The substantial phenotypic heterogeneity in autism limits our understanding of its genetic etiology. To address this gap, here we investigated genetic differences between autistic individuals (n
= ...12,893) based on core and associated features of autism, co-occurring developmental disabilities and sex. We conducted a comprehensive factor analysis of core autism features in autistic individuals and identified six factors. Common genetic variants were associated with the core factors, but de novo variants were not. We found that higher autism polygenic scores (PGS) were associated with lower likelihood of co-occurring developmental disabilities in autistic individuals. Furthermore, in autistic individuals without co-occurring intellectual disability (ID), autism PGS are overinherited by autistic females compared to males. Finally, we observed higher SNP heritability for autistic males and for autistic individuals without ID. Deeper phenotypic characterization will be critical in determining how the complex underlying genetics shape cognition, behavior and co-occurring conditions in autism.
Novel motor skills are learned through repetitive practice and, once acquired, persist long after training stops. Earlier studies have shown that such learning induces an increase in the efficacy of ...synapses in the primary motor cortex, the persistence of which is associated with retention of the task. However, how motor learning affects neuronal circuitry at the level of individual synapses and how long-lasting memory is structurally encoded in the intact brain remain unknown. Here we show that synaptic connections in the living mouse brain rapidly respond to motor-skill learning and permanently rewire. Training in a forelimb reaching task leads to rapid (within an hour) formation of postsynaptic dendritic spines on the output pyramidal neurons in the contralateral motor cortex. Although selective elimination of spines that existed before training gradually returns the overall spine density back to the original level, the new spines induced during learning are preferentially stabilized during subsequent training and endure long after training stops. Furthermore, we show that different motor skills are encoded by different sets of synapses. Practice of novel, but not previously learned, tasks further promotes dendritic spine formation in adulthood. Our findings reveal that rapid, but long-lasting, synaptic reorganization is closely associated with motor learning. The data also suggest that stabilized neuronal connections are the foundation of durable motor memory.
The human cerebellum is involved in language, motor tasks and cognitive processes such as attention or emotional processing. Therefore, an automatic and accurate segmentation method is highly ...desirable to measure and understand the cerebellum role in normal and pathological brain development. In this work, we propose a patch-based multi-atlas segmentation tool called CERES (CEREbellum Segmentation) that is able to automatically parcellate the cerebellum lobules. The proposed method works with standard resolution magnetic resonance T1-weighted images and uses the Optimized PatchMatch algorithm to speed up the patch matching process. The proposed method was compared with related recent state-of-the-art methods showing competitive results in both accuracy (average DICE of 0.7729) and execution time (around 5 minutes).
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•We present a novel method for cerebellum lobule segmentation on MRI.•The method consists of a fast multi-atlas non-local patch-based label fusion.•Our proposed method was shown to improve the state-of-the-art methods with a reduced temporal cost (5 minutes).•The pipeline presented in this work will be made available to scientific community through our web -based platform volBrain.
Independent locomotion is associated with a range of positive developmental outcomes, but unlike cognitive, linguistic, and social skills, acquiring motor skills requires infants to generate their ...own input for learning. We tested factors that shape infants' spontaneous locomotion by observing forty 12- to 22-month-olds (19 girls, 21 boys) during free play. Infants were recruited from the New York City area, and caregivers reported that 25 infants were White, six were Asian, four were Black, and five had multiple races; four were Hispanic or Latino. All infants played in four conditions: two environmental conditions (gross-motor toys, fine-motor toys) crossed with two social conditions (alone, together with a caregiver). Infants moved more in the gross-motor toy conditions than in the fine-motor toy conditions. However, the effect of playing with a caregiver differed by toy condition. In the gross-motor toy conditions, playing with a caregiver did not affect how much infants moved, but in the fine-motor toy conditions, playing with a caregiver further depressed infant locomotion. Infants with more walking experience moved more with gross-motor toys but not with fine-motor toys. Differences in the amount of locomotion between conditions were related to how infants used toys and the interactions between infants and caregivers.
Public Significance Statement
Toys like strollers, brooms, grocery carts, and balls, along with a "hands-off" caregiver play style, encourage toddlers to engage in locomotor play. In contrast, toys like pop-ups, xylophones, shape-sorters, and bricks, along with a "hands-on" caregiver play style, encourage more manual, stationary play.
Agility is an important characteristic of team sports athletes. There is a growing interest in the factors that influence agility performance as well as appropriate testing protocols and training ...strategies to assess and improve this quality.
The objective of this systematic review was to (1) evaluate the reliability and validity of agility tests in team sports, (2) detail factors that may influence agility performance, and (3) identify the effects of different interventions on agility performance.
The review was undertaken in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. We conducted a search of PubMed, Google Scholar, Science Direct, and SPORTDiscus databases. We assessed the methodological quality of intervention studies using a customized checklist of assessment criteria.
Intraclass correlation coefficient values were 0.80-0.91, 0.10-0.81, and 0.81-0.99 for test time using light, video, and human stimuli. A low-level reliability was reported for youth athletes using the video stimulus (0.10-0.30). Higher-level participants were shown to be, on average, 7.5% faster than their lower level counterparts. Reaction time and accuracy, foot placement, and in-line lunge movement have been shown to be related to agility performance. The contribution of strength remains unclear. Efficacy of interventions on agility performance ranged from 1% (vibration training) to 7.5% (small-sided games training).
