Achiral 2-pyridone and 4-aminopyridine act as chiral inducers of asymmetric autocatalysis with amplification of enantiomeric excess via the formation of chiral crystals.

Enantiomorphous crystals of achiral 2-pyridone and 4-aminopyridine served as sources of chirality, to induce the asymmetric autocatalysis of 5-pyrimidyl alkanol during the asymmetric addition of diisopropylzinc to the corresponding pyrimidine-5-carbaldehyde, that is, the Soai reaction. Following a significant amplification of enantiomeric excess through asymmetric autocatalysis, highly enantioenriched 5-pyrimidyl alkanol could be synthesized with their corresponding absolute configurations to those of chiral crystals of 2-pyridone and 4-aminopyridine.

Execution of natural manipulation in the air enhances the beta-rhythm intermuscular coherences of the human arm depending on muscle pairs.

Natural manipulation tasks in air consist of two kinematic components: a grasping component, with activation of the hand muscles, and a lifting component, with activation of the proximal muscles. However, it remains unclear whether the synchronized motor commands to the hand/proximal arm muscles are divergently controlled during the task. Therefore, we examined how intermuscular coherence was modulated depending on the muscle combinations during grip and lift (G&L) tasks. Electromyograms (EMGs) were recorded from the biceps brachii (BB), triceps brachii (TB), flexor digitorum superficialis (FDS), and extensor digitorum communis (EDC) muscles. The participants were required to maintain G&L tasks involving a small cubical box with the thumb and index and middle fingers. Consequently, we found that the beta-rhythm coherence (15-35 Hz) in BB-TB, BB-FDS, and TB-EDC pairs during G&L was significantly larger than that during the isolated task with cocontraction of the two target muscles but not BB-EDC, TB-FDS, and FDS-EDC (task and muscle pair specificities). These increases in beta-rhythm coherence were also observed in intramuscular EMG recordings. Furthermore, the results from the execution of several mimic G&L tasks revealed that the separated task-related motor signals and combinations between the motor signals/sensations of the fingertips or object load had minor contributions to the increase in the coherence. These results suggest that during G&L the central nervous system regulates synchronous drive onto motoneurons depending on the muscle pairs and that the multiple combination effect of the sensations of touch/object load and motor signals in the task promotes the synchrony of these pairs.NEW & NOTEWORTHY Natural manipulation in air consists of two kinematic components: grasping, with activation of hand muscles, and lifting, with activation of proximal muscles. We show that during the maintenance of object manipulation in air the central nervous system regulates the synchronous drive onto human motoneuron pools depending on the hand/proximal muscle pairs and that the multiple combination effect of the sensations of touch/object load and motor signals in the task promotes the synchrony of these pairs.

Dynamic Control of Upper Limb Stretch Reflex in Wrestlers.

PURPOSE: The objective of this study was to clarify the characteristics of the upper limb stretch reflex in wrestlers. METHODS: Ten wrestlers and 11 control subjects participated in the study. The experiment was divided into two sessions. In the extension perturbation session, participants either relaxed or flexed the elbow when they felt a perturbation (abrupt elbow extension induced by a dynamometer). This was done 30 times by each subject for both sessions. In the flexion perturbation session, participants also relaxed or extended the elbow when they felt a perturbation (abrupt elbow flexion). During the tasks, the stretch reflex was monitored by recording the surface EMG activities of the right biceps and triceps brachii. The EMG reflex components were divided into three periods based on the time after the perturbation (M1, 20-50 ms; M2, 50-80 ms; and M3, 80-100 ms). The averaged background EMG activity just before the disturbance was subtracted from the EMG activity in each period. The resultant value was integrated to obtain reflex magnitudes of M1 to M3. RESULTS: For the triceps brachii, in the relaxation task, the wrestler group showed a significantly smaller value for M2 than did the control group. In the extension task, the wrestler group showed a significantly larger value for M3 than did the control group. There was no difference in M1 between the two groups. For the biceps brachii, there was no significant difference between any reflex components. CONCLUSIONS: Our results suggest that high-level wrestlers have specific characteristics of the long-latency stretch reflex in the triceps brachii that are modulated in a situation-specific manner.

Subcortical Contribution of Corticospinal Transmission during Visually Guided Switching Movements of the Arm.

