Interlimb transfer of sequential motor learning between upper and lower effectors.

BACKGROUND: Interlimb transfer of sequential motor learning (SML) refers to the positive influence of prior experiences in performing the same sequential movements using different effectors. Despite evidence from intermanual SML, and while most daily living activities involve interlimb cooperation and coordination between the four limbs, nothing is known about bilateral SML transfer between the upper and lower limbs. RESEARCH QUESTION: We examined the transfer of bilateral SML from the upper to the lower limbs and vice versa. METHODS: Twenty-four participants had to learn an initial bilateral SML task using the upper limbs and then performed the same sequence using the lower limbs during a transfer SML task. They performed the reversed situation 1 month apart. The performance was evaluated at the beginning and the end of both initial and transfer SML practice phases. RESULTS: Significant and reciprocal transfer gains in performance were observed regardless of the effectors. Greater transfer gains in performance were observed at the beginning of the transfer SML from the lower to the upper limbs (44 %) but these gains vanished after practice with the transfer effectors (5 %). Although smaller gains were initially achieved in the transfer of SML from the upper to the lower limbs (15 %), these gains persisted and remained significant (9 %) after practice with the transfer effectors. SIGNIFICANCE: Our results provide evidence of a reciprocal and asymmetrical interlimb transfer of bilateral SML between the upper and lower limbs. These findings could be leveraged as a relevant strategy in the context of sports and functional rehabilitation.

Lateralization of acquisition and consolidation in direction but not amplitude of a motor skill task.

Previous research suggests that the neural processes underlying specification of movement direction and amplitude are independently represented in the nervous system. However, our understanding of acquisition and consolidation processes in the direction and distance learning remains limited. We designed a virtual air hockey task, in which the puck direction is determined by the hand direction at impact, while the puck distance is determined by the amplitude of the velocity. In two versions of this task, participants were required to either specify the direction or the distance of the puck, while the alternate variable did not contribute to task success. Separate groups of right-handed participants were recruited for each task. Each participant was randomly assigned to one of two groups with a counter-balanced arm practice sequence (right to left, or left to right). We examined acquisition and, after 24 h, we examined two aspects of consolidation: 1) same hand performance to test the durability and 2) the opposite hand to test the effector-independent consolidation (interlimb transfer) of learning. The distance task showed symmetry between hands in the extent of acquisition as well as in both aspects of consolidation. In contrast, the direction task showed asymmetry in both acquisition and consolidation: the dominant right arm showed faster and greater acquisition and greater transfer from the opposite arm training. The asymmetric acquisition and consolidation processes shown in the direction task might be explained by lateralized control and mapping of direction, an interpretation consistent with previous findings on motor adaptation paradigms.

Fundamental processes in sensorimotor learning: Reasoning, refinement, and retrieval.

Motor learning is often viewed as a unitary process that operates outside of conscious awareness. This perspective has led to the development of sophisticated models designed to elucidate the mechanisms of implicit sensorimotor learning. In this review, we argue for a broader perspective, emphasizing the contribution of explicit strategies to sensorimotor learning tasks. Furthermore, we propose a theoretical framework for motor learning that consists of three fundamental processes: reasoning, the process of understanding action-outcome relationships; refinement, the process of optimizing sensorimotor and cognitive parameters to achieve motor goals; and retrieval, the process of inferring the context and recalling a control policy. We anticipate that this '3R' framework for understanding how complex movements are learned will open exciting avenues for future research at the intersection between cognition and action.

Implicit learning provides advantage over explicit learning for gait-cognitive dual-task interference.

