Mechanisms of Human Motor Learning Do Not Function Independently

Human motor learning is governed by a suite of interacting mechanisms each one of which modifies behavior in distinct ways and rely on different neural circuits. In recent years, much attention has been given to one type of motor learning, called motor adaptation. Here, the field has generally focused on the interactions of three mechanisms: sensory prediction error SPE-driven, explicit (strategy-based), and reinforcement learning. Studies of these mechanisms have largely treated them as modular, aiming to model how the outputs of each are combined in the production of overt behavior. However, when examined closely the results of some studies also suggest the existence of additional interactions between the sub-components of each learning mechanism. In this perspective, we propose that these sub-component interactions represent a critical means through which different motor learning mechanisms are combined to produce movement; understanding such interactions is critical to advancing our knowledge of how humans learn new behaviors. We review current literature studying interactions between SPE-driven, explicit, and reinforcement mechanisms of motor learning. We then present evidence of sub-component interactions between SPE-driven and reinforcement learning as well as between SPE-driven and explicit learning from studies of people with cerebellar degeneration. Finally, we discuss the implications of interactions between learning mechanism sub-components for future research in human motor learning.

High Gamma and Beta Temporal Interference Stimulation in the Human Motor Cortex Improves Motor Functions

Background: Temporal interference (TI) stimulation is a new technique of non-invasive brain stimulation. Envelope-modulated waveforms with two high-frequency carriers can activate neurons in target brain regions without stimulating the overlying cortex, which has been validated in mouse brains. However, whether TI stimulation can work on the human brain has not been elucidated.Objective: To assess the effectiveness of the envelope-modulated waveform of TI stimulation on the human primary motor cortex (M1).Methods: Participants attended three sessions of 30-min TI stimulation during a random reaction time task (RRTT) or a serial reaction time task (SRTT). Motor cortex excitability was measured before and after TI stimulation.Results: In the RRTT experiment, only 70 Hz TI stimulation had a promoting effect on the reaction time (RT) performance and excitability of the motor cortex compared to sham stimulation. Meanwhile, compared with the sham condition, only 20 Hz TI stimulation significantly facilitated motor learning in the SRTT experiment, which was significantly positively correlated with the increase in motor evoked potential.Conclusion: These results indicate that the envelope-modulated waveform of TI stimulation has a significant promoting effect on human motor functions, experimentally suggesting the effectiveness of TI stimulation in humans for the first time and paving the way for further explorations.

PREPARATION OF PHYSICAL EDUCATION STUDENTS IN HIGHER EDUCATION INSTITUTIONS FOR INTEGRATION AND SOCIALIZATION OF PEOPLE WITH DISABILITIES BY ADAPTIVE MEANS