In animal experiments, the indirect corticospinal tract (CST) system via cervical interneurons has been shown to mediate motor commands for online adjustment of visuomotor behaviors, such as target-reaching. However, it is still unclear whether the similar CST system functions to perform similar motor behaviors in humans. To clarify this, we investigated changes in motor-evoked potentials (MEPs) in the elbow muscles following transcranial magnetic stimulation, transcranial electrical stimulation, or cervicomedullary stimulation while participants executed target-reaching and switching movements. We found that the MEP, whether elicited cortically or subcortically, was modulated depending on the direction of the switching movements. MEP facilitation began around the onset of the switching activities in an agonist muscle. Furthermore, ulnar nerve-induced MEP facilitation, which could be mediated by presumed cervical interneuronal systems, also increased at the onset of MEP facilitation. In a patient with cortical hemianopsia who showed switching movements in the scotoma, the MEPs were facilitated just before the switching activities. Our findings suggested that CST excitation was flexibly tuned with the switching movement initiation, which could partly take place in the subcortical networks, including the presumed cervical interneuronal systems.

Determinants of Neural Plastic Changes Induced by Motor Practice.

Short-term motor practice leads to plasticity in the primary motor cortex (M1). The purpose of this study is to investigate the factors that determine the increase in corticospinal tract (CST) excitability after motor practice, with special focus on two factors; "the level of muscle activity" and "the presence/absence of a goal of keeping the activity level constant." Fifteen healthy subjects performed four types of rapid thumb adduction in separate sessions. In the "comfortable task" (C) and "forceful task" (F), the subjects adducted their thumb using comfortable and strong forces. In the "comfortable with a goal task" (CG) and "forceful with a goal task" (FG), subjects controlled the muscle activity at the same level as in the C and F, respectively, by adjusting the peak electromyographic amplitude within the target ranges. Paired associative stimulation (PAS), which combines peripheral nerve (median nerve) stimulation and transcranial magnetic stimulation (TMS), with an inter-stimulus interval of 25 ms (PAS25) was also done. Before and after the motor tasks and PAS25, TMS was applied to the M1. None of the four tasks showed any temporary changes in behavior, meaning no learning occurred. Motor-evoked potential (MEP) amplitude increased only after the FG and it exhibited a positive correlation with the MEP increase after PAS25, suggesting that FG and PAS25 share at least similar plasticity mechanisms in the M1. Resting motor threshold (RMT) decreased only after FG, suggesting that FG would also be associated with the membrane depolarization of M1 neurons. These results suggest task-dependent plasticity from the synergistic effect of forceful muscle activity and of setting a goal of keeping the activity level constant.

Visual information increases the indirect corticospinal excitation via cervical interneurons in humans.

Modulatory actions of inputs from the visual system to cervical interneurons (IN) for arm muscle control are poorly understood in humans. In the present study, we examined whether visual stimulation modulates the excitation of cervical IN systems mediating corticospinal tract (CST) inputs to biceps brachii (BB). Twenty-eight healthy volunteers were seated, and electromyogram recordings from the BB were performed across six experiments, each with discrete objectives. A flash stimulator for visual stimulation (50-µs duration) was placed 60 cm from the participant's eye. The CST was stimulated with transcranial magnetic/electrical stimulation (TMS/TES, respectively) contralateral to the recording site. Visual stimulation with TMS/TES was randomly delivered during weak tonic BB contractions. Single TMS/TES-induced motor-evoked potentials (MEPs) were markedly enhanced from 60-100 ms after visual stimulation compared with the control condition. The MEPs were significantly increased by combining the electrical stimulation of the ulnar nerve at the wrist [7.5-12 ms of nerve stimulation (NERVE)/TMS interval] with and without visual stimulation compared with the algebraic summation of responses obtained with either TMS or NERVE. Interestingly, the combined stimulation-induced MEP facilitation was significantly increased after visual stimulation compared with the control. Single motor unit (MU) recording also revealed the further enhancement of combined stimulation effects on the firing probabilities of MU during visual stimulation, which was observed in the peaks of the peristimulus time histogram, 1-2 ms later than the onset latency. The present findings suggest that visual stimulation facilitates the oligosynaptic CST excitation of arm motoneurons mediated by the cervical IN system.NEW & NOTEWORTHY To date, little is known about how visual information modulates the human cervical motor systems, including the presumed interneuron (IN) circuitry. This study demonstrates that photic visual stimulation influences presumed oligosynaptic corticospinal transmission to arm motoneurons, which are mediated by cervical INs. In animals, these systems are known to be crucial for visually guided switching movements, and similar visual input systems to INs may exist in humans.

