Transcutaneous spinal cord stimulation phase-dependently modulates spinal reciprocal inhibition induced by pedaling in healthy individuals.

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.

Changes in Corticospinal Excitability and Motor Control During Cerebellar Transcranial Direct Current Stimulation in Healthy Individuals.

Cerebellar transcranial direct current stimulation (ctDCS) modulates the primary motor cortex (M1) via cerebellar brain inhibition (CBI), which affects motor control in humans. However, the effects of ctDCS on motor control are inconsistent because of an incomplete understanding of the real-time changes in the M1 excitability that occur during ctDCS, which determines motor output under regulation by the cerebellum. This study investigated changes in corticospinal excitability and motor control during ctDCS in healthy individuals. In total, 37 healthy individuals participated in three separate experiments. ctDCS (2 mA) was applied to the cerebellar hemisphere during the rest condition or a pinch force-tracking task. Motor-evoked potential (MEP) amplitude and the F-wave were assessed before, during, and after ctDCS, and pinch force control was assessed before and during ctDCS. The MEP amplitudes were significantly decreased during anodal ctDCS from 13 min after the onset of stimulation, whereas the F-wave was not changed. No significant changes in MEP amplitudes were observed during cathodal and sham ctDCS conditions. The MEP amplitudes were decreased during anodal ctDCS when combined with the pinch force-tracking task, and pinch force control was impaired during anodal ctDCS relative to sham ctDCS. The MEP amplitudes were not significantly changed before and after all ctDCS conditions. Motor cortical excitability was suppressed during anodal ctDCS, and motor control was unskilled during anodal ctDCS when combined with a motor task in healthy individuals. Our findings provided a basic understanding of the clinical application of ctDCS to neurorehabilitation.

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

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

Single-Session Cerebellar Transcranial Direct Current Stimulation Affects Postural Control Learning and Cerebellar Brain Inhibition in Healthy Individuals.

Cerebellar transcranial direct current stimulation (ctDCS) modulates cerebellar activity and postural control. However, the effects of ctDCS on postural control learning and the mechanisms associated with these effects remain unclear. To examine the effects of single-session ctDCS on postural control learning and cerebellar brain inhibition (CBI) of the primary motor cortex in healthy individuals. In this triple-blind, sham-controlled study, 36 participants were allocated randomly to one of three groups: (1) anodal ctDCS group, (2) cathodal ctDCS group, and (3) sham ctDCS group. ctDCS (2 mA) was applied to the cerebellar brain for 20 min prior to six blocks of standing postural control training (each block consisted of five trials of a 30-s tracking task). CBI and corticospinal excitability of the tibialis anterior muscle were assessed at baseline, immediately after, 1 day after, and 7 days after training. Skill acquisition following training was significantly reduced in both the anodal and cathodal ctDCS groups compared with the sham ctDCS group. Changes in performance measured 1 day after and 7 days after training did not differ among the groups. In the anodal ctDCS group, CBI significantly increased after training, whereas corticospinal excitability decreased. Anodal ctDCS-induced CBI changes were correlated with the learning formation of postural control (r = 0.55, P = 0.04). Single-session anodal and cathodal ctDCS could suppress the skill acquisition of postural control in healthy individuals. The CBI changes induced by anodal ctDCS may affect the learning process of postural control.

Predicting interindividual response to theta burst stimulation in the lower limb motor cortex using machine learning.

Using theta burst stimulation (TBS) to induce neural plasticity has played an important role in improving the treatment of neurological disorders. However, the variability of TBS-induced synaptic plasticity in the primary motor cortex prevents its clinical application. Thus, factors associated with this variability should be explored to enable the creation of a predictive model. Statistical approaches, such as regression analysis, have been used to predict the effects of TBS. Machine learning may potentially uncover previously unexplored predictive factors due to its increased capacity for capturing nonlinear changes. In this study, we used our prior dataset (Katagiri et al., 2020) to determine the factors that predict variability in TBS-induced synaptic plasticity in the lower limb motor cortex for both intermittent (iTBS) and continuous (cTBS) TBS using machine learning. Validation of the created model showed an area under the curve (AUC) of 0.85 and 0.69 and positive predictive values of 77.7 and 70.0% for iTBS and cTBS, respectively; the negative predictive value was 75.5% for both patterns. Additionally, the accuracy was 0.76 and 0.72, precision was 0.82 and 0.67, recall was 0.82 and 0.67, and F1 scores were 0.82 and 0.67 for iTBS and cTBS, respectively. The most important predictor of iTBS was the motor evoked potential amplitude, whereas it was the intracortical facilitation for cTBS. Our results provide additional insights into the prediction of the effects of TBS variability according to baseline neurophysiological factors.