Adaptive physical culture and adaptive sports are the sphere of life in which the most successful is the socialization of disabled people and people with disabilities, their integration into society, the development of rehabilitation potential - as a set of biological capabilities of social abilities and psychological aspirations, improving the quality of life (Evseev, & Shapkova, 2000). Given the opportunities available in sports for social rehabilitation and integration of people with disabilities, in recent years, almost all over the world are developing active efforts to organize and develop adaptive sports among people with disabilities (Evseev, & Shapkova, 2000). In many developed countries, comprehensive programs of physical culture and sports work among the disabled, including children (Dmitriev, 2002).Comprehensive rehabilitation - as a process of ensuring the readiness of a person with health and disability to implement a lifestyle that would not contradict the lifestyle of healthy (normally developing) people requires the mandatory use of exercise adapted to a specific disease or defect of motor activity. Physical rehabilitation is the basis, the basis of any type of rehabilitation (social-labor, social-domestic, socio-cultural, etc.). This is due to the fact that man is indivisible biological, psychological and social, which are in the closest relationship and interaction. Human motor activity is embedded in genes and is associated with a fundamental property of a living organism - biological adaptation to living conditions and living conditions. However, modern living and working conditions have reduced to almost zero all human physical activity, created a situation of unclaimed physical condition.Hypodynamia and hypokinesia are indispensable attributes of modern civilized life have become one of the main factors causing the deterioration of public health. Reducing the volume and intensity of physical activity, low costs of muscular work, simplification and impoverishment of human motor activity leads to negative results in the functioning of both internal organs and systems of man and his psyche. And if a healthy person reduces his physical activity to an unacceptable level, then only he is to blame.The responsibility for forced hypodynamics and hypokinesia of children with disabilities, whose natural physical activity is limited and they need targeted assistance and special conditions, rests entirely with parents, doctors and other professionals, including adaptive physical education. The problem here is that in the mass consciousness and even among specialists (physicians, psychologists, representatives of traditional physical culture, etc.) the idea of the need for mandatory restriction of movement, motor activity in almost any disease, stereotypes of faith only in pharmacological and other medical means and methods of treatment and prevention, in omnipotent additives, stimulants, activators, fat burners, etc. This is due, on the one hand, the insufficient level of culture of society and the individual in the field of anthropology, its physicality and psyche, and on the other - the massive advertising campaigns of manufacturers of these goods.The scientific and medical literature examines in detail the other negative changes that occur in the human body due to hypodynamics and hypokinesia, from the cellular to the body level, describes in detail the so-called motorvisceral reflexes and other mechanisms of disease, the main cause of which there is immobility.Being one of the most important factors of the educational and cultural process, adaptive physical culture is a universal means of humanization, as it realizes the reproduction of human personality as a whole in its physical and spiritual unity. In the process of adaptive physical culture a person not only socializes and is formed (strengthens and improves residual health, corrects its defects, develops compensation mechanisms, learns certain social roles, functions, etc.), but also “forms and creates the world”, forms and “conquers” the social space - first self-determined, creates its own understanding, vision, sense of the world, designs and builds its own activities, social environment. Thus, adaptive physical culture and, especially adaptive sports, are important factors in the socialization of people with disabilities and people with disabilities, their integration into society. However, these factors, which are always realized, their use lags behind both the needs and the possibilities of today.

Cerebellar GABA change during visuomotor adaptation relates to adaptation performance and cerebellar network connectivity: A Magnetic Resonance Spectroscopic Imaging study.

Motor adaptation is crucial for performing accurate movements in a changing environment and relies on the cerebellum. Although cerebellar involvement has been well characterized, the neurochemical changes in the cerebellum that underpin human motor adaptation remain unknown. We used a novel Magnetic Resonance Spectroscopic Imaging (MRSI) technique to measure changes in the major inhibitory neurotransmitter γ-aminobutyric acid (GABA) in the human cerebellum during visuomotor adaptation. Participants used their right hand to adapt to a rotated cursor in the scanner, compared with a control task requiring no adaptation. We were able to spatially resolve adaptation-driven GABA changes at the cerebellar nuclei and in the cerebellar cortex in the left and the right cerebellar hemisphere independently and found that simple movement of the right hand increases GABA in the right cerebellar nuclei and decreases GABA in the left. When isolating adaptation-driven GABA changes, we found an increase in GABA in the left cerebellar nuclei and a decrease in GABA in the right cerebellar nuclei during adaptation. Early adaptation-driven GABA change in the right cerebellar nuclei correlated with adaptation performance: Participants showing greater GABA decrease adapted better, suggesting that this early GABA change is behaviourally relevant. Early GABA change also correlated with functional connectivity change in a cerebellar network: Participants showing a greater decrease in GABA also showed greater strength increase in cerebellar network connectivity. These results were specific to GABA, specific to adaptation and specific to the cerebellar network. This study provides the first evidence for plastic changes in cerebellar neurochemistry during a motor adaptation task. Characterising these naturally occurring neurochemical changes may provide a basis for developing therapeutic interventions to facilitate neurochemical changes in the cerebellum that can improve human motor adaptation.

Firing rate trajectories of human motor units during activity-dependent muscle potentiation

During activity-dependent potentiation (ADP) motor unit firing rates (MUFRs) are lower, however, the mechanism for this response is not known. During increasing torque isometric contractions at low contraction intensities, MUFR trajectories initially accelerate and saturate demonstrating a non-linear response due to the activation of persistent inward currents (PICs) at the motoneuron. The purpose was to assess whether PICs are a factor in the reduction of MUFRs during ADP. To assess this, MUFR trajectories were fit with competing functions of linear regression and a rising exponential (i.e., acceleration and saturation). Using fine-wire electrodes, discrete MU potential trains were recorded in the tibialis anterior during slowly increasing dorsiflexion contractions to 10% of maximal voluntary contraction following both voluntary (post-activation potentiation; PAP) and evoked (post-tetanic potentiation; PTP) contractions. In 8 participants, 25 MUs were recorded across both ADP conditions and compared to the control with no ADP effect. During PAP and PTP, the average MUFRs were 16.4% and 9.2% lower (both P≤ 0.001), respectively. More MUFR trajectories were better fit to the rising exponential during control (16/25) compared to PAP (4/25, P<0.001) and PTP (8/25, P=0.03). The MU samples that had a rising exponential MUFR trajectory during PAP and PTP displayed an ~11% lower initial acceleration compared to control (P<0.05). Thus, synaptic amplification and MUFR saturation due to PIC properties are attenuated during ADP regardless of the type of conditioning contraction. This response may contribute to lower MUFRs and likely occurred because synaptic input is reduced when contractile function is enhanced.

