小宮山 伴与志

The surface electromyographic (EMG) activity of the biceps brachii during weak elbow flexion reportedly increases immediately after strong elbow flexion, even during the exertion of a given force. This phenomenon is called post-contraction potentiation (EMG-PCP). However, the effects of test contraction intensity (TCI) on EMG-PCP remain unclear. This study evaluated PCP levels at various TCI values. Sixteen healthy participants were asked to perform a force matching task (2%, 10%, or 20% of the maximum voluntary contraction [MVC]) before (Test 1) and after (Test 2) a conditioning contraction (50% of MVC). With a 2% TCI, the EMG amplitude was higher in Test 2 than in Test 1. With a 20% TCI, the EMG amplitude was lower in Test 2 than in Test 1. Furthermore, EMG spectral analyses showed that the α- and β-band power ratios in Test 2 were enhanced by 2% TCI compared with Test 1. These findings suggest that TCI is crucial in determining the EMG-force relationship immediately after a brief intensive contraction.

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 the grip and lift tasks (G&L). Electromyograms (EMGs) were recorded from the biceps brachii (BB), triceps brachii (TB), flexor digitorum sperficialis (FDS), and extensor digitorum communis (EDC) muscles. The participants were required to maintain G&L tasks involving a small cubical box with the thumb, 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 co-contraction of the two target muscles, but not BB-EDC, TB-FDS, and FDS-EDCs (task and muscle pairs 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.

<title>Abstract</title> 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.

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 to 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 peri-stimulus 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.

We examined whether repetitive electrical stimulation to discrete foot sole regions that is phase-locked to the step cycle modulates activity patterns of ankle muscles and induces neuronal adaptation during human walking. Non-noxious repetitive foot sole stimulation (STIM; 67 pulses @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) mid-stance, during every step cycle for 10 min. Stance, but not swing, durations were prolonged 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 mid-stance 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.

Low-intensity electrical stimulation of the common peroneal nerve (CPN) evokes a short latency reflex in the heteronymous knee extensor muscles (referred to as 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. 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.

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.

中枢神経系からの下行性指令の機能低下は中枢性疲労と呼ばれ、運動パフォーマンスの低下に関与する。近年、中枢神経系の活動を非侵襲性に修飾する方法の一つとして、直流電流刺激(DCS)が盛んに用いられてきた。筆者らは、腰髄に対するDCSにより、全力努力によるスプリントサイクリングパフォーマンスの疲労を軽減できることを示した。

Sprint motor performance, such as in short-distance running or cycling, gradually decreases after reaching a maximum speed or cadence. This may be attributed to the central nervous system. Brain stimulation studies have recently revealed the plastic nature of the human brain and spinal cord, but it is unclear how direct current stimulation (DCS) affects sprint motor performance. To address this issue, we investigated DCS's effect on healthy volunteers' sprint cycling performance. DCS was applied to the lumbar spinal cord (3mA) or the leg area of the motor cortex (2mA) for 15min with 3 different polarities: anodal, cathodal, and sham. After DCS, the subjects performed maximal-effort sprint cycling for 30s under a constant load. Pooled mean power during the 30s was significantly greater after cathodal transcutaneous spinal DCS to the lumbar spinal cord (tsDCS) than anodal or sham tsDCS. The improvement with cathodal stimulation was notable both 0-5 and 20-25s after the performance onset. There were no significant inter-conditional differences in peak power. Pooled mean power was significantly greater after anodal transcranial DCS to the motor cortex (tDCS) than after cathodal tDCS, although mean powers of anodal and sham tDCS were not significantly different. The increase in mean power after cathodal tsDCS could result from a reduction in central fatigue. This stimulus method might improve sprint performance.

