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Our repertoire of motor skills is filled with sequential movements that need to be performed in a specific order. Here, we used functional magnetic resonance imaging to investigate whether the human hippocampus, a region known to support temporal order in non-motor memory, represents information about the order of sequential motor actions in human participants (both sexes). We also examined such representations in other regions of the motor network (i.e., the premotor cortex, supplementary motor area, anterior superior parietal lobule, and striatum) already known for their critical role in motor sequence learning. Results showed that the hippocampus represents information about movements in their learned temporal position in the sequence, but not about movements or temporal positions in random movement patterns. Other regions of the motor network coded for movements in their learned temporal position, as well as movements and positions in random movement patterns. Importantly, movement coding contributed to sequence learning patterns in primary, supplementary, and premotor cortices but not in striatal and parietal regions. Our findings deepen our understanding of how striatal and cortical regions contribute to motor sequence learning and point to the capacity of the hippocampus to represent movements in their temporal context, an ability possibly explaining its contribution to motor learning.

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Introduction: Reward and punishment modulate behavior. In real-world motor skill learning, reward and punishment have been found to have dissociable effects on optimizing motor skill learning, but the scientific basis for these effects is largely unknown. Methods: In the present study, we investigated the effects of reward and punishment on the performance of real-world motor skill learning. Specifically, three groups of participants were trained and tested on a ping-pong ball bouncing task for three consecutive days. The training and testing sessions were identical across the three days: participants were trained with their right (dominant) hand each day under conditions of either reward, punishment, or a neutral control condition (neither). Before and after the training session, all participants were tested with their right and left hands without any feedback. Results: We found that punishment promoted early learning, while reward promoted late learning. Reward facilitated short-term memory, while punishment impaired long-term memory. Both reward and punishment interfered with long-term memory gains. Interestingly, the effects of reward and punishment transferred to the left hand. Discussion: The results show that reward and punishment have different effects on real-world motor skill learning. The effects change with training and transfer readily to novel contexts. The results suggest that reward and punishment may act on different learning processes and engage different neural mechanisms during real-world motor skill learning. In addition, high-level metacognitive processes may be enabled by the additional reinforcement feedback during real-world motor skill learning. Our findings provide new insights into the mechanisms underlying motor learning, and may have important implications for practical applications such as sports training and motor rehabilitation.

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In right-handed individuals, aphasia resulting from right hemisphere damage is termed crossed aphasia and has a very low occurrence rate. Additionally, aphasia due to thalamic lesions often involves hemorrhage, with infarction cases less frequently reported. We present the case of an 81-year-old right-handed female who developed aphasia due to a right thalamic infarction. She exhibited characteristics typical of thalamic aphasia observed in left thalamic lesions. Furthermore, jargon agraphia manifested during writing tasks. This may suggest disinhibition of the left hemisphere writing motor memory by the right hemisphere language function.

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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.

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The present study was conducted with the aim of investigating the effect of exergames in improving the motor memory and inhibitory control of children with executive functions disorder. Children, selected by simple random method were divided into two groups: experimental (n = 16) and control (n = 16). Circle drawing task, and The Serial Reaction Time Task were used to collect and analyze data. The current study is a randomized control trial (RCT) type of research with a two-group pretest, post-test, and follow up -test design in terms of the purpose of applied research and the method of data collection. T-test results for the differences in post- test mean scores between the two groups in motor memory and inhibitory control showed that the treatment group outperformed the control group. There were statistical differences between pre and post measures in favor of post test, and between pre and follow up measures in favor of follow up test, but no statistical differences between post and follow up test. This study demonstrates that it is possible to enhance motor memory and inhibitory control of children with executive functions disorder using exergames intervention.