Dual-task performance holds significant relevance in real-world scenarios. Implicit learning is a possible approach for improving dual-task performance. Analogy learning, utilizing a single metaphor to convey essential information about motor skills, has emerged as a practical method for fostering implicit learning. However, evidence supporting the effect of implicit learning on gait-cognitive dual-task performance is insufficient. This exploratory study aimed to examine the effects of implicit and explicit learning on dual-task performance in both gait and cognitive tasks. Tandem gait was employed on a treadmill to assess motor function, whereas serial seven subtraction tasks were used to gauge cognitive performance. Thirty healthy community-dwelling older individuals were randomly assigned to implicit or explicit learning groups. Each group learned the tandem gait task according to their individual learning styles. The implicit learning group showed a significant improvement in gait performance under the dual-task condition compared with the explicit learning group. Furthermore, the implicit learning group exhibited improved dual-task interference for both tasks. Our findings suggest that implicit learning may offer greater advantages than explicit learning in acquiring autonomous motor skills. Future research is needed to uncover the mechanisms underlying implicit learning and to harness its potential for gait-cognitive dual-task performance in clinical settings.

The effectiveness of different attentional foci on the acquisition of sport-specific motor skills in healthy adults: a systematic review with network meta-analysis.

Background: The acquisition of motor skills is a key element in many sports. A motor learning principle, which is frequently used to support skill acquisition is the application of different attentional foci. The effectiveness of different attentional foci on performance and the learning of motor skills has been investigated in various sports using randomised controlled trials. The aim of the present study was to investigate the effectiveness of different attentional foci (such as external (EFA) and internal attentional foci (IFA), but also holistic and switching foci) on the performance and learning of a sport-specific motor task in healthy individuals. Methods: This study was a systematic review with network meta-analysis. We followed the Prisma reporting guideline and the Cochrane handbook for systematic reviews. Cinahl, Embase, Medline and Cochrane Central were searched for eligible studies. Network meta-analyses were performed for the post-acquisition, retention and transfer test endpoints. Results: Twelve studies were included in the review. At post-acquisition an EFA was the most effective intervention compared to the control intervention (SMD: 0.9855; 95% CI [0.4-1.57]; p: 0.001). At the retention and transfer test endpoints, a holistic focus of attention had the highest effectiveness compared to an IFA (SMD 0.75; 95% CI [-0.1 to 1.6]; p: 0.09) and (SMD 1.16; 95% CI [0.47-1.86]; p: 0.001). Discussion: For all three endpoints, we analysed a greater effectiveness of an EFA and holistic focus compared to an IFA. Several promising different attentional focus interventions were identified. The largest effects were analysed for a holistic focus. However, only one study used this intervention and therefore there remains uncertainty about the effectiveness. With regard to the inconsistency observed, the analysis at post-acquisition should be interpreted with caution. Modified versions of the EFA were the imagined and the dynamic EFA. Both were only explored in single studies and should therefore be investigated in further follow-up studies that directly compare them.

A pilot cluster randomised controlled trial, of an IMPlicit learning approach versus standard care, on recovery of mobility following stroke (IMPS).

OBJECTIVES: To evaluate the delivery of rehabilitation using implicit motor learning principles in an acute stroke setting. DESIGN: Pilot, assessor-blind, cluster randomised controlled trial with nested qualitative evaluation. SETTING: Eight inpatient stroke units, UK. PARTICIPANTS: People within 14 days of stroke onset, presenting with lower limb hemiplegia. INTERVENTIONS: Participants at control clusters received usual care. Participants at intervention clusters received rehabilitation using an Implicit Learning Approach (ILA); primarily consisting of reduced frequency instructions/feedback, and promotion of an external focus of attention. Video recording was used to understand the ability of intervention site therapists to adhere to the implicit learning principles, and to compare differences between groups. MEASURES: Ability to recruit and retain clusters/participants; suitability and acceptability of data collection processes; appropriateness of fidelity monitoring methods; and appropriateness of chosen outcome measures. RESULTS: Eight stroke units participated, with four assigned to each group (intervention/control). Fifty-one participants were enrolled (intervention group 21; control group 30). Mean time since stroke was 6 days (SD 3.42; 0-14); mean age was 73 years (SD 14, 25-94). Of those approached to take part, 72% agreed. We found clear differences between groups with respect to the frequency and type of instructional statement. The ILA was acceptable to both patients and therapists. CONCLUSION: It is feasible to evaluate the application and effectiveness of motor learning principles within acute stroke rehabilitation, using a cluster randomised design. A larger study is required to evaluate the benefits of each approach; we provide a range of sample size estimates required for this.

