Human Motor Research Articles

Arm muscle synergies enhance hand posture prediction in combination with forearm muscle synergies

Objective. We analyze and interpret arm and forearm muscle activity in relation with the kinematics of hand pre-shaping during reaching and grasping from the perspective of human synergistic motor control. Approach. Ten subjects performed six tasks involving reaching, grasping and object manipulation. We recorded electromyographic (EMG) signals from arm and forearm muscles with a mix of bipolar electrodes and high-density grids of electrodes. Motion capture was concurrently recorded to estimate hand kinematics. Muscle synergies were extracted separately for arm and forearm muscles, and postural synergies were extracted from hand joint angles. We assessed whether activation coefficients of postural synergies positively correlate with and can be regressed from activation coefficients of muscle synergies. Each type of synergies was clustered across subjects. Main results. We found consistency of the identified synergies across subjects, and we functionally evaluated synergy clusters computed across subjects to identify synergies representative of all subjects. We found a positive correlation between pairs of activation coefficients of muscle and postural synergies with important functional implications. We demonstrated a significant positive contribution in the combination between arm and forearm muscle synergies in estimating hand postural synergies with respect to estimation based on muscle synergies of only one body segment, either arm or forearm (p < 0.01). We found that dimensionality reduction of multi-muscle EMG root mean square (RMS) signals did not significantly affect hand posture estimation, as demonstrated by comparable results with regression of hand angles from EMG RMS signals. Significance. We demonstrated that hand posture prediction improves by combining activity of arm and forearm muscles and we evaluate, for the first time, correlation and regression between activation coefficients of arm muscle and hand postural synergies. Our findings can be beneficial for myoelectric control of hand prosthesis and upper-limb exoskeletons, and for biomarker evaluation during neurorehabilitation.

New insights into the characterization of the mechanism of action of hyoscine butylbromide in the human colon ex vivo

IntroductionHyoscine butylbromide (HBB) is one of the most used antispasmodics in clinical practice. Recent translational consensus has demonstrated a similarity between human colonic motor patterns studied ex vivo and in vivo, suggesting ex vivo can predict in vivo results. It is unclear whether the mechanism of action of antispasmodics can predict different use in clinical practice. The aim of the present study is to bridge this gap dissecting HBB's role in excitatory and inhibitory neural pathways. Methods: 309 colon samples from 48 patients were studied in muscle bath experiments. HBB was tested on: 1-spontaneous phasic contractions (SPCs); 2-carbachol-induced contractility; electrical field stimulation (EFS)-induced selective stimulation of 3-excitatory and 4-inhibitory pathways and 5- SPCs and EFS-induced contractions enhanced by neostigmine. Atropine, AF-DX116 (M2 blocker) and DAU-5884 (M3 blocker) were used as comparators. ResultsIn the presence of tetrodotoxin (TTX), HBB and atropine 1 μM reduced SPCs. HBB and atropine concentration-dependently reduced carbachol- and EFS-induced contractions. Inhibitory effects of DAU-5884 on EFS-induced contractions were more potent than of AF-DX116. HBB did not affect the off-response associated to neural inhibitory responses. Neostigmine enhanced both SPCs and EFS-induced contractions. In the presence of TTX and ω-conotoxin (GVIA), neostigmine still enhanced SPCs. Addition of HBB and atropine reduced these responses. ConclusionsThis study demonstrates that HBB inhibits neural cholinergic contractions associated to muscarinic (mainly M3) receptors. HBB has a potential role in reducing colonic spasm induced by the release of acetylcholine from enteric motor neurons and from an atypical source including a potential non-neuronal origin.

