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Learning to sequence movements is necessary for skillful interaction with the environment. Neuroplasticity, particularly long-term potentiation (LTP), within sensorimotor networks underlies the acquisition of motor skill. Short-term immobilization of the arm, even less than 12 hours, can reduce corticospinal excitability and increase the capacity for LTP-like plasticity within the contralateral primary motor cortex. However, it is still unclear whether short-term immobilization influences motor skill acquisition. The current study aimed to evaluate the effect of short-term arm immobilization on implicit, sequence-specific motor skill acquisition using a modified Serial Reaction Time Task (SRTT). Twenty young, neurotypical adults underwent a single SRTT training session after six hours of immobilization of the non-dominant arm or an equivalent period of no immobilization. Our results demonstrated that participants improved SRTT performance overall after training, but there was no evidence of an effect of immobilization prior to task training on performance improvement. Further, improvements on the SRTT were not sequence-specific. Taken together, motor skill acquisition for sequential, individuated finger movements improved following training but the effect of six hours of immobilization was difficult to discern., Competing Interests: The authors have declared that no competing interests exist.

Objective: Activity patterns across brain regions that can be characterized at rest (ie, resting-state functional connectivity [rsFC]) are disrupted after stroke and linked to impairments in motor function. While changes in rsFC are associated with motor recovery, it is not clear how rsFC is modulated by skilled motor practice used to promote recovery. The current study examined how rsFC is modulated by skilled motor practice after stroke and how changes in rsFC are linked to motor learning., Methods: Two groups of participants (individuals with stroke and age-matched controls) engaged in 4 weeks of skilled motor practice of a complex, gamified reaching task. Clinical assessments of motor function and impairment, and brain activity (via functional magnetic resonance imaging) were obtained before and after training., Results: While no differences in rsFC were observed in the control group, increased connectivity was observed in the sensorimotor network, linked to learning in the stroke group. Relative to healthy controls, a decrease in network efficiency was observed in the stroke group following training., Conclusions: Findings indicate that rsFC patterns related to learning observed after stroke reflect a shift toward a compensatory network configuration characterized by decreased network efficiency.

Background: In individuals with chronic stroke, impairment of the paretic arm may be exacerbated by increased contralesional transcallosal inhibition (TCI). Continuous theta burst stimulation (cTBS) can decrease primary motor cortex (M1) excitability and TCI. However, contralesional cTBS shows inconsistent effects after stroke. Variable effects of cTBS could stem from failure to pair stimulation with skilled motor practice or a focus of applying cTBS over M1., Objective: Here, we investigated the effects of pairing cTBS with skilled practice on motor learning and arm function. We considered the differential effects of stimulation over two different brain regions: contralesional M1 (M1c) or contralesional primary somatosensory cortex (S1c)., Methods: 37 individuals with chronic stroke participated in five sessions of cTBS and paretic arm skilled practice of a serial targeting task (STT); participants received either cTBS over M1c or S1c or sham before STT practice. Changes in STT performance and Wolf Motor Function Test (WMFT) were assessed as primary outcomes. Assessment of bilateral corticospinal, intracortical excitability and TCI were secondary outcomes., Results: cTBS over sensorimotor cortex did not improve STT performance and paretic WMFT-rate beyond sham cTBS. TCI was reduced bi-directionally following the intervention, regardless of stimulation group. In addition, we observed an association between STT performance change and paretic WMFT-rate change in the M1c stimulation group only., Conclusions: Multiple sessions of STT practice can improve paretic arm function and decrease TCI bilaterally, with no additional benefit of prior cTBS. Our results suggest that improvement in STT practice following M1c cTBS scaled with change in paretic arm function in some individuals. Our results highlight the need for a better understanding of the mechanisms of cTBS to effectively identify who may benefit from this form of brain stimulation.

Background: Paired associative stimulation (PAS) combining repeated pairing of electrical stimulation of a peripheral nerve with transcranial magnetic stimulation (TMS) over the primary motor cortex (M1) can induce neuroplastic adaptations in the human brain and enhance motor learning in neurologically-intact individuals. However, the extent to which PAS is an effective technique for inducing associative plasticity and improving motor function in individuals post-stroke is unclear., Objective: The objective of this pilot study was to investigate the effects of a single session of PAS to modulate corticomotor excitability and motor skill performance in individuals post-stroke., Methods: Seven individuals with chronic stroke completed two separate visits separated by at least one week. We assessed general corticomotor excitability, intracortical network activity and behavioral outcomes prior to and at three time points following PAS and compared these outcomes to those following a sham PAS condition (PASSHAM)., Results: Following PAS, we found increased general corticomotor excitability but no significant difference in behavioral measures between PAS conditions. There was a relationship between PAS-induced corticomotor excitability increase and enhanced motor skill performance across post-PAS testing time points., Conclusion: These results provide preliminary evidence for the potential of PAS to increase corticomotor excitability that could favorably impact motor skill performance in chronic individuals post-stroke and are an important first step for future studies investigating the clinical application and behavioral relevance of PAS interventions in post stroke patient populations.