Simulating tDCS electrode placement to stimulate both M1 and SMA enhances motor performance and modulates cortical excitability depending on current flow direction.

Introduction: The conventional method of placing transcranial direct current stimulation (tDCS) electrodes is just above the target brain area. However, this strategy for electrode placement often fails to improve motor function and modulate cortical excitability. We investigated the effects of optimized electrode placement to induce maximum electrical fields in the leg regions of both M1 and SMA, estimated by electric field simulations in the T1and T2-weighted MRI-based anatomical models, on motor performance and cortical excitability in healthy individuals. Methods: A total of 36 healthy volunteers participated in this randomized, triple-blind, sham-controlled experiment. They were stratified by sex and were randomly assigned to one of three groups according to the stimulation paradigm, including tDCS with (1) anodal and cathodal electrodes positioned over FCz and POz, respectively, (A-P tDCS), (2) anodal and cathodal electrodes positioned over POz and FCz, respectively, (P-A tDCS), and (3) sham tDCS. The sit-to-stand training following tDCS (2 mA, 10 min) was conducted every 3 or 4 days over 3 weeks (5 sessions total). Results: Compared to sham tDCS, A-P tDCS led to significant increases in the number of sit-to-stands after 3 weeks training, whereas P-A tDCS significantly increased knee flexor peak torques after 3 weeks training, and decreased short-interval intracortical inhibition (SICI) immediately after the first session of training and maintained it post-training. Discussion: These results suggest that optimized electrode placement of the maximal EF estimated by electric field simulation enhances motor performance and modulates cortical excitability depending on the direction of current flow.

Individualized beta-band oscillatory transcranial direct current stimulation over the primary motor cortex enhances corticomuscular coherence and corticospinal excitability in healthy individuals.

BACKGROUND: Simultaneously modulating individual neural oscillation and cortical excitability may be important for enhancing communication between the primary motor cortex and spinal motor neurons, which plays a key role in motor control. However, it is unknown whether individualized beta-band oscillatory transcranial direct current stimulation (otDCS) enhances corticospinal oscillation and excitability. OBJECTIVE: This study investigated the effects of individualized beta-band otDCS on corticomuscular coherence (CMC) and corticospinal excitability in healthy individuals. METHODS: In total, 29 healthy volunteers participated in separate experiments. They received the following stimuli for 10 min on different days: 1) 2-mA otDCS with individualized beta-band frequencies, 2) 2-mA transcranial alternating current stimulation (tACS) with individualized beta-band frequencies, and 3) 2-mA transcranial direct current stimulation (tDCS). The changes in CMC between the vertex and tibialis anterior (TA) muscle and TA muscle motor-evoked potentials (MEPs) were assessed before and after (immediately, 10 min, and 20 min after) stimulation on different days. Additionally, 20-Hz otDCS for 10 min was applied to investigate the effects of a fixed beta-band frequency on CMC. RESULTS: otDCS significantly increased CMC and MEPs immediately after stimulation, whereas tACS and tDCS had no effects. There was a significant negative correlation between normalized CMC changes in response to 20-Hz otDCS and the numerical difference between the 20-Hz and individualized CMC peak frequency before the stimulation. CONCLUSIONS: These findings suggest that simultaneous modulation of neural oscillation and cortical excitability is critical for enhancing corticospinal communication. Individualized otDCS holds potential as a useful method in the field of neurorehabilitation.

Repetitive Peripheral Magnetic Stimulation of Wrist Extensors Enhances Cortical Excitability and Motor Performance in Healthy Individuals.

