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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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Myoelectric hand prostheses are effective tools for upper limb amputees to regain hand functions. Much progress has been made with pattern recognition algorithms to recognize surface electromyography (sEMG) patterns, but few attentions was placed on the amputees' motor learning process. Many potential myoelectric prostheses users could not fully master the control or had declined performance over time. It is possible that learning to produce distinct and consistent muscle activation patterns with the residual limb could help amputees better control the myoelectric prosthesis. In this study, we observed longitudinal effect of motor skill learning with 2 amputees who have developed alternative muscle activation patterns in response to the same set of target prosthetic actions. During a 10-week program, amputee participants were trained to produce distinct and constant muscle activations with visual feedback of live sEMG and without interaction with prosthesis. At the end, their sEMG patterns were different from each other and from non-amputee control groups. For certain intended hand motion, gradually reducing root mean square (RMS) variance was observed. The learning effect was also assessed with a CNN-LSTM mixture classifier designed for mobile sEMG pattern recognition. The classification accuracy had a rising trend over time, implicating potential performance improvement of myoelectric prosthesis control. A follow-up session took place 6 months after the program and showed lasting effect of the motor skill learning in terms of sEMG pattern classification accuracy. The results indicated that with proper feedback training, amputees could learn unique muscle activation patterns that allow them to trigger intended prosthesis functions, and the original motor control scheme is updated. The effect of such motor skill learning could help to improve myoelectric prosthetic control performance.

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Cholecystokinin (CCK) is an essential modulator for neuroplasticity in sensory and emotional domains. Here, we investigated the role of CCK in motor learning using a single pellet reaching task in mice. Mice with a knockout of Cck gene (Cck-/-) or blockade of CCK-B receptor (CCKBR) showed defective motor learning ability; the success rate of retrieving reward remained at the baseline level compared to the wildtype mice with significantly increased success rate. We observed no long-term potentiation upon high-frequency stimulation in the motor cortex of Cck-/- mice, indicating a possible association between motor learning deficiency and neuroplasticity in the motor cortex. In vivo calcium imaging demonstrated that the deficiency of CCK signaling disrupted the refinement of population neuronal activity in the motor cortex during motor skill training. Anatomical tracing revealed direct projections from CCK-expressing neurons in the rhinal cortex to the motor cortex. Inactivation of the CCK neurons in the rhinal cortex that project to the motor cortex bilaterally using chemogenetic methods significantly suppressed motor learning, and intraperitoneal application of CCK4, a tetrapeptide CCK agonist, rescued the motor learning deficits of Cck-/- mice. In summary, our results suggest that CCK, which could be provided from the rhinal cortex, may surpport motor skill learning by modulating neuroplasticity in the motor cortex.

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[This corrects the article DOI: 10.3389/fpsyg.2022.1032680.].

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Intervention studiescombiningcognitive and motor demands have reported far-transfer cognitive benefits in healthy ageing. This systematic review and meta-analysis evaluated the effects of music and rhythm intervention on cognition in older adulthood. Inclusion criteria specified: 1) musical instrument training; 2) healthy, musically-naïve adults (≥60 years); 3) control group; 4) measure of executive function. Ovid, PubMed, Scopus and the Cochrane Library online databases were searched in August 2023. Data from thirteen studies were analysed (N = 502 participants). Study quality was assessed using the Cochrane Risk of Bias tool (RoB 2; Sterne et al., 2019). Random effects models revealed: a low effect on inhibition (d = 0.27,p = .0335); a low-moderate effect on switching (d = -0.39, p = .0021); a low-moderate effect on verbal category switching (d =0.39,p = .0166); and a moderate effect on processing speed (d = 0.47,p < .0001). No effect was found for selective visual attention, working memory, or verbal memory. With regards to overall bias, three studies were rated as "high", nine studies were rated as having "some concerns" and one was rated "low". The meta-analysis suggests that learning to play a musical instrument enhances attention inhibition, switching and processing speed in ageing.