Long-lasting changes in muscle activation and step cycle variables induced by repetitive sensory stimulation to discrete areas of the foot sole during walking.

We examined whether repetitive electrical stimulation to discrete foot sole regions that are phase-locked to the step cycle modulates activity patterns of ankle muscles and induces neuronal adaptation during human walking. Nonnoxious repetitive foot sole stimulation (STIM; 67 pulses at 333 Hz) was given to the medial forefoot (f-M) or heel (HL) regions at 1) the stance-to-swing transition, 2) swing-to-stance transition, or 3) midstance, during every step cycle for 10 min. Stance, but not swing, durations were prolonged with f-M STIM delivered at stance-to-swing transition, and these changes remained for up to 20-30 min after the intervention. Electromyographic (EMG) burst durations and amplitudes in the ankle extensors were also prolonged and persisted for 20 min after the intervention. Interestingly, STIM to HL was ineffective at inducing modulation, suggesting stimulation location-specific adaptation. In contrast, STIM to HL (but not f-M), at the swing-to-stance phase transition, shortened the step cycle by premature termination of swing. Furthermore, the onset of EMG bursts in the ankle extensors appeared earlier than in the control condition. STIM delivered during the midstance phase was ineffective at modulating the step cycle, highlighting phase-dependent adaptation. These effects were absent when STIM was applied while mimicking static postures for each walking phase during standing. Our findings suggest that the combination of walking-related neuronal activity with repetitive sensory inputs from the foot can generate short-term adaptation that is phase-dependent and localized to the site of STIM.NEW & NOTEWORTHY Repetitive (∼10 min) long (200 ms) trains of sensory stimulation to discrete areas of the foot sole produce persistent changes in muscle activity and cycle timing during walking. Interactions between the delivery phase and stimulus location determine the expression of the adaptations. These observations bear striking similarities to those in decerebrate cat experiments and may be usefully translated to improving locomotor function after neurotrauma.

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.

Motor imagery enhances corticospinal transmission mediated by cervical premotoneurons in humans.

Motor imagery is known to affect the reacquisition of motor functioning after damage to the central nervous system. However, it remains unclear whether motor imagery influences corticospinal (CST) excitation mediated via cervical premotoneurons, which may be important for functional motor recovery in animals and humans. To investigate this, we examined the spatial facilitation of motor-evoked potentials (MEPs) induced by combined stimulation (CS) of CST and peripheral nerves. Thirty-two healthy volunteers were included and electromyograms from the biceps brachii (BB) were recorded. Transcranial magnetic stimulation (TMS) to motor cortex and electrical stimulation of ulnar nerve at wrist (NERVE) were delivered separately or in combination with 6-15 ms of interstimulus intervals (ISIs). Subjects were instructed to imagine performing an elbow flexion at rest and during tonic BB contraction. During both motor imagery and control tasks, CS (7.5-12 ms of ISIs) facilitated MEPs, compared with the mathematical summation of responses obtained with either only TMS or NERVE (P < 0.01). Interestingly, the CS-induced facilitation was significantly increased by motor imagery compared with control (P < 0.01). Single-motor unit recording also revealed increased facilitation during motor imagery, which was observed in peaks of the peristimulus time histogram 1-2 ms later than the onset latency (P < 0.01). The present findings suggest that motor imagery facilitates oligosynaptic CST excitation of arm motoneurons, mediated by cervical premotoneurons. Thus motor imagery may be a useful tool for activating the premotoneuron systems, which may contribute to motor reacquisition.NEW & NOTEWORTHY Imaging movement has positive effects on the reacquisition of motor functions after damage to the central nervous system. This study shows that motor imagery facilitates oligosynaptic corticospinal excitation that is mediated via cervical premotoneurons, which may be important for motor recovery in monkeys and humans. Current findings highlight how this imagery might be a beneficial tool for movement disorders through effects on premotoneuron circuitry.

Walking and finger tapping can be done with independent rhythms.