Recall tempo of Hebbian sequences depends on the interplay of Hebbian kernel with tutor signal timing.

Understanding how neural circuits generate sequential activity is a longstanding challenge. While foundational theoretical models have shown how sequences can be stored as memories in neural networks with Hebbian plasticity rules, these models considered only a narrow range of Hebbian rules. Here, we introduce a model for arbitrary Hebbian plasticity rules, capturing the diversity of spike-timing-dependent synaptic plasticity seen in experiments, and show how the choice of these rules and of neural activity patterns influences sequence memory formation and retrieval. In particular, we derive a general theory that predicts the tempo of sequence replay. This theory lays a foundation for explaining how cortical tutor signals might give rise to motor actions that eventually become "automatic." Our theory also captures the impact of changing the tempo of the tutor signal. Beyond shedding light on biological circuits, this theory has relevance in artificial intelligence by laying a foundation for frameworks whereby slow and computationally expensive deliberation can be stored as memories and eventually replaced by inexpensive recall.

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.

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.

Motor learning alters vision, but vision does not alter motor learning.

During visuomotor learning, improvements in motor performance accompany changes in how people use vision. However, the dependencies between altered visual reliance and improvements in motor skill is unclear. The present studies used an online sequence learning task to quantify how changing the availability of visual information affected motor skill learning (Study One) and how changing motor skill affected visual reliance (Study Two). Participants used their keyboard to respond to targets falling vertically down a game screen. In Study One (n=49), the availability of visual information was altered by manipulating where the targets were visible on the screen. Three experimental groups practiced the task during full or limited vision conditions (when the targets were only visible in specific areas). We hypothesized that limiting visual information would reduce motor learning (i.e. the rate of improvement during training trial blocks). Instead, while participants performed worse during limited vision trials (p<0.001), there was no difference in learning rate (p=0.87). In Study Two (n=119), all participants practiced the task with full vision and their visual reliance (i.e., their performance change between full and limited vision conditions) was quantified before and after training. We hypothesized that with motor learning, visual reliance on future targets would increase, while visual reliance on the current targets would decrease. The results of Study Two partially support our hypotheses with visual reliance decreasing for all visual areas (p<0.001). Together, the results suggest changing motor skill alters how people use vision, but changing visual availability does not affect motor learning.

MotorNet, a Python toolbox for controlling differentiable biomechanical effectors with artificial neural networks.

Artificial neural networks (ANNs) are a powerful class of computational models for unravelling neural mechanisms of brain function. However, for neural control of movement, they currently must be integrated with software simulating biomechanical effectors, leading to limiting impracticalities: (1) researchers must rely on two different platforms and (2) biomechanical effectors are not generally differentiable, constraining researchers to reinforcement learning algorithms despite the existence and potential biological relevance of faster training methods. To address these limitations, we developed MotorNet, an open-source Python toolbox for creating arbitrarily complex, differentiable, and biomechanically realistic effectors that can be trained on user-defined motor tasks using ANNs. MotorNet is designed to meet several goals: ease of installation, ease of use, a high-level user-friendly application programming interface, and a modular architecture to allow for flexibility in model building. MotorNet requires no dependencies outside Python, making it easy to get started with. For instance, it allows training ANNs on typically used motor control models such as a two joint, six muscle, planar arm within minutes on a typical desktop computer. MotorNet is built on PyTorch and therefore can implement any network architecture that is possible using the PyTorch framework. Consequently, it will immediately benefit from advances in artificial intelligence through PyTorch updates. Finally, it is open source, enabling users to create and share their own improvements, such as new effector and network architectures or custom task designs. MotorNet's focus on higher-order model and task design will alleviate overhead cost to initiate computational projects for new researchers by providing a standalone, ready-to-go framework, and speed up efforts of established computational teams by enabling a focus on concepts and ideas over implementation.