Experience-dependent structural changes are widely evident in gray matter. Using diffusion weighted imaging (DWI), the neuroplastic effect of motor training on white matter in the brain has been demonstrated. However, in humans it is not known whether specific features of white matter relate to motor skill acquisition or if these structural changes are associated to functional network connectivity. Myelin can be objectively quantified in vivo and used to index specific experience-dependent change. In the current study, seventeen healthy young adults completed ten sessions of visuomotor skill training (10,000 total movements) using the right arm. Multicomponent relaxation imaging was performed before and after training. Significant increases in myelin water fraction, a quantitative measure of myelin, were observed in task dependent brain regions (left intraparietal sulcus [IPS] and left parieto-occipital sulcus). In addition, the rate of motor skill acquisition and overall change in myelin water fraction in the left IPS were negatively related, suggesting that a slower rate of learning resulted in greater neuroplastic change. This study provides the first evidence for experience-dependent changes in myelin that are associated with changes in skilled movements in healthy young adults.

Background and Purpose: Imaging advances allow investigation of white matter after stroke; a growing body of literature has shown links between diffusion-based measures of white matter microstructure and motor function. However, the relationship between these measures and motor skill learning has not been considered in individuals with stroke. The aim of this study was to investigate the relationships between posttraining white matter microstructural status, as indexed by diffusion tensor imaging within the ipsilesional posterior limb of the internal capsule (PLIC), and learning of a novel motor task in individuals with chronic stroke., Methods: A total of 13 participants with chronic stroke and 9 healthy controls practiced a visuomotor pursuit task across 5 sessions. Change in motor behavior associated with learning was indexed by comparing baseline performance with a delayed retention test. Fractional anisotropy (FA) indexed at the retention test was the primary diffusion tensor imaging-derived outcome measure., Results: In individuals with chronic stroke, we discovered an association between posttraining ipsilesional PLIC FA and the magnitude of change associated with motor learning; hierarchical multiple linear regression analyses revealed that the combination of age, time poststroke, and ipsilesional PLIC FA posttraining was associated with motor learning-related change (R = 0.649; P = 0.02). Baseline motor performance was not related to posttraining ipsilesional PLIC FA., Discussion and Conclusions: Diffusion characteristics of posttraining ipsilesional PLIC were linked to the magnitude of change in skilled motor behavior. These results imply that the microstructural properties of regional white matter indexed by diffusion behavior may be an important factor to consider when determining potential response to rehabilitation in persons with stroke., Video Abstract Available: (see Video, Supplemental Digital Content 1, http://links.lww.com/JNPT/A59) for more insights from the authors.

Background: Complete recovery of motor function after stroke is rare with deficits persisting into the chronic phase of recovery. Diffusion tensor imaging (DTI) can evaluate relationships between white matter microstructure and motor function after stroke. The objective of this investigation was to characterize microstructural fiber integrity of motor and sensory regions of the corpus callosum (CC) and descending motor outputs of the posterior limb of the internal capsule (PLIC) in individuals with chronic stroke and evaluate the relationships between white matter integrity and motor function., Results: Standardized measures of upper extremity motor function were measured in thirteen individuals with chronic stroke. Manual dexterity was assessed in thirteen healthy age-matched control participants. DTI scans were completed for each participant. Fractional anisotropy (FA) of a cross-section of sensory and motor regions of the CC and the PLIC bilaterally were quantified. Multivariate analysis of variance evaluated differences between stroke and healthy groups. Correlational analyses were conducted for measures of motor function and FA. The stroke group exhibited reduced FA in the sensory (p = 0.001) region of the CC, contra- (p = 0.032) and ipsilesional (p = 0.001) PLIC, but not the motor region of the CC (p = 0.236). In the stroke group, significant correlations between contralesional PLIC FA and level of physical impairment (p = 0.005), grip strength (p = 0.006) and hand dexterity (p = 0.036) were observed., Conclusions: Microstructural status of the sensory region of the CC is reduced in chronic stroke. Future work is needed to explore relationships between callosal sensorimotor fiber integrity and interhemispheric interactions post-stroke. In addition, contralesional primary motor output tract integrity is uniquely and closely associated with multiple dimensions of motor recovery in the chronic phase of stroke suggesting it may be an important biomarker of overall motor recovery.

Sleep has been shown to benefit memory consolidation for certain motor skills, but it remains unclear if this relationship exists for motor skills with direct rehabilitation applications. We aimed to determine the neurobehavioral relationship between finger-tracking skill development and sleep following skill training in young, healthy subjects. Forty subjects received tracking training in the morning (n = 20) or the evening (n = 20). Measures of tracking skill and cortical excitability were collected before and after training. Following training, tracking skill and measures of cortical excitability were assessed at two additional follow-up visits (12 and 24 h post-training) for each subject following an episode of sleep or waking activity. Two-way repeated-measures ANOVAs with Bonferroni-adjusted post hoc tests were conducted for tracking accuracy and measures of cortical excitability. Skill performance improved after training and continued to develop offline during the first post-training interval (12 h). This development was not further enhanced by sleep during this interval. Level of skill improvement was maintained for at least one day in both training groups. Cortical excitability was reduced following training and was related to level of skill performance at follow-up assessment. These data suggest offline memory consolidation of a continuous, visuospatial, finger-tracking skill is not dependent on sleep. These findings are in agreement with recent literature, indicating characteristics of a motor skill may be sensitive to the beneficial effect of sleep on post-training information processing.