The unconscious mental inhibiting process of human maximal voluntary contraction.

Human maximal voluntary contraction (MVC) is believed to be limited by neural inhibition. Motivational goal priming alters background states of the motor system, leading to enhanced MVC. However, the mechanisms that determine the constant inhibition of force exertion in the motor system remain unclear. The primary behavioural goal of MVC is maximal voluntary force exertion. The final expected or desired state of this behavioural goal is explicitly demonstrated with words related to physical exertion, such as 'maximal', irrespective of the possibility of demand-like properties in participants' minds, such as attainability and/or desirability of the goal. For the primed maximal goal state, most trial results fail to meet expectations, demonstrating negative affect that, without awareness, contributes to the mentioned inhibitory mechanism underlying MVC. We therefore speculated that the behavioural goal of MVC contributes to neural inhibitory mechanisms underlying MVC. In our study, we used a previously developed paradigm (Takarada and Nozaki in Scientific Reports 8: 10135, 2018) in which subliminal visual priming stimuli such as the physical exertion-related words "perform" and "exert" were presented to 12 healthy participants and were followed by supraliminal words that were the word "maximal" or neutral.We found that when combined with the term 'maximal' in the consciously visible form, the effect of this subliminal motor-goal priming in inducing pupil dilation and stronger action preparation/execution was abolished without conscious awareness. This is the first objective evidence of motor inhibitory effect-predicting patterns of pupil-linked noradrenergic activity as a signature of a type of mental inhibition underlying the MVC behavioural goal.

Divisively Normalized Integration of Multisensory Error Information Develops Motor Memories Specific to Vision and Proprioception.

Both visual and proprioceptive information contribute to the accuracy of limb movement, but the mechanism of integration of these different modality signals for movement control and learning remains controversial. We aimed to elucidate the mechanism of multisensory integration for motor adaptation by evaluating single-trial adaptation (i.e., aftereffect) induced by visual and proprioceptive perturbations while male and female human participants performed reaching movements. The force-channel method was used to precisely impose several combinations of visual and proprioceptive perturbations (i.e., error), including an instance when the directions of perturbation in both stimuli opposed each another. In the subsequent probe force-channel trial, the lateral force against the channel was quantified as the aftereffect to clarify the mechanism by which the motor adaptation system corrects movement in the event of visual and proprioceptive errors. We observed that the aftereffects had complex dependence on the visual and proprioceptive errors. Although this pattern could not be explained by previously proposed computational models based on the reliability of sensory information, we found that it could be reasonably explained by a mechanism known as divisive normalization, which was the reported mechanism underlying the integration of multisensory signals in neurons. Furthermore, we discovered evidence that the motor memory for each sensory modality developed separately in accordance with a divisive normalization mechanism and that the outputs of both memories were integrated. These results provide a novel view of the utilization and integration of different sensory modality signals in motor adaptation.SIGNIFICANCE STATEMENT The mechanism of utilization of multimodal sensory information by the motor control system to perform limb movements with accuracy is a fundamental question. However, the mechanism of integration of these different sensory modalities for movement control and learning remains highly debatable. Herein, we demonstrate that multisensory integration in the motor learning system can be reasonably explained by divisive normalization, a canonical computation, ubiquitously observed in the brain (Carandini and Heeger, 2011). Moreover, we provide evidence of a novel idea that integration does not occur at the sensory information processing level, but at the motor execution level, after the motor memory for each sensory modality is separately created.

Cosine tuning determines plantarflexors' activities during human upright standing and is affected by incomplete spinal cord injury.

