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Reciprocal inhibition (RI) between leg muscles is crucial for smooth movement. Pedaling is a rhythmic movement that can increase RI in healthy individuals. Transcutaneous spinal cord stimulation (tSCS) stimulates spinal neural circuits by targeting the afferent fibers. Pedaling with simultaneous tSCS may modulate the plasticity of the spinal neural circuit and alter neural activity based on movement and muscle engagement. This study investigated the RI changes after pedaling and tSCS and determined the phase of pedaling in which tSCS should be applied for optimal RI modulation in healthy individuals. Eleven subjects underwent three interventions: pedaling combined with tSCS during the early phase of lower extension (phase 1), pedaling combined with tSCS during the late phase of lower flexion (phase 4) of the pedaling cycle, and pedaling combined with sham tSCS. The RI from the tibialis anterior to the soleus muscle was assessed before, immediately after, 15 min, and 30 min after the intervention. RI increased immediately after phase 4 and pedaling combined with sham tSCS, whereas no changes were observed after phase 1. These results demonstrate that tSCS modulates RI changes induced by pedaling in a stimulus phase-dependent manner in healthy individuals. However, the mechanism involved in this intervention needs to be explored to achieve higher efficacy.

Neuromuscular electrical stimulation (NMES) induces neural plasticity of the central nervous system (CNS) and improves motor function in patients with CNS lesions. However, the extended stimulus duration of NMES reduces its clinical applicability. Transcutaneous spinal direct current stimulation (tsDCS), which increases afferent input, may enhance the effects and reduce the stimulus duration of NMES. This study investigated the excitability of the motor cortex, somatosensory cortex, and spinal motor neurons after the combined stimulation of NMES and tsDCS. Among the 55 participants in this study, 24 were allocated to experiment 1, 15 to experiment 2, and 16 to experiment 3. They received intervention for 20 min on different days: (1) NMES combined with tsDCS (NMES + tsDCS), (2) NMES combined with sham tsDCS (NMES + sham tsDCS), and (3) sham NMES combined with tsDCS (sham NMES + tsDCS). NMES was delivered to the right common peroneal nerve at 25 Hz with the intensity at 120% of the motor threshold. For tsDCS, the cathodal electrode was positioned on the thoracic 10th-12th vertebral levels, and the anodal electrode was located on the right shoulder. The stimulus intensity was 2.5 mA. In experiment 1, motor evoked potentials (MEPs) and short-latency intracortical inhibition (SICI) were measured by transcranial magnetic stimulation up to 60 min after stimulation. The spinal motor neurons' excitability was assessed by recording the posterior root muscle reflex (PRMR) induced transcutaneous spinal cord stimulation in experiment 2, and the primary somatosensory cortex excitability was evaluated by recording the somatosensory evoked potentials (SEPs) in experiment 3 up to 15 min after stimulation. Compared to before the stimulation, NMES + tsDCS significantly increased MEP for 60 min or more, and significantly decreased SICI immediately after. Conversely contrast, the PRMR significantly decreased immediately after, and SEPs were unchanged. These results suggest that simultaneous afferent inputs from different stimulus positions critically induce primary motor cortex plasticity. The combined stimulation of NMES with tsDCS may facilitate the development of a new neurorehabilitation technique.

Spasticity affects approximately 65% of persons with spinal cord injury (SCI) and negatively impacts function and quality of life. Whole body vibration (WBV) appears to reduce spasticity and improve walking function; however, the optimal dose (frequency/duration) is not known. We compared single-session effects of four different WBV frequency/duration dose conditions on spasticity and walking speed, in preparation for a planned multi-session study. Thirty-five participants with motor-incomplete SCI received four different doses of WBV: high frequency (50 Hz)/short duration (180 s), high frequency/long duration (360 s), low frequency (30 Hz)/short duration, and low frequency/long duration, plus a control intervention consisting of sham electrical stimulation. In all conditions, participants stood on the WBV platform for 45-s bouts with 1 min rest between bouts until the requisite duration was achieved. The frequency/duration dose order was randomized across participants; sessions were separated by at least 1 week. Quadriceps spasticity was measured using the pendulum test at four time points during each session: before, immediately after, 15 min after, and 45 min after WBV. Walking speed was quantified using the 10-m walk test at three time points during each session: baseline, immediately after, and 45 min after WBV. In the full group analysis, no frequency/duration combination was significantly different from the sham-control condition. In participants with more severe spasticity, a greater reduction in stretch reflex excitability was associated with the high frequency/long duration WBV condition. The sham-control condition was associated with effects, indicating that the activity of repeated sitting and standing may have a beneficial influence on spasticity. Trial registration: NCT02340910 (assigned 01/19/2015).

