Behavioral and physiological fatigue-related factors influencing timing and force control learning in pianists.

Optimizing the training regimen depending on neuromuscular fatigue is crucial for the well-being of professionals intensively practicing motor skills, such as athletes and musicians, as persistent fatigue can hinder learning and cause neuromuscular injuries. However, accurate assessment of fatigue is challenging because of the dissociation between subjective perception and its impact on motor and cognitive performance. To address this issue, we investigated the interplay between fatigue and learning development in 28 pianists during three hours of auditory-motor training, dividing them into two groups subjected to different resting conditions. Changes in behavior and muscle activity during training were measured to identify potential indicators capable of detecting fatigue before subjective awareness. Our results indicate that motor learning and fatigue development are independent of resting frequency and timing. Learning indices, such as reduction in force and timing errors throughout training, did not differ between the groups. No discernible distinctions emerged in fatigue-related behavioral and physiological indicators between the groups. Regression analysis revealed that several fatigue-related indicators, such as tapping speed variability and electromyogram amplitude per unit force, could explain the learning of timing and force control. Our findings suggest the absence of a universal resting schedule for optimizing auditory-motor learning.

Two common issues in synchronized multimodal recordings with EEG: Jitter and latency.

Multimodal recording using electroencephalogram (EEG) and other biological signals (e.g., muscle activities, eye movement, pupil diameters, or body kinematics data) is ubiquitous in human neuroscience research. However, the precise time alignment of multiple data from heterogeneous sources (i.e., devices) is often arduous due to variable recording parameters of commercially available research devices and complex experimental setups. In this review, we introduced the versatility of a Lab Streaming Layer (LSL)-based application that can overcome two common issues in measuring multimodal data: jitter and latency. We discussed the issues of jitter and latency in multimodal recordings and the benefits of time-synchronization when recording with multiple devices. In addition, a computer simulation was performed to highlight how the millisecond-order jitter readily affects the signal-to-noise ratio of the electrophysiological outcome. Together, we argue that the LSL-based system can be used for research requiring precise time-alignment of datasets. Studies that detect stimulus-induced transient neural responses or test hypotheses regarding temporal relationships of different functional aspects with multimodal data would benefit most from LSL-based systems.

An investigation of the effectiveness of neurofeedback training on motor performance in healthy adults: A systematic review and meta-analysis.

Neurofeedback training (NFT) refers to a training where the participants voluntarily aim to manipulate their own brain activity using the sensory feedback abstracted from their brain activity. NFT has attracted attention in the field of motor learning due to its potential as an alternative or additional training method for general physical training. In this study, a systematic review of NFT studies for motor performance improvements in healthy adults and a meta-analysis on the effectiveness of NFT were conducted. A computerized search was performed using the databases Web of Science, Scopus, PubMed, JDreamIII, and Ichushi-Web to identify relevant studies published between January 1st, 1990, and August 3rd, 2021. Thirty-three studies were identified for the qualitative synthesis and 16 randomized controlled trials (374 subjects) for the meta-analysis. The meta-analysis, including all trials found in the search, revealed significant effects of NFT for motor performance improvement examined at the timing after the last NFT session (standardized mean difference = 0.85, 95% CI [0.18-1.51]), but with the existence of publication biases and substantial heterogeneity among the trials. Subsequent meta-regression analysis demonstrated the dose-response gradient between NFTs and motor performance improvements; more than 125 min of cumulative training time may benefit for the subsequent motor performance. For each motor performance measure (e.g., speed, accuracy, and hand dexterity), the effectiveness of NFT remains inconclusive, mainly due to its small sample sizes. More empirical NFT studies for motor performance improvement may be needed to show beneficial effects on motor performance and to safely incorporate NFT into real-world scenarios.

Multipulse transcranial magnetic stimulation of human motor cortex produces short-latency corticomotor facilitation via two distinct mechanisms.

