Strengthening the GABAergic System Through Neurofeedback Training Suppresses Implicit Motor Learning.

Gamma-aminobutyric acid (GABA) activity within the primary motor cortex (M1) is essential for motor learning in cortical plasticity, and a recent study has suggested that real-time neurofeedback training (NFT) can self-regulate GABA activity. Therefore, this study aimed to investigate the effect of GABA activity strengthening via NFT on subsequent motor learning. Thirty-six healthy participants were randomly assigned to either an NFT group or control group, which received sham feedback. GABA activity was assessed for short intracortical inhibition (SICI) within the right M1 using paired-pulse transcranial magnetic stimulation. During the NFT intervention period, the participants tried to modulate the size of a circle, which was altered according to the degree of SICI in the NFT group. However, the size was altered independently of the degree of SICI in the control group. We measured the reaction time before, after (online learning), and 24 h after (offline learning) the finger-tapping task. Results showed the strengthening of GABA activity induced by the NFT intervention, and the suppression of the online but not the offline learning. These findings suggest that prior GABA activity modulation may affect online motor learning.

The effects of combined static and dynamic stretching of anti-gravitational muscles on body flexibility and standing balance: A preliminary study of healthy young participants.

INTRODUCTION: Falling is a leading cause of injury-related death. Previous studies reported that an impairment of standing balance is one of the causative factors associated with falling. The combined use of static and dynamic stretching has been reported as a treatment method for improving standing balance. As one of the combined methods, stretching based on Mézières' concept, which has an efficacy on the improvement of body flexibility, has been used. However, it is not fully clear whether stretching based on Mézières' concept can improve standing balance. This study aimed to examine the effects of combined method of static and dynamic stretching of anti-gravitational muscles based on Mézières' concept on body flexibility and standing balance. METHODS: This study employed a quasi-randomized controlled trial design. Thirteen subjects were assigned randomly to one of two groups: stretching or control. A sit and reach test (SRT), functional reach test (FRT), and total trajectory length of center of pressure (COP) during static standing were assessed at pre- and post-intervention. An independent t-test was used to compare the rate of improvement between both groups at each assessment. RESULTS: The stretching group demonstrated a significantly larger rate of improvement in the total trajectory length of COP compared to the control group. In the SRT and FRT, the stretching group showed a trend toward improvement compared to the control group, but did not achieve statistical significance. CONCLUSIONS: The combined use of static and dynamic stretching of anti-gravitational muscles might have the potential to improve the standing balance.

Effect of electrical stimulation of antagonist muscles for voluntary motor drive.

Voluntary motor drive is an important central command that descends via the corticospinal tract to initiate muscle contraction. When electrical stimulation (ES) is applied to an antagonist or agonist muscle, it changes the agonist muscle's representative motor cortex and thus its voluntary motor drive. In this study, we used a reaction time task to compare the effects of weak and strong ES of the antagonist or agonist muscle during the premotor period of a wrist extension. We recorded motor evoked potentials (MEPs) induced by transcranial magnetic stimulation (TMS) that was applied to the extensor carpi radialis (ECR; agonist) and flexor carpi radialis (FCR; antagonist). When stronger ES intensities were applied to the antagonist, the MEP control ratio in the ECR significantly increased during the premotor time. Furthermore, the MEP control ratio with stronger antagonist ES intensity was significantly larger than that in the agonist for the same ES intensity. In the FCR, the MEP control ratio was also significantly greater at the strong ES intensity than at the weak ES intensity. Furthermore, the MEP control ratio in the antagonist with a strong ES intensity was significantly larger than that in the agonist with the same ES intensity. These results suggest that agonist corticomotor excitability might be enhanced by ES of the antagonist, which in turn strongly activates the descending motor system in the preparation of agonist contraction.

Real-time changes in corticospinal excitability related to motor imagery of a force control task.

