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 relationship between body sway patterns and motor and attentional functions in early childhood.

[Purpose] We focused on the relationship between body sway patterns and motor and attentional functions in early childhood, and classified diagrams of body sway into four patterns. Furthermore, the relationship between physical fitness tests and Interactive Metronome (IM) tasks was used to determine whether the body sway patterns are indicators of motor and attentional functions in early childhood. [Participants and Methods] Participants were 24 male and 26 female children with a mean age of 2,148.1 ± 103.7 days. Participants were evaluated using physical fitness tests, body sway measures, baseline scores on the IM task (the "task average"), and the percentage of perfect hits ("Super Right On") on the IM task (the "Super Right On" score, or SRO%). [Results] The association between the body sway pattern and motor and attentional functions was examined, and results revealed that the body sway pattern was only slightly associated with motor functions. However, participants with an anterior-posterior pattern of body sway had worse timing and attentional functions than participants with other patterns, as indicated by a lower task average and SRO% on the IM task. [Conclusion] These results suggested that anterior-posterior sway may reflect attentional functions when body sway is measured in children such as 6 year-olds.

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.

Work beliefs and experiential learning among proficient physical therapists in Japan: developing a method to support belief formation.

[Purpose] This study aimed to elucidate the content of work beliefs related to proficiency among physical therapists in Japan. [Participants and Methods] Participants included 50 therapists who met the definition of proficiency to participate in a questionnaire survey conducted between October 2017 and March 2019. Participants were asked to freely describe their daily work beliefs, including their thoughts, values, and ideals. This content was coded and categorized using open coding; a hierarchical cluster analysis (Ward's method) was conducted of the proficient therapists with the individuals and belief categories as the variables. All belief categories were classified into three groups. [Results] Three work beliefs were identified as follows: 1) practices that emphasize building relationships in the field, 2) broad practices with physical therapist pride (responsibility and enthusiasm), and 3) practices with awareness of treatment outcomes and social benefits. [Conclusion] A better understanding of the three aforementioned work beliefs would facilitate good support for and development of physical therapists. We recommend continuing to elucidate the three work beliefs identified among proficient therapists and verify their educational effects.

Common Motor Drive Triggers Response of Prime Movers When Two Fingers Simultaneously Respond to a Cue.

This study investigated whether the motor execution process of one finger movement in response to a start cue is influenced by the participation of another finger movement and whether the process of the finger movement is dependent on the movement direction. The participants performed a simple reaction time (RT) task, the abduction or flexion of one (index or little finger) or two fingers (index and little fingers). The RT of the prime mover for the finger abduction was significantly longer than that for the flexion, indicating that the time taken for the motor execution of the finger response is dependent on the movement direction. The RT of the prime mover was prolonged when the abduction of another finger, whose RT was longer than the flexion, was added. This caused closer RTs between the prime movers for a two-finger response compared with the RTs for a one finger response. The absolute difference in the RT between the index and little finger responses became smaller when two fingers responded together compared with one finger response. Those results are well explained by a view that the common motor drive triggers the prime movers when two fingers move together in response to a start cue.

Processes of anticipatory postural adjustment and step movement of gait initiation.

The purpose of this study was to elucidate whether the anticipatory postural adjustment (APA) and focal step movement of gait initiation are produced as a single process or different processes and whether the APA receives an inhibitory drive from the ongoing stop process of gait initiation. Healthy humans initiated gait in response to a first visual cue that instructed the initial swing leg. In some trials, a switch or stop cue was also provided after the first cue. When the stop cue was provided, participants withheld gait initiation. When the switch cue was provided, participants immediately switched the initial swing leg. In both the stop and switch tasks, the APA in response to the first cue, represented by the S1 period of the displacement of the center of pressure, appeared in more than half of the trials in which the withholding of gait initiation or switching of the initial swing leg was successfully completed. These findings indicate that the APA and focal step movement of gait initiation are produced as a dual process. In trials in which the APA in response to the first cue appeared, the amplitude and duration of the APA were decreased when the participants switched the initial swing leg or withheld gait initiation. This finding indicates that the ongoing stop process of gait initiation produces an inhibitory drive over the APA. The decreases in the amplitude and duration of the APA during the switching of the initial swing leg were similar to those during the withholding of gait initiation; moreover, the decreases during the switching of the initial swing leg were positively correlated with the decreases during the withholding of gait initiation. Thus, the stop processes during switching the initial swing leg and withholding gait initiation likely share a common inhibitory mechanism over the APA.

The Effect of Monaural Auditory Stimulus on Hand Selection When Reaching.