Single-pulse transcranial magnetic stimulation (TMS) of the precentral hand representation (M1HAND) can elicit indirect waves in the corticospinal tract at a periodicity of ∼660 Hz, called I-waves. These descending volleys are produced by transsynaptic excitation of fast-conducting corticospinal axons in M1HAND. Paired-pulse TMS can induce short-interval intracortical facilitation (SICF) of motor evoked potentials (MEPs) at interpulse intervals that match I-wave periodicity. This study examined whether short-latency corticospinal facilitation engages additional mechanisms independently of I-wave periodicity. In 19 volunteers, one to four biphasic TMS pulses were applied to left M1HAND with interpulse intervals adjusted to the first peak or trough of the individual SICF curve at different intensities to probe the intensity-response relationship. Multipulse TMSHAND at individual peak latency facilitated MEP amplitudes and reduced resting motor threshold (RMT) compared with single pulses. Multipulse TMSHAND at individual trough latency also produced a consistent facilitation of MEPs and a reduction of RMT. Short-latency facilitation at trough latency was less pronounced, but the relative difference in facilitation decreased with increasing stimulus intensity. Increasing the pulse number had only a modest effect. Two mechanisms underlie short-latency facilitation caused by biphasic multipulse TMSHAND. One intracortical mechanism is related to I-wave periodicity and engages fast-conducting direct projections to spinal motoneurons. A second corticospinal mechanism does not rely on I-wave rhythmicity and may be mediated by slower-conducting indirect pyramidal tract projections from M1HAND to spinal interneurons. The latter mechanism deserves more attention in studies of the corticomotor system and its link to manual motor control using the MEP.NEW & NOTEWORTHY TMS pairs evoke SICF at interpulse intervals (IPIs) that match I-wave periodicity. Biphasic bursts with IPIs at the latency of the first peak facilitate MEPs and reduce corticomotor threshold. Bursts at the latency of the first trough facilitate MEPs and reduce corticomotor threshold to a lesser extent. TMS bursts facilitate corticomotor excitability via two mechanisms: SICF-dependently via fast-conducting direct projections from M1HAND to spinal motoneurons and SICF-independently, probably through slower-conducting indirect pyramidal tract projections.

Spectral Power in Marmoset Frontal Motor Cortex during Natural Locomotor Behavior.

During primate arboreal locomotion, substrate orientation modifies body axis orientation and biomechanical contribution of fore- and hindlimbs. To characterize the role of cortical oscillations in integrating these locomotor demands, we recorded electrocorticographic activity from left dorsal premotor, primary motor, and supplementary motor cortices of three common marmosets moving across a branch-like small-diameter pole, fixed horizontally or vertically. Animals displayed behavioral adjustments to the task, namely, the horizontal condition mainly induced quadrupedal walk with pronated/neutral forelimb postures, whereas the vertical condition induced walk and bound gaits with supinated/neutral postures. Examination of cortical activity suggests that ß (16-35 Hz) and γ (75-100 Hz) oscillations could reflect different processes in locomotor adjustments. During task, modulation of γ ERS by substrate orientation (horizontal/vertical) and epoch (preparation/execution) suggests close tuning to movement dynamics and biomechanical demands. ß ERD was essentially modulated by gait (walk/bound), which could illustrate contribution to movement sequence and coordination. At rest, modulation of ß power by substrate orientation underlines its role in sensorimotor processes for postural maintenance.

Cortical reorganization of lower-limb motor representations in an elite archery athlete with congenital amputation of both arms.

Despite their disabilities, top Paralympic athletes have better motor skills than able-bodied athletes. However, the neural underpinnings of these better motor skills remain unclear. We investigated the reorganization of the primary motor cortex (M1) in a Paralympic athlete with congenital amputation of both arms who holds the world record for the farthest accurate shot in archery (Amputee Archer: AA). We recorded brain activity during contraction of right toe, ankle, knee, and hip joint muscles in the AA and 12 able-bodied control subjects using functional magnetic resonance imaging. The results revealed that M1 activation was more widespread in the AA compared with control subjects during all tasks, and shifted towards the lateral part of the M1 during contraction of toe and knee muscles. We also conducted a motor mapping experiment using navigated transcranial magnetic stimulation. The M1 area receiving stimulation elicited motor-evoked potentials from the toe, lower-leg, and thigh muscles, which were larger in the AA compared with 12 control subjects. Furthermore, the AA's motor maps were shifted towards the lateral side of M1. These results suggest an expansion of lower-limb M1 representation towards the lateral side of M1, including the trunk and upper-limb representations, and an expansion of the area of corticomotor neurons innervating the lower limb muscles in the AA. This unique M1 reorganization could underpin the AA's excellent archery performance in the absence of upper limbs. The current results suggest that Paralympic athletes may exhibit extreme M1 plasticity, which could arise through a combination of rigorous long-term motor training and compensatory M1 reorganization for missing body parts.

