Motor deficits in autism differ from that of developmental coordination disorder.

LAY ABSTRACT: A vast majority of individuals with autism spectrum disorder experience impairments in motor skills. Those are often labelled as additional developmental coordination disorder despite the lack of studies comparing both disorders. Consequently, motor skills rehabilitation programmes in autism are often not specific but rather consist in standard programmes for developmental coordination disorder. Here, we compared motor performance in three groups of children: a control group, an autism spectrum disorder group and a developmental coordination disorder group. Despite similar level of motor skills evaluated by the standard movement assessment battery for children, in a Reach-to-Displace Task, children with autism spectrum disorder and developmental coordination disorder showed specific motor control deficits. Children with autism spectrum disorder failed to anticipate the object properties, but could correct their movement as well as typically developing children. In contrast, children with developmental coordination disorder were atypically slow, but showed a spared anticipation. Our study has important clinical implications as motor skills rehabilitations are crucial to both populations. Specifically, our findings suggest that individuals with autism spectrum disorder would benefit from therapies aiming at improving their anticipation, maybe through the support of their preserved representations and use of sensory information. Conversely, individuals with developmental coordination disorder would benefit from a focus on the use of sensory information in a timely fashion.

Disentangling sensory precision and prior expectation of change in autism during tactile discrimination.

Predictive coding theories suggest that core symptoms in autism spectrum disorders (ASD) may stem from atypical mechanisms of perceptual inference (i.e., inferring the hidden causes of sensations). Specifically, there would be an imbalance in the precision or weight ascribed to sensory inputs relative to prior expectations. Using three tactile behavioral tasks and computational modeling, we specifically targeted the implicit dynamics of sensory adaptation and perceptual learning in ASD. Participants were neurotypical and autistic adults without intellectual disability. In Experiment I, tactile detection thresholds and adaptation effects were measured to assess sensory precision. Experiments II and III relied on two-alternative forced choice tasks designed to elicit a time-order effect, where prior knowledge biases perceptual decisions. Our results suggest a subtler explanation than a simple imbalance in the prior/sensory weights, having to do with the dynamic nature of perception, that is the adjustment of precision weights to context. Compared to neurotypicals, autistic adults showed no difference in average performance and sensory sensitivity. Both groups managed to implicitly learn and adjust a prior that biased their perception. However, depending on the context, autistic participants showed no, normal or slower adaptation, a phenomenon that computational modeling of trial-to-trial responses helped us to associate with a higher expectation for sameness in ASD, and to dissociate from another observed robust difference in terms of response bias. These results point to atypical perceptual learning rather than altered perceptual inference per se, calling for further empirical and computational studies to refine the current predictive coding theories of ASD.

Blunted emotion judgments of body movements in Parkinson's disease.

Some of the behavioral disorders observed in Parkinson's disease (PD) may be related to an altered processing of social messages, including emotional expressions. Emotions conveyed by whole body movements may be difficult to generate and be detected by PD patients. The aim of the present study was to compare valence judgments of emotional whole body expressions in individuals with PD and in healthy controls matched for age, gender and education. Twenty-eight participants (13 PD patients and 15 healthy matched control participants) were asked to rate the emotional valence of short movies depicting emotional interactions between two human characters presented with the "Point Light Displays" technique. To ensure understanding of the perceived scene, participants were asked to briefly describe each of the evaluated movies. Patients' emotional valence evaluations were less intense than those of controls for both positive (p < 0.001) and negative (p < 0.001) emotional expressions, even though patients were able to correctly describe the depicted scene. Our results extend the previously observed impaired processing of emotional facial expressions to impaired processing of emotions expressed by body language. This study may support the hypothesis that PD affects the embodied simulation of emotional expression and the potentially involved mirror neuron system.

Imaging of Podocytic Proteins Nephrin, Actin, and Podocin with Expansion Microscopy.