<p>【はじめに，目的】</p><p></p><p>ヒト空間的促通試験を用いた研究により，錐体路興奮を上肢運動ニューロンに中継する頸髄介在ニューロン（IN）系の存在が示唆されている（Pierrot-Deseilligny 2002）。しかしながら，IN系に対し前庭神経系の入力が収束しているのか，今のところ不明である。そこで，本研究は，ガルバニック前庭刺激（GVS）が錐体路と末梢神経のコンバインド刺激による筋電図の空間的促通効果に影響を与えるのか，検討を加えた。</p><p></p><p>【方法】</p><p></p><p>実験は健常成人男性7名を対象にした。被験者は椅子に座り，前腕は肘関節60度屈曲位にて固定された。筋電図は，右上腕二頭筋（BB）および第一背側骨間筋（FDI）から単極誘導法にて記録された。被験者がBBの弱い持続収縮（最大力の3%程度）を維持している最中，左右の乳様突起部間にGVS（1.5～2.0 mA）を行った。その間に，1）対側の一次運動野への経頭蓋的磁気刺激（TMS，活動時運動閾値の1.1～1.36倍），2）同側の尺骨神経への電気刺激（FDIの運動閾値の0.75倍）ならびに3）TMSと尺骨神経刺激のコンバインド刺激（刺激間間隔10ミリ秒，尺骨神経刺激先行）を実施した。右GVS電極の極性により，陽極ならびに陰極GVS条件を設定した。対照条件として，GVSを行っていない時に上記1～3）の刺激を行った。空間的促通効果を定量化するため，単独TMSによる運動誘発電位（MEP）と単独尺骨神経刺激効果の代数和（SUM）を計算した。空間的促通効果の振幅は，コンバインド刺激時MEP振幅のSUMに対する百分率として表した。</p><p></p><p>【結果】</p><p></p><p>対照，陽極および陰極条件において，コンバインド刺激によるMEP振幅は，SUMと比して，有意に増大した（p＜0.01）。その促通量（空間的促通効果）は，対照条件と比べて，陽極ならびに陰極GVS条件で有意に大きかった（p＜0.05）。しかしながら，陽極ならびに陰極GVS条件間では，空間的促通効果に有意な違いを認めなかった（p=0.898）。</p><p></p><p>【結論】</p><p></p><p>本研究において，錐体路と尺骨神経のコンバインド刺激による空間的促通効果が，GVSによって増大することが明らかとなった。コンバインド刺激の時間間隔（10ミリ秒），尺骨神経の伝導速度（54.3～83.3 m/s，Macefield, et al., 1989）ならびに尺骨神経の刺激強度（運動閾値の0.75倍）に基づけば，筋に由来した神経入力（例えばgroup Ia線維）と錐体路入力を共通して受ける頸髄IN系が，GVSにより促通されたと考えられる。サルGVSは，一次前庭神経線維の持続的な発火活動を修飾すると報告されている（Goldberg, et al., 1984）。従って，本研究の知見は，前庭系からの入力がヒトの頸髄IN系に収束していることを示唆する。</p>

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.

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.

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.

Electrical stimulation of cutaneous nerves innervating heteronymous limbs (the arms or contralateral leg) modifies the excitability of soleus Hoffmann (H-) reflexes. The differences in the sensitivities of the H-reflex pathway to cutaneous afferents from different limbs and their modulation during the performance of motor tasks (i.e., standing and walking) are not fully understood. In the present study, we investigated changes in soleus H-reflex amplitudes induced by electrical stimulation of peripheral nerves. Selected targets for conditioning stimulation included the superficial peroneal nerve, which innervates the foot dorsum in the contralateral ankle (cSP), and the superficial radial nerve, which innervates the dorsum of the hand in the ipsilateral (iSR) or contralateral wrist (cSR). Stimulation and subsequent reflex assessment took place during the standing and early-stance phase of treadmill walking in ten healthy subjects. Cutaneous stimulation produced long-latency inhibition (conditioning-test interval of ~100 ms) of the H-reflex during the early-stance phase of walking, and the inhibition was stronger following cSP stimulation compared with iSR or cSR stimulation. In contrast, although similar conditioning stimulation significantly facilitated the H-reflex during standing, this effect remained constant irrespective of the different conditioning sites. These findings suggest that cutaneous inputs from the arms and contralateral leg had reversible effects on the H-reflex amplitudes, including inhibitions with different sensitivities during the early-stance phase of walking and facilitation during standing. Furthermore, the differential sensitivities of the H-reflex modulations were expressed only during walking when the locations of the afferent inputs were functionally relevant.

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.

