Perceptual error based on Bayesian cue combination drives implicit motor adaptation.

The sensorimotor system can recalibrate itself without our conscious awareness, a type of procedural learning whose computational mechanism remains undefined. Recent findings on implicit motor adaptation, such as over-learning from small perturbations and fast saturation for increasing perturbation size, challenge existing theories based on sensory errors. We argue that perceptual error, arising from the optimal combination of movement-related cues, is the primary driver of implicit adaptation. Central to our theory is the increasing sensory uncertainty of visual cues with increasing perturbations, which was validated through perceptual psychophysics (Experiment 1). Our theory predicts the learning dynamics of implicit adaptation across a spectrum of perturbation sizes on a trial-by-trial basis (Experiment 2). It explains proprioception changes and their relation to visual perturbation (Experiment 3). By modulating visual uncertainty in perturbation, we induced unique adaptation responses in line with our model predictions (Experiment 4). Overall, our perceptual error framework outperforms existing models based on sensory errors, suggesting that perceptual error in locating one's effector, supported by Bayesian cue integration, underpins the sensorimotor system's implicit adaptation.

Online reach adjustments induced by real-time movement sonification.

Movement sonification can improve motor control in both healthy subjects (e.g., learning or refining a sport skill) and those with sensorimotor deficits (e.g., stroke patients and deafferented individuals). It is not known whether improved motor control and learning from movement sonification are driven by feedback-based real-time ("online") trajectory adjustments, adjustments to internal models over multiple trials, or both. We searched for evidence of online trajectory adjustments (muscle twitches) in response to movement sonification feedback by comparing the kinematics and error of reaches made with online (i.e., real-time) and terminal sonification feedback. We found that reaches made with online feedback were significantly more jerky than reaches made with terminal feedback, indicating increased muscle twitching (i.e., online trajectory adjustment). Using a between-subject design, we found that online feedback was associated with improved motor learning of a reach path and target over terminal feedback; however, using a within-subjects design, we found that switching participants who had learned with online sonification feedback to terminal feedback was associated with a decrease in error. Thus, our results suggest that, with our task and sonification, movement sonification leads to online trajectory adjustments which improve internal models over multiple trials, but which themselves are not helpful online corrections.

Effector-specific improvements in action prediction in left-handed individuals after short-term physical practice.

Research has established the influence of short-term physical practice for enhancing action prediction in right-handed (RH) individuals. In addition to benefits of physical practice for these later assessed perceptual-cognitive skills, effector-specific interference has been shown through action-incongruent secondary tasks (motor interference tasks). Here we investigated this experience-driven facilitation of action predictions and effector-specific interference in left-handed (LH) novices, before and after practicing a dart throwing task. Participants watched either RH (n = 19) or LH (n = 24) videos of temporally occluded dart throws, across a control condition and three secondary-task conditions: tone-monitoring, RH or LH force monitoring. These conditions were completed before and after physical practice throwing with the LH. Significantly greater improvement in prediction accuracy was shown post-practice for the LH- versus RH-video group. Consistent with previous work, effector-specific interference was shown, exclusive to the LH-video group. Only when doing the LH force monitoring task did the LH-video group show secondary task interference in prediction accuracy. These data support the idea that short-term physical practice resulted in the development of an effector-specific motor representation. The results are also consistent with other work in RH individuals (showing RH motor interference) and hence rule out the interpretation that these effector specific effects are due to the disruption of more generalized motor processes, thought to be lateralized to the left-hemisphere of the brain.

Identification of a Hippocampus-to-Zona Incerta Projection involved in Motor Learning.