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Introduction: Locomotor adaptation is a motor learning process used to alter spatiotemporal elements of walking that are driven by prediction errors, a discrepancy between the expected and actual outcomes of our actions. Sensory and reward prediction errors are two different types of prediction errors that can facilitate locomotor adaptation. Reward and punishment feedback generate reward prediction errors but have demonstrated mixed effects on upper extremity motor learning, with punishment enhancing adaptation, and reward supporting motor memory. However, an in-depth behavioral analysis of these distinct forms of feedback is sparse in locomotor tasks. Methods: For this study, three groups of healthy young adults were divided into distinct feedback groups [Supervised, Reward, Punishment] and performed a novel locomotor adaptation task where each participant adapted their knee flexion to 30 degrees greater than baseline, guided by visual supervised or reinforcement feedback (Adaptation). Participants were then asked to recall the new walking pattern without feedback (Retention) and after a washout period with feedback restored (Savings). Results: We found that all groups learned the adaptation task with external feedback. However, contrary to our initial hypothesis, enhancing sensory feedback with a visual representation of the knee angle (Supervised) accelerated the rate of learning and short-term retention in comparison to monetary reinforcement feedback. Reward and Punishment displayed similar rates of adaptation, short-term retention, and savings, suggesting both types of reinforcement feedback work similarly in locomotor adaptation. Moreover, all feedback enhanced the aftereffect of locomotor task indicating changes to implicit learning. Discussion: These results demonstrate the multi-faceted nature of reinforcement feedback on locomotor adaptation and demonstrate the possible different neural substrates that underly reward and sensory prediction errors during different motor tasks.

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Objective.The functional asymmetry between the two brain hemispheres in language and spatial processing is well documented. However, a description of difference in control between the two hemispheres in motor function is not well established. Our primary objective in this study was to examine the distribution of control in the motor hierarchy and its variation across hemispheres.Approach.We developed a computation model termed the bilateral control network and implemented the same in a neural network framework to be used to replicate certain experimental results. The network consists of a simple arm model capable of making movements in 2D space and a motor hierarchy with separate elements coding target location, estimated position of arm, direction, and distance to be moved by the arm, and the motor command sent to the arm. The main assumption made here is the division of direction and distance coding between the two hemispheres with distance coded in the non-dominant and direction coded in the dominant hemisphere.Main results.With this assumption, the network was able to show main results observed in visuomotor adaptation studies. Importantly it showed decrease in error exhibited by the untrained arm while the other arm underwent training compared to the corresponding naïve arm's performance-transfer of motor learning from trained to the untrained arm. It also showed how this varied depending on the performance variable used-with distance as the measure, the non-dominant arm showed transfer and with direction, dominant arm showed transfer.Significance.Our results indicate the possibility of shared control between the two hemispheres. If indeed found true, this result could have major significance in motor rehabilitation as treatment strategies will need to be designed in order to account for this and can no longer be confined to the arm contralateral to the affected hemisphere.

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When learning a new motor skill, people often must use trial and error to discover which movement is best. In the reinforcement learning framework, this concept is known as exploration and has been linked to increased movement variability in motor tasks. For locomotor tasks, however, increased variability decreases upright stability. As such, exploration during gait may jeopardize balance and safety, making reinforcement learning less effective. Therefore, we set out to determine if humans could acquire and retain a novel locomotor pattern using reinforcement learning alone. Young healthy male and female participants walked on a treadmill and were provided with binary reward feedback (indicated by a green checkmark on the screen) that was tied to a fixed monetary bonus, to learn a novel stepping pattern. We also recruited a comparison group who walked with the same novel stepping pattern but did so by correcting for target error, induced by providing real-time veridical visual feedback of steps and a target. In two experiments, we compared learning, motor variability, and two forms of motor memories between the groups. We found that individuals in the binary reward group did, in fact, acquire the new walking pattern by exploring (increasing motor variability). Additionally, while reinforcement learning did not increase implicit motor memories, it resulted in more accurate explicit motor memories compared with the target error group. Overall, these results demonstrate that humans can acquire new walking patterns with reinforcement learning and retain much of the learning over 24 h.

