heteronymous Ia facilitation (HFAC response). We then compared the effects of MI on unconditioned (HTEST ) and conditioned (HPSI and HFAC ) responses before, immediately after and 10 min after the 20 min session. After resting for 20 min, no changes were observed on the recorded parameters. After MI practice, the amplitude of rest HTEST was unchanged, while HPSI and HFAC significantly increased, showing a reduction of presynaptic inhibition with no impact on the afferent-motoneuronal synapse. The current results revealed the acute effect of MI practice on baseline spinal presynaptic inhibition, increasing the sensitivity of the spinal circuitry to MI. These findings will help in understanding the mechanisms of neural plasticity following chronic practice.

Vibration-induced depression in spinal loop excitability revisited.

KEY POINTS: While it has been well described that prolonged vibration locally applied to a muscle or its tendon (up to 1 h) decreases spinal loop excitability between homonymous Ia afferents and motoneurons, the involved mechanisms are not fully understood. By combining electrophysiological methods, this study aimed to provide new insights into the mechanisms involved in soleus decreased spinal excitability after prolonged local vibration. We report that prolonged vibration induces a decrease in motoneuron excitability rather than an increase in presynaptic mechanisms (as commonly hypothesized in the current literature). The present results may help to design appropriate clinical intervention and could reinforce the interest in vibration as a treatment for spastic patients who are characterized by spinal hyper-excitability responsible for spasms and long-lasting reflexes. ABSTRACT: The mechanisms that can explain the decreased spinal loop excitability in response to prolonged local vibration (LV), as assessed by the H-reflex, remain to be precisely determined. This study provides new insights into how prolonged Achilles' tendon LV (30 min, 100 Hz) acutely interacts with the spinal circuitry. The roles of presynaptic inhibition exerted on Ia afferents (Experiment A, n = 15), neurotransmitter release at the synapse level (Experiment B, n = 11) and motoneuron excitability (Experiment C, n = 11) were investigated in soleus. Modulation of presynaptic inhibition was assessed by conditioning the soleus H-reflex (tibial nerve electrical stimulation) with fibular nerve (D1 inhibition) and femoral nerve (heteronymous facilitation, HF) electrical stimulations. Potential vibration-induced changes in neurotransmitter depletion at the Ia afferent terminals was assessed through paired stimulations applied over the tibial nerve (HD). Intrinsic motoneuron excitability was assessed with thoracic motor evoked potentials (TMEPs) in response to electrical stimulation over the thoracic spine. Non-conditioned H-reflex was depressed by ∼60% after LV (P < 0.001), while D1 and HF H-reflexes increased by ∼75% after LV (P = 0.03 and 0.06, respectively). In Experiment B, HD remained unchanged after LV (P = 0.80). In Experiment C, TMEPs were reduced by ∼13% after LV (P = 0.01). Overall, presynaptic mechanisms do not seem to be involved in the depression of spinal excitability after LV. It rather seems to rely, at least in part, on a decrease in intrinsic motoneuron excitability. These results may have implications in reducing spinal hyper-excitability in spastic patients.

Vestibular modulation of muscle sympathetic nerve activity assessed over a 100-fold frequency range of sinusoidal galvanic vestibular stimulation.

We have previously shown that sinusoidal galvanic vestibular stimulation (sGVS), delivered at 0.2-2.0 Hz, evokes a partial entrainment of muscle sympathetic nerve activity (MSNA). Moreover, at lower frequencies of stimulation (0.08-0.18 Hz) sGVS produces two peaks of modulation: one (primary) peak associated with the positive peak of the sinusoidal stimulus and a smaller (secondary) peak associated with the trough. Here we assessed whether sGVS delivered at 0.05 Hz causes a more marked modulation of MSNA than at higher frequencies and tested the hypothesis that the primary and secondary peaks are of identical amplitude because of the longer cycle length. MSNA was recorded via tungsten microelectrodes inserted into the left peroneal nerve in 11 seated subjects. Bipolar binaural sGVS (±2 mA, 100 cycles) was applied to the mastoid processes at 0.05, 0.5, and 5.0 Hz (500 cycles). Cross-correlation analysis revealed two bursts of modulation of MSNA for each cycle at 0.05 and 0.5 Hz but only one at 5 Hz. There was a significant inverse linear relationship between vestibular modulation (primary peak) and frequency (P < 0.0001), with the amplitudes of the peaks being highest at 0.05 Hz. Moreover, the secondary peak at this frequency was not significantly different from the primary peak. These results indicate that vestibular modulation of MSNA operates over a large range of frequencies but is greater at lower frequencies of sGVS. We conclude that the vestibular apparatus, through its influence on muscle sympathetic outflow, preferentially contributes to the control of blood pressure at low frequencies. NEW & NOTEWORTHY Vestibulosympathetic reflexes have been documented in experimental animals and humans. Here we show that sinusoidal galvanic vestibular stimulation, a means of selectively exciting vestibular afferents in humans, induces greater modulation of muscle sympathetic nerve activity when delivered at a very low frequency (0.05 Hz) than at 0.5 or 5.0 Hz.

Estimates of persistent inward current in human motor neurons during postural sway.