Motor learning (ML), which plays a fundamental role in growth and physical rehabilitation, involves different stages of learning and memory processes through different brain regions. However, the neural mechanisms that underlie ML are not sufficiently understood. Here, a previously unreported neuronal projection from the dorsal hippocampus (dHPC) to the zona incerta (ZI) involved in the regulation of ML behaviors is identified. Using recombinant adeno-associated virus, the projections to the ZI are surprisingly identified as originating from the dorsal dentate gyrus (DG) and CA1 subregions of the dHPC. Furthermore, projection-specific chemogenetic and optogenetic manipulation reveals that the projections from the dorsal CA1 to the ZI play key roles in the acquisition and consolidation of ML behaviors, whereas the projections from the dorsal DG to the ZI mediate the retrieval/retention of ML behaviors. The results reveal new projections from the dorsal DG and dorsal CA1 to the ZI involved in the regulation of ML and provide insight into the stages over which this regulation occurs.

Ablation of oligodendrogenesis in adult mice alters brain microstructure and activity independently of behavioral deficits.

Oligodendrocytes continue to differentiate from their precursor cells even in adulthood, a process that can be modulated by neuronal activity and experience. Previous work has indicated that conditional ablation of oligodendrogenesis in adult mice leads to learning and memory deficits in a range of behavioral tasks. The current study replicated and re-evaluated evidence for a role of oligodendrogenesis in motor learning, using a complex running wheel task. Further, we found that ablating oligodendrogenesis alters brain microstructure (ex vivo MRI) and brain activity (in vivo EEG) independent of experience with the task. This suggests a role for adult oligodendrocyte formation in the maintenance of brain function and indicates that task-independent changes due to oligodendrogenesis ablation need to be considered when interpreting learning and memory deficits in this model.

Kainate receptors regulate synaptic integrity and plasticity by forming a complex with synaptic organizers in the cerebellum.

Kainate (KA)-type glutamate receptors (KARs) are implicated in various neuropsychiatric and neurological disorders through their ionotropic and metabotropic actions. However, compared to AMPA- and NMDA-type receptor functions, many aspects of KAR biology remain incompletely understood. Our study demonstrates an important role of KARs in organizing climbing fiber (CF)-Purkinje cell (PC) synapses and synaptic plasticity in the cerebellum, independently of their ion channel or metabotropic functions. The amino-terminal domain (ATD) of the GluK4 KAR subunit binds to C1ql1, provided by CFs, and associates with Bai3, an adhesion-type G protein-coupled receptor expressed in PC dendrites. Mice lacking GluK4 exhibit no KAR-mediated responses, reduced C1ql1 and Bai3 levels, and fewer CF-PC synapses, along with impaired long-term depression and oculomotor learning. Remarkably, introduction of the ATD of GluK4 significantly improves all these phenotypes. These findings demonstrate that KARs act as synaptic scaffolds, orchestrating synapses by forming a KAR-C1ql1-Bai3 complex in the cerebellum.

The effect of robot-assisted versus standard training on motor function following subacute rehabilitation after ischemic stroke - protocol for a randomised controlled trial nested in a prospective cohort (RoboRehab).

BACKGROUND: Body weight unloaded treadmill training has shown limited efficacy in further improving functional capacity after subacute rehabilitation of ischemic stroke patients. Dynamic robot assisted bodyweight unloading is a novel technology that may provide superior training stimuli and continued functional improvements in individuals with residual impairments in the chronic phase after the ischemic insult. The aim of the present study is to investigate the effect of dynamic robot-assisted versus standard training, initiated 6 months post-stroke, on motor function, physical function, fatigue, and quality of life in stroke-affected individuals still suffering from moderate-to-severe disabilities after subacute rehabilitation. METHODS: Stroke-affected individuals with moderate to severe disabilities will be recruited into a prospective cohort with measurements at 3-, 6-, 12- and 18-months post-stroke. A randomised controlled trial (RCT) will be nested in the prospective cohort with measurements pre-intervention (Pre), post-intervention (Post) and at follow-up 6 months following post-intervention testing. The present RCT will be conducted as a multicentre parallel-group superiority of intervention study with assessor-blinding and a stratified block randomisation design. Following pre-intervention testing, participants in the RCT study will be randomised into robot-assisted training (intervention) or standard training (active control). Participants in both groups will train 1:1 with a physiotherapist two times a week for 6 months (groups are matched for time allocated to training). The primary outcome is the between-group difference in change score of Fugl-Meyer Lower Extremity Assessment from pre-post intervention on the intention-to-treat population. A per-protocol analysis will be conducted analysing the differences in change scores of the participants demonstrating acceptable adherence. A priori sample size calculation allowing the detection of the minimally clinically important between-group difference of 6 points in the primary outcome (standard deviation 6 point, α = 5% and ß = 80%) resulted in 34 study participants. Allowing for dropout the study will include 40 participants in total. DISCUSSION: For stroke-affected individuals still suffering from moderate to severe disabilities following subacute standard rehabilitation, training interventions based on dynamic robot-assisted body weight unloading may facilitate an appropriate intensity, volume and task-specificity in training leading to superior functional recovery compared to training without the use of body weight unloading. TRIAL REGISTRATION: ClinicalTrials.gov. NCT06273475. TRIAL STATUS: Recruiting. Trial identifier: NCT06273475. Registry name: ClinicalTrials.gov. Date of registration on ClinicalTrials.gov: 22/02/2024.