ROSPECTS FOR THE USE OF H-REFLEXOMETRY IN THE STUDY OF HUMAN MOTOR FUNCTION

SUMMARY. The article application of H-reflexometry in the study of the central mechanisms of random human movements, which is mainly carried out on healthy subjects, is demonstrated. It has been shown that the results of clinical trials performed by H-reflexometry with the participation of injured people or people with neurological disorders provide additional information about these mechanisms, reveal the causes of human motor function disorders, contribute to the improvement of methods of their study and provide opportunities for the implementation of rehabilitation measures.&#x0D; The aim – to evaluate the prospects of using H-reflexometry in the study of central mechanisms of movements and means of restoring and maximizing the motor capabilities of people.&#x0D; Material and Methods. The analysis was carried out using the scientific biological and medical information search system PubMed.&#x0D; Results. H-reflexometry was used both for the study of motor functions of healthy people and patients with injuries and neurological disorders. The authors studied mainly H-reflexes m.soleus, m. flexor carpi radialis, m. quadriceps. The total number of publications with the results of studies performed on other muscles indicates the possibility of a wider use of H-reflexometry in the study of motor functions in humans than is generally accepted and currently implemented. It was found that H-reflexometry was used to the greatest extent in the researches of the mechanisms of motor disorders arising as a result of stroke and spinal cord injuries.&#x0D; Conclusions. The results of the review indicate that H-reflexometry provides ample opportunities to study human motor function in normal and pathological conditions, and it may be especially promising at present to examine injured people using this method, to implement and monitor their rehabilitation measures.

The partial upward migration of the laryngeal motor cortex: A window to the human brain evolution

The pioneer cortical electrical stimulation studies of the last century did not explicitly mark the location of the human laryngeal motor cortex (LMC), but only the “vocalization area” in the lower half of the lateral motor cortex. In the final years of 2010́s, neuroimaging studies did demonstrate two human cortical laryngeal representations, located at the opposing ends of the orofacial motor zone, therefore termed dorsal (LMCd) and ventral laryngeal motor cortex (LMCv). Since then, there has been a continuing debate regarding the origin, function and evolutionary significance of these areas. The “local duplication model” posits that the LMCd evolved by a duplication of an adjacent region of the motor cortex. The “duplication and migration model” assumes that the dorsal LMCd arose by a duplication of motor regions related to vocalization, such as the ancestry LMC, followed by a migration into the orofacial region of the motor cortex. This paper reviews the basic arguments of these viewpoints and suggests a new explanation, declaring that the LMCd in man is rather induced through the division of the unitary LMC in nonhuman primates, upward shift and relocation of its motor part due to the disproportional growth of the head, face, mouth, lips, and tongue motor areas in the ventral part of the human motor homunculus. This explanation may be called “expansion-division and relocation model”.

Single-cell dissection of the human motor and prefrontal cortices in ALS and FTLD

Amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD) share many clinical, pathological, and genetic features, but a detailed understanding of their associated transcriptional alterations across vulnerable cortical cell types is lacking. Here, we report a high-resolution, comparative single-cell molecular atlas of the human primary motor and dorsolateral prefrontal cortices and their transcriptional alterations in sporadic and familial ALS and FTLD. By integrating transcriptional and genetic information, we identify known and previously unidentified vulnerable populations in cortical layer 5 and show that ALS- and FTLD-implicated motor and spindle neurons possess a virtually indistinguishable molecular identity. We implicate potential disease mechanisms affecting these cell types as well as non-neuronal drivers of pathogenesis. Finally, we show that neuron loss in cortical layer 5 tracks more closely with transcriptional identity rather than cellular morphology and extends beyond previously reported vulnerable cell types.

A TBK1 variant causes autophagolysosomal and motoneuron pathology without neuroinflammation in mice.

Heterozygous mutations in the TBK1 gene can cause amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). The majority of TBK1-ALS/FTD patients carry deleterious loss-of-expression mutations, and it is still unclear which TBK1 function leads to neurodegeneration. We investigated the impact of the pathogenic TBK1 missense variant p.E696K, which does not abolish protein expression, but leads to a selective loss of TBK1 binding to the autophagy adaptor protein and TBK1 substrate optineurin. Using organelle-specific proteomics, we found that in a knock-in mouse model and human iPSC-derived motor neurons, the p.E696K mutation causes presymptomatic onset of autophagolysosomal dysfunction in neurons precipitating the accumulation of damaged lysosomes. This is followed by a progressive, age-dependent motor neuron disease. Contrary to the phenotype of mice with full Tbk1 knock-out, RIPK/TNF-α-dependent hepatic, neuronal necroptosis, and overt autoinflammation were not detected. Our in vivo results indicate autophagolysosomal dysfunction as a trigger for neurodegeneration and a promising therapeutic target in TBK1-ALS/FTD.