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Corticostriatal regions play a pivotal role in visuomotor learning. However, less research has been done on how fMRI activity in their subregions is related to task performance, which is provided as visual feedback during motor learning. To address this, we conducted an fMRI experiment in which participants acquired a complex de novo motor skill using continuous or binary visual feedback related to performance. We found a highly selective response related to performance in the entire striatum in both conditions and a relatively higher response in the caudate nucleus for the binary feedback condition. However, the ventromedial prefrontal cortex (vmPFC) response was significant only for the continuous feedback condition. Furthermore, we also found functional distinction of the striatal subregions in random versus goal-directed motor control. These findings underscore the substantial effects of the visual feedback indicating performance on distinct corticostriatal responses, thereby elucidating its significance in reinforcement-based motor learning.

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Although animal research implicates a central role for dopamine in motor skill learning, a direct causal link has yet to be established in neurotypical humans. Here, we tested if a pharmacological manipulation of dopamine alters motor learning, using a paradigm which engaged explicit, goal-directed strategies. Participants (27 females; 11 males; aged 18-29 years) first consumed either 100 mg of levodopa (n = 19), a dopamine precursor that increases dopamine availability, or placebo (n = 19). Then, during training, participants learnt the explicit strategy of aiming away from presented targets by instructed angles of varying sizes. Targets jumped mid-movement by the instructed aiming angle. Task success was thus contingent upon aiming accuracy and not speed. The effect of the dopamine manipulations on skill learning was assessed during training and after an overnight follow-up. Increasing dopamine availability at training improved aiming accuracy and lengthened reaction times, particularly for larger, more difficult aiming angles, both at training and, importantly, at follow-up, despite prominent session-by-session performance improvements in both accuracy and speed. Exogenous dopamine thus seems to result in a learnt, persistent propensity to better adhere to task goals. Results support the proposal that dopamine is important in engagement of instrumental motivation to optimize adherence to task goals, particularly when learning to execute goal-directed strategies in motor skill learning.

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This study aimed to examine the influence of different observational angles in video self-modeling on task acquisition and retention. We randomly assigned 42 Japanese university students to three camera-angle groups, i.e., a front-angle, a rear-angle, and a control group. The participants performed a 3 × 6 × 3 cup-stacking task with three sequential laps. The front- and rear-angle groups viewed video self-modeling created from previously self-chosen videos. The retention phase was conducted 1 week after the acquisition phase. The rear-angle group demonstrated the fastest movement times in the acquisition phase. Our findings indicate that viewing learner-chosen video self-modeling from a rear angle enhances motor skill acquisition but does not contribute to motor skill learning.

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Newly acquired motor skills can be critically driven by different rest periods during practice. Specifically, in the initial stages of motor skill acquisition, the interval between individual trials plays a pivotal role in facilitating effective motor performance, such as in the case of throwing. The objective of this research was to determine the optimal inter-trial rest period promoting efficient motor performance, focusing on two specific motor task actions. In a randomized counterbalanced cross-over research design 169 high-school students aged 14 were studied (M = 150; F = 19). In one block, participants performed 10 basketball free throws with a short rest interval (< 5 s) and 10 other throws with a long rest interval (∼50-60 s). In a second block, they threw a regular size tennis ball into a 1-m diameter circle on the floor at 6.75 m, again throwing 10 times with a short inter-trial rest interval and 10 times with a long inter-trial rest interval. The order of the rest intervals within each block was randomized and counterbalanced. With a repeated measures two-way analysis of variance, greater accuracy seemed to be associated with short intra-set rest intervals as there were significant main effects of both conditions (F1,167 = 368.0, p < 0.001, η2p = 0.271) and resting time (F1,167 = 18.6, p < 0.001, η2p = 0.192) and no significant interaction "condition by time". Fast practice was efficient independently of the complexity of the throwing task, suggesting robust support for schema theory.

