Modulation of somatosensory signal transmission in the primate cuneate nucleus during voluntary hand movement.

Primate hands house an array of mechanoreceptors and proprioceptors, which are essential for tactile and kinematic information crucial for daily motor action. While the regulation of these somatosensory signals is essential for hand movements, the specific central nervous system (CNS) location and mechanism remain unclear. Our study demonstrates the attenuation of somatosensory signals in the cuneate nucleus during voluntary movement, suggesting significant modulation at this initial relay station in the CNS. The attenuation is comparable to the cerebral cortex but more pronounced than in the spinal cord, indicating the cuneate nuclei's role in somatosensory perception modulation during movement. Moreover, our findings suggest that the descending motor tract may regulate somatosensory transmission in the cuneate nucleus, enhancing relevant signals and suppressing unnecessary ones for the regulation of movement. This process of recurrent somatosensory modulation between cortical and subcortical areas could be a basic mechanism for modulating somatosensory signals to achieve active perception.

Presynaptic gating of monkey proprioceptive signals for proper motor action.

Our rich behavioural repertoire is supported by complicated synaptic connectivity in the central nervous system, which must be modulated to prevent behavioural control from being overwhelmed. For this modulation, presynaptic inhibition is an efficient mechanism because it can gate specific synaptic input without interfering with main circuit operations. Previously, we reported the task-dependent presynaptic inhibition of the cutaneous afferent input to the spinal cord in behaving monkeys. Here, we report presynaptic inhibition of the proprioceptive afferent input. We found that the input from shortened muscles is transiently facilitated, whereas that from lengthened muscles is persistently reduced. This presynaptic inhibition could be generated by cortical signals because it started before movement onset, and its size was correlated with the performance of stable motor output. Our findings demonstrate that presynaptic inhibition acts as a dynamic filter of proprioceptive signals, enabling the integration of task-relevant signals into spinal circuits.

Distribution of Large and Small Dorsal Root Ganglion Neurons in Common Marmosets.

The aim of this study was to elucidate the size and distribution of dorsal root ganglion (DRG) neurons in non-human primates and to compare them with those of rodent DRG neurons. By measuring the size of NeuN-, NF200-, and peripherin-positive DRG neurons in the lumbar spinal cord of rats and marmosets, we found that the cell size distribution pattern was comparable in both species, although DRG neurons in marmosets were larger than those of rodents. This is the first demonstration that DRG neurons in marmosets have a bimodal size distribution, which has been well established in rodents and humans.

Specific gene expression in unmyelinated dorsal root ganglion neurons in nonhuman primates by intra-nerve injection of AAV 6 vector.

Adeno-associated virus 6 (AAV6) has been proposed as a potential vector candidate for specific gene expression in pain-related dorsal root ganglion (DRG) neurons, but this has not been confirmed in nonhuman primates. The aim of our study was to analyze the transduction efficiency and target specificity of this viral vector in the common marmoset by comparing it with those in the rat. When green fluorescent protein-expressing serotype-6 vector was injected into the sciatic nerve, the efficiency of gene expression in DRG neurons was comparable in both species. We found that the serotype-6 vector was largely specific to the pain-related ganglion neurons in the marmoset, as well as in the rat, whereas the serotype-9 vector resulted in contrasting effects in the two species. Neither AAV6 nor AAV9 resulted in DRG toxicity when administered via the sciatic nerve, suggesting this as a safer route of sensory nerve transduction than the currently used intrathecal or intravenous administrative routes. Furthermore, the AAV6 vector could be an optimal serotype for gene therapy for human chronic pain that has a minimal effect on other somatosensory functions of DRG neurons.

Optogenetic recruitment of spinal reflex pathways from large-diameter primary afferents in non-transgenic rats transduced with AAV9/Channelrhodopsin 2.