PEMOCS: theory derivation of a concept for PErsonalized MOtor-Cognitive exergame training in chronic Stroke-a methodological paper with an application example.

Background: Coping with residual cognitive and gait impairments is a prominent unmet need in community-dwelling chronic stroke survivors. Motor-cognitive exergames may be promising to address this unmet need. However, many studies have so far implemented motor-cognitive exergame interventions in an unstructured manner and suitable application protocols remain yet unclear. We, therefore, aimed to summarize existing literature on this topic, and developed a training concept for motor-cognitive exergame interventions in chronic stroke. Methods: The development of the training concept for personalized motor-cognitive exergame training for stroke (PEMOCS) followed Theory Derivation procedures. This comprised (1.1) a thorough (narrative) literature search on long-term stroke rehabilitation; (1.2) a wider literature search beyond the topic of interest to identify analogies, and to induce creativity; (2) the identification of parent theories; (3) the adoption of suitable content or structure of the main parent theory; and (4) the induction of modifications to adapt it to the new field of interest. We also considered several aspects of the "Framework for Developing and Evaluating Complex Interventions" by the Medical Research Council. Specifically, a feasibility study was conducted, and refining actions based on the findings were performed. Results: A training concept for improving cognitive functions and gait in community-dwelling chronic stroke survivors should consider the principles for neuroplasticity, (motor) skill learning, and training. We suggest using a step-based exergame training for at least 12 weeks, 2-3 times a week for approximately 45 min. Gentile's Taxonomy for Motor Learning was identified as suitable fundament for the personalized progression and variability rules, and extended by a third cognitive dimension. Concepts and models from related fields inspired further additions and modifications to the concept. Conclusion: We propose the PEMOCS concept for improving cognitive functioning and gait in community-dwelling chronic stroke survivors, which serves as a guide for structuring and implementing motor-cognitive exergame interventions. Future research should focus on developing objective performance parameters that enable personalized progression independent of the chosen exergame type.

Attenuation of implicit motor learning with consecutive exposure to visual errors.

Visual errors induced by movement drive implicit corrections of that movement. When similar errors are experienced consecutively, does sensitivity to the error remain consistent each time? This study aimed to investigate the modulation of implicit error sensitivity through continuous exposure to the same errors. In the reaching task using visual error-clamp feedback, participants were presented with the same error in direction and magnitude for four consecutive trials. We found that implicit error sensitivity decreased after exposure to the second error. These results indicate that when visual errors occur consecutively, the sensorimotor system exhibits different responses, even for identical errors. The continuity of errors may be a factor that modulates error sensitivity.

Reconfigurations of cortical manifold structure during reward-based motor learning.