Plantarflexors such as the soleus (SOL) and medial gastrocnemius (MG) play key roles in controlling bipedal stance; however, how the central nervous system controls the activation levels of these plantarflexors is not well understood. Here we investigated how the central nervous system controls the plantarflexors' activation level during quiet standing in a cosine tuning manner where the maximal activation is achieved in a preferred direction (PD). Furthermore, we investigated how spinal cord injury affects these plantarflexors' activations. Thirteen healthy adults (AB) and thirteen individuals with chronic, incomplete spinal cord injury (iSCI) performed quiet standing trials. Their body kinematics and kinetics as well as electromyography signals from the MG and SOL were recorded. In the AB group, we found that the plantarflexors followed the cosine tuning manner during quiet standing. That is, MG was most active when the ratio of plantarflexion torque to knee extension torque was ~2:-3, whereas SOL was most active when the ratio was ~2:1. This suggests that the SOL muscle, despite being a monoarticular muscle, is sensitive to both ankle plantarflexion and knee extension during quiet standing. The difference in the PDs accounts for the phasic activity of MG and for the tonic activity of SOL. Unlike the AB group, the MG's activity was similar to the SOL's activity in the iSCI group, and the SOL PDs were similar to those in the AB group. This result suggests that chronic iSCI affects the control strategy, i.e., cosine tuning, for MG, which may affect standing balance in individuals with iSCI.NEW & NOTEWORTHY Soleus muscle shows a tonic activity whereas medial gastrocnemius muscle shows a phasic activity during quiet standing. Cosine tuning and their preferred direction account for the different muscle activation patterns between these two muscles. In individuals with chronic incomplete spinal cord injury, the preferred direction of gastrocnemius medial head is affected, which may result in their deteriorated standing balance.

Functional modulation of corticospinal excitability with adaptation of wrist movements to novel dynamical environments.

Adaptation of reaching movements to a novel dynamic environment is associated with changes in neuronal activity in the primary motor cortex (M1), suggesting that M1 neurons are part of the internal model. Here, we investigated whether such changes in neuronal activity, resulting from motor adaptation, were also accompanied by changes in human corticospinal excitability, which reflects M1 activity at a macroscopic level. Participants moved a cursor on a display using the right wrist joint from the starting position toward one of eight equally spaced peripheral targets. Motor-evoked potentials (MEPs) were elicited from the wrist muscles by transcranial magnetic stimulation delivered over the left M1 before and after adaptation to a clockwise velocity-dependent force field. We found that the MEP elicited even during the preparatory period exhibited a directional tuning property, and that the preferred direction shifted clockwise after adaptation to the force field. In a subsequent experiment, participants simultaneously adapted an identical wrist movement to two opposing force fields, each of which was associated with unimanual or bimanual contexts, and the MEP during the preparatory period was flexibly modulated, depending on the context. In contrast, such modulation of the MEP was not observed when participants tried to adapt to two opposing force fields that were each associated with a target color. These results suggest that the internal model formed in the M1 is retrieved flexibly even during the preparatory period, and that the MEP could be a very useful probe for evaluating the formation and retrieval of motor memory.

Lateralized sensitivity of motor memories to the kinematics of the opposite arm reveals functional specialization during bimanual actions.

It is generally believed that the dominant arm exhibits greater functional advantages over the nondominant arm in every respect, including muscular strength and movement accuracy. Recent studies have proposed that this laterality is due to different underlying control strategies for each limb rather than different limb capabilities constraining performance. However, the functional role and mechanisms of these different control strategies have yet to be elucidated. Here, we report a specialized function of the nondominant arm that plays a significant role only during bimanual movements. Right-handed human participants performed bimanual reaching movements while only one arm was subjected to a force field. Consistent with our previous study, adaptation to the force field decreased gradually as the movement direction of the opposite arm deviated from the trained direction. We also observed that the decrement of the adaptation was significantly greater for the nondominant left arm. According to our previously proposed theory, this poorer generalization of the left arm originated from a difference in parameters characterizing motor memory; the nondominant arm's motor memory was more strongly influenced by the opposite arm's kinematics. Remarkably, a model incorporating this lateralized memory predicted that the nondominant arm would demonstrate greater adaptability to force fields associated with the opposite arm's movement. We confirmed this prediction experimentally and found that this advantage of the left arm disappeared in left-handed human participants. We concluded that the secondary supporting role often played by the nondominant arm in bimanual actions reflects its specialization rather than its inferiority.