OBJECTIVE: To investigate real-time excitability changes in corticospinal pathways related to motor imagery in a changing force control task, using transcranial magnetic stimulation (TMS). METHODS: Ten healthy volunteers learnt to control the contractile force of isometric right wrist dorsiflexion in order to track an on-screen sine wave form. Participants performed the trained task 40 times with actual muscle contraction in order to construct the motor image. They were then instructed to execute the task without actual muscle contraction, but by imagining contraction of the right wrist in dorsiflexion. Motor evoked potentials (MEPs), induced by TMS in the right extensor carpi radialis muscle (ECR) and flexor carpi radialis muscle (FCR), were measured during motor imagery. MEPs were induced at five time points: prior to imagery, during the gradual generation of the imaged wrist dorsiflexion (Increasing phase), the peak value of the sine wave, during the gradual reduction (Decreasing phase), and after completion of the task. The MEP ratio, as the ratio of imaged MEPs to resting-state, was compared between pre- and post-training at each time point. RESULTS: In the ECR muscle, the MEP ratio significantly increased during the Increasing phase and at the peak force of dorsiflexion imagery after training. Moreover, the MEP ratio was significantly greater in the Increasing phase than in the Decreasing phase. In the FCR, there were no significant consistent changes. CONCLUSION: Corticospinal excitability during motor imagery in an isometric contraction task was modulated in relation to the phase of force control after image construction.

Influence of transcutaneous electrical nerve stimulation conditions on disynaptic reciprocal Ia inhibition and presynaptic inhibition in healthy adults.

This study investigated the influence of stimulus conditions of transcutaneous electrical nerve stimulation (TENS) on disynaptic reciprocal Ia inhibition (RI) and presynaptic inhibition (D1 inhibition) in healthy adults. Eight healthy participants received TENS (stimulus frequencies of 50, 100, and 200 Hz) over the deep peroneal nerve and tibialis anterior (TA) muscle in the resting condition for 30 min. At pre- and post-intervention, the RI from the TA to the soleus (SOL) and D1 inhibition of the SOL alpha motor neuron were assessed by evoked electromyography. The results showed that RI was not changed by TENS at any stimulus frequency condition. Conversely, D1 inhibition was significantly changed by TENS regardless of the stimulus frequency. The present results and previous studies pertaining to RI suggest that the resting condition might strongly influence the lack of pre- vs. post-intervention change in the RI. Regarding the D1 inhibition, the present results suggest that the effect of TENS might be caused by post-tetanic potentiation. The knowledge gained from the present study might contribute to a better understanding of fundamental studies of TENS in healthy adults and its clinical application for stroke survivors.

Effect of neuromuscular electrical stimulation on motor cortex excitability upon release of tonic muscle contraction.

The aim of the present study was to investigate the neurophysiological triggers underlying muscle relaxation from the contracted state, and to examine the mechanisms involved in this process and their subsequent modification by neuromuscular electrical stimulation (NMES). Single-pulse transcranial magnetic stimulation (TMS) was used to produce motor-evoked potentials (MEPs) and short-interval intracortical inhibition (SICI) in 23 healthy participants, wherein motor cortex excitability was examined at the onset of voluntary muscle relaxation following a period of voluntary tonic muscle contraction. In addition, the effects of afferent input on motor cortex excitability, as produced by NMES during muscle contraction, were examined. In particular, two NMES intensities were used for analysis: 1.2 times the sensory threshold and 1.2 times the motor threshold (MT). Participants were directed to execute constant wrist extensions and to release muscle contraction in response to an auditory "GO" signal. MEPs were recorded from the flexor carpi radialis (FCR) and extensor carpi radialis (ECR) muscles, and TMS was applied at three different time intervals (30, 60, and 90 ms) after the "GO" signal. Motor cortex excitability was greater during voluntary ECR and FCR relaxation using high-intensity NMES, and relaxation time was decreased. Each parameter differed significantly between 30 and 60 ms. Moreover, in both muscles, SICI was larger in the presence than in the absence of NMES. Therefore, the present findings suggest that terminating a muscle contraction triggers transient neurophysiological mechanisms that facilitate the NMES-induced modulation of cortical motor excitability in the period prior to muscle relaxation. High-intensity NMES might facilitate motor cortical excitability as a function of increased inhibitory intracortical activity, and therefore serve as a transient trigger for the relaxation of prime mover muscles in a therapeutic context.

Preparatory state and postural adjustment strategies for choice reaction step initiation.

A loud auditory stimulus (LAS) presented simultaneously with a visual imperative stimulus can reduce reaction time (RT) by automatically triggering a movement prepared in the brain and has been used to investigate a movement preparation. It is still under debate whether or not a response is prepared in advance in RT tasks involving choice responses. The purpose of the present study was to investigate the preparatory state of anticipatory postural adjustments (APAs) during a choice reaction step initiation. Thirteen young adults were asked to step forward in response to a visual imperative stimulus in two choice stepping conditions: (i) the responding side is not known and must be selected and (ii) the responding side is known but whether to initiate or inhibit a step response must be selected. LAS was presented randomly and simultaneously with the visual imperative stimulus. LAS significantly increased the occurrence rates of inappropriately initiated APAs while reducing the RTs of correct and incorrect trials in both task conditions, demonstrating that LAS triggered the prepared APA automatically. This observation suggests that APAs are prepared in advance and withheld from release until the appropriate timing during a choice reaction step initiation. The preparatory activity of APAs might be modulated by the inhibitory activity required by the choice tasks. The preparation strategy may be chosen for fast responses and is judged most suitable to comply with the tasks because inappropriately initiated APAs can be corrected without making complete stepping errors.