This study investigated the effect of monaural auditory stimulus on hand selection when reaching. Healthy right-handed participants were asked to reach to a visual target and were free to use either the right or left hand. A visual target appeared at one of 11 positions in the visual field between -25 and 25 degrees of the horizontal visual angle. An auditory stimulus was given either in the left or right ear 100 ms after the presentation of the visual target, or no auditory stimulus was given. An auditory stimulus in the right ear increased right hand selection, and that in the left ear slightly increased left hand selection when reaching to a target around the midline of the visual field. The horizontal visual angle, where the probabilities of right hand selection and left hand selection were equal when reaching, shifted leftward when an auditory stimulus was given in the right ear, but the angle did not shift in either direction when an auditory stimulus was given in the left ear. The right-ear-dominant auditory stimulus effect on hand selection indicates hemispheric asymmetry of cortical activity for hand selection.

Interhemispheric Inhibition Induced by Transcranial Magnetic Stimulation Over Primary Sensory Cortex.

The present study investigated whether the long-interval interhemispheric inhibition (LIHI) is induced by the transcranial magnetic stimulation over the primary sensory area (S1-TMS) without activation of the conditioning side of the primary motor area (M1) contributing to the contralateral motor evoked potential (MEP), whether the S1-TMS-induced LIHI is dependent on the status of the S1 modulated by the tactile input, and whether the pathways mediating the LIHI are different from those mediating the M1-TMS-induced LIHI. In order to give the TMS over the S1 without eliciting the MEP, the intensity of the S1-TMS was adjusted to be the sub-motor-threshold level and the trials with the MEP response elicited by the S1-TMS were discarded online. The LIHI was induced by the S1-TMS given 40 ms before the test TMS in the participants with the attenuation of the tactile perception of the digit stimulation (TPDS) induced by the S1-TMS, indicating that the LIHI is induced by the S1-TMS without activation of the conditioning side of the M1 contributing to the contralateral MEP in the participants in which the pathways mediating the TPDS is sensitive to the S1-TMS. The S1-TMS-induced LIHI was positively correlated with the attenuation of the TPDS induced by the S1-TMS, indicating that the S1-TMS-induced LIHI is dependent on the effect of the S1-TMS on the pathways mediating the TPDS at the S1. In another experiment, the effect of the digit stimulation given before the conditioning TMS on the S1- or M1-TMS-induced LIHI was examined. The digit stimulation produces tactile input to the S1 causing change in the status of the S1. The S1-TMS-induced LIHI was enhanced when the S1-TMS was given in the period in which the tactile afferent volley produced by the digit stimulation just arrived at the S1, while the LIHI induced by above-motor-threshold TMS over the contralateral M1 was not enhanced by the tactile input. Thus, the S1-TMS-induced LIHI is dependent on the status of the S1 modulated by the tactile input, and the pathways mediating the sub-motor-threshold S1-TMS-induced LIHI are not the same as the pathways mediating the above-motor-threshold M1-TMS-induced LIHI.

Corticospinal Excitability in the Hand Muscles is Decreased During Eye Movement with Visual Occlusion.

Corticospinal excitability in the hand muscles decreases during smooth pursuit eye movement. The present study tested a hypothesis that the decrease in corticospinal excitability in the hand muscles at rest during eye movement is not caused by visual feedback but caused by motor commands to the eye muscles. Healthy men (M age = 28.4 yr., SD = 5.2) moved their eyes to the right with visual occlusion (dark goggles) while their arms and hands remained at rest. The motor-evoked potential in the hand muscles was suppressed by 19% in the third quarter of the eye-movement period, supporting a view that motor commands to the eye muscles are the cause of the decrease in corticospinal excitability in the hand muscles. The amount of the suppression was not significantly different among the muscles, indicating that modulation of corticospinal excitability in one muscle induced by eye movement is not dependent on whether eye movement direction and the direction of finger movement when the muscle contracts are identical. Thus, the finding failed to support a hypothetical view that motor commands to the eye muscles concomittantly produce motor commands to the hand muscles. Moreover, the amount of the suppression was not significantly different between the forearm positions, indicating that the suppression was not affected by proprioception of the forearm muscles when visual feedback is absent.

Change in Excitability of Corticospinal Pathway and GABA-Mediated Inhibitory Circuits of Primary Motor Cortex Induced by Contraction of Adjacent Hand Muscle.