Learning feedback and feedforward control in a mirror-reversed visual environment.

When we learn a novel task, the motor system needs to acquire both feedforward and feedback control. Currently, little is known about how the learning of these two mechanisms relate to each other. In the present study, we tested whether feedforward and feedback control need to be learned separately, or whether they are learned as common mechanism when a new control policy is acquired. Participants were trained to reach to two lateral and one central target in an environment with mirror (left-right)-reversed visual feedback. One group was allowed to make online movement corrections, whereas the other group only received visual information after the end of the movement. Learning of feedforward control was assessed by measuring the accuracy of the initial movement direction to lateral targets. Feedback control was measured in the responses to sudden visual perturbations of the cursor when reaching to the central target. Although feedforward control improved in both groups, it was significantly better when online corrections were not allowed. In contrast, feedback control only adaptively changed in participants who received online feedback and remained unchanged in the group without online corrections. Our findings suggest that when a new control policy is acquired, feedforward and feedback control are learned separately, and that there may be a trade-off in learning between feedback and feedforward controllers.

Intermittent visual feedback can boost motor learning of rhythmic movements: evidence for error feedback beyond cycles.

Movement error is a driving force behind motor learning. For motor learning with discrete movements, such as point-to-point reaching, it is believed that the brain uses error information of the immediately preceding movement only. However, in the case of continuous and repetitive movements (i.e., rhythmic movements), there is a ceaseless inflow of performance information. Thus, an accurate temporal association of the motor commands with the resultant movement errors is not necessarily guaranteed. We investigated how the brain overcomes this challenging situation. Human participants adapted rhythmic movements between two targets to visuomotor rotations, the amplitudes of which changed randomly from cycle to cycle (the duration of one cycle was ∼400 ms). A system identification technique revealed that the motor adaptation was affected not just by the preceding movement error, but also by a history of errors from the previous cycles. Error information obtained from more than one previous cycle tended to increase, rather than decrease, movement error. This result led to a counterintuitive prediction: providing visual error feedback for only a fraction of cycles should enhance visuomotor adaptation. As predicted, we observed that motor adaptation to a constant visual rotation (30°) was significantly enhanced by providing visual feedback once every fourth or fifth cycle rather than for every cycle. These results suggest that the brain requires a specific processing time to modify the motor command, based on the error information, and so is unable to deal appropriately with the overwhelming flow of error information generated during rhythmic movements.

Learning with slight forgetting optimizes sensorimotor transformation in redundant motor systems.

Recent theoretical studies have proposed that the redundant motor system in humans achieves well-organized stereotypical movements by minimizing motor effort cost and motor error. However, it is unclear how this optimization process is implemented in the brain, presumably because conventional schemes have assumed a priori that the brain somehow constructs the optimal motor command, and largely ignored the underlying trial-by-trial learning process. In contrast, recent studies focusing on the trial-by-trial modification of motor commands based on error information suggested that forgetting (i.e., memory decay), which is usually considered as an inconvenient factor in motor learning, plays an important role in minimizing the motor effort cost. Here, we examine whether trial-by-trial error-feedback learning with slight forgetting could minimize the motor effort and error in a highly redundant neural network for sensorimotor transformation and whether it could predict the stereotypical activation patterns observed in primary motor cortex (M1) neurons. First, using a simple linear neural network model, we theoretically demonstrated that: 1) this algorithm consistently leads the neural network to converge at a unique optimal state; 2) the biomechanical properties of the musculoskeletal system necessarily determine the distribution of the preferred directions (PD; the direction in which the neuron is maximally active) of M1 neurons; and 3) the bias of the PDs is steadily formed during the minimization of the motor effort. Furthermore, using a non-linear network model with realistic musculoskeletal data, we demonstrated numerically that this algorithm could consistently reproduce the PD distribution observed in various motor tasks, including two-dimensional isometric torque production, two-dimensional reaching, and even three-dimensional reaching tasks. These results may suggest that slight forgetting in the sensorimotor transformation network is responsible for solving the redundancy problem in motor control.