Role of compliant mechanics and motor control in hopping - from human to robot

Compliant leg function found during bouncy gaits in humans and animals can be considered a role model for designing and controlling bioinspired robots and assistive devices. The human musculoskeletal design and control differ from distal to proximal joints in the leg. The specific mechanical properties of different leg parts could simplify motor control, e.g., by taking advantage of passive body dynamics. This control embodiment is complemented by neural reflex circuitries shaping human motor control. This study investigates the contribution of specific passive and active properties at different leg joint levels in human hopping at different hopping frequencies. We analyze the kinematics and kinetics of human leg joints to design and control a bioinspired hopping robot. In addition, this robot is used as a test rig to validate the identified concepts from human hopping. We found that the more distal the joint, the higher the possibility of benefit from passive compliant leg structures. A passive elastic element nicely describes the ankle joint function. In contrast, a more significant contribution to energy management using an active element (e.g., by feedback control) is predicted for the knee and hip joints. The ankle and knee joints are the key contributors to adjusting hopping frequency. Humans can speed up hopping by increasing ankle stiffness and tuning corresponding knee control parameters. We found that the force-modulated compliance (FMC) as an abstract reflex-based control beside a fixed spring can predict human knee torque-angle patterns at different frequencies. These developed bioinspired models for ankle and knee joints were applied to design and control the EPA-hopper-II robot. The experimental results support our biomechanical findings while indicating potential robot improvements. Based on the proposed model and the robot’s experimental results, passive compliant elements (e.g. tendons) have a larger capacity to contribute to the distal joint function compared to proximal joints. With the use of more compliant elements in the distal joint, a larger contribution to managing energy changes is observed in the upper joints.

The Role of Human Pluripotent Stem Cells in Amyotrophic Lateral Sclerosis: From Biological Mechanism to Practical Implications.

Amyotrophic Lateral Sclerosis (ALS) is a neurodegenerative disorder, characterized by progressive loss of both upper and lower motor neurons, resulting in clinical features such as muscle weakness, paralysis, and ultimately, respiratory failure. Nowadays, there is not effective treatment to reverse the progression of the disease, that leads to death within 3-5 years after the onset. Nevertheless, the induced pluripotent stem cells (iPS) technology could be the answer, providing disease modelling, drug testing, and cell-based therapies for this pathology. The aim of this work was to conduct a literature review of the past 5 years about the role of iPS in ALS, to better define the neurobiological mechanisms involved in the pathogenesis and the potential future therapies. The review also deals with advanced and currently available technologies used to reprogram cell lines and generate human motor neurons in vitro, which represent the source to study the pathological processes, the relationship between phenotype and genotype, the disease progression and the potential therapeutic targets of these group of disorders. Specific treatment options with stem cells involve Advance Gene Editing Technology, neuroprotective agents, and cells or exosomes transplantation, aimed to replace dead or damaged nerve cells. In summary, this review comprehensively addresses the role of human pluripotent stem cells (hPSCs) in motor neuron diseases (MND), with a focus on physiopathology, diagnostic and prognostic implications, specific and potential future treatment options. Understanding the biological mechanisms and practical implications of hPSCs in MND is crucial for advancing therapeutic strategies and improving outcomes for patients affected by these devastating diseases.

Antagonism of 5-HT2 receptors attenuates self-sustained firing of human motor units.