The present study examined whether the excitability of the corticospinal pathway and the GABA-mediated inhibitory circuits of the primary motor cortex that project onto the corticospinal neurons in the tonically contracting hand muscle are changed by tonic contraction of the adjacent hand muscle. The motor evoked potential (MEP) and cortical silent period (CSP) in the tonically contracting hand muscle were obtained while the adjacent hand muscle was either tonically contracting or at rest. The MEP and CSP of the first dorsal interosseous (FDI) muscle elicited across the scalp sites where the MEP is predominantly elicited in the FDI muscle were decreased by tonic contraction of the abductor digiti minimi (ADM) muscle. The centers of the area of the MEP and the duration of the CSP in the FDI muscle elicited across the sites where the MEP is predominantly elicited in the FDI muscle were lateral to those in the FDI muscle elicited across the sites where the MEP is elicited in both the FDI and ADM muscles. They were also lateral to those in the ADM muscle elicited either across the sites where the MEP is predominantly elicited in the ADM muscle, or across the sites where the MEP is elicited in both the FDI and ADM muscles. The decrease in the corticospinal excitability and the excitability of the GABA-mediated inhibitory circuits of the primary motor cortex that project onto the corticospinal neurons in the FDI muscle may be due either to (1) the interaction between the activity of the lateral area of the FDI representation and the descending drive to the ADM muscle, or (2) the decreased susceptibility of the primary motor area that predominantly projects onto the corticospinal neurons in the FDI muscle, which also plays a role in independent finger movement when both the FDI and ADM muscles act together as synergists.

Corticospinal Modulations during Bimanual Movement with Different Relative Phases.

The purpose of this study was to investigate corticospinal modulation of bimanual (BM) movement with different relative phases (RPs). The participants rhythmically abducted and adducted the right index finger (unimanual (UM) movement) or both index fingers (BM movement) with a cyclic duration of 1 s. The RP of BM movement, defined as the time difference between one hand movement and the other hand movement, was 0°, 90°, or 180°. Motor evoked potentials (MEPs) in the right flexor dorsal interosseous muscle elicited by transcranial magnetic stimulation (TMS) were obtained during UM or BM movement. Corticospinal excitability in the first dorsal interosseous muscle during BM movement with 90° RP was higher than that during UM movement or BM movement with 0° or 180° RP. The correlation between muscle activity level and corticospinal excitability during BM movement with 90° RP was smaller than that during UM movement or BM movement with 0° or 180° RP. The higher corticospinal excitability during BM movement with 90° RP may be caused by the greater effort expended to execute a difficult task, the involvement of interhemispheric interaction, a motor binding process, or task acquisition. The lower dependency of corticospinal excitability on the muscle activity level during BM movement with 90° RP may reflect the minor corticospinal contribution to BM movement with an RP that is not in the attractor state.

Time and direction preparation of the long latency stretch reflex.

This study investigated time and direction preparation of motor response to force load while intending to maintain the finger at the initial neutral position. Force load extending or flexing the index finger was given while healthy humans intended to maintain the index finger at the initial neutral position. Electromyographic activity was recorded from the first dorsal interosseous muscle. A precue with or without advanced information regarding the direction of the forthcoming force load was given 1000ms before force load. Trials without the precue were inserted between the precued trials. A long latency stretch reflex was elicited by force load regardless of its direction, indicating that the long latency stretch reflex is elicited not only by muscle stretch afferents, but also by direction-insensitive sensations. Time preparation of motor response to either direction of force load enhanced the long latency stretch reflex, indicating that time preparation is not mediated by afferent discharge of muscle stretch. Direction preparation enhanced the long latency stretch reflex and increased corticospinal excitability 0-20ms after force load when force load was given in the direction stretching the muscle. These enhancements must be induced by preset of the afferent pathway mediating segmental stretch reflex.

Monaural Auditory Cue Affects the Process of Choosing the Initial Swing Leg in Gait Initiation.

The authors investigated the effect of an auditory cue on the choice of the initial swing leg in gait initiation. Healthy humans initiated a gait in response to a monaural or binaural auditory cue. When the auditory cue was given in the ear ipsilateral to the preferred leg side, the participants consistently initiated their gait with the preferred leg. In the session in which the side of the monaural auditory cue was altered trial by trial randomly, the probability of initiating the gait with the nonpreferred leg increased when the auditory cue was given in the ear contralateral to the preferred leg side. The probability of choosing the nonpreferred leg did not increase significantly when the auditory cue was given in the ear contralateral to the preferred leg side in the session in which the auditory cue was constantly given in the ear contralateral to the preferred leg side. The reaction time of anticipatory postural adjustment was shortened, but the probability of choosing the nonpreferred leg was not significantly increased when the gait was initiated in response to a binaural auditory cue. An auditory cue in the ear contralateral to the preferred leg side weakens the preference for choosing the preferred leg as the initial swing leg in gait initiation when the side of the auditory cue is unpredictable.

