Modulation Dynamics in the Orofacial Sensorimotor Cortex during Motor Skill Acquisition

Recent neurophysiological studies have demonstrated that frontal midline theta (FMT) activity plays a significant role in motor learning. One of the key challenges in motor learning is to understand the interindividual variability in learning proficiency rates, yet the underlying neural mechanisms remain unclear. To address this open question, this study recorded electroencephalogram activity from twenty-one healthy participants during a visuomotor tracking task to investigate whether modulation of FMT power and the theta phase synchronization across trials (theta phase consistency) during motor preparation could explain individual differences in learning proficiency. We found a significant positive correlation between increased FMT power during motor preparation and learning proficiency rates. Specifically, individuals with greater FMT power exhibited faster learning rates. In contrast, no significant correlation was observed between the consistency of the theta phase during motor preparation and learning proficiency. Together, these findings highlight that the FMT power, rather than phase synchrony, is closely associated with motor learning efficiency. This study provides a novel perspective for understanding the causes of individual differences in motor learning and further corroborates the previous evidence showing FMT power contributes to motor learning processes.

A modified model of the Hebbian synapse and its role in motor learning

The synaptic pathways in the striatum are central to basal ganglia functions including motor control, learning and organization, action selection, acquisition of motor skills, cognitive function, and emotion. Here, we review the role of the striatum and its connections in motor learning and performance. The development of new techniques to record neuronal activity and animal models of motor disorders using neurotoxin, pharmacological, and genetic manipulations are revealing pathways that underlie motor performance and motor learning, as well as how they are altered by pathophysiological mechanisms. We discuss approaches that can be used to analyze complex motor skills, particularly in rodents, and identify specific questions central to understanding how striatal circuits mediate motor learning.

Interference with Existing Memories Alters Offline Intrinsic Functional Brain Connectivity

Selective Engagement of Plasticity Mechanisms for Motor Memory Storage

Motor-linked implicit learning is the learning of a sequence of movements without conscious awareness. Although motor symptoms are frequently reported in individuals with autism spectrum disorder (ASD), recent behavioral studies have suggested that motor-linked implicit learning may be intact in ASD. The serial reaction time (SRT) task is one of the most common measures of motor-linked implicit learning. The present study used a 3T functional magnetic resonance imaging scanner to examine the behavioral and neural correlates of real-time motor sequence learning in adolescents and adults with ASD (n = 15) compared with age- and intelligence quotient-matched individuals with typical development (n = 15) during an SRT task. Behavioral results suggested less robust motor sequence learning in individuals with ASD. Group differences in brain activation suggested that individuals with ASD, relative to individuals with typical development, showed decreased activation in the right superior parietal lobule (SPL) and right precuneus (Brodmann areas 5 and 7, and extending into the intraparietal sulcus) during learning. Activation in these areas (and in areas such as the right putamen and right supramarginal gyrus) was found to be significantly related to behavioral learning in this task. Additionally, individuals with ASD who had more severe repetitive behavior/restricted interest symptoms demonstrated greater decreased activation in these regions during motor learning. In conjunction, these results suggest that the SPL may play an important role in motor learning and repetitive behavior in individuals with ASD.

The qualitative behavioral reorganizations that occurred during the acquisition of a complex motor skill were examined. Five novice participants practiced for 39 sessions of ten 1-min trials on a modified version of the ski-simulator. Analyses focused on the motion of the apparatus platform, modeled as a self-sustained oscillator. At the beginning of the experiment, all participants adopted a behavior that could be modeled with a highly nonlinear stiffness function and a Rayleigh damping function. The behavior in the final part of the experiment was captured by a qualitatively different model, with a linear stiffness function and a van der Pol damping behavior. The transition from the initial to the final model was gradual and was marked in most cases by an abrupt increase of oscillation frequency. During the transition stage, the 2 damping behaviors seemed alternately exploited within each trial. The results are discussed in the framework of the dynamical systems approach to motor coordination and learning, considering motor skill acquisition as a phase transition.