Persistent inward current (PIC) plays a critical role in setting the gain of spinal motor neurons. In humans, most estimates of PIC are made from plantarflexor or dorsiflexor motor units in a seated position. This seated and static posture negates the task-dependent nature of the monoaminergic drive and afferent inhibition that modulate PIC activation. Our purpose was to estimate PIC during both the conventional seated posture and in a more functionally relevant anterior postural sway. We hypothesized that paired motor unit estimates of PIC would be greater when during standing compared with sitting. Soleus motor neuron PIC was estimated via the paired motor unit (PMU) technique. For each motor unit pair, difference in reference unit firing frequency (ΔF) estimates of PIC were made during isometric ramps in plantarflexion force during sitting (conventional approach) and during standing anterior postural sway (new approach). Baseline reciprocal inhibition (RI) was also measured in each posture using the poststimulus time histogram technique. ΔF estimates during standing postural sway were not different [2.64 ± 0.95 pulses/s (pps), P = 0.098] from seated PIC estimates (3.15 ± 1.45 pps) measured from the same motor unit pair. Similarly, reciprocal inhibition at the onset of each task was the same in standing (-0.60 ± 0.32, P = 0.301) and seated (-0.86 ± 0.82) postures. PMU recordings made during standing postural sway met all assumptions that underlay the PMU technique, including rate modulation ≥0.5 pps (3.11 ± 1.90 pps), rate-rate correlation r ≥ 0.7 (0.84 ± 0.13), and time between reference and test unit recruitment ≥1 s (1.83 ± 0.81 s). This study presents a novel, functionally relevant standing method for investigating PIC in humans.NEW & NOTEWORTHY Paired motor unit (PMU) estimates of persistent inward current (PIC) in human soleus motor units are typically made in seated posture. Our study demonstrates that these estimates can be made during standing forward sway, a task that more accurately reflects the postural role of human soleus muscle. PMU recordings made during standing postural sway were validated using all previously published criteria used to test the assumptions of the PMU technique. Standing estimates of PIC did not differ from seated estimates made from the same motor unit pairs.

Central command increases muscle sympathetic nerve activity more to contracting than noncontracting muscle during rhythmic isotonic leg exercise.

We have previously shown that the increase in muscle sympathetic nerve activity (MSNA) to contracting muscle during sustained isometric exercise is due primarily to central command and that contracting muscle does not express a metaboreceptor-driven increase in MSNA. Here we tested the hypothesis that MSNA increases to the contracting muscle also during rhythmic isotonic exercise, in which muscle metabolites will not accumulate because the contraction is performed without external load. MSNA was recorded from the common peroneal nerve in 10 participants, and negative-going sympathetic spikes were extracted during 50 cycles of sinusoidal (0.15 Hz) isotonic dorsiflexions of the ipsilateral or contralateral ankle. Electromyographic activity (EMG) was recorded from the tibialis anterior muscle on both sides. Cross-correlation analysis between MSNA and EMG revealed a marked cyclic modulation of MSNA to the contracting (ipsilateral) muscle. This modulation, in which MSNA increased during the contraction phase, was three times greater than that to the noncontracting muscle (modulation index = 27.4 ± 3.2% vs. 9.2 ± 1.5%; P < 0.002). There were no differences in either the intensity or the magnitude of modulation of EMG during ipsilateral and contralateral contractions. We conclude that central command increases MSNA to the contracting muscle during rhythmic isotonic exercise. NEW & NOTEWORTHY Muscle sympathetic nerve activity (MSNA) increases to contracting muscle during isometric exercise, but whether this occurs during rhythmic isotonic exercise is unknown. We recorded MSNA to the pretibial flexors during cyclic dorsiflexion of the ipsilateral or contralateral ankle. MSNA showed a cyclic increase during the contraction phase that was significantly higher to the contracting than the noncontracting muscle, supporting central command as the primary mechanism responsible for increasing MSNA.

Effects of tonic muscle pain on fusimotor control of human muscle spindles during isometric ankle dorsiflexion.

Studies on anesthetized animals have revealed that nociceptors can excite fusimotor neurons and thereby change the sensitivity of muscle spindles to stretch; such nociceptive reflexes have been suggested to underlie the mechanisms that lead to chronic musculoskeletal pain syndromes. However, the validity of the "vicious cycle" hypothesis in humans has yielded results contrasting with those found in animals. Given that spindle firing rates are much lower in humans than in animals, it is possible that some of the discrepancies between human experimental data and those obtained in animals could be explained by differences in background fusimotor drive when the leg muscles are relaxed. We examined the effects of tonic muscle pain during voluntary contractions of the ankle dorsiflexors. Unitary recordings were obtained from 10 fusimotor-driven muscle spindle afferents (6 primary, 4 secondary) supplying the ankle dorsiflexors via a microelectrode inserted percutaneously into the common peroneal nerve. A series of 1-min weak contractions was performed at rest and during 1 h of muscle pain induced by intramuscular infusion of 5% hypertonic saline into the tibialis anterior muscle. We did not observe any statistically significant increases in muscle spindle firing rates of six afferents followed during tonic muscle pain, although discharge variability increased slightly. Furthermore, a participant's capacity to maintain a constant level of force, while relying on proprioceptive feedback in the absence of visual feedback, was not compromised during pain. We conclude that nociceptive inputs from contracting muscle do not excite fusimotor neurons during voluntary isometric contractions in humans. NEW & NOTEWORTHY Data obtained in the cat have shown that muscle pain causes a marked increase in the firing of muscle spindles, attributed to a nociceptor-driven fusimotor reflex. However, our studies of muscle spindles in relaxed leg muscles failed to find any effect on spindle discharge. Here we showed that experimental muscle pain failed to increase the firing of muscle spindle afferents during weak voluntary contractions, when fusimotor drive sufficient to increase their firing is present.