Neural interactions between regulatory systems for rhythmic arm and leg movements are an intriguing issue in locomotor neuroscience. Amplitudes of early latency cutaneous reflexes (ELCRs) in stationary arm muscles are modulated during rhythmic leg or arm cycling but not during limb positioning or voluntary contraction. This suggests that interneurons mediating ELCRs to arm muscles integrate outputs from neural systems controlling rhythmic limb movements. Alternatively, outputs could be integrated at the motoneuron and/or supraspinal levels. We examined whether a separate effect on the ELCR pathways and cortico-motoneuronal excitability during arm and leg cycling is integrated by neural elements common to the lumbo-sacral and cervical spinal cord. The subjects performed bilateral leg cycling (LEG), contralateral arm cycling (ARM), and simultaneous contralateral arm and bilateral leg cycling (A&L), while ELCRs in the wrist flexor and shoulder flexor muscles were evoked by superficial radial (SR) nerve stimulation. ELCR amplitudes were facilitated by cycling tasks and were larger during A&L than during ARM and LEG. A low stimulus intensity during ARM or LEG generated a larger ELCR during A&L than the sum of ELCRs during ARM and LEG. We confirmed this nonlinear increase in single motor unit firing probability following SR nerve stimulation during A&L. Furthermore, motor-evoked potentials following transcranial magnetic and electrical stimulation did not show nonlinear potentiation during A&L. These findings suggest the existence of a common neural element of the ELCR reflex pathway that is active only during rhythmic arm and leg movement and receives convergent input from contralateral arms and legs.

PURPOSE: We previously reported that suppressive middle latency cutaneous reflexes (MLRs) in the peroneus longus (PL) are exaggerated in subjects with chronic ankle instability, and the changes are related to functional instability. However, the time-varying history of these neurophysiological changes after an ankle sprain is yet to be elucidated. Therefore, in the present study, we investigated the time course of the changes in the PL MLR after an ankle sprain in relation to the number of sprain recurrences. METHODS: Twenty-three subjects with ankle sprain were classified into 3 groups according to their history of ankle sprain: first ankle sprain, 2-3 ankle sprains, and ≥4 ankle sprains. Twenty-three age-matched control subjects also participated. The PL MLRs were elicited by stimulating the sural nerve while the subjects performed different levels of isometric ankle eversion. Gain of MLR was estimated using linear regression analysis (slope value) of the amplitude modulation of MLRs obtained from graded isometric contractions. RESULT: The gain of MLRs first increased 4 weeks after the injury. In subjects with their first ankle sprain, the MLRs returned to almost baseline levels after 3 months. In contrast, the increase in MLR gain persisted even after 3 months in subjects with recurrent ankle sprains. In addition, the MLR gains were closely related to functional recovery of the ankle joint. CONCLUSIONS: Our findings suggest that the recovery process of MLR gains were strongly affected by the history of ankle sprains as well as the functional recovery of the ankle joint.

We previously demonstrated that non-noxious electrical stimulation of the cutaneous nerve innervating the contralateral foot modified the excitability of the Hoffmann (H-) reflex in the soleus muscle (SOL) in a task-dependent manner during standing and walking in humans. To date, however, it remains unclear how the crossed conditioning effect on the SOL H-reflex from the contralateral foot is modified during the various phases of walking. We sought to answer this question in the present study. The SOL H-reflex was evoked in healthy volunteers by an electrical test stimulation (TS) of the right (ipsilateral) posterior tibial nerve at five different phases during treadmill walking (4 km/h). A non-noxious electrical stimulation was delivered to the superficial peroneal nerve of the left (contralateral) ankle ~100 ms before the TS as a conditioning stimulation (CS). This CS significantly suppressed the H-reflex amplitude during the early stance phase, whereas the same CS significantly facilitated the H-reflex amplitude during the late stance phase. The CS alone did not produce detectable changes in the full-wave rectified electromyogram of the SOL. This result indicates that presynaptic mechanisms driven by the activation of low-threshold cutaneous afferents in the contralateral foot play a role in regulating the transmission between the Ia terminal and motoneurons in a phase-dependent manner. The modulation pattern of the crossed conditioning effect on the SOL H-reflex may be functionally relevant for the left-right coordination of leg movements during bipedal walking.

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.