Divisively normalized neuronal processing of uncertain visual feedback for visuomotor learning.

When encountering a visual error during a reaching movement, the motor system improves the motor command for the subsequent trial. This improvement is impaired by visual error uncertainty, which is considered evidence that the motor system optimally estimates the error. However, how such statistical computation is accomplished remains unclear. Here, we propose an alternative scheme implemented with a divisive normalization (DN): the responses of neuronal elements are normalized by the summed activity of the population. This scheme assumes that when an uncertain visual error is provided by multiple cursors, the motor system processes the error conveyed by each cursor and integrates the information using DN. The DN model reproduced the patterns of learning response to 1-3 cursor errors and the impairment of learning response with visual error uncertainty. This study provides a new perspective on how the motor system updates motor commands according to uncertain visual error information.

Gain field encoding of the kinematics of both arms in the internal model enables flexible bimanual action.

Bimanual action requires the neural controller (internal model) for each arm to predictively compensate for mechanical interactions resulting from movement of both that arm and its counterpart on the opposite side of the body. Here, we demonstrate that the brain may accomplish this by constructing the internal model with primitives multiplicatively encoding information from the kinematics of both arms. We had human participants adapt to a novel force field imposed on one arm while both arms were moving in particular directions and examined the generalization pattern of motor learning when changing the movement directions of both arms. The generalization pattern was consistent with the pattern predicted from the multiplicative encoding scheme. As proposed by previous theoretical studies, the strength of multiplicative encoding was manifested in the observation that participants could adapt reaching movements to complicated force fields depending nonlinearly on the movement directions of both arms. These results indicate that multiplicative neuronal influence of the kinematics of the opposing arm on the internal models enables the brain to control bimanual movement by providing great flexible ability to handle arbitrary dynamical environments resulting from the interactions of both arms.

Shouting strengthens voluntary force during sustained maximal effort through enhancement of motor system state via motor commands.

Previous research indicates that shouting during momentary maximal exertion effort potentiates the maximal voluntary force through the potentiation of motor cortical excitability. However, the muscular force-enhancing effects of shouting on sustained maximal force production remain unclear. We investigated the effect of shouting on the motor system state by examining motor evoked potentials in response to transcranial magnetic stimulation applied over the hand area of the contralateral primary motor cortex (M1) during sustained maximal voluntary contraction, and by assessing handgrip maximal voluntary force. We observed that shouting significantly increased handgrip maximal voluntary force and reduced the silent period. Our results indicate that shouting increased handgrip voluntary force during sustained maximal exertion effort through the reduced silent period. This is the first objective evidence that the muscular force of shouting during maximal force exertion is associated with the potentiation of motor system activity produced by the additional drive of shouting operating on the motor system (i.e., shouting-induced excitatory input to M1).

The "cutaneous rabbit" hopping out of the body.

Rapid sequential taps delivered first to one location and then to another on the skin create the somatosensory illusion that the tapping is occurring at intermediate locations between the actual stimulus sites, as if a small rabbit were hopping along the skin from the first site to the second (called the "cutaneous rabbit"). Previous behavioral studies have attributed this illusion to the early unimodal somatosensory body map. A functional magnetic resonance imaging study recently confirmed the association of the illusion with somatotopic activity in the primary somatosensory cortex. Thus, the cutaneous rabbit illusion has been confined to one's own body. In the present paper, however, we show that the cutaneous rabbit can "hop out of the body" onto an external object held by the subject. We delivered rapid sequential taps to the left and right index fingers. When the subjects held a stick such that it was laid across the tips of their index fingers and received the taps via the stick, they reported sensing the illusory taps in the space between the actual stimulus locations (i.e., along the stick). This suggests that the cutaneous rabbit effect involves not only the intrinsic somatotopic representation but also the representation of the extended body schema that results from body-object interactions.

Asymmetric transfer of visuomotor learning between discrete and rhythmic movements.