Rhythmic movements occur in many aspects of daily life. Examples include clapping the hands and walking. The production of two independent rhythms with multiple limbs is considered to be extremely difficult. In the present study we evaluated whether two different, independent rhythms that involved finger tapping and walking could be produced. In Experiment I, twenty subjects that had no experience of musical instrument training performed rhythmic finger tapping with the right index finger and one of four different lower limb movements; (1) self-paced walking, (2) given-paced walking, (3) alternative bilateral heel tapping from a sitting position, and (4) unilateral heel tapping with the leg ipsilateral to the tapping finger from a sitting position. The target intervals of finger tapping and heel strikes for walking step/heel tapping were set at 375 ms and 600 ms, respectively. The even distribution of relative phases between instantaneous finger tapping and heel strike was taken as the criteria of independency for the two rhythms. In the self-paced walking and given-paced walking tasks, 16 out of 20 subjects successfully performed finger tapping and walking with independent rhythms without any special practice. On the other hand, in the bipedal heels striking and unipedal heel striking tasks 19 subjects failed to perform the two movements independently, falling into interrelated rhythms with the ratio mostly being 2:1. In Experiment II, a similar independency of finger tapping and walking at a given pace was observed for heel strike intervals of 400, 600, and 800 ms, as well as at the constant 375 ms for finger tapping. These results suggest that finger tapping and walking are controlled by separate neural control mechanisms, presumably with a supra-spinal locus for finger tapping, and a spinal location for walking.

Transducin-like enhancer of split 3 regulates proliferation of melanoma cells via histone deacetylase activity.

Melanoma, one of the most aggressive neoplasms, is characterized by rapid cell proliferation. Transducin-like Enhancer of Split (TLE) is an important regulator of cell proliferation via Histone deacetylase (HDAC) recruitment. Given that HDAC activity is associated with melanoma progression, we examined the relationship between TLE3, a TLE family member, and melanoma. TLE3 expression was increased during the progression of human patient melanoma (p < 0.05). Overexpression of Tle3 in B16 murine melanoma cells led to an increase in cell proliferation (p < 0.01) as well as the number of cyclinD1-positive cells. in vivo injection of mice with B16 cells overexpressing Tle3 resulted in larger tumor formation than in mice injected with control cells (p < 0.05). In contrast, siRNA-mediated knockdown of Tle3 in B16 cells or TLE3 in HMV-II human melanoma cells decreased proliferation (p < 0.01). Treatment of B16 cells with trichostatin A (2.5 µM), a class I and II HDAC inhibitor, prevented the effect s of Tle3 on proliferation. In conclusion, these data indicate that Tle3 is required, at least in part, for proliferation in the B16 mouse melanoma model.

Geranylgeraniol-induced Myogenic Differentiation of C2C12 Cells.

BACKGROUND: Geranylgeraniol (GGOH) is a C20 isoprenoid found in fruits, vegetables, and grains, including rice. As a food substance, GGOH is categorized as 'Generally Recognized as Safe'. GGOH is an intermediate product in the mevalonate pathway and acts as a precursor to geranylgeranyl pyrophosphate. MATERIALS AND METHODS: C2C12 mouse myoblasts derived from muscle satellite cells were used. Quantitative reverse-transcriptase polymerase chain reaction, western blotting analysis, and immunocytochemical analysis were performed to respectively assess mRNA expression, protein levels, and the number of myofibers. RESULTS: GGOH reduced the expression levels of skeletal muscle atrophy-related ubiquitin ligases in myofibers derived from C2C12 cells. GGOH induced myogenic differentiation of C2C12 cells via geranylgeranylation. GGOH did not adversely affect the proliferation of C2C12 cells. CONCLUSION: GGOH induces myoblast differentiation in C2C12 cells.

Hand Dexterity Impairment in Patients with Cervical Myelopathy: A New Quantitative Assessment Using a Natural Prehension Movement.

Cervical myelopathy (CM) caused by spinal cord compression can lead to reduced hand dexterity. However, except for the 10 sec grip-and-release test, there is no objective assessment system for hand dexterity in patients with CM. Therefore, we evaluated the hand dexterity impairment of patients with CM objectively by asking them to perform a natural prehension movement. Twenty-three patients with CM and 30 age-matched controls were asked to reach for and grasp a small object with their right thumb and index finger and to subsequently lift and hold it. To examine the effects of tactile afferents from the fingers, objects with surface materials of differing textures (silk, suede, and sandpaper) were used. All patients also underwent the Japanese Orthopedic Association (JOA) test. Preoperative patients showed significantly greater grip aperture during reach-to-grasp movements and weaker grip force than controls only while attempting to lift the most slippery object (silk). Patients, immediately after surgery, (n = 15) tended to show improvements in the JOA score and in reaction time and movement time with respect to reaching movements. Multiple regression analysis demonstrated that some parameters of the prehension task could successfully predict subjective evaluations of dexterous hand movements based on JOA scores. These results suggest that quantitative assessments using prehension movements could be useful to objectively evaluate hand dexterity impairment in patients with CM.