歩行運動中の体幹筋群の皮膚反射は下肢筋や上肢筋の皮膚反射と同様に歩行位相依存的に変化し、また、立位時とは異なる動態を示すという仮説を立て、検証を行った。方法は、健常成人11名を対象とし、足部皮膚神経刺激によって誘発される僧帽筋上部線維(TRAP)・腰部脊柱起立筋(ES)・腹直筋(RA)の皮膚反射動態をトレッドミル歩行運動中および静止立位保持中に解析した。結果、これらの筋群の皮膚反射は歩行時には促通成分が主体であり、皮膚反射振幅は歩行位相依存的に変化した。TRAPとRAは、立位時には背景筋電図量と皮膚反射振幅との間に有意な相関が認められ、歩行運動時には有意な相関は認められなかった。ESは立位時・歩行運動時とも有意な相関が認められた。背景筋電図量に対する皮膚反射振幅の反射比は、全ての筋で立位時よりも歩行運動時のほうが有意に高値であった。これらの結果から、立位時・歩行運動時における体幹筋群の皮膚反射は、各筋の機能的役割に応じて異なる神経機序により制御されている可能性が示唆された。

Neural output from the locomotor system for each arm and leg influences the spinal motoneuronal pools directly and indirectly through interneuronal (IN) reflex networks. This review article mainly describes the recent findings concerning the existence, features and functions of common IN systems on spinal reflex pathways induced by multisensory inputs during human locomotion. In particular, we focus on regulation of polysynaptic cutaneous reflex pathways assessed by spatial facilitation. Furthermore, we provide evidence for activation of common presynaptic inhibitory INs that integrate locomotor-related commands and antagonist group Ia inputs. The experimental results are discussed in light of recent advances in motor control in humans and other animals with implications for locomotor rehabilitation.

Although sensory inputs from the contralateral limb strongly modify the amplitude of the Hoffmann (H-) reflex in a static posture, it remains unknown how these inputs affect the excitability of the monosynaptic H-reflex during walking. Here, we investigated the effect of the electrical stimulation of a cutaneous (CUT) nerve innervating the skin on the dorsum of the contralateral foot on the excitability of the soleus H-reflex during standing and walking. The soleus H-reflex was conditioned by non-noxious electrical stimulation of the superficial peroneal nerve in the contralateral foot. Significant crossed facilitation of the soleus H-reflex was observed at conditioning-to-test intervals in a range of 100-130 ms while standing, without any change in the background soleus electromyographic (EMG) activity. In contrast, the amplitude of the soleus H-reflex was significantly suppressed by the contralateral CUT stimulation in the early-stance phase of walking. The background EMG activity of the soleus muscle was equivalent between standing and walking tasks and was unaffected by CUT stimulation alone. These findings suggest that the crossed CUT volleys can affect the presynaptic inhibition of the soleus Ia afferents and differentially modulate the excitability of the soleus H-reflex in a task-dependent manner during standing and walking.

Gait disturbance in individuals with spinal cord lesion is attributed to the interruption of descending pathways to the spinal locomotor center, whereas neural circuits below and above the lesion maintain their functional capability. An artificial neural connection (ANC), which bridges supraspinal centers and locomotor networks in the lumbar spinal cord beyond the lesion site, may restore the functional impairment. To achieve an ANC that sends descending voluntary commands to the lumbar locomotor center and bypasses the thoracic spinal cord, upper limb muscle activity was converted to magnetic stimuli delivered noninvasively over the lumbar vertebra. Healthy participants were able to initiate and terminate walking-like behavior and to control the step cycle through an ANC controlled by volitional upper limb muscle activity. The walking-like behavior stopped just after the ANC was disconnected from the participants even when the participant continued to swing arms. Furthermore, additional simultaneous peripheral electrical stimulation to the foot via the ANC enhanced this walking-like behavior. Kinematics of the induced behaviors were identical to those observed in voluntary walking. These results demonstrate that the ANC induces volitionally controlled, walking-like behavior of the legs. This paradigm may be able to compensate for the dysfunction of descending pathways by sending commands to the preserved locomotor center at the lumbar spinal cord and may enable individuals with paraplegia to regain volitionally controlled walking.