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Previous research has shown that learning procedural tasks enhances REM sleep the following night. Here, we investigate whether complex motor learning affects sleep architecture. An experiment in which twenty-two subjects either learned a motor task (trampolining) or engaged in a control task (ergometer) was carried out in a balanced within-group design. After an initial laboratory adaptation night, two experimental nights were consecutive. The results indicate that learning a motor task had an effect on REM sleep parameters and, therefore, support the hypothesis that learning a procedural skill is related to an increase in REM sleep parameters. However, the statistical effect on REM sleep is smaller than found in previous studies. One might speculate that the motor learning was not intense enough compared to other studies. For sports practice, the results suggest that REM sleep, which is particularly rich in the morning, plays an important role in motor memory consolidation. Thus, this phase should not be interrupted after complex motor skill learning sessions. In future studies, other motor tasks should be applied.

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Alzheimer disease (AD) is a widespread neurodegenerative disease characterized by the accumulation of oligomeric toxic forms of ß-amyloid (Aß1-42) and dysfunction of the cholinergic system in the different brain regions. However, the exact mechanisms of AD pathogenesis and the role of the nicotinic acetylcholine receptors (nAChRs) in the disease progression remain unclear. Here, we revealed a decreased expression of a number of the Ly6/uPAR proteins targeting nAChRs in the cerebellum of 2xTg-AD mice (model of early AD) in comparison with non-transgenic mice both at mRNA and protein levels. We showed that co-localization of one of them, - neuromodulator Lynx1, with α7-nAChR was diminished in the vicinity of cerebellar astrocytes of 2xTg-AD mice, while Aß1-42 co-localization with this receptor present was increased. Moreover, the expression of anti-inflammatory transcription factor KLF4 regulating transcription of the Ly6/uPAR genes was decreased in the cerebellum of 2xTg-AD mice, while expression of inflammatory cytokine TNF-α was increased. Based on these data together with observed astrocyte degeneration in the cerebellum of 2xTg-AD mice, we suggest the mechanism by which expression of the Ly6/uPAR proteins upon Aß pathology results in dysregulation of the cholinergic system and particularly of α7-nAChR function in the cerebellum. This leads to enhanced neuroinflammation and cerebellar astrocyte degeneration.

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A single bout of cardiovascular exercise (CE) performed after practice can facilitate the consolidation of motor memory. However, the effect is variable and may be modulated by different factors such as the motor task's or participant's characteristics and level of awareness during encoding (implicit vs explicit learning). This study examines the effects of acute CE on the consolidation of motor sequences learned explicitly and implicitly, exploring the potential moderating effect of fitness level and awareness. Fifty-six healthy adults (24.1 ± 3.3 years, 32 female) were recruited. After practicing with either the implicit or explicit variant of the Serial Reaction Time Task (SRTT), participants either performed a bout of 16 min of vigorous CE or rested for the same amount of time. Consolidation was quantified as the change in SRTT performance from the end of practice to a 24 h retention test. Fitness level (V̇O2peak) was determined through a graded exercise test. Awareness (implicit vs explicit learning) was operationalized using a free recall test conducted immediately after retention. Our primary analysis indicated that CE had no statistically significant effects on consolidation, regardless of the SRTT's variant utilized during practice. However, an exploratory analysis, classifying participants based on the level of awareness gained during motor practice, showed that CE negatively influenced consolidation in unfit participants who explicitly acquired the motor sequence. Our findings indicate that fitness level and awareness in sequence acquisition can modulate the interaction between CE and motor memory consolidation. These factors should be taken into account when assessing the effects of CE on motor memory.