As long as we only focus on kinematics, rhythmic movement appears to be a concatenation of discrete movements or discrete movement appears to be a truncated rhythmic movement. However, whether or not the neural control processes of discrete and rhythmic movements are distinct has not yet been clearly understood. Here, we address this issue by examining the motor learning transfer between these two types of movements testing the hypothesis that distinct neural control processes should lead to distinct motor learning and transfer. First, we found that the adaptation to an altered visuomotor condition was almost fully transferred from the discrete out-and-back movements to the rhythmic out-and-back movements; however, the transfer from the rhythmic to discrete movements was very small. Second, every time a new set of rhythmic movements was started, a considerable amount of movement error reappeared in the first and the following several cycles although the error converged to a small level by the end of each set. Last, we observed that when the discrete movement training was performed with intertrial intervals longer than 4 s, a significantly larger error appeared, specifically for the second and third cycles of the subsequent rhythmic movements, despite a seemingly full transfer to the first cycle. These results provide strong behavioral evidence that different neuronal control processes are involved in the two types of movements and that discrete control processes contribute to the generation of the first cycle of the rhythmic movement.

Cross talk in implicit assignment of error information during bimanual visuomotor learning.

When a neural movement controller, called an "internal model," is adapted to a novel environment, the movement error needs to be appropriately associated with the controller. However, their association is not necessarily guaranteed for bimanual movements in which two controllers--one for each hand--result in two movement errors. Considering the implicit nature of the adaptation process, the movement error of one hand can be erroneously associated with the controller of the other hand. Here, we investigated this credit-assignment problem in bimanual movement by having participants perform bimanual, symmetric back-and-forth movements while displaying the position of the right hand only with a cursor. In the training session, the cursor position was gradually rotated clockwise, such that the participants were unaware of the rotation. The movement of the right hand gradually rotated counterclockwise as a consequence of adaptation. Although the participants knew that the cursor reflected the movement of the right hand, such gradual adaptation was also observed for the invisible left hand, especially when the cursor was presented on the left side of the display. Thus the movement error of the right hand was implicitly assigned to the left-hand controller. Such cross talk in credit assignment might influence motor adaptation performance, even when two cursors are presented; the adaptation was impaired when the rotations imposed on the cursors were opposite compared with when they were in the same direction. These results indicate the inherent presence of cross talk in the process of associating action with consequence in bimanual movement.

Shouting strengthens maximal voluntary force and is associated with augmented pupillary dilation.

Previous research has demonstrated that human maximal voluntary force is generally limited by neural inhibition. Producing a shout during maximal exertion effort enhances the force levels of maximal voluntary contraction. However, the mechanisms underlying this enhancement effect on force production remain unclear. We investigated the influence of producing a shout on the pupil-linked neuromodulatory system state by examining pupil size. We also examined its effects on the motor system state by examining motor evoked potentials in response to transcranial magnetic stimulation applied over the contralateral primary motor cortex, and by evaluating handgrip maximal voluntary force. Analysis revealed that producing a shout significantly increased handgrip maximal voluntary force, followed by an increase in pupil size and a reduction of the cortical silent period. Our results indicate that producing a shout increased handgrip maximal voluntary force through the enhancement of motor cortical excitability, possibly via the enhancement of noradrenergic system activity. This study provides evidence that the muscular force-enhancing effect of shouting during maximal force exertion is related to both the motor system state and the pupil-linked neuromodulatory system state.

Effects of Simulated Microgravity and Hypergravity Conditions on Arm Movements in Normogravity.