Disruption of the glomerular filter composed of the glomerular endothelium, glomerular basement membrane and podocytes, results in albuminuria. Podocyte foot processes contain actin bundles that bind to cytoskeletal adaptor proteins such as podocin. Those adaptor proteins, such as podocin, link the backbone of the glomerular slit diaphragm, such as nephrin, to the actin cytoskeleton. Studying the localization and function of these and other podocytic proteins is essential for the understanding of the glomerular filter's role in health and disease. The presented protocol enables the user to visualize actin, podocin, and nephrin in cells with super resolution imaging on a conventional microscope. First, cells are stained with a conventional immunofluorescence technique. All proteins within the sample are then covalently anchored to a swellable hydrogel. Through digestion with proteinase K, structural proteins are cleaved allowing isotropical swelling of the gel in the last step. Dialysis of the sample in water results in a 4-4.5-fold expansion of the sample and the sample can be imaged via a conventional fluorescence microscope, rendering a potential resolution of 70 nm.

A de novo frameshift pathogenic variant in TBR1 identified in autism without intellectual disability.

BACKGROUND: In order to be able to provide accurate genetic counseling to patients with Autism Spectrum Disorder (ASD), it is crucial to identify correlations between heterogeneous phenotypes and genetic alterations. Among the hundreds of de novo pathogenic variants reported in ASD, single-nucleotide variations and small insertions/deletions were reported in TBR1. This gene encodes a transcription factor that plays a key role in brain development. Pathogenic variants in TBR1 are often associated with severe forms of ASD, including intellectual disability and language impairment. METHODS: Adults diagnosed with ASD but without intellectual disability (diagnosis of Asperger syndrome, according to the DSM-IV) took part in a genetic consultation encompassing metabolic assessments, a molecular karyotype and the screening of a panel of 268 genes involved in intellectual disability, ASD and epilepsy. In addition, the patient reported here went through a neuropsychological assessment, structural magnetic resonance imaging and magnetic resonance spectroscopy measurements. RESULTS: Here, we report the case of a young adult male who presents with a typical form of ASD. Importantly, this patient presents with no intellectual disability or language impairment, despite a de novo heterozygous frameshift pathogenic variant in TBR1, leading to an early premature termination codon (c.26del, p.(Pro9Leufs*12)). CONCLUSION: Based on this case report, we discuss the role of TBR1 in general brain development, language development, intellectual disability and other symptoms of ASD. Providing a detailed clinical description of the individuals with such pathogenic variants should help to understand the genotype-phenotype relationships in ASD.

Highs and Lows in Motor Control Development.

Motor control is classically described as relying on two components: anticipatory control (feedforward processing) and online control (feedback processing). Here we aimed to unveil the developmental steps of both feedback and feedforward control in 5-10 years old children, using a simple and ecological task. We manipulated object's weight in a reach-to-displace paradigm. When the weight was known before lifting it, anticipatory processes were quantifiable during the reaching phase. Conversely, an unknown weight triggered online corrections during the displacing phase. Movement kinematics revealed that children anticipate this objet property as young as 5 y-o. This anticipation becomes adequate around 7 y-o and is paralleled by poor online corrections. This simple yet relevant paradigm should allow quantifying deviations from neurotypical patterns in disorders of motor control.

Tracking the acquisition of anticipatory postural adjustments during a bimanual load-lifting task: A MEG study.

During bimanual coordination, that is, manipulating with the dominant hand an object held by the postural hand, anticipatory postural adjustments are required to cancel the perturbations and ensure postural stabilization. Using magnetoencephalography (MEG), we investigated changes mediating the acquisition of anticipatory postural adjustments during a bimanual load-lifting task. Participants lifted a load with their right hand, hence triggering the fall of a second load fixed to their left (postural) forearm. During Acquisition, the onset of load-lifting and the fall of the second load were experimentally delayed after few trials. During Control, load-lifting triggered the fall of the second load without delay. Upward elbow rotation decreased with trial repetition during Acquisition, hence attesting the ongoing acquisition of anticipatory postural adjustments. Bilateral event-related desynchronisation (ERD) of the alpha rhythm (8-12 Hz) was recorded. Generators of the mu rhythm were found within central and associative motor regions. Their spatial distribution within the hemisphere contralateral to the load-lifting arm was less refined and circumscribed during Acquisition compared to Control. Regression analyses emphasized the specific involvement of the precuneus in the right hemisphere contralateral to the postural forearm, and a medial prefrontal region in the left hemisphere. Analyses of the time course power showed that an increase in preunloading activation within the precuneus and a decrease in postunloading inhibition within the medial prefrontal region were associated with the acquisition of anticipatory postural adjustments. The study provides original insights into cortical activations mediating the progressive tuning of anticipatory postural adjustments during the acquisition stage of motor learning.