The effect of tonic contraction of the finger muscle on the motor cortical representation of the contracting adjacent muscle.

This study examined the effect of tonic contraction of the finger muscle on the motor cortical representation of the contracting adjacent muscle. A representation map of the motor evoked potential (MEP) in the first dorsal interosseous (FDI) and abductor digiti minimi (ADM) muscles was obtained with the subject at rest or during tonic contraction of the ADM muscle while the FDI muscle was tonically contracted. The center of gravity (COG) of the MEP map in the FDI muscle shifted medially during contraction of the ADM muscle. Motor cortical excitability in the motor cortical representation of the FDI muscle that did not overlap with the motor cortical representation of the ADM muscle was suppressed, but motor cortical excitability in the motor cortical representation of the FDI muscle overlapping with the motor cortical representation of the ADM muscle was not suppressed during contraction of the ADM muscle. The motor cortical representation of the FDI muscle not overlapping with the motor cortical representation of the ADM muscle was located lateral to that of the FDI muscle that did overlap with the motor cortical representation of the ADM muscle. Medial shift of the COG of the motor cortical representation of the contracting finger muscle induced by tonic contraction of the adjacent finger muscle must be due to suppression of motor cortical excitability in the lateral part of the representation, which is not shared by the adjacent representation.

Asymmetry of anticipatory postural adjustment during gait initiation.

The purpose of this study was to investigate the asymmetry of anticipatory postural adjustment (APA) during gait initiation and to determine whether the process of choosing the initial swing leg affects APA during gait initiation. The participants initiated gait with the leg indicated by a start tone or initiated gait with the leg spontaneously chosen. The dependent variables of APA were not significantly different among the condition of initiating gait with the preferred leg indicated by the start tone, the condition of initiating gait with the non-preferred leg indicated by the start tone, and the condition of initiating gait with the leg spontaneously chosen. These findings fail to support the view that the process of choosing the initial swing leg affects APA during gait initiation. The lateral displacement of the center of pressure in the period in which shifting the center of pressure to the initial swing phase before initiating gait with the left leg indicated by the external cue was significantly larger than that when initiating gait with the right leg indicated by the external cue, and significantly larger than that when initiating gait with the leg spontaneously chosen. Weight shift to the initial swing side during APA during gait initiation was found to be asymmetrical when choosing the leg in response to an external cue.

Bimanual coordination of force enhances interhemispheric inhibition between the primary motor cortices.

The purpose of this study was to elucidate whether bimanual coordination of force affects interhemispheric inhibition (IHI) between the primary motor cortices (M1s). IHI with the index fingers isometrically abducted against a fixed plate (AAP task) was compared with IHI with the index fingers isometrically abducted against each other (AAF task). The index fingers were held stationary at the midline and activity levels of the first dorsal interosseous muscles were equalized between the tasks. The abduction force of each index finger was individually controlled during the AAP task, and bimanually coordinated during the AAF task. IHI during the AAF task was significantly higher than that during the AAP task. IHI between the M1s is related not only to the suppression of unwanted activity of the M1 contralateral to the active M1 but also to bimanual coordination of force.

Different corticospinal control between discrete and rhythmic movement of the ankle.

We investigated differences in corticospinal and spinal control between discrete and rhythmic ankle movements. Motor evoked potentials (MEPs) in the tibialis anterior and soleus muscles and soleus H-reflex were elicited in the middle of the plantar flexion phase during discrete ankle movement or in the initial or later cycles of rhythmic ankle movement. The H-reflex was evoked at an intensity eliciting a small M-wave and MEPs were elicited at an intensity of 1.2 times the motor threshold of the soleus MEPs. Only trials in which background EMG level, ankle angle, and ankle velocity were similar among the movement conditions were included for data analysis. In addition, only trials with a similar M-wave were included for data analysis in the experiment evoking H-reflexes. Results showed that H reflex and MEP amplitudes in the soleus muscle during discrete movement were not significantly different from those during rhythmic movement. MEP amplitude in the tibialis anterior muscle during the later cycles of rhythmic movement was significantly larger than that during the initial cycle of the rhythmic movement or during discrete movement. Higher corticospinal excitability in the tibialis anterior muscle during the later cycles of rhythmic movement may reflect changes in corticospinal control from the initial cycle to the later cycles of rhythmic movement.