Adaptive motor behavior depends on the coordinated activity of multiple neural systems distributed across the brain. While the role of sensorimotor cortex in motor learning has been well established, how higher-order brain systems interact with sensorimotor cortex to guide learning is less well understood. Using functional MRI, we examined human brain activity during a reward-based motor task where subjects learned to shape their hand trajectories through reinforcement feedback. We projected patterns of cortical and striatal functional connectivity onto a low-dimensional manifold space and examined how regions expanded and contracted along the manifold during learning. During early learning, we found that several sensorimotor areas in the dorsal attention network exhibited increased covariance with areas of the salience/ventral attention network and reduced covariance with areas of the default mode network (DMN). During late learning, these effects reversed, with sensorimotor areas now exhibiting increased covariance with DMN areas. However, areas in posteromedial cortex showed the opposite pattern across learning phases, with its connectivity suggesting a role in coordinating activity across different networks over time. Our results establish the neural changes that support reward-based motor learning and identify distinct transitions in the functional coupling of sensorimotor to transmodal cortex when adapting behavior.

Short-Term Reproduction of Active Movement with Visual Feedback and Passive Movement with a Therapist's Hands.

Reproducing instructed movements is crucial for practice in motor learning. In this study, we compared the short-term reproduction of active pelvis movements with visual feedback and passive movement with the therapist's hands in an upright stance. Sixteen healthy males (M age = 34.1; SD = 10.2 years) participated in this study. In one condition, healthy males maintained an upright stance while a physical therapist moved the participant's pelvis (passive movement instruction), and in a second condition, the participant actively moved their pelvis with visual feedback of the target and the online trajectory of the center of pressure (active movement instruction). Reproduction errors (displacement of the center of pressure in the medial-lateral axis) 10 s after the passive movement instruction were significantly greater than after the active movement instruction (p < 0.001), but this difference disappeared 30 s after the instruction (p = 0.118). Error of movement reproduction in the anterior-posterior axis after the passive movement instruction was significantly greater than after the active movement instruction, no matter how long the retention interval was between the instruction and reproduction phases (p = 0.025). Taken together, active pelvis movements with visual feedback, rather than passive movement with the therapist's hand, is better to be used for instructing pelvis movements.

Investigation of Motor Learning Effects Using a Hybrid Rehabilitation System Based on Motion Estimation.

Upper-limb paralysis requires extensive rehabilitation to recover functionality for everyday living, and such assistance can be supported with robot technology. Against such a background, we have proposed an electromyography (EMG)-driven hybrid rehabilitation system based on motion estimation using a probabilistic neural network. The system controls a robot and functional electrical stimulation (FES) from movement estimation using EMG signals based on the user's intention, enabling intuitive learning of joint motion and muscle contraction capacity even for multiple motions. In this study, hybrid and visual-feedback training were conducted with pointing movements involving the non-dominant wrist, and the motor learning effect was examined via quantitative evaluation of accuracy, stability, and smoothness. The results show that hybrid instruction was as effective as visual feedback training in all aspects. Accordingly, passive hybrid instruction using the proposed system can be considered effective in promoting motor learning and rehabilitation for paralysis with inability to perform voluntary movements.

Realizing the gravity of the simulation: adaptation to simulated hypogravity leads to altered predictive control.

Accurate predictive abilities are important for a wide variety of animal behaviors. Inherent to many of these predictions is an understanding of the physics that underlie the behavior. Humans are specifically attuned to the physics on Earth but can learn to move in other environments (e.g., the surface of the Moon). However, the adjustments made to their physics-based predictions in the face of altered gravity are not fully understood. The current study aimed to characterize the locomotor adaptation to a novel paradigm for simulated reduced gravity. We hypothesized that exposure to simulated hypogravity would result in updated predictions of gravity-based movement. Twenty participants took part in a protocol that had them perform vertically targeted countermovement jumps before (PRE), during, and after (POST) a physical simulation of hypogravity. Jumping in simulated hypogravity had different neuromechanics from the PRE condition, with reduced ground impulses (p ≤ .009) and muscle activity prior to the time of landing (i.e., preactivation; p ≤ .016). In the 1 g POST condition, muscle preactivation remained reduced (p ≤ .033) and was delayed (p ≤ .008) by up to 33% for most muscles of the triceps surae, reflecting an expectation of hypogravity. The aftereffects in muscle preactivation, along with little-to-no change in muscle dynamics during ground contact, point to a neuromechanical adaptation that affects predictive, feed-forward systems over feedback systems. As such, we conclude that the neural representation, or internal model, of gravity is updated after exposure to simulated hypogravity.

