Repetitive transcranial magnetic stimulation focusing on patients with neuropathic pain in the upper limb: a randomized sham-controlled parallel trial.

This study aimed to evaluate the efficacy and safety of navigation-guided repetitive transcranial magnetic stimulation (rTMS) over the primary motor cortex in patients with neuropathic pain in the upper limb. This randomized, blinded, sham-controlled, parallel trial included a rTMS protocol (10-Hz, 2000 pulses/session) consisting of five daily sessions, followed by one session per week for the next seven weeks. Pain intensity, as well as pain-related disability, quality of life, and psychological status, were assessed. For the primary outcome, pain intensity was measured daily using a numerical rating scale as a pain diary. Thirty patients were randomly assigned to the active rTMS or sham-stimulation groups. In the primary outcome, the decrease (least square [LS] mean ± standard error) in the weekly average of a pain diary at week 9 compared to the baseline was 0.84 ± 0.31 in the active rTMS group and 0.58 ± 0.29 in the sham group (LS mean difference, 0.26; 95% confidence interval, - 0.60 to 1.13). There was no significant effect on the interaction between the treatment group and time point. Pain-related disability score improved, but other assessments showed no differences. No serious adverse events were observed. This study did not show significant pain relief; however, active rTMS tended to provide better results than sham. rTMS has the potential to improve pain-related disability in addition to pain relief.Clinical Trial Registration number: jRCTs052190110 (20/02/2020).

The Neurorehabilitation of Neurological Movement Disorders Requires Rigorous and Sustained Research.

Movement disorders that stem from neurological conditions such as stroke, cerebral palsy, multiple sclerosis (MS), Parkinson's disease (PD), and spinocerebellar degeneration (SCD) can significantly impair a person's activities of daily living (ADL) [...].

Excessive excitability of inhibitory cortical circuit and disturbance of ballistic targeting movement in degenerative cerebellar ataxia.

This study aimed to investigate abnormalities in inhibitory cortical excitability and motor control during ballistic-targeting movements in individuals with degenerative cerebellar ataxia (DCA). Sixteen participants took part in the study (DCA group [n = 8] and healthy group [n = 8]). The resting motor-threshold and cortical silent period (cSP) were measured in the right-hand muscle using transcranial magnetic stimulation over the left primary motor cortex. Moreover, the performance of the ballistic-targeting task with right wrist movements was measured. The Scale for the Assessment and Rating of Ataxia was used to evaluate the severity of ataxia. The results indicated that the cSP was significantly longer in participants with DCA compared to that in healthy controls. However, there was no correlation between cSP and severity of ataxia. Furthermore, cSP was linked to the ballistic-targeting task performance in healthy participants but not in participants with DCA. These findings suggest that there is excessive activity in the gamma-aminobutyric acid-mediated cortical inhibitory circuit in individuals with DCA. However, this increase in inhibitory activity not only fails to contribute to the control of ballistic-targeting movement but also shows no correlation with the severity of ataxia. These imply that increased excitability in inhibitory cortical circuits in the DCA may not contribute the motor control as much as it does in healthy older adults under limitations associated with a small sample size. The study's results contribute to our understanding of motor control abnormalities in people with DCA and provide potential evidence for further research in this area.

Effects of non-invasive brain stimulation for degenerative cerebellar ataxia: a protocol for a systematic review and meta-analysis.

INTRODUCTION: To date, the medical and rehabilitation needs of people with degenerative cerebellar ataxia (DCA) are not fully met because no curative treatment has yet been established. Movement disorders such as cerebellar ataxia and balance and gait disturbance are common symptoms of DCA. Recently, non-invasive brain stimulation (NIBS) techniques, including repetitive transcranial magnetic stimulation and transcranial electrical stimulation, have been reported as possible intervention methods to improve cerebellar ataxia. However, evidence of the effects of NIBS on cerebellar ataxia, gait ability, and activity of daily living is insufficient. This study will aim to systematically evaluate the clinical effects of NIBS on patients with DCA. METHODS AND ANALYSIS: We will conduct a preregistered systematic review and meta-analysis based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. We will include randomised controlled trials to assess the effects of NIBS on patients with DCA. The primary clinical outcome will be cerebellar ataxia, as measured by the Scale for Assessment and Rating of Ataxia and the International Cooperative Ataxia Rating Scale. The secondary outcomes will include gait speed, functional ambulatory capacity and functional independence measure, as well as any other reported outcomes that the reviewer considers important. The following databases will be searched: PubMed, Cochrane Central Register of Controlled Trials, CINAHL and PEDro. We will assess the strength of the evidence included in the studies and estimate the effects of NIBS. ETHICS AND DISSEMINATION: Because of the nature of systematic reviews, no ethical issues are anticipated. This systematic review will provide evidence on the effects of NIBS in patients with DCA. The findings of this review are expected to contribute to clinical decision-making towards selecting NIBS techniques for treatment and generating new clinical questions to be addressed. PROSPERO REGISTRATION NUMBER: CRD42023379192.