Individuals with cognitive impairment may have motor learning deficits due to the high engagement of cognitive mechanisms during motor skill acquisition. We conducted a scoping review to address the quality of current research on the relationship between cognitive impairments (i.e., deficits in attention, memory, planning and executive functions) and motor learning among older adults with Alzheimer's Disease or Mild Cognitive Impairment. After screening thousands of articles, we selected 15 studies describing cognitive assessment tools, experimental designs, and the severity of cognitive impairment. Although seven studies reported that cognitive impairment impaired motor learning, most studies included a high risk of bias. We identified multiple assessment tools across these studies that make comparisons among findings difficult. Future research in this area should focus on the influence of increased practice days during motor learning acquisition and incorporate both retention and transfer tests. Cognitive assessments should target the specific cognitive skills or deficits most closely related to the motor learning process.

In addition to its role in the vascular system, plasminogen activator (PA) is involved in neural development, excitotoxic cell death, and has been implicated in aspects of cerebral synaptic remodeling associated with cerebellar motor learning, visual cortex ocular dominance columns, and hippocampal & corticostriatal LTP. During a complex motor task cerebellar granule neurons show a rapid and transient induction of mRNA for the extracellular protease tissue plasminogen activator (tPA). This induction of tPA is cerebellar specific, and is not seen in the cerebella of exercised or stressed mice, and is distinct from simple performance phenomena. Knock-out mice lacking the tPA gene show a significant reduction in both rate and extent of learning the complex motor task. Furthermore, blocking tPA activity by infusion of PAI-1 or tPA-STOP during training dramatically impairs motor learning. Thus, tPA plays and important role in motor learning, in which tPA may facilitate synaptic plasticity. We have explored the possibility that PA may also play a role in synaptic plasticity in the spinal cord. The crossed phrenic phenomenon (CPP) describes respiratory functional plasticity that arises following spinal cord injury; whereby, phrenic motoneuron drive to the diaphragm is restored following activation of functionally ineffective medullary respiratory neuron synapses on phrenic motoneurons (PMN). Synaptic remodeling is thought to occur during the characteristic delay period following spinal cord injury before the CPP becomes functional. The mechanisms underlying this synaptic plasticity are not well-defined. Our ultimate aim is to understand the underlying molecular mechanisms of this functional recovery using a mouse model amenable to a molecular genetic approach, and ours is the first report of CPP in mice. Using electromyographic (EMG) recordings from the diaphragm, we examined the inter-operative delay time between spinal cord hemisection and contralateral phrenicotomy required for diaphragm response, as compared to animal death from asphyxia at zerotime. For each animal, a spinal cord hemisection was performed on the left side at C2. A contralateral phrenicotomy was performed the next day (overnight animals), 6–8 hours, 4–5 hours, or 1–2 hours post-hemisection. As the inter-operative delay was reduced, the proportion of mice displaying the CPP decreased from 100% for overnight animals, 94% in 6–8 h, 82% in 4–5 h, to 76% for 1–2 h mice. A critical 1–2 hr window is required for this synaptic plasticity. In situ hybridization shows that uPA and tPA mRNAs are rapidly induced in C4-5 ventral spinal cord neurons in the ipsilateral phrenic nucleus compared to the contralateral PMN and sham controls, with markedly elevated tPA protein at 1hr. post-hemisection. This specific and concomitant induction of PA suggests a role in CPP spinal cord plasticity, which may ultimately lead to therapeutic uses for PA in spinal cord injury.

The cerebellum is not necessary for visually driven recalibration of hand proprioception

The alterations in the basal ganglia circuitry are core pathological hallmark in Huntington's Disease (HD) and traditionally linked to its sever motor symptoms. Recently it was shown that optogenetic stimulation of cortical afferences to the striatum is able to reverse motor symptoms in HD mice. However, the specific contribution of the direct and indirect striatal output pathways from the dorsolateral (DLS) and dorsomedial striatum (DMS) to the motor phenotype is still not clear. Here, we aim to uncover the contributions of these striatal subcircuits to motor control in wild type (WT) and HD mice by using the symptomatic R6/1 mice. We systematically evaluated locomotion, exploratory behavior, and motor learning effects of the selective optogenetic stimulation of D1 or A2A expressing neurons (direct and indirect pathway, respectively), in DLS or DMS. Bilateral optogenetic stimulation of the direct pathway from DLS and the indirect pathway from DMS resulted in subtle locomotor enhancements, while unaltering exploratory behavior. Additionally, bilateral stimulation of the indirect pathway from the DLS improved performance in the accelerated rotarod task, suggesting a role in motor learning. In contrast, in HD mice, stimulation of these pathways did not modulate any of these behaviors. Overall, this study highlights that selective stimulation of direct and indirect pathways from DLS and DMS have subtle impact in locomotion, exploratory activity or motor learning. The lack of responses in HD mice also suggests that strategies involving cortico-striatal circuits rather than striatal output circuits might be a better strategy for managing motor symptoms in movement disorders.