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Objective.Unsupervised myocontrol methods aim to create control models for myoelectric prostheses while avoiding the complications of acquiring reliable, regular, and sufficient labeled training data. A limitation of current unsupervised methods is that they fix the number of controlled prosthetic functions a priori, thus requiring an initial assessment of the user's motor skills and neglecting the development of novel motor skills over time.Approach.We developed a progressive unsupervised myocontrol (PUM) paradigm in which the user and the control model coadaptively identify distinct muscle synergies, which are then used to control arbitrarily associated myocontrol functions, each corresponding to a hand or wrist movement. The interaction starts with learning a single function and the user may request additional functions after mastering the available ones, which aligns the evolution of their motor skills with an increment in system complexity. We conducted a multi-session user study to evaluate PUM and compare it against a state-of-the-art non-progressive unsupervised alternative. Two participants with congenital upper-limb differences tested PUM, while ten non-disabled control participants tested either PUM or the non-progressive baseline. All participants engaged in myoelectric control of a virtual hand and wrist.Main results.PUM enabled autonomous learning of three myocontrol functions for participants with limb differences, and of all four available functions for non-disabled subjects, using both existing or newly identified muscle synergies. Participants with limb differences achieved similar success rates to non-disabled ones on myocontrol tests, but faced greater difficulties in internalizing new motor skills and exhibited slightly inferior movement quality. The performance was comparable with either PUM or the non-progressive baseline for the group of non-disabled participants.Significance.The PUM paradigm enables users to autonomously learn to operate the myocontrol system, adapts to the users' varied preexisting motor skills, and supports the further development of those skills throughout practice.

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BACKGROUND: Many studies have started integrating virtual reality (VR) into neurorehabilitation for children with cerebral palsy (CP). The results of the effects of VR on motor skill learning, including the short- to long-term results of relevant studies, must be pooled in a generic framework. OBJECTIVE: This systematic review and meta-analysis aimed to investigate the short- to long-term effects of therapies including VR on motor skill learning in children with CP. METHODS: Two examiners followed the inclusion and exclusion criteria of the "Participant, Intervention, Control, and Outcome" framework. Randomized controlled trials (RCTs) and non-RCTs were considered if they compared VR-included interventions with control groups on motor functions and daily life activities in children with CP. PubMed, ScienceDirect, Embase, and IEEE Xplore databases were searched. The modified Downs and Black assessment was used to assess the methodological quality of the included studies. Meta-analyses and subgroup analyses for RCTs were conducted whenever possible. RESULTS: A total of 7 RCTs, 2 non-RCTs, and 258 children with CP were included. The priority focus of 78% (7/9) of the studies was upper limb functions. There was a significant short-term effect of adding VR to conventional therapies on upper limb functions when compared with conventional therapies (P=.04; standardized mean difference [SMD]=0.39, 95% CI 0.01-0.76). The overall medium- to long-term effects showed a trend toward favoring the VR group, although the difference was not statistically significant (P=.06; SMD=0.37, 95% CI -0.02 to 0.77). For balance (P=.06; SMD=1.04, 95% CI -0.04 to 2.12), gross motor functions (P=.30; SMD=2.85, 95% CI -2.57 to 8.28), and daily life activities outcomes (P=.21; SMD=0.29, 95% CI -0.16 to 0.74), the overall effect in the short term also showed a trend toward favoring the VR group, but these results were not statistically significant. CONCLUSIONS: VR seems to have additional benefits for motor skill learning in children with CP. Studies with follow-up outcomes of VR training focusing on balance and gross motor functions in patients with CP were quite limited. Future research on balance and gross motor function outcomes should target particularly long-term results of therapies including VR on motor skill learning. TRIAL REGISTRATION: PROSPERO International Prospective Register of Systematic Reviews CRD42021227734; https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021227734.