Cerebellar TMS Induces Motor Responses Mediating Modulation of Spinal Excitability: A Literature Review.

Since individuals with cerebellar lesions often exhibit hypotonia, the cerebellum may contribute to the regulation of muscle tone and spinal motoneuron pool excitability. Neurophysiological methods using transcranial magnetic stimulation (TMS) of the cerebellum have been recently proposed for testing the role of the cerebellum in spinal excitability. Under specific conditions, single-pulse TMS administered to the cerebellar hemisphere or vermis elicits a long-latency motor response in the upper or lower limb muscles and facilitates the H-reflex of the soleus muscle, indicating increased excitability of the spinal motoneuron pool. This literature review examined the methods and mechanisms by which cerebellar TMS modulates spinal excitability.

Usefulness of the Cognitive Composition Test as an Early Discriminator of Mild Cognitive Impairment.

Mild cognitive impairment (MCI) is the preliminary stage of dementia, which is a serious social problem worldwide. This study aimed to investigate whether the Cognitive Composition Test (CCT) is effective for the early diagnosis of MCI. A total of 104 older adults underwent the Montreal Cognitive Assessment (MoCA), the Mini-Mental State Examination (MMSE), the Trail Making Test Parts A (TMT-A) and B (TMT-B), and our newly prototyped cognitive composition test (CCT). We created three types of CCT (CCT-A, CCT-B, and CCT-C) with different degrees of difficulty. First, we examined the concurrent validity of CCT-A, CCT-B, and CCT-C with the MoCA, MMSE, TMT-A, and TMT-B. All participants were classified into the healthy control (HC) and MCI groups based on their scores in the Japanese versions of the MoCA and MMSE. The HC and MCI groups were compared using the TMT-A, TMT-B, CCT-A, CCT-B, and CCT-C. Finally, we examined the sensitivity for discrimination of CCT-C. CCT-C had a higher discrimination sensitivity than TMT-A, TMT-B, CCT-A, and CCT-B, with a cut-off value of 65.75 s, a sensitivity level of 0.844, and a specificity of 0.776. It may be a useful screening tool for the early diagnosis of the early-stages of dementia, such as MCI, in asymptomatic older adults.

Impact of Repetitive Transcranial Magnetic Stimulation to the Cerebellum on Performance of a Ballistic Targeting Movement.

This study aimed to investigate the effects of repetitive transcranial magnetic stimulation (rTMS) of the cerebellum on changes in motor performance during a series of repetitive ballistic-targeting tasks. Twenty-two healthy young adults (n = 12 in the active-rTMS group and n = 10 in the sham rTMS group) participated in this study. The participants sat on a chair in front of a monitor and fixed their right forearms to a manipulandum. They manipulated the handle with the flexion/extension of the wrist to move the bar on the monitor. Immediately after a beep sound was played, the participant moved the bar as quickly as possible to the target line. After the first 10 repetitions of the ballistic-targeting task, active or sham rTMS (1 Hz, 900 pulses) was applied to the right cerebellum. Subsequently, five sets of 100 repetitions of this task were conducted. Participants in the sham rTMS group showed improved reaction time, movement time, maximum velocity of movement, and targeting error after repetition. However, improvements were inhibited in the active-rTMS group. Low-frequency cerebellar rTMS may disrupt motor learning during repetitive ballistic-targeting tasks. This supports the hypothesis that the cerebellum contributes to motor learning and motor-error correction in ballistic-targeting movements.

Randomized, sham-controlled, clinical trial of repetitive transcranial magnetic stimulation for patients with Alzheimer's dementia in Japan.