5-HT2 receptors on motoneurones play a critical role in facilitating persistent inward currents (PICs). Although facilitation of PICs can enhance self-sustained firing after periods of excitation, the relationship between 5-HT2 receptor activity and self-sustained firing in human motor units (MUs) has not been resolved. MU activity was assessed from the tibialis anterior of 10 healthy adults (24.9 ± 2.8 years) during two contraction protocols. Both protocols featured steady-state isometric contractions with constant descending drive to the motoneurone pool. However, one protocol also included an additional phase of superimposed descending drive. Adding and then removing descending drive in the middle of steady-state contractions altered MU firing behaviour across the motor pool, where newly recruited units in the superimposed phase were unable to switch off (P=0.0002), and units recruited prior to additional descending drive reduced their discharge rates (P<0.0001, difference in estimated marginal means (∆)=2.24 pulses/s). The 5-HT2 receptor antagonist, cyproheptadine, was then administered to determine whether changes in MU firing were mediated by serotonergic mechanisms. 5-HT2 receptor antagonism caused reductions in MU discharge rate (P<0.001, ∆=1.65 pulses/s), recruitment threshold (P=0.00112, ∆=1.09% maximal voluntary contraction) and self-sustained firing duration (P<0.0001, ∆=1.77s) after the additional descending drive was removed in the middle of the steady-state contraction. These findings indicate that serotonergic neuromodulation plays a key role in facilitating discharge and self-sustained firing of human motoneurones, where adaptive changes in MU recruitment must occur to meet the demands of the contraction. KEY POINTS: Animal and cellular preparations indicate that somato-dendritic 5-HT2 receptors regulate the intrinsic excitability of motoneurones. 5-HT2 receptor antagonism reduces estimates of persistent inward currents in motoneurones, which contribute to self-sustained firing when synaptic inputs are reduced or removed. This human study employed a contraction task that slowly increased (and then removed) the additional descending drive in the middle of a steady-state contraction where marked self-sustained firing occurred when the descending drive was removed. 5-HT2 receptor antagonism caused widespread reductions in motor unit (MU) discharge rates during contractions, which was accompanied by reduced recruitment threshold and attenuation of self-sustained firing duration after the removal of the additional descending drive to motoneurones. These findings support the role that serotonergic neuromodulation is a key facilitator of MU discharge and self-sustained firing of human motoneurones, where adaptative changes in MU recruitment must occur to meet the demands of the contraction.

Influence of oral motor tasks on postural muscle activity during dynamic reactive balance.

Jaw clenching improves dynamic reactive balance on an oscillating platform during forward acceleration and is associated with decreased mean sway speed of different body regions. It is suggested that jaw clenching as a concurrent muscle activity facilitates human motor excitability, increasing the neural drive to distal muscles. The underlying mechanism behind this phenomenon was studied based on leg and trunk muscle activity (iEMG) and co-contraction ratio (CCR). Forty-eight physically active and healthy adults were assigned to three groups, performing three oral motor tasks (jaw clenching, tongue pressing against the palate or habitual lower jaw position) during a dynamic one-legged stance reactive balance task on an oscillating platform. The iEMG and CCR of posture-relevant muscles and muscle pairs were analysed during platform forward acceleration. Tongue pressing caused an adjustment of co-contraction patterns of distal muscle groups based on changes in biomechanical coupling between the head and trunk during static balancing at the beginning of the experiment. Neither iEMG nor CCR measurement helped detect a general neuromuscular effect of jaw clenching on the dynamic reactive balance. The findings might indicate the existence of robust fixed patterns of rapid postural responses during the important initial phases of balance recovery.

Operational encoding enhances action knowledge integration: insights from event-related potential analysis.

In this study, we conducted an examination of knowledge integration concerning action information and assessed the impact of operational on this process. Additionally, we delved into the underlying mechanisms of how operational encoding influences the processing of knowledge integration of action information, utilizing the event-related potential technique. The results of our investigation revealed that operational encoding, encompassing the observed operational encoding and the imagined operational encoding, exhibited superior performance in the integration of action knowledge compared to verbal encoding. This distinction may be attributed to the greater efficiency of operant encoding in activating motor cortical areas, thereby inducing more robust brain activity. These findings suggest the potential advantages of operational encoding in facilitating the integration of knowledge related to movement information at both cognitive and neural levels, underscoring its significant role in the processing of such information. Future studies can further explore the applications of operational encoding in domains, such as motor learning, skill training, and rehabilitation therapy. Such investigations may offer novel insights into enhancing human behavior and motor control.