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Complex behaviors depend on the coordinated activity of neural ensembles in interconnected brain areas. The behavioral function of such coordination, often measured as co-fluctuations in neural activity across areas, is poorly understood. One hypothesis is that rapidly varying co-fluctuations may be a signature of moment-by-moment task-relevant influences of one area on another. We tested this possibility for error-corrective adaptation of birdsong, a form of motor learning which has been hypothesized to depend on the top-down influence of a higher-order area, LMAN (lateral magnocellular nucleus of the anterior nidopallium), in shaping moment-by-moment output from a primary motor area, RA (robust nucleus of the arcopallium). In paired recordings of LMAN and RA in singing birds, we discovered a neural signature of a top-down influence of LMAN on RA, quantified as an LMAN-leading co-fluctuation in activity between these areas. During learning, this co-fluctuation strengthened in a premotor temporal window linked to the specific movement, sequential context, and acoustic modification associated with learning. Moreover, transient perturbation of LMAN activity specifically within this premotor window caused rapid occlusion of pitch modifications, consistent with LMAN conveying a temporally localized motor-biasing signal. Combined, our results reveal a dynamic top-down influence of LMAN on RA that varies on the rapid timescale of individual movements and is flexibly linked to contexts associated with learning. This finding indicates that inter-area co-fluctuations can be a signature of dynamic top-down influences that support complex behavior and its adaptation.

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Although motor coordination or motor skill learning are improved by taking vitamin D in the animal experiment, muscle function have not been estimated. Here we examined the effect of vitamin D3 administration on motor coordination and motor skill learning, muscle strength, and muscle volume in mice fed a vitamin D deficient diet. In mice fed a vitamin D deficient diet, serum calcium and 25(OH)D3 concentrations were measured. We then conducted Rotarod test, beam walking assay, micro-CT analysis, and forelimb grip strength test. Administration of vitamin D3 elongated the retention time in the Rotarod test in a time dependent manner. In contrast, the time to reach a beam goal box in beam walking assay was not changed in mice administered with vitamin D3, compared to the control. Oral administration of vitamin D3 did not affect muscle strength nor muscle volume. Oral administration of vitamin D3 promotes not motor coordination but motor skill learning and does not affect muscle function.

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We revisit an agenda that was outlined in a previous paper in this journal focusing on the importance of skill acquisition research in enhancing practice and instruction in sport. In this current narrative review, we reflect on progress made since our original attempt to highlight several potential myths that appeared to exist in coaching, implying the existence of a theory-practice divide. Most notably, we present five action points that would impact positively on coaches and practitioners working to improve skill learning across sports, as well as suggesting directions for research. We discuss the importance of practice quality in enhancing learning and relate this concept to notions of optimising challenge. We discuss how best to assess learning, the right balance between repetition and practice that is specific to competition, the relationship between practice conditions, instructions, and individual differences, and why a more "hands-off" approach to instruction may have advantages over more "hands-on" methods. These action points are considered as a broad framework for advancing skill acquisition for excellence (SAFE) in applied practice. We conclude by arguing the need for increased collaboration between researchers, coaches, and other sport practitioners.

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Neurotransmitters are released at synapses by synaptic vesicles (SVs), which originate from SV precursors (SVPs) that have traveled along the axon. Because each synapse maintains a pool of SVs, only a small fraction of which are released, it has been thought that axonal transport of SVPs does not affect synaptic function. Here, studying the corticostriatal network both in microfluidic devices and in mice, we find that phosphorylation of the Huntingtin protein (HTT) increases axonal transport of SVPs and synaptic glutamate release by recruiting the kinesin motor KIF1A. In mice, constitutive HTT phosphorylation causes SV over-accumulation at synapses, increases the probability of SV release, and impairs motor skill learning on the rotating rod. Silencing KIF1A in these mice restored SV transport and motor skill learning to wild-type levels. Axonal SVP transport within the corticostriatal network thus influences synaptic plasticity and motor skill learning.