Substantia gelatinosa (SG) neurons, which are located in the spinal dorsal horn (lamina II), have been identified as the “central gate” for the transmission and modulation of nociceptive information. Rebound depolarization (RD), a biophysical property mediated by membrane hyperpolarization that is frequently recorded in the central nervous system, contributes to shaping neuronal intrinsic excitability and, in turn, contributes to neuronal output and network function. However, the electrophysiological and morphological properties of SG neurons exhibiting RD remain unclarified. In this study, whole-cell patch-clamp recordings were performed on SG neurons from parasagittal spinal cord slices. RD was detected in 44.44% (84 out of 189) of the SG neurons recorded. We found that RD-expressing neurons had more depolarized resting membrane potentials, more hyperpolarized action potential (AP) thresholds, higher AP amplitudes, shorter AP durations, and higher spike frequencies in response to depolarizing current injection than neurons without RD. Based on their firing patterns and morphological characteristics, we propose that most of the SG neurons with RD mainly displayed tonic firing (69.05%) and corresponded to islet cell morphology (58.82%). Meanwhile, subthreshold currents, including the hyperpolarization-activated cation current (I h ) and T-type calcium current (I T ), were identified in SG neurons with RD. Blockage of I h delayed the onset of the first spike in RD, while abolishment of I T significantly blunted the amplitude of RD. Regarding synaptic inputs, SG neurons with RD showed lower frequencies in both spontaneous and miniature excitatory synaptic currents. Furthermore, RD-expressing neurons received either Aδ- or C-afferent-mediated monosynaptic and polysynaptic inputs. However, RD-lacking neurons received afferents from monosynaptic and polysynaptic Aδ fibers and predominantly polysynaptic C-fibers. These findings demonstrate that SG neurons with RD have a specific cell-type distribution, and may differentially process somatosensory information compared to those without RD.

Objective The globus pallidus externa (GPe) is involved in mediating physiological functions and contains two types of neurons: Forkhead box protein P2‐expressing (GPeFoxP2) neurons which inhibit motor, and parvalbumin‐expressing (GPePV) neurons which improve motor. The functional complexity of the GPe, directly linked to its neuronal heterogeneity, necessitates exploring the neuroanatomical circuits of its distinct neuron types as a foundation for functional research. Methods In this study, we employed specific, modified rabies viruses and adeno‐associated viruses to investigate the monosynaptic inputs of GPeFoxP2 and GPePV neurons. Results We found that the input projections to both types of neurons are widespread, including the cortex, subcortical structures, amygdala, thalamus, hypothalamus, and brainstem. These inputs exhibit significant similarity, with 49 nuclei simultaneously innervating both types of neurons. However, GPePV neurons receive a lower proportion of inputs from the cortex and a higher proportion of inputs from the thalamus, compared to GPeFoxP2 neurons. Clustering analysis indicates that GPeFoxP2 neurons receive extensive afferent inputs from four nuclear clusters in the brain, whereas GPePV neurons receive afferent inputs from only three clusters, suggesting GPeFoxP2 neurons may be involved in more diverse functional regulations than GPePV. Conclusion Collectively, our results reveal the similarities and differences in the input projections to the two types of neurons in the GPe and lay the neuroanatomic groundwork for further studies to explore the critical physiological functions of GPe. Our results reveal the similarities and differences in the input projections to the two types of GABAergic neurons in the globus pallidus externa (GPe) and lay the neuroanatomic groundwork for further studies to explore the critical physiological functions of GPe.

The prefrontal cortex (PFC) plays an important role in several cognitive functions, such as planning, decision making, and social behavior. We previously reported that periodontal sensory input significantly increases PFC activity during the motor task of maintaining occlusal (biting) force. However, the relationships between periodontal sensation, PFC activity, and the performance of motor tasks have not been evaluated in detail. Therefore, using functional near-infrared spectroscopy, we investigated PFC activity by monitoring changes in cerebral blood flow (CBF) to specific areas of the PFC that corresponded to changes in occlusal force generated during four different biting tasks: (1) occlusion with the central incisor with an interocclusal distance of 5 mm (BI-5 mm); or (2) 10 mm (BI-10 mm); (3) occlusion with the first molars with an interocclusal distance of 5 mm (BM-5 mm), or (4) 10 mm (BM-10 mm). Occlusion of molars generated increased PFC regional CBF as the interocclusal distance decreased (BM-10 mm vs BM-5 mm). No significant differences in CBF during occlusion of incisors were found when comparing 5 mm and 10 mm intercostal distances (BI-5 mm vs BI-10 mm). The mean occlusal force generated by BM-5 mm occlusion was significantly lower than that generated by BM-10 mm occlusion. Taken together, our results suggest that the PFC decreases efferent signaling to motor units, to reduce occlusal force generated when periodontal sensation, which is greater when the interocclusal distance is reduced, is primarily responsible for maintaining occlusal force in the absence of sensations from the temporomandibular joint and muscle spindles.