Neuronal STING activation in amyotrophic lateral sclerosis and frontotemporal dementia

The stimulator of interferon genes (STING) pathway has been implicated in neurodegenerative diseases, including Parkinson’s disease and amyotrophic lateral sclerosis (ALS). While prior studies have focused on STING within immune cells, little is known about STING within neurons. Here, we document neuronal activation of the STING pathway in human postmortem cortical and spinal motor neurons from individuals affected by familial or sporadic ALS. This process takes place selectively in the most vulnerable cortical and spinal motor neurons but not in neurons that are less affected by the disease. Concordant STING activation in layer V cortical motor neurons occurs in a mouse model of C9orf72 repeat-associated ALS and frontotemporal dementia (FTD). To establish that STING activation occurs in a neuron-autonomous manner, we demonstrate the integrity of the STING signaling pathway, including both upstream activators and downstream innate immune response effectors, in dissociated mouse cortical neurons and neurons derived from control human induced pluripotent stem cells (iPSCs). Human iPSC-derived neurons harboring different familial ALS-causing mutations exhibit increased STING signaling with DNA damage as a main driver. The elevated downstream inflammatory markers present in ALS iPSC-derived neurons can be suppressed with a STING inhibitor. Our results reveal an immunophenotype that consists of innate immune signaling driven by the STING pathway and occurs specifically within vulnerable neurons in ALS/FTD.

Measuring and monitoring skill learning in closed-loop myoelectric hand prostheses using speed-accuracy tradeoffs

Objective. Closed-loop myoelectric prostheses, which combine supplementary sensory feedback and electromyography (EMG) based control, hold the potential to narrow the divide between natural and bionic hands. The use of these devices, however, requires dedicated training. Therefore, it is crucial to develop methods that quantify how users acquire skilled control over their prostheses to effectively monitor skill progression and inform the development of interfaces that optimize this process. Approach. Building on theories of skill learning in human motor control, we measured speed-accuracy tradeoff functions (SAFs) to comprehensively characterize learning-induced changes in skill—as opposed to merely tracking changes in task success across training—facilitated by a closed-loop interface that combined proportional control and EMG feedback. Sixteen healthy participants and one individual with a transradial limb loss participated in a three-day experiment where they were instructed to perform the box-and-blocks task using a timed force-matching paradigm at four specified speeds to reach two target force levels, such that the SAF could be determined. Main results. We found that the participants’ accuracy increased in a similar way across all speeds we tested. Consequently, the shape of the SAF remained similar across days, at both force levels. Further, we observed that EMG feedback enabled participants to improve their motor execution in terms of reduced trial-by-trial variability, a hallmark of skilled behavior. We then fit a power law model of the SAF, and demonstrated how the model parameters could be used to identify and monitor changes in skill. Significance. We comprehensively characterized how an EMG feedback interface enabled skill acquisition, both at the level of task performance and movement execution. More generally, we believe that the proposed methods are effective for measuring and monitoring user skill progression in closed-loop prosthesis control.

Motor neurons and endothelial cells additively promote development and fusion of human iPSC-derived skeletal myocytes

BackgroundNeurovascular cells have wide-ranging implications on skeletal muscle biology regulating myogenesis, maturation, and regeneration. Although several in vitro studies have investigated how motor neurons and endothelial cells interact with skeletal myocytes independently, there is limited knowledge about the combined effect of neural and vascular cells on muscle maturation and development.MethodsHere, we report a triculture system comprising human-induced pluripotent stem cell (iPSC)-derived skeletal myocytes, human iPSC-derived motor neurons, and primary human endothelial cells maintained under controlled media conditions. Briefly, iPSCs were differentiated to generate skeletal muscle progenitor cells (SMPCs). These SMPCs were seeded at a density of 5 × 104 cells/well in 12-well plates and allowed to differentiate for 7 days before adding iPSC-derived motor neurons at a concentration of 0.5 × 104 cells/well. The neuromuscular coculture was maintained for another 7 days in coculture media before addition of primary human umbilical vein endothelial cells (HUVEC) also at 0.5 × 104 cells/well. The triculture was maintained for another 7 days in triculture media comprising equal portions of muscle differentiation media, coculture media, and vascular media. Extensive morphological, genetic, and molecular characterization was performed to understand the combined and individual effects of neural and vascular cells on skeletal muscle maturation.ResultsWe observed that motor neurons independently promoted myofiber fusion, upregulated neuromuscular junction genes, and maintained a molecular niche supportive of muscle maturation. Endothelial cells independently did not support myofiber fusion and downregulated expression of LRP4 but did promote expression of type II specific myosin isoforms. However, neurovascular cells in combination exhibited additive increases in myofiber fusion and length, enhanced production of Agrin, along with upregulation of several key genes like MUSK, RAPSYN, DOK-7, and SLC2A4. Interestingly, more divergent effects were observed in expression of genes like MYH8, MYH1, MYH2, MYH4, and LRP4 and secretion of key molecular factors like amphiregulin and IGFBP-4.ConclusionsNeurovascular cells when cultured in combination with skeletal myocytes promoted myocyte fusion with concomitant increase in expression of various neuromuscular genes. This triculture system may be used to gain a deeper understanding of the effects of the neurovascular niche on skeletal muscle biology and pathophysiology.