Background: Several medications have been applied to Alzheimer's dementia patients (AD) but their efficacies have been insufficient. The efficacy and safety of 4 weeks of repetitive transcranial magnetic stimulation (rTMS) in Japanese AD were evaluated in this exploratory clinical trial. Methods: Forty-two patients, aged 60-93 years (average, 76.4 years), who were taking medication (> 6 months) and had Mini-Mental State Examination (MMSE) scores ≤ 25 and Clinical Dementia Rating Scale scores (CDR-J) of 1 or 2, were enrolled in this single-center, prospective, randomized, three-arm study [i.e., 120% resting motor threshold (120% RMT), 90% RMT for the bilateral dorsolateral prefrontal cortex, and Sham]. Alzheimer's Disease Assessment Scale-Japanese Cognitive (ADAS-J cog), Montreal Cognitive Assessment (MoCA-J), Clinical Global Impression of Change (CGIC), Neuropsychiatric inventory (NPI), and EuroQOL 5 Dimensions 5-Level (EQ-5D-5L) were administered. The primary endpoint was the mean change from baseline in the MMSE score (week 4). An active rTMS session involved applying 15 trains bilaterally (40 pulses/train at 10 Hz; intertrain interval, 26 s). Participants received ≥ 8 interventions within the first 2 weeks and at least one intervention weekly in the 3rd and 4th weeks. Full Analysis set (FAS) included 40 patients [120% RMT (n = 15), 90% RMT (n = 13), and Sham (n = 12)]. Results: In the FAS, MMSE, ADAS-J cog, MoCA-J, CDR-J, CGIC, NPI, and EQ-5D-5L scores between the three groups were not significantly different. Two patients were erroneously switched between the 120% RMT and 90% RMT groups, therefore, "as treated" patients were mainly analyzed. Post hoc analysis revealed significant treatment efficacy in participants with MMSE scores ≥ 15, favoring the 120% RMT group over the Sham group. Responder analysis revealed 41.7% of the 120% RMT group had a ≥ 3-point improvement in the ADAS-J cog versus 0% in the Sham group (Fisher's exact test, p = 0.045). The MoCA-J showed the same tendency but was not significant. Efficacy disappeared in week 20, based on the ADAS-cog and MoCA-J. No intervention-related serious adverse events occurred. Conclusion: This paper is the first report of using rTMS in Japanese AD patients. The treatment seems safe and moderate-mild stage AD should be target population of pivotal clinical trial with 120% RMT rTMS.

Cerebellar repetitive transcranial magnetic stimulation modulates the motor learning of visually guided voluntary postural control task.

We investigated whether vermal cerebellar low-frequency repetitive transcranial magnetic stimulation (crTMS) affects motor learning of visually guided postural tracking training (VTT) using foot center of pressure (COP) as well as the stability and sensory contribution of upright standing. Twenty-one healthy volunteers participated (10 in the sham-crTMS group and 11 in the active-crTMS group). For VTT, participants stood on the force plate 1.5 m from the monitor on which the COP and target moved in a circle. Participants tracked the target with their own COP for 1 min, and 10 VTT sessions were conducted. The tracking error (TE) was compared between trials. Active- or sham-crTMS sessions were conducted prior to VTT. At baseline (before crTMS), pre-VTT (after crTMS), and post-VTT, the COP trajectory during upright static standing under four conditions (eyes, open/closed; surface, hard/rubber) was recorded. Comparison of the length of the COP trajectory or path and sensory-contribution-rate showed no significant difference between baseline and pre- and post-VTT. There was a significant decrease in TE in the sham-crTMS but not in the active-crTMS group. VTT and crTMS did not immediately affect the stability and sensory contribution of upright standing; however, crTMS immediately affected motor learning. The vermal cerebellum may contribute to motor learning of voluntary postural control.

Eye Position Shifts Body Sway Under Foot Dominance Bias in the Absence of Visual Feedback.

Purpose: The purpose of this study was to investigate whether information on extraocular muscle proprioception without visual information affects postural control. Methods: Thirty-five healthy young volunteers participated in the study. Postural control outcomes included the center of pressure (CoP) for static standing, the total length of the sway of the CoP (LNG), and the sway area (SA), as well as the mean CoP in the mediolateral and anteroposterior directions. The following five eye-fixing positions were used: eye-up (E-Up), eye-down (E-Down), eye-right (E-Right), eye-left (E-Left), and eye-center (Center eye position). One-way ANOVA and Bonferroni correction was performed for statistical processing. Electrooculograms were recorded to detect eye orientation errors, measured with the eyes closed. Results: The results of this study showed no significant difference between the LNG and SA results when comparing respective eye positions (E-up, E-down, E-right, E-left) relative to E-Center (control). However, the average CoP was shifted to the right at E-Up, E-Down, and E-Left. Conclusion: These findings indicate that postural control may be affected by eye-body coordination depending on the position of the eyes, even without visual information.

Vestibulo-Ocular Reflex Is Modulated by Noisy Galvanic Vestibular Stimulation.