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Performing a single bout of exercise can enhance motor learning and long-term retention of motor skills. Parameters such as the intensity and when the exercise bout is performed in relation to skill practice (i.e., timing) likely influence the effectiveness. However, it is still not fully understood how exercise should be administered to maximize its effects and how exercise interacts with distinct components of skill learning. Here, we expand this knowledge by investigating the potential synergistic effects of performing acute exercise both prior to and following motor practice. Sixty-four, able-bodied, young adult male participants practiced a sequential visuomotor accuracy tracking (SVAT) task requiring rapid and accurate force modulation and high levels of precision control using intrinsic hand muscles. The task also contained a repeated pattern of targets that allowed sequence-specific skill improvements. Sequential and non-sequential motor performance was assessed at baseline, immediately after motor practice, and again seven days later. One group performed moderate-intensity exercise before practice (PREMO), a second group performed high-intensity exercise after practice (POSTHI), a third group exercised both before and after practice (PREMO + POSTHI), and a fourth group did not exercise during these periods (CON). Regardless of the exercise condition, acute exercise improved long-term retention of the skill by countering performance decay between experimental sessions (i.e., a 7-day interval). Furthermore, exercising both before and after motor practice led to the greatest improvements in skilled performance over time. We found that the effects of exercise were not specific to the practiced sequence. Namely, the effects of exercise generalized across sequential and non-sequential target positions and orders. This suggests that acute exercise works through mechanisms that promote general aspects of motor memory (e.g., lasting improvements in fast and accurate motor execution). The results demonstrate that various exercise protocols can promote the stabilization and long-term retention of motor skills. This effect can be enhanced when exercise is performed both before and after practice.

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This study investigated strategies based on the reconsolidation process to promote the strengthening effect of human motor memory. The aim of this study was to evaluate the influence of reactivating the memory of a newly acquired motor skill and performing interventions during its reconsolidation process on motor performance. Sixty healthy participants learned a new Sequential Visual Isometric Pinch Task - SVIPT during the first experimental session. In the second experimental session that was held on the same day, 6 h after session 1, the participants were divided into six different groups. In session 2, there were distinctions between the experimental groups concerning two issues: the presence or absence of a formal memory reactivation session characterized by the execution of repetitions of the learned motor task and the execution of different types of interventions after reactivation (training with the original, slightly modified, or moderately modified motor task). All groups performed the third session to retest the learned motor skill, 24 h after session 1. The results showed that using training with moderate task variability during memory reconsolidation provides greater motor skill performance gain when compared to repetitive training of the same learned task. Furthermore, performing a session exclusively dedicated to reactivation with the practice of the originally learned task was not a determining condition for recent motor memory reactivation, but rather the induction of prediction error during the reactivation.

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Motor adaptation to novel dynamics occurs rapidly using sensed errors to update the current motor memory. This adaption is strongly driven by proprioceptive and visual signals that indicate errors in the motor memory. Here, we extend this previous work by investigating whether the presence of additional visual cues could increase the rate of motor adaptation, specifically when the visual motion cue is congruent with the dynamics. Six groups of participants performed reaching movements while grasping the handle of a robotic manipulandum. A visual cue (small red circle) was connected to the cursor (representing the hand position) via a thin red bar. After a baseline, a unidirectional (3 groups) or bidirectional (3 groups) velocity-dependent force field was applied during the reach. For each group, the movement of the red object relative to the cursor was either congruent with the force field dynamics, incongruent with the force field dynamics, or constant (fixed distance from the cursor). Participants adapted more to the unidirectional force fields than to the bidirectional force field groups. However, across both force fields, groups in which the visual cues matched the type of force field (congruent visual cue) exhibited higher final adaptation level at the end of learning than the control or incongruent conditions. In all groups, we observed that an additional congruent cue assisted the formation of the motor memory of the external dynamics. We then demonstrate that a state estimation-based model that integrates proprioceptive and visual information can successfully replicate the experimental data.NEW & NOTEWORTHY We demonstrate that adaptation to novel dynamics is stronger when additional online visual cues that are congruent with the dynamics are presented during adaptation, compared with either a constant or incongruent visual cue. This effect was found regardless of whether a bidirectional or unidirectional velocity-dependent force field was presented to the participants. We propose that this effect might arise through the inclusion of this additional visual cue information within the state estimation process.