Is Resting State Functional MRI Effective Connectivity in Movement Disorders Helpful? A Focused Review Across Lifespan and Disease

In the evolving modern era of neuromodulation for movement disorders in adults and children, much progress has been made recently characterizing the human motor network (MN) with potentially important treatment implications. Herein is a focused review of relevant resting state fMRI functional and effective connectivity of the human motor network across the lifespan in health and disease. The goal is to examine how the transition from static functional to dynamic effective connectivity may be especially informative of network-targeted movement disorder therapies, with hopeful implications for children.Impact StatementWhile functional connectivity has elucidated much MN properties with relation to age, disease, and behavior, effective connectivity has been shown to be useful in MN-informed therapies in adults. Thus, effective connectivity may have potential to impact childhood movement disorder therapies, given the lower to no patient demand.

Task-dependent switching of feedback controllers

The separation of distinct motor memories by contextual cues is a well known and well studied phenomenon of feedforward human motor control. However, there is no clear evidence of such context-induced separation in feedback control. Here we test both experimentally and computationally if context-dependent switching of feedback controllers is possible in the human motor system. Specifically, we probe visuomotor feedback responses of our human participants in two different tasks – stop and hit – and under two different schedules. The first, blocked schedule, is used to measure the behaviour of stop and hit controllers in isolation, showing that it can only be described by two independent controllers with two different sets of control gains. The second, mixed schedule, is then used to compare how such behaviour evolves when participants regularly switch from one task to the other. Our results support our hypothesis that there is contextual switching of feedback controllers, further extending the accumulating evidence of shared features between feedforward and feedback control.

Optogenetically controlled human functional motor endplate for testing botulinum neurotoxins

Background The lack of physiologically relevant and predictive cell-based assays is one of the major obstacles for testing and developing botulinum neurotoxins (BoNTs) therapeutics. Human-induced pluripotent stem cells (hiPSCs)-derivatives now offer the opportunity to improve the relevance of cellular models and thus the translational value of preclinical data. Methods We investigated the potential of hiPSC-derived motor neurons (hMNs) optical stimulation combined with calcium imaging in cocultured muscle cells activity to investigate BoNT-sensitivity of an in vitro model of human muscle-nerve system. Results Functional muscle-nerve coculture system was developed using hMNs and human immortalized skeletal muscle cells. Our results demonstrated that hMNs can innervate myotubes and induce contractions and calcium transient in muscle cells, generating an in vitro human motor endplate showing dose-dependent sensitivity to BoNTs intoxication. The implementation of optogenetics combined with live calcium imaging allows to monitor the impact of BoNTs intoxication on synaptic transmission in human motor endplate model. Conclusions Altogether, our findings demonstrate the promise of optogenetically hiPSC-derived controlled muscle-nerve system for pharmaceutical BoNTs testing and development.

Sub-cellular elemental imaging of human muscle tissues affected by neuromuscular diseases

Various types of neuromuscular diseases differ in symptoms, pathology, and clinical picture but one of their common elements is muscle weakness, which could lead to human motor activities impairment and in many cases to shortening of life span and even death due to respiratory failure. That is why it is very important to better understand the underlying causes of these diseases to be able to implement new methods of treatment more effectively. This paper presents the results of the elemental analysis of human muscular tissues affected by dystrophy and myopathy. For this purpose, the particle-induced X-ray emission method was used, which is perfectly suited for measuring light elements. The samples were analysed for differences in the elemental composition of Na, Mg, P, S, Cl, K, Fe, Zn, and Br. The results were presented in the form of elemental concentration maps and a thorough statistical analysis of the obtained data using the advanced statistical methods.