KEY POINTS: We demonstrated optical activation of primary somatosensory afferents with high selectivity to fast-conducting fibres by means of adeno-associated virus 9 (AAV9)-mediated gene transduction in dorsal root ganglion (DRG) neurons. AVV9 expressing green fluorescent protein showed high selectivity and transduction efficiency for fast-conducting, large-sized DRG neurons. Compared with conventional electrical stimulation, optically elicited volleys in primary afferents had higher sensitivity with stimulus amplitude, but lower sensitivity with stimulus frequency. Optically elicited dorsal root volleys activated postsynaptic neurons in the segmental spinal pathway. This proposed technique will help establish the causal relationships between somatosensory afferent inputs and neural responses in the CNS as well as behavioural outcomes in higher mammals where transgenic animals are not available. ABSTRACT: Previously, fundamental structures and their mode of action in the spinal reflex circuit were determined by confirming their input-output relationship using electrophysiological techniques. In those experiments, the electrical stimulation of afferent fibres was used as a core element to identify different types of reflex pathways; however, a major disadvantage of this technique is its non-selectivity. In this study, we investigated the selective activation of large-diameter afferents by optogenetics combined with a virus vector transduction technique (injection via the sciatic nerve) in non-transgenic male Jcl:Wistar rats. We found that green fluorescent protein gene transduction of rat dorsal root ganglion (DRG) neurons with a preference for medium-to-large-sized cells was achieved using the adeno-associated virus 9 (AAV9) vector compared with the AAV6 vector (P = 0.021). Furthermore, the optical stimulation of Channelrhodopsin 2 (ChR2)-expressing DRG neurons (transduced by AAV9) produced compound action potentials in afferent nerves originating from fast-conducting nerve fibres. We also confirmed that physiological responses to different stimulus amplitudes were comparable between optogenetic and electrophysiological activation. However, compared with electrically elicited responses, the optically elicited responses had lower sensitivity with stimulus frequency. Finally, we showed that afferent volleys evoked by optical stimulation were sufficient to activate postsynaptic neurons in the spinal reflex arc. These results provide new ways for understanding the role of sensory afferent input to the central nervous system regarding behavioural control, especially when genetically manipulated animals are not available, such as higher mammals including non-human primates.

Acquisition of motor memory determines the interindividual variability of learning-induced plasticity in the primary motor cortex.

Acquisition of new motor skills induces plastic reorganization in the primary motor cortex (M1). Previous studies have demonstrated the increases in the M1 excitability through motor skill learning. However, this M1 reorganization is highly variable between individuals even though they improve their skill performance through the same training protocol. To reveal the source of this interindividual variability, we examined the relationship between an acquisition of memory-guided feedforward movements and the learning-induced increases in the M1 excitability. Twenty-eight subjects participated in experiment 1. We asked subjects to learn a visuomotor tracking task. The subjects controlled a cursor on a PC monitor to pursue a target line by performing ankle dorsiflexion and plantar flexion. In experiment 1, we removed the online visual feedback provided by the cursor movement once every six trials, which enabled us to assess whether the subjects could perform accurate memory-guided movements. Motor-evoked potentials (MEP) were elicited in the tibialis anterior muscle by transcranial magnetic stimulation of the relevant M1 before and after the learning of the visuomotor tracking task and after half the trials. We found that the MEP amplitude was increased along with the improvement in memory-guided movements. In experiment 2 ( n = 10), we confirmed this relationship by examining whether the improvement in memory-guided movements induces increases in MEP amplitude. The results of this study indicate that the plastic reorganization of the M1 induced by the learning of a visuomotor skill is associated with the acquisition of memory-guided movements. NEW & NOTEWORTHY Acquisition of novel motor skills increases excitability of the primary motor cortex (M1). We recently reported that the amount of increases in the M1 excitability is highly variable between individuals even though they learned the same skill to the similar extent, yet the sources of this interindividual variability still remain unclear. The present study revealed that this interindividual variability is associated with whether individuals acquire a motor memory, which enables them to produce accurate memory-guided movements.

Acquisition of skilled finger movements is accompanied by reorganization of the corticospinal system.

Dexterous finger movements are often characterized by highly coordinated movements. Such coordination might be derived from reorganization of the corticospinal system. In this study, we investigated 1) the manner in which finger movement covariation patterns are acquired, by examining the effects of the implicit and explicit learning of a serial reaction time task (SRTT), and 2) how such changes in finger coordination are represented in the corticospinal system. The subjects learned a button press sequence in both implicit and explicit learning conditions. In the implicit conditions, they were naive about what they were learning, whereas in the explicit conditions the subjects consciously learned the order of the sequence elements. Principal component analysis decomposed both the voluntary movements produced during the SRTT and the passive movements evoked by transcranial magnetic stimulation (TMS) over the primary motor cortex into a set of five finger joint covariation patterns. The structures of the voluntary and passive TMS-evoked movement patterns were reorganized by implicit learning but not explicit learning. Furthermore, in the implicit learning conditions the finger covariation patterns derived from the TMS-evoked and voluntary movements spanned similar movement subspaces. These results provide the first evidence that skilled sequential finger movements are acquired differently through implicit and explicit learning, i.e., the changes in finger coordination patterns induced by implicit learning are accompanied by functional reorganization of the corticospinal system, whereas explicit learning results in faster recruitment of individual finger movements without causing any changes in finger coordination. NEW & NOTEWORTHY Skilled sequential multifinger movements are characterized as highly coordinated movement patterns. These finger coordination patterns are represented in the corticospinal system, yet it still remains unclear how these patterns are acquired through implicit and explicit motor sequence learning. A direct comparison of learning-related changes between actively generated finger movements and passively evoked finger movements by TMS provided evidence that finger coordination patterns represented in the corticospinal system are reorganized through implicit, but not explicit, sequence learning.