Repetitive peripheral magnetic stimulation (rPMS) may improve motor function following central nervous system lesions, but the optimal parameters of rPMS to induce neural plasticity and mechanisms underlying its action remain unclear. We examined the effects of rPMS over wrist extensor muscles on neural plasticity and motor performance in 26 healthy volunteers. In separate experiments, the effects of rPMS on motor evoked potentials (MEPs), short-interval intracortical inhibition (SICI), intracortical facilitation (ICF), direct motor response (M-wave), Hoffmann-reflex, and ballistic wrist extension movements were assessed before and after rPMS. First, to examine the effects of stimulus frequency, rPMS was applied at 50, 25, and 10 Hz by setting a fixed total number of stimuli. A significant increase in MEPs of wrist extensors was observed following 50 and 25 Hz rPMS, but not 10 Hz rPMS. Next, we examined the time required to induce plasticity by increasing the number of stimuli, and found that at least 15 min of 50 and 25 Hz rPMS was required. Based on these parameters, lasting effects were evaluated following 15 min of 50 or 25 Hz rPMS. A significant increase in MEP was observed up to 60 min following 50 and 25 Hz rPMS; similarly, an attenuation of SICI and enhancement of ICF were also observed. The maximal M-wave and Hoffmann-reflex did not change, suggesting that the increase in MEP was due to plastic changes at the motor cortex. This was accompanied by increasing force and electromyograms during wrist ballistic extension movements following 50 and 25 Hz rPMS. These findings suggest that 15 min of rPMS with 25 Hz or more induces an increase in cortical excitability of the relevant area rather than altering the excitability of spinal circuits, and has the potential to improve motor output.

Interindividual Variability of Lower-Limb Motor Cortical Plasticity Induced by Theta Burst Stimulation.

Theta burst stimulation (TBS) has been used as a tool to induce synaptic plasticity and improve neurological disorders. However, there is high interindividual variability in the magnitude of the plastic changes observed after TBS, which hinders its clinical applications. The electric field induced by transcranial magnetic stimulation (TMS) is strongly affected by the depth of the stimulated brain region. Therefore, it is possible that the variability in the response to TBS over the lower-limb motor cortex is different for the hand area. This study investigated the variability of TBS-induced synaptic plasticity in the lower-limb motor cortex, for intermittent TBS (iTBS), continuous TBS (cTBS), and sham iTBS, in 48 healthy young participants. The motor cortical and intracortical excitability of the tibialis anterior was tested before and after TBS using TMS. The results showed that iTBS had facilitatory effects on motor cortex excitability and intracortical inhibition, whereas cTBS exerted opposite effects. Twenty-seven percent of individuals exhibited enhanced motor cortical plasticity after iTBS, whereas 63% of participants showed enhanced plasticity after cTBS. In addition, the amount of TBS-induced plasticity was correlated with the intracortical excitability and the variability of the motor evoked potential prior to TBS. Our study demonstrated the high variability of the iTBS-induced lower-limb motor cortical plasticity, which was affected by the sensitivity of intracortical interneuronal circuits. These findings provide further insights into the variation of the response to TBS according to the anatomy of the stimulated brain region and the excitability of the intracortical circuit.

Does the balance strategy during walking in elderly persons show an association with fall risk assessment?

The primary objective of this study was to clarify whether balance evaluation during walking in elderly people was related to fall risk assessment; the second objective was to clarify the difference in balance strategy between young and elderly people based on the balance evaluation through a gait cycle. Thirty healthy young adults and 25 healthy elderly adults participated. All participants performed walking at their preferred speed and at a fast speed. Based on the margin of stability (MoS), balance during a gait cycle was divided into medial/lateral and anterior/posterior direction (ML/AP-MoS). Positive/negative integral values of ML-MoS were defined as ML-MoSPOS/ML-MoSNEG, and the average of AP-MoS over the gait cycle was defined as AP-MoSmean. The fast/preferred ratio of AP-MoSmean/ML-MoSPOS (AP-MoSmean (Fast/Preferred)/ML-MoSPOS (Fast/Preferred)) and the fast-preferred difference of ML-MoSNEG (ML-MoSNEG (Fast-Preferred)) were compared between groups. ML/AP-MoS at the preferred/fast gait was also compared between 12 gait events and groups. The Japanese version of the Mini-Balance Evaluation Systems Test (J-Mini-BESTest), the Japanese version of the Activities-specific Balance Confidence Scale (J-ABC scale), and the number of falls in the past year were obtained from all subjects. ML-MoSPOS (Fast/Preferred), ML-MoSNEG (Fast-Preferred), and AP-MoSmean (Fast/Preferred) were significantly correlated with J-Mini-BESTest. Gait balance evaluation based on MoS may reflect an individual's balance function. In fast gait, ML-MoS at foot flat and toe off and AP-MoS at just before heel strike were highly likely to be gait events to identify elderly adults with balance disorders.