Robotic realization of human perceptual changes with lateral balance task

Human motor learning affects not only motion pattern but also perception. On the basis of this idea, we investigated some human-balancing tasks to observe changes in the balance perception. We simulated one of the results to replay the human behavior. In this study, we aim to demonstrate the human adaptive behavior in a motor and sensory system using a robot in a real-world scenario. The subjective upright, i.e., the inclination angle was considered as upright, was evaluated as perception in a balance position, and its lateral shift was determined after a motor-learning task under lateral disturbances. The adaptation dynamics were defined based on our hypothesis that stated that the subjective upright tends to vary toward the posture in which balance can be best maintained. Consequently, the change in the subjective upright similar to the human result was reproduced using a two-link robot that was subjected to the same environmental condition as that in the human experiment.

Highly sensitive, anti-freeze, repairable, and conductive double-network organohydrogel for flexible pressure sensors

Flexible strain sensors based on double network conductive hydrogels have attracted much attention due to their great potential for human motion health and smart detection. However, the development of conductive hydrogels with high sensitivity and anti-freezing properties for a wide range of use environments is still a challenge. Herein, a novel organohydrogel-based PVA-P-TA-MWCNTs (PPTME) double network capable of pressure and strain sensing was reported with high ambient stability, excellent anti-freezing capability, smart reparability and superior sensitivity. The multiple interactions within the PPTME organohydrogel have been substantiated through Density Functional Theory (DFT) analysis. The organohydrogel utilizing strong hydrogel bonds, crystalline microphases, and chain entanglement of PTA/PVA exhibited good mechanical properties (374%) and excellent cycling performance. Meanwhile, owing to the addition of H2O/EG (ethylene glycol) binary solvent, this organohydrogel exhibited long-term water retention (15 days), anti-freezing properties (−61.9 °C), greatly improving the applications at low temperatures. Furthermore, the assembled pressure sensors showed ultrahigh sensitivity (1.88 kPa−1) in wide detection range (0–266.2 kPa). Based on these excellent properties, a flexible organohydrogel sensor was prepared, demonstrating its enormous potential in the field of human motor behavior detection and wearable.

Structural insights into the modulation Of SOD1 aggregation By a fungal metabolite Phialomustin-B: Therapeutic potential in ALS.

Amyotrophic lateral sclerosis (ALS) is a fatal human motor neuron disease leading to muscle atrophy and paralysis. Mutations in superoxide dismutase 1 (SOD1) are associated with familial ALS (fALS). The SOD1 mutants in ALS have a toxic-gain of function by destabilizing the functional SOD1 homodimer, consequently inducing fibril-like aggregation with a cytotoxic non-native trimer intermediate. Therefore, reducing SOD1 oligomerization via chemical modulators is an optimal therapy in ALS. Here, we report the discovery of Phialomustin-B, an unsaturated secondary metabolite from the endophytic fungus Phialophora mustea, as a modulator of SOD1 aggregation. The crystal structure of the SOD1-Phialomustin complex refined to 1.90 Å resolution demonstrated for the first time that the ligand binds to the dimer interface and the lateral region near the electrostatic loop. The aggregation analyses of SOD1WT and the disease mutant SOD1A4V revealed that Phialomustin-B reduces cytotoxic trimerization. We propose that Phialomustin-B is a potent lead molecule with therapeutic potential in fALS.