No Additional Effects of Sequential Facilitatory Cerebral and Cerebellar rTMS in Subacute Stroke Patients.

The aim of this study was to investigate the additional effects of cerebellar rTMS on the motor recovery of facilitatory rTMS over affected primary motor cortex (M1) in subacute stroke patients. Twenty-eight subacute stroke patients were recruited in this single-blind, randomized, controlled trial. The Cr-Cbll group received Cr-Cbll rTMS stimulation consisting of high-frequency rTMS over affected M1 (10 min), motor training (10 min), and high-frequency rTMS over contralesional Cbll (10 min). The Cr-sham group received sham rTMS instead of high-frequency rTMS over the cerebellum. Ten daily sessions were performed for 2 weeks. A Fugl-Meyer Assessment (FMA) was measured before (T0), immediately after (T1), and 2 months after the intervention (T2). A total of 20 participants (10 in the Cr-Cbll group and 10 in the Cr-sham group) completed the intervention. There was no significant difference in clinical characteristics between the two groups at T0. FMA was significantly improved after the intervention in both Cr-Cbll and Cr-sham groups (p < 0.05). However, there was no significant interaction in FMA between time and group. In conclusion, these results could not demonstrate that rTMS over the contralesional cerebellum has additional effects to facilitatory rTMS over the affected M1 for improving motor function in subacute stroke patients.

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.

Sensorimotor Challenges in Minimally Invasive Surgery: A Theoretically-Oriented Review.

OBJECTIVE: This review surveys the literature on sensorimotor challenges impacting performance in laparoscopic minimally invasive surgery (MIS). BACKGROUND: Despite its well-known benefits for patients, achieving proficiency in MIS can be challenging for surgeons due to many factors including altered visual perspectives and fulcrum effects in instrument handling. Research on these and other sensorimotor challenges has been hindered by imprecise terminology and the lack of a unified theoretical framework to guide research questions in the field. METHOD: We conducted a systematic survey of the MIS literature, focusing on studies investigating sensorimotor challenges affecting laparoscopic performance. To provide a common foundation for cross-study comparisons, we propose a standardized taxonomy that distinguishes between different experimental paradigms used in the literature. We then show how the computational motor learning perspective provides a unifying theoretical framework for the field that can facilitate progress and motivate future research along clearer, hypothesis-driven lines. RESULTS: The survey identified diverse sensorimotor perturbations in MIS, which can be effectively categorized according to our proposed taxonomy. Studies investigating monitor-, camera-, and tool-based perturbations were systematically analyzed, elucidating their impact on surgical performance. We also show how the computational motor learning perspective provides deeper insights and potential strategies to mitigate challenges. CONCLUSION: Sensorimotor challenges significantly impact MIS, necessitating a systematic, empirically informed approach. Our proposed taxonomy and theoretical framework shed light on the complexities involved, paving the way for more structured research and targeted training approaches to enhance surgical proficiency. APPLICATION: Understanding the sensorimotor challenges inherent to MIS can guide the design of improved training curricula and inform the configuration of setups in the operating room to enhance surgeon performance and ultimately patient outcomes. This review offers key insights for surgeons, educators, and researchers in surgical performance and technology development.

The effects of reward and punishment on the performance of ping-pong ball bouncing.

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.

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.

The effects of corticotropin-releasing factor on motor learning.

Corticotropin-releasing factor (CRF) is mainly secreted from the hypothalamic paraventricular nuclei and plays a crucial role in stress-related responses. Recent studies have reported that CRF is a neuromodulator in the central nervous system. In the cerebellum, CRF is essential for the induction of long-term depression (LTD) at the parallel fiber-Purkinje cell synapses. Given that LTD is thought to be one of the fundamental mechanisms of motor learning, CRF may affect motor learning. However, the role of CRF in motor learning in vivo remains unclear. In this study, we aimed to examine the role of CRF in motor learning. This was achieved through a series of behavioral experiments involving the in vivo administration of CRF and its antagonists. Rats injected with CRF directly into the cerebellum exhibited superior performance on the rotarod test, especially during initial training phases, compared to control subjects. Conversely, rats receiving a CRF receptor antagonist demonstrated reduced endurance on the rotating rod compared to controls. Notably, CRF mRNA expression levels in the cerebellum did not show significant variance between the CRF-injected and control groups. These findings imply a critical role of endogenous CRF in cerebellar motor learning and suggest that exogenous CRF can augment this process. (199 words).