Recent studies indicate that human locomotion is quadrupedal in nature. An automatic rhythm-generating system is thought to play a crucial role in controlling arm and leg movements. In the present study, we attempted to elucidate differences between intrinsic arm and leg automaticity by investigating cadence variability during simultaneous arm and leg (AL) cycling. Participants performed AL cycling with visual feedback of arm or leg cadence. Participants were asked to focus their attention to match the predetermined cadence; this affects the automaticity of the rhythm-generating system. Leg cadence variability was only mildly affected when the participants intended to precisely adjust either their arm or leg cycling cadence to a predetermined value. In contrast, arm cadence variability significantly increased when the participants adjusted their leg cycling cadence to a predetermined value. These findings suggest that different neural mechanisms underlie the automaticities of arm and leg cycling and that the latter is stronger than the former during AL cycling.

Bipedal humans operate using elements of quadrupedal neuronal limb control during locomotion. This has significant implications for supporting transfer of the huge body of quadrupedal animal literature to human rehabilitation. In particular, this has translational applications for neurological rehabilitation after stroke where interlimb coordination is compromised. The data supports including arm activity in addition to leg activity as a component of gait retraining after stroke. An additional component is to consider strength training of the less affected limb to improve motor output of the more affected limb when that limb is too weak to be initially incorporated in functional rehabilitation. The major concept is to use activity related to the less affected limbs to modulate output of the more affected limbs after stroke. A key example is to incorporate arm activity into rehabilitation of leg motion in stepping after stroke.

Neural output from the locomotor system for each arm and leg influences the spinal motoneuronal pools directly and indirectly through interneuronal (IN) reflex networks. While well documented in other species, less is known about the functions and features of convergence in common IN reflex system from cutaneous afferents innervating different foot regions during remote arm and leg movement in humans. The purpose of the present study was to use spatial facilitation to examine possible convergence in common reflex pathways during rhythmic locomotor limb movements. Cutaneous reflexes were evoked in ipsilateral tibialis anterior muscle by stimulating (in random order) the sural nerve (SUR), the distal tibial nerve (TIB), and combined simultaneous stimulation of both nerves (TIB&SUR). Reflexes were evoked while participants performed rhythmic stepping and arm swinging movement with both arms and the leg contralateral to stimulation (ARM&LEG), with just arm movement (ARM) and with just contralateral leg movement (LEG). Stimulation intensities were just below threshold for evoking early latency (<80 ms to peak) reflexes. For each stimulus condition, rectified EMG signals were averaged while participants held static contractions in the stationary (stimulated) leg. During ARM&LEG movement, amplitudes of cutaneous reflexes evoked by combined TIB&SUR stimulation were significantly larger than simple mathematical summation of the amplitudes evoked by SUR or TIB alone. Interestingly, this extra facilitation seen during combined nerve stimulation was significantly reduced when performing ARM or LEG compared to ARM&LEG. We conclude that locomotor rhythmic limb movement induces excitation of common IN reflex pathways from cutaneous afferents innervating different foot regions. Importantly, activity in this pathway is most facilitated during ARM&LEG movement. These results suggest that transmission in IN reflex pathways is weighted according to the number of limbs directly engaged in human locomotor activity and underscores the importance of arm swing to support neuronal excitability in leg muscles.

BACKGROUND: While the neural and mechanical effects of whole nerve cutaneous stimulation on human locomotion have been previously studied, there is less information about effects evoked by activation of discrete skin regions on the sole of the foot. Electrical stimulation of discrete foot regions evokes position-modulated patterns of cutaneous reflexes in muscles acting at the ankle during standing but data during walking are lacking. Here, non-noxious electrical stimulation was delivered to five discrete locations on the sole of the foot (heel, and medial and lateral sites on the midfoot and forefoot) during treadmill walking. EMG activity from muscles acting at the hip, knee and ankle were recorded along with movement at these three joints. Additionally, 3 force sensing resistors measuring continuous force changes were placed at the heel, and the medial and lateral aspects of the right foot sole. All data were sorted based on stimulus occurrence in twelve step-cycle phases, before being averaged together within a phase for subsequent analysis. METHODS: Non-noxious electrical stimulation was delivered to five discrete locations on the sole of the foot (heel, and medial and lateral sites on the midfoot and forefoot) during treadmill walking. EMG activity from muscles acting at the hip, knee and ankle were recorded along with movement at these three joints. Additionally, 3 force sensing resistors measuring continuous force changes were placed at the heel, and the medial and lateral aspects of the right foot sole. All data were sorted based on stimulus occurrence in twelve step-cycle phases, before being averaged together within a phase for subsequent analysis. RESULTS: The results demonstrate statistically significant dynamic changes in reflex amplitudes, kinematics and foot sole pressures that are site-specific and phase-dependent. The general trends demonstrate responses producing decreased underfoot pressure at the site of stimulation. CONCLUSIONS: The responses to stimulation of discrete locations on the foot sole evoke a kind of "sensory steering" that may promote balance and maintenance of locomotion through the modulation of limb loading and foot placement. These results have implications for using sensory stimulation as a therapeutic modality during gait retraining (e.g. after stroke) as well as for footwear design and implementation of foot sole contact surfaces during gait.