Bilateral Reflex Fluctuations during Rhythmic Movement of Remote Limb Pairs.

The modulation of spinal cord excitability during rhythmic limb movement reflects the neuronal coordination underlying actions of the arms and legs. Integration of network activity in the spinal cord can be assessed by reflex variability between the limbs, an approach so far very little studied. The present work addresses this question by eliciting Hoffmann (H-) reflexes in both limbs to assess if common drive onto bilateral pools of motoneurons influence spinal cord excitability simultaneously or with a delay between sides. A cross-covariance (CCV) sequence between reflexes in both arms or legs was evaluated under conditions providing common drive bilaterally through voluntary muscle contraction and/or rhythmic movement of the remote limbs. For H-reflexes in the flexor carpi radialis (FCR) muscle, either contraction of the FCR or leg cycling induced significant reduction in the amplitude of the peak at the zero lag in the CCV sequence, indicating independent variations in spinal excitability between both sides. In contrast, for H-reflexes in the soleus (SO) muscle, arm cycling revealed no reduction in the amplitude of the peak in the CCV sequence at the zero lag. This suggests a more independent control of the arms compared with the legs. These results provide new insights into the organization of human limb control in rhythmic activity and the behavior of bilateral reflex fluctuations under different motor tasks. From a functional standpoint, changes in the co-variability might reflect dynamic adjustments in reflex excitability that are subsumed under more global control features during locomotion.

Vestibular stimulation-induced facilitation of cervical premotoneuronal systems in humans.

It is unclear how descending inputs from the vestibular system affect the excitability of cervical interneurons in humans. To elucidate this, we investigated the effects of galvanic vestibular stimulation (GVS) on the spatial facilitation of motor-evoked potentials (MEPs) induced by combined pyramidal tract and peripheral nerve stimulation. To assess the spatial facilitation, electromyograms were recorded from the biceps brachii muscles (BB) of healthy subjects. Transcranial magnetic stimulation (TMS) over the contralateral primary motor cortex and electrical stimulation of the ipsilateral ulnar nerve at the wrist were delivered either separately or together, with interstimulus intervals of 10 ms (TMS behind). Anodal/cathodal GVS was randomly delivered with TMS and/or ulnar nerve stimulation. The combination of TMS and ulnar nerve stimulation facilitated BB MEPs significantly more than the algebraic summation of responses induced separately by TMS and ulnar nerve stimulation (i.e., spatial facilitation). MEP facilitation significantly increased when combined stimulation was delivered with GVS (p < 0.01). No significant differences were found between anodal and cathodal GVS. Furthermore, single motor unit recordings showed that the short-latency excitatory peak in peri-stimulus time histograms during combined stimulation increased significantly with GVS. The spatial facilitatory effects of combined stimulation with short interstimulus intervals (i.e., 10 ms) indicate that facilitation occurred at the premotoneuronal level in the cervical cord. The present findings therefore suggest that GVS facilitates the cervical interneuron system that integrates inputs from the pyramidal tract and peripheral nerves and excites motoneurons innervating the arm muscles.

Reassessment of Non-Monosynaptic Excitation from the Motor Cortex to Motoneurons in Single Motor Units of the Human Biceps Brachii.