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Motor learning is defined as an improvement in performance through practice. The ability to learn new motor skills may be particularly challenged in patients with Parkinson's disease, in whom motor execution is impaired by the disease-defining motor symptoms such as bradykinesia. Subthalamic deep brain stimulation is an effective treatment in advanced Parkinson's disease, and its beneficial effects on Parkinsonian motor symptoms and motor execution have been widely demonstrated. Much less is known about whether deep brain stimulation directly interacts with motor learning independent of modulation of motor execution. We investigated motor sequence learning in 19 patients with Parkinson's disease treated with subthalamic deep brain stimulation and 19 age-matched controls. In a cross-over design, patients performed an initial motor sequence training session with active and inactive stimulation, respectively (experiments separated by ≥14 days). Performance was retested after 5 min and after a 6 h consolidation interval with active stimulation. Healthy controls performed a similar experiment once. We further investigated neural correlates underlying stimulation-related effects on motor learning by exploring the association of normative subthalamic deep brain stimulation functional connectivity profiles with stimulation-related differences in performance gains during training. Pausing deep brain stimulation during initial training resulted in the inhibition of performance gains that could have been indicative of learning at the behavioural level. Task performance improved significantly during training with active deep brain stimulation, but did not reach the level of learning dynamics of healthy controls. Importantly, task performance after the 6 h consolidation interval was similar across patients with Parkinson's disease independent of whether the initial training session had been performed with active or inactive deep brain stimulation. This indicates that early learning and subsequent consolidation were relatively intact despite severe impairments of motor execution during training with inactive deep brain stimulation. Normative connectivity analyses revealed plausible and significant connectivity of volumes of tissue activated by deep brain stimulation with several cortical areas. However, no specific connectivity profiles were associated with stimulation-dependent differences in learning during initial training. Our results show that motor learning in Parkinson's disease is independent of modulation of motor execution by subthalamic deep brain stimulation. This indicates an important role of the subthalamic nucleus in regulating general motor execution, whereas its role in motor learning appears negligible. Because longer-term outcomes were independent of performance gains during initial training, patients with Parkinson's disease may not need to wait for an optimal motor state to practice new motor skills.

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Retrieving previously stored information makes memory traces labile again and can trigger restabilization in a strengthened or weakened form depending on the reactivation condition. Available evidence for long-term performance changes upon reactivation of motor memories and the effect of post-learning sleep on their consolidation remains scarce, and so does the data on the ways in which subsequent reactivation of motor memories interacts with sleep-related consolidation. Eighty young volunteers learned (Day 1) a 12-element Serial Reaction Time Task (SRTT) before a post-training Regular Sleep (RS) or Sleep Deprivation (SD) night, either followed (Day 2) by morning motor reactivation through a short SRTT testing or no motor activity. Consolidation was assessed after three recovery nights (Day 5). A 2 × 2 ANOVA carried on proportional offline gains did not evidence significant Reactivation (Morning Reactivation/No Morning Reactivation; p = 0.098), post-training Sleep (RS/SD; p = 0.301) or Sleep*Reactivation interaction (p = 0.257) effect. Our results are in line with prior studies suggesting a lack of supplementary performance gains upon reactivation, and other studies that failed to disclose post-learning sleep-related effects on performance improvement. However, lack of overt behavioural effects does not detract from the possibility of sleep- or reconsolidation-related covert neurophysiological changes underlying similar behavioural performance levels.

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Increasing evidence suggests that reactivation of newly acquired memory traces during postlearning wakefulness plays an important role in memory consolidation. Here, we sought to boost the reactivation of a motor memory trace during postlearning wakefulness (quiet rest) immediately following learning using somatosensory targeted memory reactivation (TMR). Using functional magnetic resonance imaging, we examined the neural correlates of the reactivation process as well as the effect of the TMR intervention on brain responses elicited by task practice on 24 healthy young adults. Behavioral data of the post-TMR retest session showed a faster learning rate for the motor sequence that was reactivated as compared to the not-reactivated sequence. Brain imaging data revealed that motor, parietal, frontal, and cerebellar brain regions, which were recruited during initial motor learning, were specifically reactivated during the TMR episode and that hippocampo-frontal connectivity was modulated by the reactivation process. Importantly, the TMR-induced behavioral advantage was paralleled by dynamical changes in hippocampal activity and hippocampo-motor connectivity during task practice. Altogether, the present results suggest that somatosensory TMR during postlearning quiet rest can enhance motor performance via the modulation of hippocampo-cortical responses.