Relationship between the changes in M1 excitability after motor learning and arousal state as assessed by short-latency afferent inhibition.

To examine the factors that influence the inter-individual differences in the changes in primary motor cortex (M1) excitability seen after motor learning, we investigated the relationship between the amplitude of transcranial magnetic stimulation-induced motor evoked potentials (MEP) and short-latency afferent inhibition (SAI) after motor learning, based on the working hypothesis that SAI can be used to evaluate cortical acetylcholine (ACh) activity. To confirm this working hypothesis, we manipulated the arousal state of the subjects using a vigilance task, the outcomes of which might be correlated with cortical ACh activity, and investigated the effects of arousal state on SAI. As a result, we showed that SAI was significantly affected by arousal state. Consequently, we concluded that the subjects' arousal state during motor learning tasks is one of factors to influence on inter-individual differences in the changes in M1 excitability seen after motor learning tasks.

Different Effects of Implicit and Explicit Motor Sequence Learning on Latency of Motor Evoked Potential Evoked by Transcranial Magnetic Stimulation on the Primary Motor Cortex.

Motor training induces plastic changes in the primary motor cortex (M1). However, it is unclear whether and how the latency of motor-evoked potentials (MEP) and MEP amplitude are affected by implicit and/or explicit motor learning. Here, we investigated the changes in M1 excitability and MEP latency induced by implicit and explicit motor learning. The subjects performed a serial reaction time task (SRTT) with their five fingers. In this task, visual cues were lit up sequentially along with a predetermined order. Through training, the subjects learned the order of sequence implicitly and explicitly. Before and after the SRTT, we recorded MEP at 25 stimulation points around the hot spot for the flexor pollicis brevis (FPB) muscle. Although no changes in MEP amplitude were observed in either session, we found increases in MEP latency and changes in histogram of MEP latency after implicit learning. Our results suggest that reorganization across the motor cortices occurs during the acquisition of implicit knowledge. In contrast, acquisition of explicit knowledge does not appear to induce the reorganization based on the measures we recorded. The fact that the above mentioned increases in MEP latency occurred without any alterations in MEP amplitude suggests that learning has different effects on different physiological signals. In conclusion, our results propose that analyzing a combination of some indices of M1 excitability, such as MEP amplitude and MEP latency, is encouraged in order to understand plasticity across motor cortices.

Changes in the Spinal Neural Circuits are Dependent on the Movement Speed of the Visuomotor Task.

Previous studies have shown that spinal neural circuits are modulated by motor skill training. However, the effects of task movement speed on changes in spinal neural circuits have not been clarified. The aim of this research was to investigate whether spinal neural circuits were affected by task movement speed. Thirty-eight healthy subjects participated in this study. In experiment 1, the effects of task movement speed on the spinal neural circuits were examined. Eighteen subjects performed a visuomotor task involving ankle muscle slow (nine subjects) or fast (nine subjects) movement speed. Another nine subjects performed a non-visuomotor task (controls) in fast movement speed. The motor task training lasted for 20 min. The amounts of D1 inhibition and reciprocal Ia inhibition were measured using H-relfex condition-test paradigm and recorded before, and at 5, 15, and 30 min after the training session. In experiment 2, using transcranial magnetic stimulation (TMS), the effects of corticospinal descending inputs on the presynaptic inhibitory pathway were examined before and after performing either a visuomotor (eight subjects) or a control task (eight subjects). All measurements were taken under resting conditions. The amount of D1 inhibition increased after the visuomotor task irrespective of movement speed (P < 0.01). The amount of reciprocal Ia inhibition increased with fast movement speed conditioning (P < 0.01), but was unchanged by slow movement speed conditioning. These changes lasted up to 15 min in D1 inhibition and 5 min in reciprocal Ia inhibition after the training session. The control task did not induce changes in D1 inhibition and reciprocal Ia inhibition. The TMS conditioned inhibitory effects of presynaptic inhibitory pathways decreased following visuomotor tasks (P < 0.01). The size of test H-reflex was almost the same size throughout experiments. The results suggest that supraspinal descending inputs for controlling joint movement are responsible for changes in the spinal neural circuits, and that task movement speed is one of the critical factors for inducing plastic changes in reciprocal Ia inhibition.