Corticospinal excitation is mediated by polysynaptic pathways in several vertebrates, including dexterous monkeys. However, indirect non-monosynaptic excitation has not been clearly observed following transcranial electrical stimulation (TES) or cervicomedullary stimulation (CMS) in humans. The present study evaluated indirect motor pathways in normal human subjects by recording the activities of single motor units (MUs) in the biceps brachii (BB) muscle. The pyramidal tract was stimulated with weak TES, CMS, and transcranial magnetic stimulation (TMS) contralateral to the recording side. During tasks involving weak co-contraction of the BB and hand muscles, all stimulation methods activated MUs with short latencies. Peristimulus time histograms (PSTHs) showed that responses with similar durations were induced by TES (1.9 ± 1.4 ms) and CMS (2.0 ± 1.4 ms), and these responses often showed multiple peaks with the PSTH peak having a long duration (65.3% and 44.9%, respectively). Such long-duration excitatory responses with multiple peaks were rarely observed in the finger muscles following TES or in the BB following stimulation of the Ia fibers. The responses obtained with TES were compared in the same 14 BB MUs during the co-contraction and isolated BB contraction tasks. Eleven and three units, respectively, exhibited activation with multiple peaks during the two tasks. In order to determine the dispersion effects on the axon conduction velocities (CVs) and synaptic noise, a simulation study that was comparable to the TES experiments was performed with a biologically plausible neuromuscular model. When the model included the monosynaptic-pyramidal tract, multiple peaks were obtained in about 34.5% of the motoneurons (MNs). The experimental and simulation results indicated the existence of task-dependent disparate inputs from the pyramidal tract to the MNs of the upper limb. These results suggested that intercalated interneurons are present in the spinal cord and that these interneurons might be equivalent to those identified in animal experiments.

Short-Term Plasticity in a Monosynaptic Reflex Pathway to Forearm Muscles after Continuous Robot-Assisted Passive Stepping.

Both active and passive rhythmic limb movements reduce the amplitude of spinal cord Hoffmann (H-) reflexes in muscles of moving and distant limbs. This could have clinical utility in remote modulation of the pathologically hyperactive reflexes found in spasticity after stroke or spinal cord injury. However, such clinical translation is currently hampered by a lack of critical information regarding the minimum or effective duration of passive movement needed for modulating spinal cord excitability. We therefore investigated the H-reflex modulation in the flexor carpi radialis (FCR) muscle during and after various durations (5, 10, 15, and 30 min) of passive stepping in 11 neurologically normal subjects. Passive stepping was performed by a robotic gait trainer system (Lokomat(®)) while a single pulse of electrical stimulation to the median nerve elicited H-reflexes in the FCR. The amplitude of the FCR H-reflex was significantly suppressed during passive stepping. Although 30 min of passive stepping was sufficient to elicit a persistent H-reflex suppression that lasted up to 15 min, 5 min of passive stepping was not. The duration of H-reflex suppression correlated with that of the stepping. These findings suggest that the accumulation of stepping-related afferent feedback from the leg plays a role in generating short-term interlimb plasticity in the circuitry of the FCR H-reflex.

Neuromechanical interactions between the limbs during human locomotion: an evolutionary perspective with translation to rehabilitation.

During bipedal locomotor activities, humans use elements of quadrupedal neuronal limb control. Evolutionary constraints can help inform the historical ancestry for preservation of these core control elements support transfer of the huge body of quadrupedal non-human animal literature to human rehabilitation. In particular, this has translational applications for neurological rehabilitation after neurotrauma where interlimb coordination is lost or compromised. The present state of the field supports including arm activity in addition to leg activity as a component of gait retraining after neurotrauma.

Regionally distinct cutaneous afferent populations contribute to reflex modulation evoked by stimulation of the tibial nerve during walking.

During walking, cutaneous reflexes in ankle flexor muscle [tibialis anterior (TA)] evoked by tibial nerve (TIB) stimulation are predominantly facilitatory at early swing phase but reverse to suppression at late swing phase. Although the TIB innervates a large portion of the skin of the foot sole, the extent to which specific foot-sole regions contribute to the reflex reversals during walking remains unclear. Therefore, we investigated regional cutaneous contributions from discrete portions of the foot sole on reflex reversal in TA following TIB stimulation during walking. Summation effects on reflex amplitudes, when applying combined stimulation from foot-sole regions with TIB, were examined. Middle latency responses (MLRs; 70-120 ms) after TIB stimulation were strongly facilitated during the late stance to mid-swing phases and reversed to suppression just before heel (HL) strike. Both forefoot-medial (f-M) and forefoot-lateral stimulation in the foot sole induced facilitation during stance-to-swing transition phases, but HL stimulation evoked suppression during the late stance to the end of swing phases. At the stance-to-swing transition, a summation of MLR amplitude occurred only for combined f-M&TIB stimulation. However, the same was not true for the combined HL&TIB stimulation. At the swing-to-stance transition, there was a suppressive reflex summation only for HL&TIB stimulation. In contrast, this summation was not observed for the f-M&TIB stimulation. Our results suggest that reflex reversals evoked by TIB stimulation arise from distinct reflex pathways to TA produced by separate afferent populations innervating specific regions of the foot sole.