Modulation of spinal inhibitory reflexes depends on the frequency of transcutaneous electrical nerve stimulation in spastic stroke survivors.

Neurophysiological studies in healthy subjects suggest that increased spinal inhibitory reflexes from the tibialis anterior (TA) muscle to the soleus (SOL) muscle might contribute to decreased spasticity. While 50 Hz is an effective frequency for transcutaneous electrical nerve stimulation (TENS) in healthy subjects, in stroke survivors, the effects of TENS on spinal reflex circuits and its appropriate frequency are not well known. We examined the effects of different frequencies of TENS on spinal inhibitory reflexes from the TA to SOL muscle in stroke survivors. Twenty chronic stroke survivors with ankle plantar flexor spasticity received 50-, 100-, or 200-Hz TENS over the deep peroneal nerve (DPN) of the affected lower limb for 30 min. Before and immediately after TENS, reciprocal Ia inhibition (RI) and presynaptic inhibition of the SOL alpha motor neuron (D1 inhibition) were assessed by adjusting the unconditioned H-reflex amplitude. Furthermore, during TENS, the time courses of spinal excitability and spinal inhibitory reflexes were assessed via the H-reflex, RI, and D1 inhibition. None of the TENS protocols affected mean RI, whereas D1 inhibition improved significantly following 200-Hz TENS. In a time-series comparison during TENS, repeated stimulation did not produce significant changes in the H-reflex, RI, or D1 inhibition regardless of frequency. These results suggest that the frequency-dependent effect of TENS on spinal reflexes only becomes apparent when RI and D1 inhibition are measured by adjusting the amplitude of the unconditioned H-reflex. However, 200-Hz TENS led to plasticity of synaptic transmission from the antagonist to spastic muscles in stroke survivors.

NMES with rTMS for moderate to severe dysfunction after stroke.

BACKGROUND: Motor dysfunction after stroke might be improved by neuromuscular electrical stimulation (NMES) combined with 1 Hz repetitive transcranial magnetic stimulation (rTMS) in patients with moderate and severe motor dysfunction. OBJECTIVE: This preliminary study tested the effect of this treatment combination. METHODS: Fifteen patients (60.5 ± 10.3 years old) participated in the study. All patients had been affected by cerebral artery infarction or hemorrhage and had moderate or severe motor dysfunction in their affected hand. The patients received NMES at paretic wrist extensor muscles combined with rTMS over the unaffected M1 hemisphere twice a day, six days/week over two weeks. All participants underwent the following battery of tests to evaluate the motor function of the affected hand: Upper limb Fugl-Meyer Assessment (UFMA), Wolf Motor Function Test (WMFT), and Box and Block Test (BBT). RESULTS: UFMA, WMFT, and BBT scores improved significantly after the study. CONCLUSIONS: These results suggest that NMES combined with rTMS could be useful for recovery of moderate and severe motor function after stroke.

Specifications of an electromyogram-driven neuromuscular stimulator for upper limb functional recovery.

An electromyogram (EMG)-driven neuromuscular stimulator for upper limb functional recovery (Muraoka et al., 1998) can stimulate target muscles in proportion to the amount of voluntary EMG of the identical target muscles. Furthermore, it can facilitate the contraction of paralyzed muscles by electrical stimulation at subthreshold intensity level. Although it has been suggested that to use the stimulator for as long a time as possible might be needed for more effective treatment, the utilization time was limited by the size of the stimulator, which involved a laptop personal computer. To use in daily life, the device was improved to be a smaller size of 95×65×40 mm (including batteries) which was equivalent to a mobile phone (in 2002). The stimulator was called the Integrated Volitional-control Electrical Stimulator (IVES). IVES has already been manufactured and its use has spread in Japan since 2008. Nowadays, therapy using IVES is an effective therapy to improve the motor function of the upper limb in post-stroke patients with hemiparesis. However, the signal processing and internal structure of IVES has not yet been reported. In this study the device specification of IVES is described, especially its electrical circuits and signal processing that detect voluntary EMG and stimulate from the same electrodes. IVES uses two DIACs for detecting voluntary EMG from stimulating electrodes. The DIACs switch passively between the stimulation circuit and the EMG amplifier circuit. Furthermore, the signal processing of the time-shifted difference of the 2-cycle EMG signal following identical stimulation pulses eliminates stimulation artifacts and evoked potentials, and extracts voluntary EMG.