Conditioning of Motor Evoked Responses After Anterior Cruciate Ligament Reconstruction: Effects of Stimulus Intensity.

BACKGROUND: Operant conditioning of motor evoked torque (MEPTORQUE) can directly target the corticospinal pathway in patients with anterior cruciate ligament (ACL) reconstruction. However, it remains unclear whether operant conditioning can elicit short-term improvements in corticospinal excitability and whether these improvements are influenced by stimulus intensity. HYPOTHESIS: Quadriceps MEPTORQUE responses can be upconditioned in a single session and will elicit short-term adaptations in corticospinal excitability, with higher stimulus intensities eliciting greater effects. STUDY DESIGN: Randomized controlled laboratory study. LEVEL OF EVIDENCE: Level 2. METHODS: Thirty-six participants were assessed during a single session of an operant conditioning protocol. Participants were randomized into 1 of 3 groups for stimulus intensity used during operant conditioning based on the participant's active motor threshold (AMT: 100%, 120%, and 140%). Quadriceps MEPTORQUE amplitude was evaluated during a block of control transcranial magnetic stimulation trials (CTRL) to establish baseline corticospinal excitability, and 3 blocks of conditioning trials (COND) during which participants trained to upcondition their MEPTORQUE. MEPTORQUE recruitment curves were collected to evaluate the effect of operant conditioning on acute corticospinal adaptations. RESULTS: Participants with ACL reconstruction could upcondition their MEPTORQUE in a single session (P < 0.01; CTRL, 17.27 ± 1.28; COND, 21.35 ± 1.28 [mean ± standard error [SE] in N·m]), but this ability was not influenced by the stimulus intensity used during training (P = 0.84). Furthermore, significant improvements in corticospinal excitability were observed (P = 0.05; PRE, 687.91 ± 50.15; POST, 761.08 ± 50.15 [mean ± SE in N·m %AMT]), but stimulus intensity did not influence corticospinal adaptations (P = 0.67). CONCLUSION: Operant conditioning can elicit short-term neural adaptations in ACL-reconstructed patients. Future operant conditioning paradigms may effectively use any of the 3 stimulus intensities studied herein. CLINICAL RELEVANCE: Operant conditioning may be a feasible approach to improve corticospinal excitability after ACL reconstruction.

Improving rehabilitation motivation and motor learning ability of stroke patients using different reward strategies: study protocol for a single-center, randomized controlled trial.

Background: Stroke survivors often face challenges in motor learning and motivation during rehabilitation, which can impede their recovery progress. Traditional rehabilitation methods vary in effectiveness, prompting the exploration of novel approaches such as reward strategies. Previous research indicates that rewards can enhance rehabilitation motivation and facilitate motor learning. However, most reward paradigms have utilized fixed reward amounts, which also have limitations. Exploring alternative, more effective reward strategies, such as probabilistic rewards, is warranted to optimize stroke patient rehabilitation. Methods: A total of 81 stroke patients will be recruited and randomly assigned to control, fixed reward, or probabilistic reward groups at a ratio of 1:1:1 using a randomized number table method. Participants will undergo 10 days of daily hand motor function rehabilitation training, with sessions lasting 20 min each. The training will involve pegboard tests and box and block tests. Control group participants will receive standard training, while fixed reward group members will receive monetary incentives for completing tests, and probabilistic reward group members will have the chance to win monetary rewards through a lottery box. Rehabilitation motivation and motor performance and functional near-infrared spectroscopy brain imaging will be conducted at designated time points. The primary outcome measure is the stroke rehabilitation motivation scale, and the second outcome measures include motor performance, simple test for evaluating hand function, motivation and pleasure scale self-report, and Pittsburgh rehabilitation participation scale. Discussion: Reward-based training enhance rehabilitation participation and adherence, it also improve motor learning speed and memory retention of stroke patients. The fixed reward applied in the past studies could diminish the sensitivity of stroke patients to rewards, while probabilistic reward may provide unpredictable or variable incentives or reinforcements for motor rehabilitation. This study will compare the efficacy of different reward strategies in enhancing motor learning ability and rehabilitation motivation among stroke patients. By conducting a randomized controlled trial, the study seeks to provide valuable insights into optimizing stroke rehabilitation protocols and improving patient outcomes.Clinical Trial Registration:https://www.chictr.org.cn/, ChiCTR2400082419.