Interactions Among Learning Stage, Retention, and Primary Motor Cortex Excitability in Motor Skill Learning.

BACKGROUND: Previous studies have shown that primary motor cortex (M1) excitability is modulated by motor skill learning and that the M1 plays a crucial role in motor memory. However, the following questions remain: (1) At what stage do changes in M1 excitability occur? (2) Are learning-induced changes in leg M1 excitability associated with motor memory? Here, we did two experiments to answer these questions. METHODS AND RESULTS: In experiment 1, subjects learned a visuomotor tracking task over two consecutive days. Before and after the task in Day 1, we recorded input-output curves of the motor evoked potentials (I-O curve) produced in the tibialis anterior muscle by transcranial magnetic stimulation. We found that the changes in M1 excitability were affected by learning stage. In addition, the changes in M1 excitability in Day 1 were correlated with the retention. In experiment 2, we recorded I-O curves before learning, after the fast-learning stage, and after learning. We found no changes in M1 excitability immediately after the fast-learning stage. Furthermore, a significant relationship between the length of slow-learning stage and the changes in M1 excitability was detected. CONCLUSIONS: Previous studies have suggested that optimal motor commands are repeatedly used during the slow-learning stage. Therefore, present results indicate that changes in M1 excitability occur during the slow-learning stage and that such changes are proportional to motor skill retention because use-dependent plasticity occur by repetitive use of same motor commands during the slow-learning stage.

Effect of tactile stimulation on primary motor cortex excitability during action observation combined with motor imagery.

We aimed to investigate the effects of the tactile stimulation to an observer's fingertips at the moment that they saw an object being pinched by another person on the excitability of observer's primary motor cortex (M1) using transcranial magnetic stimulation (TMS). In addition, the above effects were also examined during action observation combined with the motor imagery. Motor evoked potentials (MEP) were evoked from the subjects' right first dorsal interosseous (FDI) and abductor digiti minimi (ADM) muscles. Electrical stimulation (ES) inducing tactile sensation was delivered to the subjects' first and second fingertips at the moment of pinching action performed by another person. Although neither the ES nor action observation alone had significant effects on the MEP amplitude of the FDI or ADM, the FDI MEP amplitude which acts as the prime mover during pinching was reduced when ES and action observation were combined; however, no such changes were seen in the ADM. Conversely, that reduced FDI MEP amplitude was increased during the motor imagery. These results indicated that the M1 excitability during the action observation of pinching action combined with motor imagery could be enhanced by the tactile stimulation delivered to the observer's fingertips at the moment corresponding to the pinching being observed.

How effective is the early fast treadmill gait speed training for stroke patients at the 2nd week after admission: comparison with comfortable gait speed at the 6th week.

[Purpose] The purpose of this study was to find whether a fast treadmill gait training speed is effective for the gait training of stroke patients in the early rehabilitation stage. [Subjects and Methods] Thirty-nine stroke patients were the subjects of our investigation. They walked on a treadmill with handrail supports at a fast speed (130% of their comfortable gait speed in the 2nd week). The treadmill gaits of the patients were recorded using a 3-dimensional analysis system at two and six weeks after their admissions. Intraclass Correlation Coefficients (ICC) of the temporal and spatial parameters of the two periods were statistically analyzed. [Results] For all of the patients, the ICCs of the measured parameters were greater than 0.58. In the case of patients whose gait speeds of the two periods were close, the ICC units were greater than 0.7. [Conclusion] The fast gait speed training allowed us to expose the patients to a gait speed that they were expected to acquire at a later stage of their rehabilitation. This training method was found to be beneficial for the mildly paralyzed patients.

Excitability changes in the left primary motor cortex innervating the hand muscles induced during speech about hand or leg movements.