Real-time changes in corticospinal excitability during voluntary contraction with concurrent electrical stimulation.

While previous studies have assessed changes in corticospinal excitability following voluntary contraction coupled with electrical stimulation (ES), we sought to examine, for the first time in the field, real-time changes in corticospinal excitability. We monitored motor evoked potentials (MEPs) elicited by transcranial magnetic stimulation and recorded the MEPs using a mechanomyogram, which is less susceptible to electrical artifacts. We assessed the MEPs at each level of muscle contraction of wrist flexion (0%, 5%, or 20% of maximum voluntary contraction) during voluntary wrist flexion (flexor carpi radialis (FCR) voluntary contraction), either with or without simultaneous low-frequency (10 Hz) ES of the median nerve that innervates the FCR. The stimulus intensity corresponded to 1.2 × perception threshold. In the FCR, voluntary contraction with median nerve stimulation significantly increased corticospinal excitability compared with FCR voluntary contraction without median nerve stimulation (p<0.01). In addition, corticospinal excitability was significantly modulated by the level of FCR voluntary contraction. In contrast, in the extensor carpi radialis (ECR), FCR voluntary contraction with median nerve stimulation significantly decreased corticospinal excitability compared with FCR voluntary contraction without median nerve stimulation (p<0.05). Thus, median nerve stimulation during FCR voluntary contraction induces reciprocal changes in cortical excitability in agonist and antagonist muscles. Finally we also showed that even mental imagery of FCR voluntary contraction with median nerve stimulation induced the same reciprocal changes in cortical excitability in agonist and antagonist muscles. Our results support the use of voluntary contraction coupled with ES in neurorehabilitation therapy for patients.

Functional plasticity of surround inhibition in the motor cortex during single finger contraction training.

We investigated the functional changes in short intracortical inhibitory (SICI) circuits to determine whether surround inhibition is altered during a simple finger movement training. Using an electromyographic (EMG) feedback system linked to a computer monitor, participants practiced sustained index finger abduction by 40% maximum voluntary contraction of the first dorsal interosseous (FDI) while decreasing overflow EMG activity of the abductor digiti minimi (ADM) to less than 5% maximum voluntary contraction. Single transcranial magnetic stimuli (TMS) and paired-pulse TMS were applied to the left primary motor cortex to elicit motor-evoked potentials (MEPs) in the right FDI and ADM before/after training. In addition to recording MEPs from both muscles during voluntary FDI contraction, MEPs were recorded during motor imagery. MEPs from the FDI were not altered by training, indicating no functional changes in SICI circuits associated with the FDI field. In contrast, SICI circuits associated with ADM were significantly strengthened by training, as indicated by reduced baseline EMG activity during both actual FDI contraction and motor imagery and by reduced MEPs in response to post-training TMS. We propose that SICI circuits show functional plasticity during motor training and that surround circuit inhibition of nontarget muscle groups increases in proportion to the acquisition of motor skills.

Immediate effects of electrical stimulation combined with passive locomotion-like movement on gait velocity and spasticity in persons with hemiparetic stroke: a randomized controlled study.

OBJECTIVE: Research to examine the immediate effects of electrical stimulation combined with passive locomotion-like movement on gait velocity and spasticity. DESIGN: A single-masked, randomized controlled trial design. SUBJECTS: Twenty-seven stroke inpatients in subacute phase (ischemic n = 16, hemorrhagic n = 11). INTERVENTIONS: A novel approach using electrical stimulation combined with passive locomotion-like movement. MAIN MEASURES: We assessed the maximum gait speed and modified Ashworth scale before and 20 minutes after the interventions. RESULTS: The gait velocity of the electrical stimulation combined with passive locomotion-like movement group showed the increase form 0.68 ± 0.28 (mean ± SD, unit: m) to 0.76 ± 0.32 after the intervention. Both the electrical stimulation group and passive locomotion-like movement group also showed increases after the interventions (from 0.76 ± 0.37 to 0.79 ± 0.40, from 0.74 ± 0.35 to 0.77 ± 0.36, respectively). The gait velocity of the electrical stimulation combined with passive locomotion-like movement group differed significantly from those of the other groups (electrical stimulation combined with passive locomotion-like movement versus electrical stimulation: P = 0.049, electrical stimulation combined with passive locomotion-like movement versus passive locomotion-like movement: P = 0.025). Although there was no statistically significant difference in the modified Ashworth scale among the three groups, six of the nine subjects (66.6%) in the electrical stimulation combined with passive locomotion-like movement group showed improvement in the modified Ashworth scale score, while only three of the nine subjects (33.3%) in the electrical stimulation group and two of the nine subjects (22.2%) improved in the passive locomotion-like movement group. CONCLUSION: These findings suggest electrical stimulation combined with passive locomotion-like movement could improve gait velocity in stroke patients.