Tactile hypersensitivity and GABA concentration in the sensorimotor cortex of adults with autism.

Sensory hypersensitivity is frequently encountered in autism spectrum disorder (ASD). Gamma-aminobutyric acid (GABA) has been hypothesized to play a role in tactile hypersensitivity. The aim of the present study was twofold. First, as a study showed that children with ASD have decreased GABA concentrations in the sensorimotor cortex, we aimed at determining whether the GABA reduction remained in adults with ASD. For this purpose, we used magnetic resonance spectroscopy to measure GABA concentration in the sensorimotor cortex of neurotypical adults (n = 19) and ASD adults (n = 18). Second, we aimed at characterizing correlations between GABA concentration and tactile hypersensitivity in ASD. GABA concentration in the sensorimotor cortex of adults with ASD was lower than in neurotypical adults (decrease by 17%). Interestingly, GABA concentrations were positively correlated with self-reported tactile hypersensitivity in adults with ASD (r = 0.50, P = 0.01), but not in neurotypical adults. In addition, GABA concentrations were negatively correlated with the intra-individual variation during threshold measurement, both in neurotypical adults (r = -0.47, P = 0.04) and in adults with ASD (r = -0.59, P = 0.01). In other words, in both groups, the higher the GABA level, the more precise the tactile sensation. These results highlight the key role of GABA in tactile sensitivity, and suggest that atypical GABA modulation contributes to tactile hypersensitivity in ASD. We discuss the hypothesis that hypersensitivity in ASD could be due to suboptimal predictions about sensations. Autism Research 2019, 12: 562-575. © 2019 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: People with autism spectrum disorder (ASD) often experience tactile hypersensitivity. Here, our goal was to highlight a link between tactile hypersensitivity and the concentration of gamma-aminobutyric acid (GABA) (an inhibitory neurotransmitter) in the brain of adults with ASD. Indeed, self-reported hypersensitivity correlated with reduced GABA levels in brain areas processing touch. Our study suggests that this neurotransmitter may play a key role in tactile hypersensitivity in autism.

Correction to: Adults with Autism Tend to Underestimate the Hidden Environmental Structure: Evidence from a Visual Associative Learning Task.

The original version of this article unfortunately contained a mistake in the article title.

Mu-oscillation changes related to the development of anticipatory postural control in children and adolescents.

Anticipatory postural adjustments (APAs) cancel the destabilizing effects of movement on posture. Across development, the maturation of APAs is characterized by an accurate adjustment of the timing parameters of electromyographic (EMG) response. The study aimed at investigating the maturation of cortical oscillations involved in the improvement of APAs efficiency. Thirty-six healthy participants (8-16 yr) performed the bimanual load-lifting task in which subjects are instructed to lift a load, placed on the left forearm, with the right hand. EMG data were acquired over the biceps brachii on the postural arm to the determine EMG response onset. Electroencephalographic signals were analyzed in the time-frequency domain by convolution with complex Gaussian Morlet wavelets. Electrophysiological signature of APAs in children and adolescents consisted of a mu-rhythm desynchronization over the sensorimotor cortex contralateral to the postural arm. Across development, the mu-rhythm desynchronization was characterized by a progressive shift forward of the onset of the desynchronization, lower amplitude, and velocity. These changes occurred along with an alteration of the timing of the EMG response, as shown by an earlier onset of the flexor inhibition with increasing age. The maturational changes in the Mu-oscillations might sustain the development of APAs. A possible role of the Mu-oscillation in the generation of postural command is discussed. NEW & NOTEWORTHY Across development, our study showed a progressive shift forward of the parameters of the mu-rhythm desynchronization. These changes occurred along with an alteration of the timing parameters of the electromyographic response, as shown by an earlier onset of the flexor inhibition with increasing age. The progressive development of APAs during childhood and adolescence might therefore be sustained by maturational electrophysiological changes that include mu-rhythm oscillation modifications in the postural sensorimotor cortex.