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This study aimed to determine whether heat exposure attenuates motor control performance and learning, and blunts cardiovascular and thermoregulatory responses to visuomotor accuracy tracking (VAT) tasks. Twenty-nine healthy young adults (22 males) were divided into two groups performing VAT tasks (5 trials × 10 blocks) in thermoneutral (NEUT: 25 °C, 45% RH, n = 14) and hot (HOT: 35 °C, 45% RH, n = 15) environments (acquisition phase). One block of the VAT task was repeated at 1, 2, and 4 h after the acquisition phase (retention phase). Heat exposure elevated skin temperature to ~3 °C with a marginally increased core body temperature. VAT performance (error distance of curve tracking) was more attenuated overall in HOT than in NEUT in the acquisition phase without improvement in magnitude alteration. Heat exposure did not affect VAT performance in the retention phase. The mean arterial blood pressure and heart rate, but not for sweating and cutaneous vascular responses to VAT acquisition trials, were more attenuated in HOT than in NEUT without any retention phase alternations. We conclude that skin temperature elevation exacerbates motor control performance and blunts cardiovascular response during the motor skill acquisition period. However, these alternations are not sustainable thereafter.

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The neurochemical mechanisms underlying motor memory consolidation remain largely unknown. Based on converging work showing that ethyl alcohol retrogradely enhances declarative memory consolidation, this work tested the hypothesis that post-learning alcohol ingestion would enhance motor memory consolidation. In a within-subject and fully counterbalanced design, participants (n = 24; 12M; 12F) adapted to a gradually introduced visual deviation and ingested, immediately after adaptation, a placebo (PBO), a medium (MED) or high (HIGH) dose of alcohol. The alcohol doses were bodyweight- and gender-controlled to yield peak breath alcohol concentrations of 0.00% in the PBO, ~0.05% in the MED and ~0.095% in the HIGH condition. Retention was evaluated 24 h later through reach aftereffects when participants were sober. The results revealed that retention levels were neither significantly nor meaningfully different in both the MED and HIGH conditions as compared to PBO (all absolute Cohen's dz values < ~0.2; small to negligible effects), indicating that post-learning alcohol ingestion did not alter motor memory consolidation. Given alcohol's known pharmacological GABAergic agonist and NMDA antagonist properties, one possibility is that these neurochemical mechanisms do not decisively contribute to motor memory consolidation. As converging work demonstrated alcohol's retrograde enhancement of declarative memory, the present results suggest that distinct neurochemical mechanisms underlie declarative and motor memory consolidation. Elucidating the neurochemical mechanisms underlying the consolidation of different memory systems may yield insights into the effects of over-the-counter drugs on everyday learning and memory but also inform the development of pharmacological interventions seeking to alter human memory consolidation.

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Previous research has shown that resting-state functional connectivity (rsFC) between different brain regions (seeds) is related to motor learning and motor memory consolidation. Using high-density electroencephalography (hdEEG), we addressed this question from a brain network perspective. Specifically, we examined frequency-dependent functional connectivity in resting-state networks from twenty-nine young healthy participants before and after they were trained on a motor sequence learning task. Consolidation was assessed with an overnight retest on the motor task. Our results showed training-related decreases in gamma-band connectivity within the motor network, and between the motor and functionally distinct resting-state networks including the attentional network. Brain-behavior correlation analyses revealed that baseline beta, delta, and theta rsFC were related to subsequent motor learning and memory consolidation such that lower connectivity within the motor network and between the motor and several distinct resting-state networks was correlated with better learning and overnight consolidation. Lastly, training-related increases in beta-band connectivity between the motor and the visual networks were related to greater consolidation. Altogether, our results indicate that connectivity in large-scale resting-state brain networks is related to-and modulated by-motor learning and memory consolidation processes. These finding corroborate previous seed-based connectivity research and provide evidence that frequency-dependent functional connectivity in resting-state networks is critically linked to motor learning and memory consolidation.