Effects of different sonication parameters of theta burst transcranial ultrasound stimulation on human motor cortex

BackgroundTheta burst TUS (tbTUS) can induce increased cortical excitability in human, but how different sonication parameters influence the effects are still unknown. ObjectiveTo examine how a range of sonication parameters, including acoustic intensity, pulse repetition frequency, duty cycle and sonication duration, influence the effects of tbTUS on human motor cortical excitability. Methods14 right-handed healthy subjects underwent 8 sessions with different tbTUS parameters in a randomized, cross-over design on separate days. The original tbTUS protocol was studied in one session and one parameter was changed in each of the seven sessions. To examine changes in cortical excitability induced by tbTUS, we measured the motor-evoked potential (MEP) amplitude, resting motor threshold, short-interval intracortical inhibition and intracortical facilitation, as well as short-interval intracortical facilitation before and up to 90 min after tbTUS. ResultsAll conditions increased MEP amplitudes except the condition with low acoustic intensity of 10 W/cm2. Pulse repetition frequency of 5 Hz produced higher MEP amplitudes compared to pulse repetition frequencies of 2 and 10 Hz. In addition, higher duty cycles (5%, 10%, and 15%) and longer sonication durations (40, 80, and 120 s) were associated with longer duration of increased MEP amplitudes. Resting motor threshold remained stable in all conditions. For paired-pulse TMS measures, tbTUS reduced short-interval intracortical inhibition and enhanced short-interval intracortical facilitation, but had no effect on intracortical facilitation. ConclusionsUltrasound bursts repeated at theta (∼5 Hz) frequency is optimal to produce increased cortical excitability with the range of 2–10 Hz. Furthermore, there was a dose-response effect regarding duty cycle and sonication duration in tbTUS for plasticity induction. The aftereffects of tbTUS were associated with a shift of the inhibition/excitation balance toward less inhibition and more excitation in the motor cortex. These findings can be used to determine the optimal tbTUS parameters in neuroscience research and treatment of neurological and psychiatric disorders.

Classical conditioning of the facilitatory influence of paired-pulse TMS on the excitability of the human motor cortex – A proof-of-concept study

Classical conditioning of the facilitatory influence of paired-pulse TMS on the excitability of the human motor cortex – A proof-of-concept study

INSIGHTS INTO HUMAN LOCOMOTION STRATEGIES AND MOTOR LEARNING FOR AN AGEING POPULATION USING TRANSFER TESTING AND COUPLED SIMULATIONS

The elucidation of human locomotion strategies has potential applications in the prevention of sarcopenia and in the reduction of falls. Given the diverse biochemical, mechanical and functional age-related changes seen in the neuro-musculoskeletal system, the decline in motor function is difficult to study experimentally. In this study, we use transfer testing and coupled simulation strategies within a deep reinforcement learning environment to better understand the complex problem of motor control adaptation to age-related changes. Using transfer testing, a 3D musculoskeletal model is separately trained on parameters of the young adult model (Y) for either forward or backward falls after completing two steps forward, and tested using a 30% age-related reduction for all parameters (M_all). This strategy produces a backward fall for a forwardly trained simulation, showing potential sensitivity of these parameters to a given fall direction. Second, a coupled simulation solution is used to simulate recovery from falls by considering the center-of-mass position relative to the base of support. Results for the M_all trained model showed a longer simulation time and a greater vertical pelvis velocity with a maximal value of 4.26[Formula: see text]m/s. In particular, the results of the coupled simulations clearly show that both the young and M_all condition models respond with a step back and stronger leg extensor activations to propel the model forward to recover from the simulated fall. We developed a novel coupling between transfer testing and coupled simulation strategies to improve upon muscle models for characterizing muscle function, and also to begin testing different hypotheses, such as the strategy and force required to avoid a fall at different limits. This opens new avenues for precision rehabilitation with patient-specific muscle-driven recovery exercises.