Effects of integrated volitional control electrical stimulation (IVES) on upper extremity function in chronic stroke.

We evaluated the efficacy of a novel electromyogram (EMG)-controlled electrical stimulation system, called the integrated volitional control electrical stimulator (IVES), on the recovery of upper extremity motor functions in patients with chronic hemiparetic stroke. Ten participants in the chronic stage (more than 12 months post-stroke with partial paralysis of their wrist and fingers) received treatment with IVES to the extensor carpi radialis and extensor digitorum communis 6 h/day for 5 days. Before and after the intervention, participants were assessed using upper-extremity Fugl-Meyer motor assessment (FMA), the active range of motion (A-ROM), the nine-hole peg test (NHPT), and surface EMG recordings. The upper extremity FMA showed a statistically significant increase from 50.8 ± 5.8 to 56.8 ± 6.2 after the intervention (P < 0.01). The A-ROM of wrist extension was also significantly improved from 36.0° ± 15.4° to 45.0° ± 15.5° (P < 0.01). The NHPT significantly decreased from 85.3 ± 52.0 to 63.3 ± 29.7 (P = 0.04). EMG measurements demonstrated statistically significant improvements in the coactivation ratios for the wrist flexor and extensor muscles after the intervention. This study suggested that 5 days of IVES treatment yields a noticeable improvement in upper extremity motor functions in patients with chronic hemiparetic stroke.

Changes of excitability in M1 induced by neuromuscular electrical stimulation differ between presence and absence of voluntary drive.

The aim of this study is to investigate excitability changes in the human motor cortex induced by variable therapeutic electrical stimulations (TESs) with or without voluntary drive. We recorded motor-evoked potentials (MEPs) from extensor and flexor carpi radialis (FCR) muscles at rest and during FCR muscle contraction after the application of TES on FCR. TES application conditions were changed intensities, frequencies, and trains. In addition, to evaluate the contribution of M1 inhibitory circuits to the effects of TES application, we also recorded MEPs using paired-pulse transcranial magnetic stimulation. In resting muscle states, an increase in TES intensity resulted in an increase in MEP ratio in both the muscles. In contrast, when TES was applied to FCR during contraction, MEP ratios of both the muscles decreased with increased number of pulse trains. However, under both the states, MEP ratios decreased induced by paired-pulse transcranial magnetic stimulation in extensor carpi radialis to which TES was not applied. Excitability changes in M1 induced by TES application were reversibly modulated depending on the presence or absence of voluntary drive. This study showed that the therapy and the voluntary drive of the target muscles act together, and complement the effects of each other, which may be beneficial for optimizing the rehabilitation if the therapy accompanies voluntary drive.

Effects of transcutaneous electrical stimulation combined with locomotion-like movement in the treatment of post-stroke gait disorder: a single-case study. Short report.

PURPOSE: This study was designed to examine the effects of electrical stimulation combined with locomotion-like movement (ES/LM) for improving gait disorder in a stroke patient. METHOD: A four-phase ABAB single-subject design with five therapy sessions per phase was employed. In the intervention phases, transcutaneous electrical stimulation was applied to the tibialis anterior (at the end of the hip extension phase and in the initial hip flexion phase) and the soleus (in the initial hip extension phase) during passive hip flexion and extension. To assess improvement, the soleus H-reflex and the ambulatory function were measured (gait velocity and step length). RESULTS: Application of ES/LM resulted in a decrease of the soleus H-reflex and significant increase of gait velocity and step length. CONCLUSION: These findings suggest that ES/LM is a feasible treatment method for impaired ambulatory function in stroke patients at the subacute stage after the event.