<title>Abstract</title> <sec> <title>Background</title> Widespread interlimb reflexes evoked in leg muscles by cutaneous stimulation of the hand are phase-modulated and behaviorally relevant to produce functional changes in ankle trajectory during walking. These reflexes are complementary to the segmental responses evoked by stimulation at the ankle. Despite differences in the expression of reflex amplitude based upon site of nerve stimulation, there are some common features as well, suggesting the possibility of shared interneuronal pathways. Currently little is known about integration or shared reflex systems from interlimb cutaneous networks during human locomotion. Here we investigated convergent reflex effects following cutaneous stimulation of the hand and foot during arm and leg cycling (AL) by using spatial facilitation. Participants performed AL cycling and static activation of the target muscle knee extensor vastus lateralis (VL) in 3 different randomly ordered nerve stimulation conditions: 1) superficial radial nerve (SR; input from hand); 2) superficial peroneal nerve (SP; input from foot); and, 3) combined stimulation (SR + SP). Stimuli were applied around the onset of rhythmic EMG bursts in VL corresponding to the onset of the power or leg extension phase. </sec> <sec> <title>Results</title> During AL cycling, small inhibitory (~80 ms) and large facilitatory reflexes (~100 ~ 150 ms) were seen in VL. The amplitudes of the facilitatory responses with SR + SP stimulation were significantly larger than those for SP or SR stimulation alone. The facilitation was also significantly larger than the simple mathematical summation of amplitudes from SP and SR trials. This indicates extra facilitation beyond what would be accounted for by serial neuronal processing and was not observed during static activation. </sec> <sec> <title>Conclusions</title> We conclude that AL cycling activates shared interneurons in convergent reflex pathways from cutaneous inputs innervating the hand and leg. This enhanced activity has functional implications for corrective responses during locomotion and for translation to rehabilitation after neurotrauma. </sec>

OBJECTIVE: To investigate the neural alteration of reflex pathways arising from cutaneous afferents in patients with chronic ankle instability. METHODS: Cutaneous reflexes were elicited by applying non-noxious electrical stimulation to the sural nerve of subjects with chronic ankle instability (n=17) and control subjects (n=17) while sitting. Electromyographic (EMG) signals were recorded from each ankle and thigh muscle. The middle latency response (MLR; latency: 70-120 ms) component was analyzed. RESULTS: In the peroneus longus (PL) and vastus lateralis (VL) muscles, linear regression analyses between the magnitude of the inhibitory MLR and background EMG activity showed that, compared to the uninjured side and the control subjects, the gain of the suppressive MLR was increased in the injured side. This was also confirmed by the pooled data for both groups. The degree of MLR alteration was significantly correlated to that of chronic ankle instability in the PL. CONCLUSIONS: The excitability of middle latency cutaneous reflexes in the PL and VL is modulated in subjects with chronic ankle instability. SIGNIFICANCE: Cutaneous reflexes may be potential tools to investigate the pathological state of the neural system that controls the lower limbs in subjects with chronic ankle instability.

The Hoffmann (H-) reflex can be depressed when elicited repetitively at a frequency of ~1 Hz. This H-reflex depression is termed homosynaptic depression (HD) and is attributed to impaired neurotransmitter release from the presynaptic Ia terminal. In the present study, we systematically evaluated the extent to which HD in the soleus was modulated by the level of homonymous muscle contraction and the size of the test H-reflex. Changes in HD were also assessed while the target muscle was subjected to fatigue. The participants were 11 healthy male volunteers aged 20−25 years. HD was induced by delivering a percutaneous electrical stimulus at 1 Hz to the right posterior peroneal nerve. HD was proportional to the size of the test reflex size up to 60% of the maximum size of the direct motor response (M_max), at which point values plateaued. HD decreased significantly during voluntary contraction of the homonymous muscle (range, <20% of maximal voluntary contraction [MVC]), irrespective of the degree of contraction. Within 1−5 minutes after completing 4 sets of the MVC for 60 s with ischemic arterial blockade, the degree of HD decreased significantly when the test reflex size was <60% of the M_max. We conclude that test reflex size is a crucial factor when evaluating the nature of HD. Furthermore, HD reduction during voluntary contraction and muscle fatigue may represent an innate mechanism that serves to retain Ia transmission.