In the present study, we used transcranial magnetic stimulation (TMS) to investigate the changes in the excitability of the left primary motor cortex (M1) innervating the hand muscles and in short-interval intracortical inhibition (SICI) during speech describing hand or leg movements. In experiment 1, we investigated the effects of the contents of speech on the amplitude of the motor evoked potentials (MEPs) induced during reading aloud and silent reading. In experiment 2, we repeated experiment 1 with an additional condition, the non-vocal oral movement (No-Voc OM) condition, and investigated the change in SICI induced in each condition using the paired TMS paradigm. The MEP observed in the reading aloud and No-Voc OM conditions exhibited significantly greater amplitudes than those seen in the silent reading conditions, irrespective of the content of the sentences spoken by the subjects or the timing of the TMS. There were no significant differences in SICI between the experimental conditions. Our findings suggest that the increased excitability of the left M1 hand area detected during speech was mainly caused by speech-related oral movements and the activation of language processing-related brain functions. The increased left M1 excitability was probably also mediated by neural mechanisms other than reduced SICI; i.e., disinhibition.

Patterned sensory nerve stimulation enhances the reactivity of spinal Ia inhibitory interneurons.

Patterned sensory nerve stimulation has been shown to induce plastic changes in the reciprocal Ia inhibitory circuit. However, the mechanisms underlying these changes have not yet been elucidated in detail. The aim of the present study was to determine whether the reactivity of Ia inhibitory interneurons could be altered by patterned sensory nerve stimulation. The degree of reciprocal Ia inhibition, the conditioning effects of transcranial magnetic stimulation (TMS) on the soleus (SOL) muscle H-reflex, and the ratio of the maximum H-reflex amplitude versus maximum M-wave (H(max)/M(max)) were examined in 10 healthy individuals. Patterned electrical nerve stimulation was applied to the common peroneal nerve every 1 s (100 Hz-5 train) at the motor threshold intensity of tibialis anterior muscle to induce activity changes in the reciprocal Ia inhibitory circuit. Reciprocal Ia inhibition, the TMS-conditioned H-reflex amplitude, and H(max)/M(max) were recorded before, immediately after, and 15 min after the electrical stimulation. The patterned electrical nerve stimulation significantly increased the degree of reciprocal Ia inhibition and decreased the amplitude of the TMS-conditioned H-reflex in the short-latency inhibition phase, which was presumably mediated by Ia inhibitory interneurons. However, it had no effect on H(max)/M(max). Our results indicated that patterned sensory nerve stimulation could modulate the activity of Ia inhibitory interneurons, and this change may have been caused by the synaptic modification of Ia inhibitory interneuron terminals. These results may lead to a clearer understanding of the spinal cord synaptic plasticity produced by repetitive sensory inputs.

Different modulation of short- and long-latency interhemispheric inhibition from active to resting primary motor cortex during a fine-motor manipulation task.

Performing a complex unimanual motor task markedly increases activation not only in the hemisphere contralateral to the task-performing hand but also in the ipsilateral hemisphere. Transcranial magnetic stimulation studies showed increased motor evoked potential amplitude recorded in resting hand muscles contralateral to the task-performing hand during a unimanual motor task, and transcallosal inputs from the active hemisphere have been suggested to have responsibilities for this phenomenon. In the present study, we used a well-established double-pulse transcranial magnetic stimulation paradigm to measure two phases of interhemispheric inhibition from the active to the resting primary motor cortex during the performance of a complex unimanual motor task. Two different unimanual motor tasks were carried out: a fine-motor manipulation task (using chopsticks to pick up, transport, and release glass balls) as a complex task and a pseudo fine-motor manipulation task as a control task (mimicking the fine-motor manipulation task without using chopsticks and picking glass balls). We found increased short-latency interhemispheric inhibition and decreased long-latency interhemispheric inhibition from the active to the resting primary motor cortex during the fine-motor manipulation task. To the best of our knowledge, the present study is the first to demonstrate different modulation of two phases of interhemispheric inhibition from the active to the resting primary motor cortex during the performance of a complex unimanual motor task. The different modulation of short- and long-latency interhemispheric inhibition may suggest that two phases of interhemispheric inhibition are implemented in distinct circuits with different functional meaning.

Time-dependent effects of neuromuscular electrical stimulation on changes in spinal excitability are dependent on stimulation frequency: a preliminary study in healthy adults.