A single-center, assessor-blinded, randomized controlled clinical trial to test the safety and efficacy of a novel brain-computer interface controlled functional electrical stimulation (BCI-FES) intervention for gait rehabilitation in the chronic stroke population.

BACKGROUND: In the United States, there are over seven million stroke survivors, with many facing gait impairments due to foot drop. This restricts their community ambulation and hinders functional independence, leading to several long-term health complications. Despite the best available physical therapy, gait function is incompletely recovered, and this occurs mainly during the acute phase post-stroke. Therapeutic options are limited currently. Novel therapies based on neurobiological principles have the potential to lead to long-term functional improvements. The Brain-Computer Interface (BCI) controlled Functional Electrical Stimulation (FES) system is one such strategy. It is based on Hebbian principles and has shown promise in early feasibility studies. The current study describes the BCI-FES clinical trial, which examines the safety and efficacy of this system, compared to conventional physical therapy (PT), to improve gait velocity for those with chronic gait impairment post-stroke. The trial also aims to find other secondary factors that may impact or accompany these improvements and establish the potential of Hebbian-based rehabilitation therapies. METHODS: This Phase II clinical trial is a two-arm, randomized, controlled, longitudinal study with 66 stroke participants in the chronic (> 6 months) stage of gait impairment. The participants undergo either BCI-FES paired with PT or dose-matched PT sessions (three times weekly for four weeks). The primary outcome is gait velocity (10-meter walk test), and secondary outcomes include gait endurance, range of motion, strength, sensation, quality of life, and neurophysiological biomarkers. These measures are acquired longitudinally. DISCUSSION: BCI-FES holds promise for gait velocity improvements in stroke patients. This clinical trial will evaluate the safety and efficacy of BCI-FES therapy when compared to dose-matched conventional therapy. The success of this trial will inform the potential utility of a Phase III efficacy trial. TRIAL REGISTRATION: The trial was registered as "BCI-FES Therapy for Stroke Rehabilitation" on February 19, 2020, at clinicaltrials.gov with the identifier NCT04279067.

Cross-Education of Skill: Assessment of Overhand Throwing Using Product- and Process-Oriented Assessment.

Purpose: The aims of the present study were to: (1) investigate the magnitude and direction of the cross-education effect in a unilateral sport skill (overhand throw) and (2) to establish which practice condition (dominant hand only or alternating hands) would yield the best results. Methods: The study involved three experimental groups of 11-year-old children (n = 59). The first group (n = 20) used only the dominant hand to throw the ball. The second group (n = 19) used the nondominant hand only, while the third (n = 20) alternated hands for each throw. A pre- and post-testing of both hands preceded and followed the intervention period. Results: The results of our study revealed no asymmetry in cross-education effect between the limbs for children's overhand ball throwing. It was also shown that training both hands is superior to training the dominant hand alone. Conclusion: Our findings would be of particular interest to physical education teachers and coaches of unilateral sports who are advised to review their unilateral skill teaching methods as bilateral training offers a superior approach to augmenting the process of motor learning and performance.

The importance of observing the master's hand: Action Observation Training promotes the acquisition of new musical skills.