Adults with Autism Tend to Underestimate the Hidden Environmental Structure: Evidence from a Visual Associative Learning Task.

The learning-style theory of Autism Spectrum Disorders (ASD) (Qian, Lipkin, Frontiers in Human Neuroscience 5:77, 2011) states that ASD individuals differ from neurotypics in the way they learn and store information about the environment and its structure. ASD would rather adopt a lookup-table strategy (LUT: memorizing each experience), while neurotypics would favor an interpolation style (INT: extracting regularities to generalize). In a series of visual behavioral tasks, we tested this hypothesis in 20 neurotypical and 20 ASD adults. ASD participants had difficulties using the INT style when instructions were hidden but not when instructions were revealed. Rather than an inability to use rules, ASD would be characterized by a disinclination to generalize and infer such rules.

The Glasgow Sensory Questionnaire: Validation of a French Language Version and Refinement of Sensory Profiles of People with High Autism-Spectrum Quotient.

Sensory sensitivity peculiarities represent an important characteristic of Autism Spectrum Disorders (ASD). We first validated a French language version of the Glasgow Sensory Questionnaire (GSQ) (Robertson and Simmons in J Autism Dev Disord 43(4):775-784, 2013). The GSQ score was strongly positively correlated with the Autism-Spectrum Quotient (AQ) (r = 0.81, p < 10-6, n = 245). We further examined sensory profiles of groups with high versus low AQ. The high AQ group scored higher at the GSQ than the low AQ group for every sensory modality. Moreover, the high AQ group showed greater consistency in their patterns of hypersensitivity and hyposensitivity between sensory modalities, and stronger correlations between hyper and hyposensitivity. Results are discussed in the context of theories accounting for atypical sensory perception in ASD.

Gravity Cues Embedded in the Kinematics of Human Motion Are Detected in Form-from-Motion Areas of the Visual System and in Motor-Related Areas.

The present study investigated the cortical areas engaged in the perception of graviceptive information embedded in biological motion (BM). To this end, functional magnetic resonance imaging was used to assess the cortical areas active during the observation of human movements performed under normogravity and microgravity (parabolic flight). Movements were defined by motion cues alone using point-light displays. We found that gravity modulated the activation of a restricted set of regions of the network subtending BM perception, including form-from-motion areas of the visual system (kinetic occipital region, lingual gyrus, cuneus) and motor-related areas (primary motor and somatosensory cortices). These findings suggest that compliance of observed movements with normal gravity was carried out by mapping them onto the observer's motor system and by extracting their overall form from local motion of the moving light points. We propose that judgment on graviceptive information embedded in BM can be established based on motor resonance and visual familiarity mechanisms and not necessarily by accessing the internal model of gravitational motion stored in the vestibular cortex.

Deciphering human motion to discriminate social interactions: a developmental neuroimaging study.