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BACKGROUND: The implementation of virtual devices can facilitate the role of therapists (e.g., patient motivation, intensity of practice) to improve the effectiveness of treatment for children with cerebral palsy. Among existing therapeutic devices, none has been specifically designed to promote the application of principles underlying evidence-based motor skill learning interventions. Consequently, evidence is lacking regarding the effectiveness of virtual-based sessions in motor function rehabilitation with respect to promoting the transfer of motor improvements into daily life activities. We tested the effectiveness of implementing a recently developed virtual device (REAtouch®), specifically designed to enable the application of therapeutic motor skill learning principles, during a Hand Arm Bimanual Intensive Therapy Including Lower Extremities (HABIT-ILE) intervention. METHODS: Forty children with unilateral cerebral palsy (5-18 years; MACS I-III; GMFCS I-II) were randomly assigned to a control group or a "REAtouch®" experimental group for a 90-h HABIT-ILE day-camp intervention (two weeks). Children in the REAtouch® group spent nearly half of their one-on-one therapeutic time using the REAtouch®. Participants underwent three testing sessions: the week before (T1), after intervention (T2), and at three months follow-up (T3). The primary outcome was the Assisting Hand Assessment (T3-T1; blinded). Secondary outcomes measured uni-bimanual hand function, stereognosis, gait endurance, daily life abilities, and functional goals. Accelerometers and a manual report of daily activities served to document therapeutic dosage and treatment characteristics. We used one-way RMANOVA to compare the efficacies of the two interventions, and non-inferiority analyses to contrast changes in the "REAtouch®" group versus the "HABIT-ILE" control group. RESULTS: We found significant improvements in both groups for most of the outcome measures (p < 0.05). There was significant non-inferiority of changes in the REAtouch® group for upper extremities motor function, functional goals attainment, and abilities in daily life activities (p < 0.05). CONCLUSIONS: Use of the REAtouch® device during HABIT-ILE showed non-inferior efficacy compared to the conventional evidence-based HABIT-ILE intervention in children with unilateral cerebral palsy. This study demonstrates the feasibility of using this virtual device in a high dosage camp model, and establishes the possibility of applying the therapeutic principles of motor skill learning during specifically designed virtual-based sessions. TRIAL REGISTRATION: Trial registration number: NCT03930836-Registration date on the International Clinical Trials Registry Platform (ICTRP): June 21th, 2018; Registration date on NIH Clinical Trials Registry: April 29th, 2019. First patient enrollment: July 3rd, 2018.

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The basal ganglia are important modulators of the cognitive and motor benefits of exercise. However, the neural networks underlying these benefits remain poorly understood. Our study systematically analyzed exercise-associated changes in metabolic connectivity in the cortico-basal ganglia-thalamic network during the performance of a new motor task, with regions-of-interest defined based on mesoscopic domains recently defined in the mouse brain structural connectome. Mice were trained on a motorized treadmill for six weeks or remained sedentary (control), thereafter undergoing [14C]-2-deoxyglucose metabolic brain mapping during wheel walking. Regional cerebral glucose uptake (rCGU) was analyzed in 3-dimensional brains reconstructed from autoradiographic brain sections using statistical parametric mapping. Metabolic connectivity was assessed by calculating inter-regional correlation of rCGU cross-sectionally across subjects within a group. Compared to controls, exercised animals showed broad decreases in rCGU in motor areas, but increases in limbic areas, as well as the visual and association cortices. In addition, exercised animals showed (i) increased positive metabolic connectivity within and between the motor cortex and caudoputamen (CP), (ii) newly emerged negative connectivity of the substantia nigra pars reticulata with the globus pallidus externus, and CP, and (iii) reduced connectivity of the prefrontal cortex (PFC). Increased metabolic connectivity in the motor circuit in the absence of increases in rCGU strongly suggests greater network efficiency, which is also supported by the reduced involvement of PFC-mediated cognitive control during the performance of a new motor task. Our study delineates exercise-associated changes in functional circuitry at the subregional level and provides a framework for understanding the effects of exercise on functions of the cortico-basal ganglia-thalamic network.