Cortico-basal ganglia plasticity in motor learning.

One key function of the brain is to control our body's movements, allowing us to interact with the world around us. Yet, many motor behaviors are not innate but require learning through repeated practice. Among the brain's motor regions, the cortico-basal ganglia circuit is particularly crucial for acquiring and executing motor skills, and neuronal activity in these regions is directly linked to movement parameters. Cell-type-specific adaptations of activity patterns and synaptic connectivity support the learning of new motor skills. Functionally, neuronal activity sequences become structured and associated with learned movements. On the synaptic level, specific connections become potentiated during learning through mechanisms such as long-term synaptic plasticity and dendritic spine dynamics, which are thought to mediate functional circuit plasticity. These synaptic and circuit adaptations within the cortico-basal ganglia circuitry are thus critical for motor skill acquisition, and disruptions in this plasticity can contribute to movement disorders.

Minimal impact of chronic proprioceptive loss on implicit sensorimotor adaptation and perceived movement outcome.

Implicit sensorimotor adaptation keeps our movements well-calibrated amid changes in the body and environment. We have recently postulated that implicit adaptation is driven by a perceptual error: the difference between the desired and perceived movement outcome. According to this perceptual re-alignment model, implicit adaptation ceases when the perceived movement outcome - a multimodal percept determined by a prior belief conveying the intended action, the motor command, and feedback from proprioception and vision - is aligned with the desired movement outcome. Here, we examined the role of proprioception in implicit motor adaptation and perceived movement outcome by examining individuals who experience deafferentation (i.e., individuals with impaired proprioception and touch). We used a modified visuomotor rotation task designed to isolate implicit adaptation and probe perceived movement outcome throughout the experiment. Surprisingly, both implicit adaptation and perceived movement outcome were minimally impacted by chronic deafferentation, posing a challenge to the perceptual re-alignment model of implicit adaptation.

Sex differences in motor learning flexibility are accompanied by sex differences in mushroom spine pruning of the mouse primary motor cortex during adolescence.

Background: Although males excel at motor tasks requiring strength, females exhibit greater motor learning flexibility. Cognitive flexibility is associated with low baseline mushroom spine densities achieved by pruning which can be triggered by α4ßδ GABAA receptors (GABARs); defective synaptic pruning impairs this process. Methods: We investigated sex differences in adolescent pruning of mushroom spine pruning of layer 5 pyramidal cells of primary motor cortex (L5M1), a site essential for motor learning, using microscopic evaluation of Golgi stained sections. We assessed α4GABAR expression using immunohistochemical and electrophysiological techniques (whole cell patch clamp responses to 100 nM gaboxadol, selective for α4ßδ GABARs). We then compared performance of groups with different post-pubertal mushroom spine densities on motor learning (constant speed) and learning flexibility (accelerating speed following constant speed) rotarod tasks. Results: Mushroom spines in proximal L5M1 of female mice decreased >60% from PND35 (puberty onset) to PND56 (Pubertal: 2.23 ± 0.21 spines/10 µm; post-pubertal: 0.81 ± 0.14 spines/10 µm, P < 0.001); male mushroom spine density was unchanged. This was due to greater α4ßδ GABAR expression in the female (P < 0.0001) because α4 -/- mice did not exhibit mushroom spine pruning. Although motor learning was similar for all groups, only female wild-type mice (low mushroom spine density) learned the accelerating rotarod task after the constant speed task (P = 0.006), a measure of motor learning flexibility. Conclusions: These results suggest that optimal motor learning flexibility of female mice is associated with low baseline levels of post-pubertal mushroom spine density in L5M1 compared to male and female α4 -/- mice.