The human sensorimotor control has evolved in the Earth's environment where all movement is influenced by the gravitational force. Changes in this environmental force can severely impact the performance of arm movements which can be detrimental in completing certain tasks such as piloting or controlling complex vehicles. For this reason, subjects that are required to perform such tasks undergo extensive training procedures in order to minimize the chances of failure. We investigated whether local gravity simulation of altered gravitational conditions on the arm would lead to changes in kinematic parameters comparable to the full-body experience of microgravity and hypergravity onboard a parabolic flight. To see if this would be a feasible approach for on-ground training of arm reaching movements in altered gravity conditions we developed a robotic device that was able to apply forces at the wrist in order to simulate micro- or hypergravity conditions for the arm while subjects performed pointing movements on a touch screen. We analyzed and compared the results of several kinematic parameters along with muscle activity using this system with data of the same subjects being fully exposed to microgravity and hypergravity conditions on a parabolic flight. Both in our simulation and in-flight, we observed a significant increase in movement durations in microgravity conditions and increased velocities in hypergravity for upward movements. Additionally, we noted a reduced accuracy of pointing both in-flight and in our simulation. These promising results suggest, that locally simulated altered gravity can elicit similar changes in some movement characteristics for arm reaching movements. This could potentially be exploited as a means of developing devices such as exoskeletons to aid in training individuals prior to undertaking tasks in changed gravitational conditions.

Effects of Local Gravity Compensation on Motor Control During Altered Environmental Gravity.

Our sensorimotor control is well adapted to normogravity environment encountered on Earth and any change in gravity significantly disturbs our movement. In order to produce appropriate motor commands for aimed arm movements such as pointing or reaching, environmental changes have to be taken into account. This adaptation is crucial when performing successful movements during microgravity and hypergravity conditions. To mitigate the effects of changing gravitational levels, such as the changed movement duration and decreased accuracy, we explored the possible beneficial effects of gravity compensation on movement. Local gravity compensation was achieved using a motorized robotic device capable of applying precise forces to the subject's wrist that generated a normogravity equivalent torque at the shoulder joint during periods of microgravity and hypergravity. The efficiency of the local gravity compensation was assessed with an experiment in which participants performed a series of pointing movements toward the target on a screen during a parabolic flight. We compared movement duration, accuracy, movement trajectory, and muscle activations of movements during periods of microgravity and hypergravity with conditions when local gravity compensation was provided. The use of local gravity compensation at the arm mitigated the changes in movement duration, accuracy, and muscle activity. Our results suggest that the use of such an assistive device helps with movements during unfamiliar environmental gravity.

A generalized method to estimate waveforms common across trials from EEGs.

We propose a generalized method to estimate waveforms common across trials from electroencephalographic (EEG) data. From single/multi-channel EEGs, the proposed method estimates the number of waveforms common across trials, their delays in individual trials, and all of the waveforms. After verifying the performance of this method by a number of simulation tests with artificial EEGs, we apply it to EEGs during a Go/NoGo task. This method can be used in general situations where the number and the delays of EEG waveforms common across trials are unknown.

Limited transfer of learning between unimanual and bimanual skills within the same limb.

Although a limb's motion appears to be similar across unimanual and bimanual movements, here we demonstrate partial, but not complete, transfer of learning across these behavioral contexts, hidden learning that remains intact (but invisible) until the original context is again encountered, and the ability to associate two conflicting force fields simultaneously, one with each context. These results suggest partial, but not complete, overlap in the learning processes involved in the acquisition of unimanual and bimanual skills.

"Paralympic Brain". Compensation and Reorganization of a Damaged Human Brain with Intensive Physical Training.

The main aim of the study was to evaluate how the brain of a Paralympic athlete with severe disability due to cerebral palsy has reorganized after continuous training geared to enhance performance. Both corticospinal excitability of upper-limb muscles and electromyographic activity during swimming were investigated for a Paralympic gold medalist in swimming competitions. Transcranial magnetic stimulation (TMS) to the affected and intact hand motor cortical area revealed that the affected side finger muscle cortical representation area shifted towards the temporal side, and cortico-spinal excitability of the target muscle was prominently facilitated, i.e., the maximum motor evoked potential in the affected side, 6.11 ± 0.19 mV was greater than that in the intact side, 4.52 ± 0.39 mV (mean ± standard error). Electromyographic activities during swimming demonstrated well-coordinated patterns as compared with rather spastic activities observed in the affected side during walking on land. These results suggest that the ability of the brain to reorganize through intensive training in Paralympic athletes can teach interesting lessons to the field neurorehabilitation.