We investigated whether noisy galvanic vestibular stimulation (nGVS) modulates the vestibulo-ocular reflex (VOR) and whether this effect is correlated with the effect of nGVS on body sway. Thirty healthy young adults participated. The video head impulse test (vHIT) was used to estimate the ratio of eye motion velocity/head motion velocity to VOR-gain. The gain 60 ms after the start of head motion (VOR-gain-60 ms) and regression slope (RS) (i.e., gain in eye and head motion; VOR-gain-RS) were calculated. The total path length of the foot center of pressure (COP-TL) during upright standing was calculated to estimate body sway. Noisy Galvanic Vestibular Stimulation at 0.2, 0.6, 1.2 mA, or sham stimulation (direct current: 0 mA) was delivered to the bilateral mastoid process in random order during vHIT and COP measurements. Application of nGVS at 0.2 mA significantly reduced VOR-gain-RS, while application of nGVS at 0.6 mA significantly increased COP-TL. Vestibulo-ocular reflex-gain-60 ms differed significantly between 0.2 and 1.2 mA. There was no significant correlation between COP-TL and VOR-related parameters. These findings suggest that nGVS at 0.2 mA inhibits the VOR, while nGVS at 0.6 mA increases body sway during upright standing, although there may be no relationship between the respective effects in healthy individuals.

Exploratory study of optimal parameters of repetitive transcranial magnetic stimulation for neuropathic pain in the lower extremities.

INTRODUCTION: Pain relief from repetitive transcranial magnetic stimulation (rTMS) over the primary motor cortex (M1) is particularly poor in patients with leg pain. The optimal parameters for relieving leg pain remain poorly understood. The purpose of this study was to explore the optimal stimulation parameters of M1-rTMS for patients with leg pain. METHODS: Eleven patients with neuropathic pain in the leg randomly underwent 6 conditions of M1-rTMS with different stimulation intensities, sites, and coil directions, including sham stimulation. The 5 active conditions were as follows: 90% or 110% of the resting motor threshold (RMT) on the M1 hand with an anteroposterior coil direction, 90% or 110% RMT on the M1 foot in the anteroposterior direction, and 90% RMT on the M1 foot in the mediolateral direction. Each condition was administered for 3 days. Pain intensity was evaluated using the Visual Analogue Scale and Short-Form McGill Pain Questionnaire 2 at baseline and up to 7 days after each intervention. RESULTS: Visual Analogue Scale scores were significantly reduced after the following active rTMS conditions: 90% RMT on the M1 hand, 90% RMT on the M1 foot with any coil direction, and 110% RMT on the M1 foot. The Short-Form McGill Pain Questionnaire 2 results were similar to those obtained using the Visual Analogue Scale. The analgesic effect of rTMS with stimulus intensity above the RMT was not superior to that below the RMT. CONCLUSION: We suggest that the optimal stimulation parameters of rTMS for patients with neuropathic pain in the leg may target the M1 foot or M1 hand with an intensity below the RMT.

Sensory Nerve Conduction Velocity Predicts Improvement of Hand Function with Nerve Gliding Exercise Following Carpal Tunnel Release Surgery.

This study aims to investigate the effects of nerve gliding exercise following carpal tunnel release surgery (NGE-CTRS) and the probing factors affecting the effect of NGE-CTRS on hand function. A total of 86 patients after CTRS participated. Grip strength (grip-s), pinch strength (pinch-s), Semmes-Weinstein monofilament test (SWMT), two-point discrimination (2PD), numbness, pain, and Phalen test (Phalen) were measured and compared between pre- and post-NGE-CTRS. The results showed that the combination of surgery and NGE significantly improved the postoperative grip-s, pinch-s, SWMT, 2PD, numbness, and Phalen; however, no improvement was observed in pain. Background factors that influenced the improved grip-s and pinch-s included gender and preoperative sensory nerve conduction velocity (SCV). Additionally, numbness and Phalen were not affected by age, gender, fault side, bilateral, trigger finger, dialysis, thenar eminence atrophy, motor nerve conduction velocity, SCV, the start of treatment, and occupational therapy intervention. In conclusion, the combination of surgical procedures and NGE showed a high improvement. SCV and time-to-start treatment of intervention for carpal tunnel syndrome may be useful in predicting the function after the intervention.

Effect of Increased Flexor Hallucis Longus Muscle Activity on Ground Reaction Force during Landing.