Introduction: Via mirror mechanism, motor training approaches based on the alternation of action observation and execution (i.e., Action Observation Training-AOT) promote the acquisition of motor abilities. Previous studies showed that both visual and auditory stimuli may elicit a common motor representation of music-related gestures; however, the potentialities of AOT for the acquisition of musical skills are still underexplored. Methods: Twenty-one music-naïve participants underwent two blocks of training: AOT and Key-light Observation Training (KOT). AOT consisted of the observation of a melodic sequence played on a keyboard with the right hand by an expert model, followed by participant's imitation. Observation and execution were repeated six consecutive times (T1-T6). KOT followed the same procedure, except for the visual content of the stimulus, depicting the sequential highlighting of the piano keys corresponding to the melody. The rate of correct notes (C), the trainee-model similarity of key-pressure strength (S), and the trainee-model consistency of note duration (R) were collected across T1-T6. Results: Both AOT and KOT improved musical performance. Noteworthy, AOT showed a higher learning magnitude relative to KOT in terms of C and S. Discussion: Action Observation Training promotes the acquisition of key elements of melodic sequences, encompassing not only the accurate sequencing of notes but also their expressive characteristics, such as key-pressure dynamics. The convergence of listening and observation of actions onto a shared motor representation not only explains several pedagogical approaches applied in all musical cultures worldwide, but also enhances the potential efficacy of current procedures for music training.

An external focus promotes motor learning of an aiming task in individuals with hearing impairments.

Research has shown that external relative to internal focus (IF) instructions may improve motor performance as well as cognitive function (e.g., attentional stability and task-focus). The aim of the study was to examine the influence of attentional focus instructions on skill acquisition and learning of an aiming task in individuals with hearing impairments. The participants (N = 39, Mage = 17.87 ± 1.88 years) performed a bowling task with their dominant hand to knock down as many pins as possible. On day 1, they were randomly divided into three attentional focus groups; IF (focus on your throwing hand), external focus (EF) (focus on the pins), and control (no-focus) instructions. Each participant performed 36 trials, divided into 3 blocks of 12 trials. Attentional focus instructions were given before each block, with a brief reminder provided after each 3 trials. On day 2, retention and transfer (further distance) tests were performed. Results showed that while there were no significant differences between groups in the pre-test, the EF group outperformed both IF and control groups in retention and transfer tests. No significant difference was found between the control and IF. The findings suggest that the advantages of the external relative to the IF and no-focus instructions may generalize to individuals with hearing impairments.

Motor skill learning modulates striatal extracellular vesicles' content in a mouse model of Huntington's disease.

Huntington's disease (HD) is a neurological disorder caused by a CAG expansion in the Huntingtin gene (HTT). HD pathology mostly affects striatal medium-sized spiny neurons and results in an altered cortico-striatal function. Recent studies report that motor skill learning, and cortico-striatal stimulation attenuate the neuropathology in HD, resulting in an amelioration of some motor and cognitive functions. During physical training, extracellular vesicles (EVs) are released in many tissues, including the brain, as a potential means for inter-tissue communication. To investigate how motor skill learning, involving acute physical training, modulates EVs crosstalk between cells in the striatum, we trained wild-type (WT) and R6/1 mice, the latter with motor and cognitive deficits, on the accelerating rotarod test, and we isolated their striatal EVs. EVs from R6/1 mice presented alterations in the small exosome population when compared to WT. Proteomic analyses revealed that striatal R6/1 EVs recapitulated signaling and energy deficiencies present in HD. Motor skill learning in R6/1 mice restored the amount of EVs and their protein content in comparison to naïve R6/1 mice. Furthermore, motor skill learning modulated crucial pathways in metabolism and neurodegeneration. All these data provide new insights into the pathogenesis of HD and put striatal EVs in the spotlight to understand the signaling and metabolic alterations in neurodegenerative diseases. Moreover, our results suggest that motor learning is a crucial modulator of cell-to-cell communication in the striatum.