After brain damage, use-dependent plasticity of the spared neural network plays a crucial role in improving neural deficits and promoting motor learning and relearning using the impaired limbs. In degenerative cerebellar diseases, it is to be elucidated whether a similar mechanism works or not, since pathological processes are basically progressive. The fundamental question regarding the efficacy of neurorehabilitation in cerebellar degenerative diseases, is whether it is beneficial in terms of both the short- and long-term effect. To answer this question, two important issues need to be considered. The first is whether impaired motor learning due to cerebellar dysfunction is compensated for by repeated practice, since the cerebellum plays a crucial role in motor learning. The second issue is how long functional gains can be sustained provided that intensive rehabilitation results in significant gains. Recent studies have shown that intensive rehabilitation focusing on balance and mobility improves motor function for a period of up to 1 year in patients with degenerative cerebellar diseases. To obtain meaningful long-term gains, a combination of intermittent intensive short-term rehabilitation and home-based practice and support may be a practical way of managing patients. Future studies may elucidate a potential role of neuromodulation coupled with rehabilitative intervention to enhance the gains and to minimize functional decline.

Variable training does not lead to better motor learning compared to repetitive training in children with and without DCD when exposed to active video games

The mechanisms subserving motor skill acquisition and learning in the intact human brain are not fully understood. Previous studies in animals have demonstrated a causal relationship between motor learning and structural rearrangements of synaptic connections, raising the question of whether neurite-specific changes are also observable in humans. Here, we use advanced diffusion magnetic resonance imaging (MRI), sensitive to dendritic and axonal processes, to investigate neuroplasticity in response to long-term motor learning. We recruited healthy male and female human participants (age range 19-29) who learned a challenging dynamic balancing task (DBT) over four consecutive weeks. Diffusion MRI signals were fitted using Neurite Orientation Dispersion and Density Imaging (NODDI), a theory-driven biophysical model of diffusion, yielding measures of tissue volume, neurite density and the organizational complexity of neurites. While NODDI indices were unchanged and reliable during the control period, neurite orientation dispersion increased significantly during the learning period mainly in primary sensorimotor, prefrontal, premotor, supplementary, and cingulate motor areas. Importantly, reorganization of cortical microstructure during the learning phase predicted concurrent behavioral changes, whereas there was no relationship between microstructural changes during the control phase and learning. Changes in neurite complexity were independent of alterations in tissue density, cortical thickness, and intracortical myelin. Our results are in line with the notion that structural modulation of neurites is a key mechanism supporting complex motor learning in humans.SIGNIFICANCE STATEMENT The structural correlates of motor learning in the human brain are not fully understood. Results from animal studies suggest that synaptic remodeling (e.g., reorganization of dendritic spines) in sensorimotor-related brain areas is a crucial mechanism for the formation of motor memory. Using state-of-the-art diffusion magnetic resonance imaging (MRI), we found a behaviorally relevant increase in the organizational complexity of neocortical microstructure, mainly in primary sensorimotor, prefrontal, premotor, supplementary, and cingulate motor regions, following training of a challenging dynamic balancing task (DBT). Follow-up analyses suggested structural modulation of synapses as a plausible mechanism driving this increase, while colocalized changes in cortical thickness, tissue density, and intracortical myelin could not be detected. These results advance our knowledge about the neurobiological basis of motor learning in humans.

Binding of glutamate receptor δ2 to its scaffold protein, Delphilin, is regulated by PKA