The corpus callosum is essential for neural communication between the left and right hemispheres. Although spatiotemporal coordination of bimanual movements is mediated by the activity of the transcallosal circuit, it remains to be addressed how transcallosal neural activity is involved in the dynamic control of bimanual force execution in human. To address this issue, we investigated transcallosal inhibition (TCI) elicited by single-pulse transcranial magnetic stimulation (TMS) in association with the coordination condition of bimanual force regulation. During a visually-guided bimanual force tracking task, both thumbs were abducted either in-phase (symmetric condition) or 180° out-of-phase (asymmetric condition). TMS was applied to the left primary motor cortex to elicit the disturbance of ipsilateral left force tracking due to TCI. The tracking accuracy was equivalent between the two conditions, but the synchrony of the left and right tracking trajectories was higher in the symmetric condition than in the asymmetric condition. The magnitude of force disturbance and TCI were larger during the symmetric condition than during the asymmetric condition. Right unimanual force tracking influenced neither the force disturbance nor TCI during tonic left thumb abduction. Additionally, these TMS-induced ipsilateral motor disturbances only appeared when the TMS intensity was strong enough to excite the transcallosal circuit, irrespective of whether the crossed corticospinal tract was activated. These findings support the hypotheses that interhemispheric interactions between the motor cortices play an important role in modulating bimanual force coordination tasks, and that TCI is finely tuned depending on the coordination condition of bimanual force regulation.

Presynaptic inhibition of transmission between Ia afferent terminals and alpha motoneurons (Ia PSI) is a major control mechanism associated with soleus H-reflex modulation during human locomotion. Rhythmic arm cycling suppresses soleus H-reflex amplitude by increasing segmental Ia PSI. There is a reciprocal organization in the human nervous system such that arm cycling modulates H-reflexes in leg muscles and leg cycling modulates H-reflexes in forearm muscles. However, comparatively little is known about mechanisms subserving the effects from leg to arm. Using a conditioning-test (C-T) stimulation paradigm, the purpose of this study was to test the hypothesis that changes in Ia PSI underlie the modulation of H-reflexes in forearm flexor muscles during leg cycling. Subjects performed leg cycling and static activation while H-reflexes were evoked in forearm flexor muscles. H-reflexes were conditioned with either electrical stimuli to the radial nerve (to increase Ia PSI; C-T interval  = 20 ms) or to the superficial radial (SR) nerve (to reduce Ia PSI; C-T interval  = 37-47 ms). While stationary, H-reflex amplitudes were significantly suppressed by radial nerve conditioning and facilitated by SR nerve conditioning. Leg cycling suppressed H-reflex amplitudes and the amount of this suppression was increased with radial nerve conditioning. SR conditioning stimulation removed the suppression of H-reflex amplitude resulting from leg cycling. Interestingly, these effects and interactions on H-reflex amplitudes were observed with subthreshold conditioning stimulus intensities (radial n., ∼0.6×MT; SR n., ∼ perceptual threshold) that did not have clear post synaptic effects. That is, did not evoke reflexes in the surface EMG of forearm flexor muscles. We conclude that the interaction between leg cycling and somatosensory conditioning of forearm H-reflex amplitudes is mediated by modulation of Ia PSI pathways. Overall our results support a conservation of neural control mechanisms between the arms and legs during locomotor behaviors in humans.