Repeated high-impact ground forces can lead to injury and decreased performance. While increasing flexor hallucis longus (FHL) muscle activity is known to increase stiffness and elasticity, it is unknown if this also decreases ground reaction forces by shock absorption during landing. This study aimed to determine whether increasing FHL muscle activity affects ground reaction force during landing in healthy subjects. Eight subjects performed single-leg steps onto a force platform for five trials, with and without flexion of the metatarsophalangeal (MTP) joint at the moment of landing. Integrated surface electromyography (sEMG) of the FHL and medial gastrocnemius (MG) and ground reaction forces (GRFs) were measured. sEMG and GRF during the 50 ms before and 100 ms following initial ground contact were analyzed and compared. Flexion of the MTP joint condition significantly decreased the vertical and mediolateral force peaks of GRF, and FHL muscle activity increased. Flexion of the MTP joint at the moment of landing reduces GRF in healthy subjects through force dissipation in the foot, by increased FHL muscle activity. The results suggest that this may contribute to injury prevention by reducing the impact force through flexing the MTP joint at the moment of landing.

No Impact of Stochastic Galvanic Vestibular Stimulation on Arterial Pressure and Heart Rate Variability in the Elderly Population.

OBJECTIVE: Noisy galvanic vestibular stimulation (nGVS) is often used to improve postural stability in disorders, such as neurorehabilitation montage. For the safe use of nGVS, we investigated whether arterial pressure (AP) and heart rate vary during static supine and slow whole-body tilt with random nGVS (0.4 mA, 0.1-640 Hz, gaussian distribution) in a healthy elderly population. METHODS: This study was conducted with a double-blind, sham-controlled, cross-over design. Seventeen healthy older adults were recruited. They were asked to maintain a static supine position on a bed for 10 min, and the bed was tilted up (TU) to 70 degrees within 30 s. After maintaining this position for 3 min, the bed was passively tilted down (TD) within 30 s. Real-nGVS or sham-nGVS was applied from 4 to 15 min. The time course of mean arterial pressure (MAP) and RR interval variability (RRIV) were analyzed to estimate the autonomic nervous activity. RESULT: nGVS and/or time, including pre-/post-event (nGVS-start, TU, and TD), had no impact on MAP and RRIV-related parameters. Further, there was no evidence supporting the argument that nGVS induces pain, vertigo/dizziness, and uncomfortable feeling. CONCLUSION: nGVS may not affect the AP and RRIV during static position and whole-body tilting or cause pain, vertigo/dizziness, and discomfort in the elderly.

Premature oral pre-shaping for feeding in elderly population with risk of aspiration pneumonia.

The aim of this study was to determine the abnormal hand and mouth behavior before actual swallowing for eating in elderly people with high risk of aspiration pneumonia. Ten elderly people with a diagnosis of aspiration pneumonia (EAP), 15 healthy elderly (HE) people, and 21 young adults (YA) were enrolled. The feeding time and the timing of the maximum distance between the upper and lower lips were extracted using a motion analyzer during self-feeding and assisted-feeding. The results showed that feeding time in EAP was significantly longer than that for the other groups in self- and assisted-feeding. In self-feeding, the timing of mouth-preparation in the EAP group was significantly earlier than that in the other groups; conversely, in assisted-feeding, the timing in EAP was significantly delayed. Our results indicate that abnormal preparation of mouth-shape and movement time of hand before actual swallowing in both self- and assisted-feeding may exist in elderly people with previous experience of aspiration pneumonia.

The Effects of Stochastic Galvanic Vestibular Stimulation on Body Sway and Muscle Activity.

Objective: This study aimed to investigate whether galvanic vestibular stimulation with stochastic noise (nGVS) modulates the body sway and muscle activity of the lower limbs, depending on visual and somatosensory information from the foot using rubber-foam. Methods: Seventeen healthy young adults participated in the study. Each subject maintained an upright standing position on a force plate with/without rubber-foam, with their eyes open/closed, to measure the position of their foot center of pressure. Thirty minutes after baseline measurements under four possible conditions (eyes open/closed with/without rubber-foam) performed without nGVS (intensity: 1 mA, duration: 40 s), the stimulation trials (sham-nGVS/real-nGVS) were conducted under the same conditions in random order, which were then repeated a week or more later. The total center of pressure (COP) path length movement (COP-TL) and COP movement velocity in the mediolateral (Vel-ML) and anteroposterior (Vel-AP) directions were recorded for 30 s during nGVS. Furthermore, electromyography activity of the right tibial anterior muscle and soleus muscle was recorded for the same time and analyzed. Results: Three-way analysis of variance and post-hoc multiple comparison revealed a significant increment in COP-related parameters by nGVS, and a significant increment in soleus muscle activity on rubber. There was no significant effect of eye condition on any parameter. Conclusions: During nGVS (1 mA), body sway and muscle activity in the lower limb may be increased depending not on the visual condition, but on the foot somatosensory condition.