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Parkinson's disease (PD) belongs to an α-synucleinopathy and manifests motor dysfunction attributed to nigrostriatal dopaminergic degeneration. In clinical practice, the beneficial role of physical therapy such as motor skill learning training has been recognized in PD-linked motor defects. Nevertheless, the disease-modifying effects of motor skill learning training on PD-related pathology remain unclear. Here, we investigated the disease-modifying effects of rotarod walking exercise (RWE), a modality of motor skill learning training, in a subacute 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of PD. In motor function and dopaminergic degeneration, RWE improved MPTP-induced deficits. In addition, RWE enhanced the expression of neurotrophic factors BDNF/GDNF, PGC1-α, Nurr1, and p-AMPK, thereby recovering dopaminergic neuronal cell death. Moreover, RWE inhibited microglial activation and the expression of pro-inflammatory markers, such as p-IκBα, iNOS, IL-1ß, TNF-α, and cathepsin D, while elevating anti-inflammatory IL-10 and TGF-ß. RWE also decreased oxidative stress markers in the substantia nigra, such as 4-HNE and 8-OHdG-positive cells, while increasing Nrf2-controlled antioxidant enzymes. Regarding the effect of RWE on α-synuclein, it reduced the monomer/oligomer forms of α-synuclein and phosphorylation at serine 129. Further mechanistic studies revealed that RWE suppressed the expression of matrix metalloproteinase-3 and p-GSK3ß (Y216), which play key roles in α-synuclein aggregation. These data collectively suggest that inhibition of neuroinflammation and α-synuclein oligomerization by RWE may contribute to the improvement of PD pathology.

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Parkinson's disease (PD) is characterized pathologically by abnormal aggregation of alpha-synuclein (α-Syn) in the brain and clinically by fine movement deficits at the early stage, but the roles of α-Syn and associated neural circuits and neuromodulator bases in the development of fine movement deficits in PD are poorly understood, in part due to the lack of appropriate behavioral testing paradigms and PD models without motor confounding effects. Here, we coupled two unique behavioral paradigms with two PD models to reveal the following: (i) Focally injecting α-Syn fibrils into the dorsolateral striatum (DLS) and the transgenic expression of A53T-α-Syn in the dopaminergic neurons in the substantia nigra (SN, PITX3-IRES2-tTA/tetO-A53T mice) selectively impaired forelimb fine movements induced by the single-pellet reaching task. (ii) Injecting α-Syn fibers into the SN suppressed the coordination of cranial and forelimb fine movements induced by the sunflower seed opening test. (iii) Treatments with the adenosine A2A receptor (A2AR) antagonist KW6002 reversed the impairment of forelimb and cranial fine movements induced by α-Syn aggregates in the SN. These findings established a causal role of α-Syn in the SNc-DLS dopaminergic pathway in the development of forelimb and cranial fine movement deficits and suggest a novel therapeutic strategy to improve fine movements in PD by A2AR antagonists.

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From observations in rodents, it has been suggested that the cellular basis of learning-dependent changes, detected using structural MRI, may be increased dendritic spine density, alterations in astrocyte volume, and adaptations within intracortical myelin. Myelin plasticity is crucial for neurological function, and active myelination is required for learning and memory. However, the dynamics of myelin plasticity and how it relates to morphometric-based measurements of structural plasticity remains unknown. We used a motor skill learning paradigm in male mice to evaluate experience-dependent brain plasticity by voxel-based morphometry (VBM) in longitudinal MRI, combined with a cross-sectional immunohistochemical investigation. Whole-brain VBM revealed nonlinear decreases in gray matter volume (GMV) juxtaposed to nonlinear increases in white matter volume (WMV) within GM that were best modeled by an asymptotic time course. Using an atlas-based cortical mask, we found nonlinear changes with learning in primary and secondary motor areas and in somatosensory cortex. Analysis of cross-sectional myelin immunoreactivity in forelimb somatosensory cortex confirmed an increase in myelin immunoreactivity followed by a return towards baseline levels. Further investigations using quantitative confocal microscopy confirmed these changes specifically to the length density of myelinated axons. The absence of significant histological changes in cortical thickness suggests that nonlinear morphometric changes are likely due to changes in intracortical myelin for which morphometric WMV in somatosensory cortex significantly correlated with myelin immunoreactivity. Together, these observations indicate a nonlinear increase of intracortical myelin during learning and support the hypothesis that myelin is a component of structural changes observed by VBM during learning.

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