Muscle-selective disinhibition of corticomotor representations using a motor imagery-based brain-computer interface.

Bridging between brain activity and machine control, brain-computer interface (BCI) can be employed to activate distributed neural circuits implicated in a specific aspect of motor control. Using a motor imagery-based BCI paradigm, we previously found a disinhibition within the primary motor cortex contralateral to the imagined movement, as evidenced by event-related desynchronization (ERD) of oscillatory cortical activity. Yet it is unclear whether this BCI approach does selectively facilitate corticomotor representations targeted by the imagery. To address this question, we used brain state-dependent transcranial magnetic stimulation while participants performed kinesthetic motor imagery of wrist movements with their right hand and received online visual feedback of the ERD. Single and paired-pulse magnetic stimulation were given to the left primary motor cortex at a low or high level of ERD to assess intracortical excitability. While intracortical facilitation showed no modulation by ERD, short-latency intracortical inhibition was reduced the higher the ERD. Intracortical disinhibition was only found in the agonist muscle targeted by motor imagery at high ERD level, but not in the antagonist muscle. Single pulse motor-evoked potential was also increased the higher the ERD. However, at high ERD level, this facilitatory effect on overall corticospinal excitability was not selective to the agonist muscle. Analogous results were found in two independent experiments, in which participants either performed kinesthetic motor imagery of wrist extension or flexion. Our results showed that motor imagery-based BCI can selectively disinhibit the corticomotor output to the agonist muscle, enabling effector-specific training in patients with motor paralysis.

Accurate motor mapping in awake common marmosets using micro-electrocorticographical stimulation and stochastic threshold estimation.

OBJECTIVE: Motor map has been widely used as an indicator of motor skills and learning, cortical injury, plasticity, and functional recovery. Cortical stimulation mapping using epidural electrodes is recently adopted for animal studies. However, several technical limitations still remain. Test-retest reliability of epidural cortical stimulation (ECS) mapping has not been examined in detail. Many previous studies defined evoked movements and motor thresholds by visual inspection, and thus, lacked quantitative measurements. A reliable and quantitative motor map is important to elucidate the mechanisms of motor cortical reorganization. The objective of the current study was to perform reliable ECS mapping of motor representations based on the motor thresholds, which were stochastically estimated by motor evoked potentials and chronically implanted micro-electrocorticographical (µECoG) electrode arrays, in common marmosets. APPROACH: ECS was applied using the implanted µECoG electrode arrays in three adult common marmosets under awake conditions. Motor evoked potentials were recorded through electromyographical electrodes implanted in upper limb muscles. The motor threshold was calculated through a modified maximum likelihood threshold-hunting algorithm fitted with the recorded data from marmosets. Further, a computer simulation confirmed reliability of the algorithm. MAIN RESULTS: Computer simulation suggested that the modified maximum likelihood threshold-hunting algorithm enabled to estimate motor threshold with acceptable precision. In vivo ECS mapping showed high test-retest reliability with respect to the excitability and location of the cortical forelimb motor representations. SIGNIFICANCE: Using implanted µECoG electrode arrays and a modified motor threshold-hunting algorithm, we were able to achieve reliable motor mapping in common marmosets with the ECS system.

Rapid Identification of Cortical Motor Areas in Rodents by High-Frequency Automatic Cortical Stimulation and Novel Motor Threshold Algorithm.