Non-verbal communication plays a major role in social interaction understanding. Using functional magnetic resonance imaging, we explored the development of the neural networks involved in social interaction recognition based on human motion in children (8-11), adolescents (13-17), and adults (20-41). Participants watched point-light videos depicting two actors interacting or moving independently and were asked whether these agents were interacting or not. All groups successfully performed the discrimination task, but children had a lower performance and longer response times than the older groups. In all three groups, the posterior parts of the superior temporal sulci and middle temporal gyri, the inferior frontal gyri and the anterior temporal lobes showed greater activation when observing social interactions. In addition, adolescents and adults recruited the caudate nucleus and some frontal regions that are part of the mirror system. Adults showed greater activations in parietal and frontal regions (part of them belonging to the social brain) than adolescents.An increased number of regions that are part of the mirror system network or the social brain, as well as the caudate nucleus, were recruited with age. In conclusion, a shared set of brain regions enabling the discrimination of social interactions from neutral movements through human motion is already present in 8-year-old children. Developmental processes such as refinements in the social brain and mirror system would help grasping subtle cues in non-verbal aspects of social interactions.

Shift of the Muscular Inhibition Latency during On-Line Acquisition of Anticipatory Postural Adjustments.

During action, Anticipatory Postural Adjustments (APAs) cancel the consequences of a movement on postural stabilization. Their muscular expression is characterized by early changes in the activity of the postural muscles, before the movement begins. To explore the mechanisms enabling the acquisition of APAs, a learning paradigm was designed in which the voluntary lifting of a load with one hand triggered the unloading of another load suspended below the contralateral forearm. The aim of this study was to investigate changes in the muscular expression that uncovers the progressive learning of new APAs. A trial-by-trial analysis of kinematic and electromyographic signals recorded on the right arm was conducted in twelve adults through six sessions of learning. Kinematic results reported an enhancement of the postural stabilization across learning. The main EMG pattern found during learning consisted of a flexor inhibition, where latency was shifted towards an earlier occurrence in parallel with the improvement of the postural performance. A linear regression analysis conducted between the inhibition latency and the maximal amplitude of elbow rotation showed that the earlier the inhibition onset, the better the postural stabilization. This study revealed that the progressive shift of the postural flexor inhibition latency could be considered as a reliable neurophysiological marker of the progressive learning of new APAs. Importantly, this marker could be used to track motor learning abnormalities in pathology. We relate our findings to the update of a forward predictive model of action, defined as a system that predicts beforehand the consequences of the action on posture.

Face the hierarchy: ERP and oscillatory brain responses in social rank processing.

Recognition of social hierarchy is a key feature that helps us navigate through our complex social environment. Neuroimaging studies have identified brain structures involved in the processing of hierarchical stimuli but the precise temporal dynamics of brain activity associated with such processing remains largely unknown. Here, we used electroencephalography to examine the effect of social hierarchy on neural responses elicited by faces. In contrast to previous studies, the key manipulation was that a hierarchical context was constructed, not by varying facial expressions, but by presenting neutral-expression faces in a game setting. Once the performance-based hierarchy was established, participants were presented with high-rank, middle-rank and low-rank player faces and had to evaluate the rank of each face with respect to their own position. Both event-related potentials and task-related oscillatory activity were investigated. Three main findings emerge from the study. First, the experimental manipulation had no effect on the early N170 component, which may suggest that hierarchy did not modulate the structural encoding of neutral-expression faces. Second, hierarchy significantly modulated the amplitude of the late positive potential (LPP) within a 400-700 ms time-window, with more a prominent LPP occurring when the participants processed the face of the highest-rank player. Third, high-rank faces were associated with the highest reduction of alpha power. Taken together these findings provide novel electrophysiological evidence for enhanced allocation of attentional resource in the presence of high-rank faces. At a broader level, this study brings new insights into the neural processing underlying social categorization.

From action to interaction: exploring the contribution of body motion cues to social understanding in typical development and in autism spectrum disorders.

Two studies investigated whether typically developing children (TD) and children with autism spectrum disorders (ASD) were able to decide whether two characters were communicating or not on the basis of point-light displays. Point-lights portrayed actors engaged or not in a social interaction. In study 1, TD children (4-10 years old; n = 36) grasped social intentions from body language, with a notable improvement around 7/8. In study 2, children with ASD (6-12 years old; n = 12) could categorize the point-light displays at above-chance levels, but performed less efficiently, especially for the social interaction displays, than TD children (matched to chronological and non-verbal mental age, 6-12 years old; n = 24). An action representation deficit is discussed in relation to a social representation deficit and it is suggested that these deficits might be linked to altered maturational process of the mirror system in ASD.