Neuromuscular electrical stimulation (NMES) can be used as treatment for spasticity. The present study examined differences in time-dependent effects of NMES depending on stimulation frequency. Forty healthy subjects were separated into four groups (no-stim, NMES of 50, 100, and 200 Hz). The un-conditioned H-reflex amplitude and the H-reflex conditioning-test paradigm were used to measure the effectiveness on monosynaptic Ia excitation of motoneurons in the soleus (SOL) muscle, disynaptic reciprocal Ia inhibition from tibialis anterior (TA) to SOL, and presynaptic inhibition of SOL Ia afferents. Each trial consisted of a 30-min period of NMES applied to the deep peroneal nerve followed by a 30-min period with no stimulation to measure prolonged effects. Measurements were performed periodically. Stimulation applied at all frequencies produced a significant reduction in monosynaptic Ia excitation of motoneurons in the SOL muscle, however, only stimulation with 50 Hz showed prolonged reduction after NMES. NMES frequency did not affect the amount of disynaptic reciprocal Ia inhibition and presynaptic inhibition of Ia afferents. The results show a frequency-dependent effect of NMES on the monosynaptic Ia excitation of motoneurons. This result has implications for selecting the optimal NMES frequency for treatment in patients with spasticity.

Long-term practice induced plasticity in the primary motor cortex innervating the ankle flexor in football juggling experts.

The aim of this study was to investigate the plasticity of M1 innervating the tibialis anterior muscle (TA) induced by the long-term practice of football juggling using a transcranial magnetic stimulation (TMS) technique. Ten football juggling experts and ten novices participated in this study. Motor evoked potentials (MEP) and the H-reflex were recorded from the right TA during isometric dorsiflexion at 10% of maximum voluntary contraction. The MEP input-output curve of the experts was steeper than that of the novices, and reduced short-interval intracortical inhibition and long-interval intracortical inhibition were observed in the experts. In contrast, the ratio of Hmax to Mmax did not differ between the groups. Our results show that football juggling experts displayed enhanced excitability in the M1 innervating the TA, which was induced by the long-term practice of the ankle movements required to perform football juggling well.

Inter-individual variation in reciprocal Ia inhibition is dependent on the descending volleys delivered from corticospinal neurons to Ia interneurons.

INTRODUCTION: We investigated the extent to which the corticospinal inputs delivered to Ia inhibitory interneurons influence the strength of disynaptic reciprocal Ia inhibition. METHODS: Seventeen healthy subjects participated in this study. The degree of reciprocal Ia inhibition was determined via short-latency (condition-test interval: 1-3ms) suppression of Sol H-reflex by conditioning stimulation of common peroneal nerve. The effect of corticospinal descending inputs on Ia inhibitory interneurons was assessed by evaluating the conditioning effect of transcranial magnetic stimulation (TMS) on the Sol H-reflex. Then, we determined the relationship between the degree of reciprocal Ia inhibition and the conditioning effect of TMS on the Sol H-reflex. RESULT: We found that the degree of reciprocal Ia inhibition and the extent of change in the amplitude of the TMS-conditioned H-reflex, which was measured from short latency facilitation to inhibition, displayed a strong correlation (r=0.76, p<0.01) in the resting conditions. CONCLUSION: The extent of reciprocal Ia inhibition is affected by the corticospinal descending inputs delivered to Ia inhibitory interneurons, which might explain the inter-individual variations in reciprocal Ia inhibition.

Functional difference in short- and long-latency interhemispheric inhibitions from active to resting hemisphere during a unilateral muscle contraction.

The aim of the present study was to investigate whether there is a functional difference in short-latency (SIHI) and long-latency (LIHI) interhemispheric inhibition from the active to the resting primary motor cortex (M1) with paired-pulse transcranial magnetic stimulation during a unilateral muscle contraction. In nine healthy right-handed participants, IHI was tested from the dominant to the nondominant M1 and vice versa under resting conditions or during performance of a sustained unilateral muscle contraction with the right or left first dorsal interosseous muscle at 10% and 30% maximum voluntary contraction. To obtain measurements of SIHI and LIHI, a conditioning stimulus (CS) was applied over the M1 contralateral to the muscle contraction, followed by a test stimulus over the M1 ipsilateral to the muscle contraction at short (10 ms) and long (40 ms) interstimulus intervals. We used four CS intensities to investigate SIHI and LIHI from the active to the resting M1 systematically. The amount of IHI during the unilateral muscle contractions showed a significant difference between SIHI and LIHI, but the amount of IHI during the resting condition did not. In particular, SIHI during the muscle contractions, but not LIHI, significantly increased with increase in CS intensity compared with the resting condition. Laterality of IHI was not detected in any of the experimental conditions. The present study provides novel evidence that a functional difference between SIHI and LIHI from the active to the resting M1 exists during unilateral muscle contractions.