Cortical stimulation mapping is a valuable tool to test the functional organization of the motor cortex in both basic neurophysiology (e.g., elucidating the process of motor plasticity) and clinical practice (e.g., before resecting brain tumors involving the motor cortex). However, compilation of motor maps based on the motor threshold (MT) requires a large number of cortical stimulations and is therefore time consuming. Shortening the time for mapping may reduce stress on the subjects and unveil short-term plasticity mechanisms. In this study, we aimed to establish a cortical stimulation mapping procedure in which the time needed to identify a motor area is reduced to the order of minutes without compromising reliability. We developed an automatic motor mapping system that applies epidural cortical surface stimulations (CSSs) through one-by-one of 32 micro-electrocorticographic electrodes while examining the muscles represented in a cortical region. The next stimulus intensity was selected according to previously evoked electromyographic responses in a closed-loop fashion. CSS was repeated at 4 Hz and electromyographic responses were submitted to a newly proposed algorithm estimating the MT with smaller number of stimuli with respect to traditional approaches. The results showed that in all tested rats (n = 12) the motor area maps identified by our novel mapping procedure (novel MT algorithm and 4-Hz CSS) significantly correlated with the maps achieved by the conventional MT algorithm with 1-Hz CSS. The reliability of the both mapping methods was very high (intraclass correlation coefficients ≧0.8), while the time needed for the mapping was one-twelfth shorter with the novel method. Furthermore, the motor maps assessed by intracortical microstimulation and the novel CSS mapping procedure in two rats were compared and were also significantly correlated. Our novel mapping procedure that determined a cortical motor area within a few minutes could help to study the functional significance of short-term plasticity in motor learning and recovery from brain injuries. Besides this advantage, particularly in the case of human patients or experimental animals that are less trained to remain at rest, shorter mapping time is physically and mentally less demanding and might allow the evaluation of motor maps in awake individuals as well.

Synchronizing the transcranial magnetic pulse with electroencephalographic recordings effectively reduces inter-trial variability of the pulse artefact.

BACKGROUND: Electroencephalography (EEG) can capture the cortical response evoked by transcranial magnetic stimulation (TMS). The TMS pulse provokes a large artefact, which obscures the cortical response in the first milliseconds after TMS. Removing this artefact remains a challenge. METHODS: We delivered monophasic and biphasic TMS to a melon as head phantom and to four healthy participants and recorded the pulse artefact at 5 kHz with a TMS-compatible EEG system. Pulse delivery was either synchronized or non-synchronized to the clock of the EEG recording system. The effects of synchronization were tested at 10 and 20 kHz using the head phantom. We also tested the effect of a soft sheet placed between the stimulation coil and recording electrodes in both human and melon. RESULTS & CONCLUSION: Synchronizing TMS and data acquisition markedly reduced trial-to-trial variability of the pulse artefact in recordings from the phantom or from the scalp. Reduced trial-to-trial variability was also observed at high sampling frequencies. The use of a soft sheet reduced the variability in recordings on the head phantom, but not in human participants. Effective reduction of the trial-to-trial variability renders it possible to create an artefact template for off-line filtering. Template-based subtraction of the artefact from the EEG signals is a prerequisite to effectively recover the immediate physiological response in the stimulated cortex and inter-connected areas.

Cortical control of object-specific grasp relies on adjustments of both activity and effective connectivity: a common marmoset study.

KEY POINTS: The cortical mechanisms of grasping have been extensively studied in macaques and humans; here, we investigated whether common marmosets could rely on similar mechanisms despite strong differences in hand morphology and grip diversity. We recorded electrocorticographic activity over the sensorimotor cortex of two common marmosets during the execution of different grip types, which allowed us to study cortical activity (power spectrum) and physiologically inferred connectivity (phase-slope index). Analyses were performed in beta (16-35 Hz) and gamma (75-100 Hz) frequency bands and our results showed that beta power varied depending on grip type, whereas gamma power displayed clear epoch-related modulation. Strength and direction of inter-area connectivity varied depending on grip type and epoch. These findings suggest that fundamental control mechanisms are conserved across primates and, in future research, marmosets could represent an adequate model to investigate primate brain mechanisms. ABSTRACT: The cortical mechanisms of grasping have been extensively studied in macaques and humans. Here, we investigated whether common marmosets could rely on similar mechanisms despite striking differences in manual dexterity. Two common marmosets were trained to grasp-and-pull three objects eliciting different hand configurations: whole-hand, finger and scissor grips. The animals were then chronically implanted with 64-channel electrocorticogram arrays positioned over the left premotor, primary motor and somatosensory cortex. Power spectra, reflecting predominantly cortical activity, and phase-slope index, reflecting the direction of information flux, were studied in beta (16-35 Hz) and gamma (75-100 Hz) bands. Differences related to grip type, epoch (reach, grasp) and cortical area were statistically assessed. Results showed that whole-hand and scissor grips triggered stronger beta desynchronization than finger grip. Task epochs clearly modulated gamma power, especially for finger and scissor grips. Considering effective connectivity, finger and scissor grips evoked stronger outflow from primary motor to premotor cortex, whereas whole-hand grip displayed the opposite pattern. These findings suggest that fundamental control mechanisms, relying on adjustments of cortical activity and connectivity, are conserved across primates. Consistently, marmosets could represent a good model to investigate primate brain mechanisms.