Frequency of Salmonella detection in a broiler flock depending on different litter materials--a field study.

During the fattening period of a broiler flock four different litter materials (peat, chopped straw, shavings, silage) were tested simultaneously.The separated sections were tested for the presence of Salmonella bacteria using the sock-sampling method as described in the regulation EC No. 646/2007 with slight modifications in the sampling technique and the laboratory protocol. In addition, some chemical and physical parameters regarding litter quality and house climate were analysed. Samples were taken at day 0 (housing of animals), day 14, and day 30. At the end of the fattening period Salmonella Paratyphi B (d-tartrate +), representing a common strain in German broiler flocks, were isolated from culture. According to the various types of bedding materials some differences in the frequency of Salmonella detection were found. With three samples out of six samples being positive, wood shavings showed the highest Salmonella prevalence, followed by peat with two positive results. Corn silage was found to be a suitable alternative for common litter materials and revealed only one positive sample. Chopped straw was found to be free of Salmonella in our study. However, the latter had a higher risk for negative side effects concerning animal health and house climate. The study showed that the choice of an appropriate litter material might be of considerable importance in order to decrease the Salmonella burden within poultry flocks.

Recruitment of both the mirror and the mentalizing networks when observing social interactions depicted by point-lights: a neuroimaging study.

BACKGROUND: Understanding social interactions requires the ability to accurately interpret conspecifics' actions, sometimes only on the basis of subtle body language analysis. Here we address an important issue that has not yet received much attention in social neuroscience, that of an interaction between two agents. We attempted to isolate brain responses to two individuals interacting compared to two individuals acting independently. METHODOLOGY/PRINCIPAL FINDINGS: We used minimalistic point-light displays to depict the characters, as they provide the most straightforward way to isolate mechanisms used to extract information from motion per se without any interference with other visual information. Functional magnetic resonance imaging (fMRI) method was used to determine which brain regions were recruited during the observation of two interacting agents, mimicking everyday social scenes. While the mirror and mentalizing networks are rarely concurrently active, we found that both of them might be needed to catch the social intentions carried by whole-body motion. CONCLUSIONS/SIGNIFICANCE: These findings shed light on how motor cognition contributes to social cognition when social information is embedded in whole-body motion only. Finally, the approach described here provides a valuable and original tool for investigating the brain networks responsible for social understanding, in particular in psychiatric disorders.

Time-Frequency and ERP Analyses of EEG to Characterize Anticipatory Postural Adjustments in a Bimanual Load-Lifting Task.

Anticipatory postural adjustments (APAs) compensate in advance for the destabilizing effect of a movement. This study investigated the specific involvement of each primary motor cortex (M1) during a bimanual load-lifting task in which subjects were required to maintain a stable forearm position during voluntary unloading. Kinematics, electromyographic, and electroencephalographic (EEG) data were recorded in eight right-handed healthy subjects lifting a load placed on their left forearm. Two EEG analyses were performed: a time-frequency (TF) analysis and an event-related potential (ERP) analysis. The TF analysis revealed a mean power decrease in the mu rhythm over the left and right M1 concomitant with lifting onset. Each decrease showed specific features: over the right M1, contralateral to the postural forearm, there was a steeper slope and a greater amplitude than over the left M1. Although a mu rhythm desynchronization has until now been the signature of cortical activity related to a motor component, we show that it can also be related to postural stabilization. We discuss the involvement of the mu rhythm desynchronization over the postural M1 in the high temporal precision enabling efficient APAs. ERP analysis showed a negative wave over the left M1 and a concomitant positive wave over the right M1. While the negative wave classically reflects M1 recruitment related to the forthcoming lifting, the novelty here is that the positive wave reflects the transmission of inhibitory commands toward the postural forearm.