Agility tests generally offer good reliability, although this may be compromised in younger participants responding to various scenarios. A human and/or video stimulus seems the most appropriate method to discriminate between standard of playing ability. Decision-making and perceptual factors are often propositioned as discriminant factors; however, the underlying mechanisms are relatively unknown. Research has focused predominantly on the physical element of agility. Small-sided games and video training may offer effective methods of improving agility, although practical issues may hinder the latter.
Numerosity, the set size of a group of items, is processed by the association cortex, but certain aspects mirror the properties of primary senses. Sensory cortices contain topographic maps reflecting ...the structure of sensory organs. Are the cortical representation and processing of numerosity organized topographically, even though no sensory organ has a numerical structure? Using high-field functional magnetic resonance imaging (at a field strength of 7 teslas), we described neural populations tuned to small numerosities in the human parietal cortex. They are organized topographically, forming a numerosity map that is robust to changes in low-level stimulus features. The cortical surface area devoted to specific numerosities decreases with increasing numerosity, and the tuning width increases with preferred numerosity. These organizational properties extend topographic principles to the representation of higher-order abstract features in the association cortex.
The experimental findings herein reported are aimed at gaining a perspective on the complex neural events that follow lesions of the motor cortical areas. Cortical damage, whether by trauma or ...stroke, interferes with the flow of descending signals to the modular interneuronal structures of the spinal cord. These spinal modules subserve normal motor behaviors by activating groups of muscles as individual units (muscle synergies). Damage to the motor cortical areas disrupts the orchestration of the modules, resulting in abnormal movements. To gain insights into this complex process, we recorded myoelectric signals from multiple upper-limb muscles in subjects with cortical lesions. We used a factorization algorithm to identify the muscle synergies. Our factorization analysis revealed, in a quantitative way, three distinct patterns of muscle coordination—including preservation, merging, and fractionation of muscle synergies—that reflect the multiple neural responses that occur after cortical damage. These patterns varied as a function of both the severity of functional impairment and the temporal distance from stroke onset. We think these muscle-synergy patterns can be used as physiological markers of the status of any patient with stroke or trauma, thereby guiding the development of different rehabilitation approaches, as well as future physiological experiments for a further understanding of postinjury mechanisms of motor control and recovery.
Electrical neuromodulation of lumbar segments improves motor control after spinal cord injury in animal models and humans. However, the physiological principles underlying the effect of this ...intervention remain poorly understood, which has limited the therapeutic approach to continuous stimulation applied to restricted spinal cord locations. Here we developed stimulation protocols that reproduce the natural dynamics of motoneuron activation during locomotion. For this, we computed the spatiotemporal activation pattern of muscle synergies during locomotion in healthy rats. Computer simulations identified optimal electrode locations to target each synergy through the recruitment of proprioceptive feedback circuits. This framework steered the design of spatially selective spinal implants and real-time control software that modulate extensor and flexor synergies with precise temporal resolution. Spatiotemporal neuromodulation therapies improved gait quality, weight-bearing capacity, endurance and skilled locomotion in several rodent models of spinal cord injury. These new concepts are directly translatable to strategies to improve motor control in humans.
Abstract
Introduction
Sleep consolidates memory, including newly acquired procedural skills. One putative systems-level mechanism for this function of sleep is via sleep-dependent strengthening of ...functional connectivity between the putamen and the cortico-hippocampal-striatal-cerebellar network, which supports procedural motor skills. For procedural motor skills that also require problem solving and rule-learning, sleep preferentially benefits the cognitively complex aspects over the motor skills required to execute the solution itself. The caudate is implicated in higher-order cognitive components of skill learning, which include error monitoring and automizing new information. In the current study, we investigated how sleep alters functional connectivity in higher-order learning networks that support problem solving and rule learning-related procedural skills.
Methods
Participants (n = 38) were trained on a procedural skills task; the Tower of Hanoi (ToH), that requires the acquisition of a novel cognitive strategy (e.g., recursive logic), while undergoing functional magnetic resonance imaging (fMRI). After either a full night of sleep (n=19) or a full day of wakefulness (n=19), participants were retested on the same task in the fMRI. Resting state activity was acquired before (R1) and after the training session (R2), and before the retest session (R3).
Results
Behavioral performance on the ToH improved following sleep compared to wake (reduced number of errors: t(38)=2.92, p=0.006, d=1.24). Regions associated with higher-order learning and cognitive complexity (i.e., the caudate) and regions typically implicated in sequence learning (i.e., the putamen, hippocampus, cerebellum) were selected as regions of interest (ROI). Increased functional connectivity across the retention interval (R3-R2) was observed in the sleep vs. wake condition between the caudate and the motor cortex (t(36)=3.32, p=0.042, FWE). By contrast, changes in functional connectivity were not observed between the putamen and other ROIs.
Conclusion
These results suggest that sleep supports improved consolidation of motor skills that involve the acquisition of a novel cognitive strategy. Sleep enhanced functional connectivity in brain areas associated with higher-order cognitive skills (i.e., the caudate), but not regions typically associated with motor skills (i.e., the putamen) that are required to execute the solution to the cognitive procedural skill.
Support (if any)
Natural Science and Engineering Research Council of Canada
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