For many locomotor behaviors, such as walking or running, we count on subliminal somatosensory information to smoothly maintain on-going movement and avoid falling down when disturbances are presented to the stability of the body. Reflex responses induced by disturbances to stability play important roles in generating quick corrective responses. Reflex outputs to the arm and leg muscles generated by muscle and cutaneous afferents during locomotor movement show quite different features compared to those generated by simple voluntary contraction during sitting or standing, irrespective of the similar background activity of motoneurons. In particular, the excitability of cutaneous reflex pathways elicited by the electrical stimulation of low threshold mechanoreceptors on the skin is strongly modulated in a phase-, nerve-, task-dependent manner during locomotor movement. The pattern generating system in the spinal cord, which has been studied intensively in quadrupedal animals, may be responsible for both generating locomotor movement and reflex modulation even in humans. However, due to methodological difficulties, the accumulated evidence derived from human experiments is indirect. In this review, we will outline these unique features of the cutaneous reflexes during locomotor and rhythmic movements in humans.

ヒトにおける四肢によるリズミックな運動は多種多様であるが、最も基本的であり、生活を支える重要な基盤となる移動行動は歩行運動であろう。歩行運動は、大脳からの運動指令を受けて大脳基底核、小脳、脳幹、脊髄など様々な運動中枢が協調的に働くことにより実行される。特に、四足歩行動物では、上位運動中枢と末梢感覚入力なしに四肢の屈筋-伸筋の活動交代を再現可能な中枢パターン発振器(central pattern generator、CPG)が存在することが確かめられている。また、CPGは、屈筋-伸筋感のリズミックな活動交代を再現するだけではなく、歩行運動の円滑な遂行に必要な様々な反射の利得調整を行っている。ヒトにおけるCPGの存在とその機能的意義を証明することは実験的に困難であるが、現在まで様々な間接的な証拠が提出されている。本稿では、歩行運動、リハビリテーション、四肢の協調運動の基盤としてのCPGの神経機構ついて概観する。(著者抄録)

Voluntary contraction of a muscle generates electromyographic (EMG) activity in the homologous muscle on the opposite side (mirror-like activity), not only in pathological states and in infants but also in healthy adults. Few studies have examined whether the cutaneous reflexes during the preparatory period of a reaction time task are affected by mirror-like activity. In the present study, we investigated the modulation of the cutaneous reflexes in the left first interosseous (FDI) muscle in 9 healthy subjects while they performed a quick abduction of the right index finger during a reaction time task. Cutaneous reflexes were elicited by applying non-noxious electrical stimulation to the left index finger. We found that mirror-like activity occurred in the left FDI at approximately the onset of EMG activity in the right FDI. The excitatory E2 component was selectively increased at ~75 ms after the "Go" signal, which corresponded to the onset of mirror-like activity. The inhibitory I2 (~90 ms) component was tuned consistently into excitation after the "Go" signal. These findings suggest that long latency reflexes, possibly transcortical cutaneous reflexes, are finely tuned in relation to mirror-like activity.

Although the amplitude of the Hoffmann (H)-reflex in the forelimb muscles is known to be suppressed during rhythmic leg movement, it is unknown which factor plays a more important role in generating this suppression-movement-related afferent feedback or feedback related to body loading. To specifically explore the movement- and load-related afferent feedback, we investigated the modulation of the H-reflex in the flexor carpi radialis (FCR) muscle during robotic-assisted passive leg stepping. Passive stepping and standing were performed using a robotic gait-trainer system (Lokomat). The H-reflex in the FCR, elicited by electrical stimulation to the median nerve, was recorded at 10 different phases of the stepping cycle, as well as during quiet standing. We confirmed that the magnitude of the FCR H-reflex was suppressed significantly during passive stepping compared with during standing. The suppressive effect on the FCR H-reflex amplitude was seen at all phases of stepping, irrespective of whether the stepping was conducted with body weight loaded or unloaded. These results suggest that movement-related afferent feedback, rather than load-related afferent feedback, plays an important role in suppressing the FCR H-reflex amplitude.

総腓骨神経(CPN)反射の解析に最適な方法を見出すため、複数の方法を用いて解析を行った。その結果、最適な解析方法は、CPN反射の最大振幅値を全波整流処理していない筋電図で加算平均を行い、その面積または最大振幅値(PTP)を計測する方法であると考えられた。次に、この方法を用いてCPN反射の姿勢依存性について検討した。PTPを指標としてCPN反射の解析を行った結果、座位・立位・歩行周期における前期立脚相、後期立脚相を模した姿勢維持においてそれぞれ異なる制御を受けていることが明らかになった。