Involuntary contractions of paralyzed muscles (spasms) commonly disrupt daily activities and rehabilitation after human spinal cord injury (SCI). Our aim was to examine the recruitment, firing rate modulation, and derecruitment of motor units that underlie spasms of thenar muscles after cervical SCI. Intramuscular electromyographic activity (EMG), surface EMG, and force were recorded during thenar muscle spasms that occurred spontaneously or that were triggered by movement of a shoulder or leg. Most spasms were submaximal (mean: 39%, SD: 33 of the force evoked by median nerve stimulation at 50 Hz) with strong relationships between EMG and force (R (2) > 0.69). Unit recruitment occurred over a wide force range (0.2-103% of 50 Hz force). Significant unit rate modulation occurred during spasms (frequency at 25% maximal force: 8.8 Hz, 3.3 SD; at maximal force: 16.1 Hz, 4.1 SD). Mean recruitment frequency (7.1 Hz, 3.2 SD) was significantly higher than derecruitment frequency (5.4 Hz, 2.4 SD). Coactive unit pairs that fired for more than 4 s showed high (R (2) > 0.7, n = 4) or low (R (2):0.3-0.7, n = 12) rate-rate correlations, and derecruitment reversals (21 pairs, 29%). Later recruited units had higher or lower maximal firing rates than lower threshold units. These discrepant data show that coactive motoneurons are drive both by common inputs and by synaptic inputs from different sources during muscle spasms. Further, thenar motoneurons can still fire at high rates in response to various peripheral inputs after SCI, supporting the idea that low maximal voluntary firing rates and forces in thenar muscles result from reduced descending drive.

The purpose of this study was to investigate the effects of peripheral afferent stimuli on the synchrony between brain and muscle activity as estimated by corticomuscular coherence (CMC). Electroencephalogram (EEG) from sensorimotor cortex and electromyogram (EMG) from two intrinsic hand muscles were recorded during a key grip motor task, and the modulation of CMC caused by afferent electrical and mechanical stimulation was measured. The particular stimuli used were graded single-pulse electrical stimuli, above threshold for perception and activating cutaneous afferents, applied to the dominant or non-dominant index finger, and a pulsed mechanical displacement of the gripped object causing the subject to feel as if the object may be dropped. Following electrical stimulation of the dominant index finger, the level of β-range (14–36 Hz) CMC was reduced in a stimulus intensity-dependent fashion for up to 400 ms post-stimulus, then returned with greater magnitude before falling to baseline levels over 2.5 s, outlasting the reflex and evoked changes in EMG and EEG. Subjects showing no baseline β-range CMC nevertheless showed post-stimulus increases in β-range CMC with the same time course as those with baseline β-range CMC. The mechanical stimuli produced similar modulation of β-range CMC. Electrical stimuli to the non-dominant index finger produced no significant increase in β-range CMC. The results suggest that both cutaneous and proprioceptive afferents have access to circuits generating CMC, but that only a functionally relevant stimulus produces significant modulation of the background β-range CMC, providing further evidence that β-range CMC has an important role in sensorimotor integration.

The purpose of this study was to investigate whether repetitive electrical stimulation of the common peroneal nerve (CPN) is associated with changes in the motor response of the tibialis anterior (TA) muscle elicited by focal magnetic stimulation of the motor cortex. Motor evoked potentials (MEP) with a stimulation intensity of 125% of the threshold of the relaxed right TA were obtained before, during, and after repetitive electrical stimulation of the CPN (trains of five pulses of 1 ms, at a frequency of 200 Hz, repeated every second with a 30-min duration). The MEP of the TA muscle elicited after repetitive electrical stimulation were increased by 104% (range: 18-263%), and the increase was maintained for up to 110 min (range: 15-110 min) after the end of nerve stimulation. This increase in the MEP of the TA muscle was associated with a decrease in the threshold from the stimulation-response curve. Furthermore, during that period the early component of the TA stretch reflex as well as the latency of the MEP did not significantly change. To further test the origin of the increased MEP, complementary experiments showed that MEP elicited by transcranial electrical stimulation (TES) were also increased, but to a lesser degree (approximately 50%) than MEP elicited by TMS. It can be concluded that short-term nerve repetitive electrical stimulation of the lower extremities in healthy human participants can lead to a long-term increase in the contralateral MEP. As TES is believed to mainly activate the axon and not the soma of the cortical cells, the increased MEP cannot be explained exclusively by changes in the motor cortex cell excitability, but also by changes in subcortical neural structures involved in the excitation of spinal motoneurons. The results of this study allow the speculation that it would be possible to use repetitive electrical stimulation in the rehabilitation of patients with lower limb muscle weakness and spasticity.