Three-dimensional motion analysis of arm-reaching movements in healthy and hemispinalized common marmosets.

Spinal cord injury (SCI) is a devastating neurological injury. At present, pharmacological, regenerative, and rehabilitative approaches are widely studied as therapeutic interventions for motor recovery after SCI. Preclinical research has been performed on model animals with experimental SCI, and those studies often evaluate hand and arm motor function using various indices, such as the success rate of the single pellet reaching test and the grip force. However, compensatory movement strategies, involuntary muscle contraction, and the subject's motivation could affect the scores, resulting in failure to assess direct recovery from impairment. Identifying appropriate assessments of motor impairment is thus important for understanding the mechanisms of motor recovery. In this study, we developed a motion capture system capable of reconstructing three-dimensional hand positions with millimeter and millisecond accuracy and evaluated hand kinematics during food retrieval movement in both healthy and hemispinalized common marmosets. As a result, the endpoint jerk, representing the accuracy of hand motor control, was asserted to be an appropriate index of upper limb motor impairment by eliminating the influence of the subject's motivation, involuntary muscle contraction, and compensatory strategies. The result also suggested that the kinematics of the limb more consistently reflects motor restoration from deficit due to spinal cord injury than the performance in the single pellet reaching test. Because of recent attention devoted to the common marmoset as a nonhuman primate model for human diseases, the present study, which clarified arm-reaching movements in spinalized marmosets, provides fundamental knowledge for future therapeutic studies.

Is event-related desynchronization a biomarker representing corticospinal excitability?

Brain computer interfaces (BCIs) using event-related desynchronization (ERD) of the electroencephalogram (EEG), which is believed to represent increased activation of the sensorimotor cortex, have attracted attention as tools for rehabilitation of upper limb motor functions in hemiplegic stroke patients. However, it remains unclear whether the corticospinal excitability is actually correlated with ERD. The purpose of this study was to assess the association between the ERD magnitude and the excitability of primary motor cortex (M1) and spinal motoneurons. M1 excitability was tested by motor evoked potentials (MEPs), short-interval intracortical inhibition (SICI) and intracortical facilitation (ICF) using transcranial magnetic stimulation, and spinal motoneuronal excitability was tested by F-waves using peripheral nerve stimulation. Results showed that large ERD during motor imagery was associated with significantly increased F-wave persistence and reduced SICI, but no significant changes in ICF and the response average of F-wave amplitudes. Our findings suggest that ERD magnitude during motor imagery represents the instantaneous excitability of both M1 and spinal motoneurons. This study provides electrophysiological evidence that ERD-based BCI with motor imagery task increases corticospinal excitability as changes accompanying actual movements.

Event-related desynchronization reflects downregulation of intracortical inhibition in human primary motor cortex.

There is increasing interest in electroencephalogram (EEG)-based brain-computer interface (BCI) as a tool for rehabilitation of upper limb motor functions in hemiplegic stroke patients. This type of BCI often exploits mu and beta oscillations in EEG recorded over the sensorimotor areas, and their event-related desynchronization (ERD) following motor imagery is believed to represent increased sensorimotor cortex excitability. However, it remains unclear whether the sensorimotor cortex excitability is actually correlated with ERD. Thus we assessed the association of ERD with primary motor cortex (M1) excitability during motor imagery of right wrist movement. M1 excitability was tested by motor evoked potentials (MEPs), short-interval intracortical inhibition (SICI), and intracortical facilitation (ICF) with transcranial magnetic stimulation (TMS). Twenty healthy participants were recruited. The participants performed 7 s of rest followed by 5 s of motor imagery and received online visual feedback of the ERD magnitude of the contralateral hand M1 while performing the motor imagery task. TMS was applied to the right hand M1 when ERD exceeded predetermined thresholds during motor imagery. MEP amplitudes, SICI, and ICF were recorded from the agonist muscle of the imagined hand movement. Results showed that the large ERD during wrist motor imagery was associated with significantly increased MEP amplitudes and reduced SICI but no significant changes in ICF. Thus ERD magnitude during wrist motor imagery represents M1 excitability. This study provides electrophysiological evidence that a motor imagery task involving ERD may induce changes in corticospinal excitability similar to changes accompanying actual movements.