STING-dependent interferon signatures restrict osteoclast differentiation and bone loss in mice.

Stimulator of interferon genes (STING) is a key mediator of type-I interferon (IFN-I) signaling in response to a variety of stimuli, but the contribution of STING to homeostatic processes is not fully characterized. Previous studies showed that ligand activation of STING limits osteoclast differentiation in vitro through the induction of IFNß and IFN-I interferon-stimulated genes (ISGs). In a disease model (SAVI) driven by the V154M gain-of-function mutation in STING, fewer osteoclasts form from SAVI precursors in response to receptor activator of NF-kappaB ligand (RANKL) in an IFN-I-dependent manner. Due to the described role of STING-mediated regulation of osteoclastogenesis in activation settings, we sought to determine whether basal STING signaling contributes to bone homeostasis, an unexplored area. Using whole-body and myeloid-specific deficiency, we show that STING signaling prevents trabecular bone loss in mice over time and that myeloid-restricted STING activity is sufficient for this effect. STING-deficient osteoclast precursors differentiate with greater efficiency than wild types. RNA sequencing of wild-type and STING-deficient osteoclast precursor cells and differentiating osteoclasts reveals unique clusters of ISGs including a previously undescribed ISG set expressed in RANKL naïve precursors (tonic expression) and down-regulated during differentiation. We identify a 50 gene tonic ISG signature that is STING dependent and shapes osteoclast differentiation. From this list, we identify interferon-stimulated gene 15 (ISG15) as a tonic STING-regulated ISG that limits osteoclast formation. Thus, STING is an important upstream regulator of tonic IFN-I signatures shaping the commitment to osteoclast fates, providing evidence for a nuanced and unique role for this pathway in bone homeostasis.

Visual Motion and Decision-Making in Dyslexia: Reduced Accumulation of Sensory Evidence and Related Neural Dynamics.

Children with and without dyslexia differ in their behavioral responses to visual information, particularly when required to pool dynamic signals over space and time. Importantly, multiple processes contribute to behavioral responses. Here we investigated which processing stages are affected in children with dyslexia when performing visual motion processing tasks, by combining two methods that are sensitive to the dynamic processes leading to responses. We used a diffusion model which decomposes response time and accuracy into distinct cognitive constructs, and high-density EEG. Fifty children with dyslexia (24 male) and 50 typically developing children (28 male) 6-14 years of age judged the direction of motion as quickly and accurately as possible in two global motion tasks (motion coherence and direction integration), which varied in their requirements for noise exclusion. Following our preregistered analyses, we fitted hierarchical Bayesian diffusion models to the data, blinded to group membership. Unblinding revealed reduced evidence accumulation in children with dyslexia compared with typical children for both tasks. Additionally, we identified a response-locked EEG component which was maximal over centro-parietal electrodes which indicated a neural correlate of reduced drift rate in dyslexia in the motion coherence task, thereby linking brain and behavior. We suggest that children with dyslexia tend to be slower to extract sensory evidence from global motion displays, regardless of whether noise exclusion is required, thus furthering our understanding of atypical perceptual decision-making processes in dyslexia.SIGNIFICANCE STATEMENT Reduced sensitivity to visual information has been reported in dyslexia, with a lively debate about whether these differences causally contribute to reading difficulties. In this large preregistered study with a blind modeling approach, we combine state-of-the art methods in both computational modeling and EEG analysis to pinpoint the stages of processing that are atypical in children with dyslexia in two visual motion tasks that vary in their requirement for noise exclusion. We find reduced evidence accumulation in children with dyslexia across both tasks, and identify a neural marker, allowing us to link brain and behavior. We show that children with dyslexia exhibit general difficulties with extracting sensory evidence from global motion displays, not just in tasks that require noise exclusion.

The impact of foetal restrictions on mode of delivery in women with inherited bleeding disorders.

OBJECTIVES: Management of pregnancy in women with congenital bleeding disorders (CBD) is challenging and requires understanding of risks conferred to both the mother and the foetus. Some elements of labour management are considered to increase the risk of neonatal bleeding and are not recommended for neonates at risk of a significant bleeding disorder. The impact of these restrictions on obstetric outcomes in women with CBD is unknown. METHODS: We retrospectively reviewed obstetric outcomes in a large cohort of women with CBD attending a specialised obstetric/haematology antenatal clinic over a 6-year period. RESULTS: Ninety-four pregnancies in 76 women with a wide variety of CBDs were assessed. Foetal precautions were recommended in the majority of cases (88%). Twenty (21.2%) were delivered by elective Caesarean section (CS), predominantly for obstetric indications. Of the 63 women who laboured with foetal precautions in place, 6 (10%) had a CS that was performed because of these precautions. There was no neonatal bleeding but primary postpartum haemorrhage (PPH) occurred in 12.2% of women. CONCLUSIONS: These data show that foetal precautions in labour recommended for women with CBDs will influence mode of delivery in approximately 10% of cases. This is important information for counselling these women about labour and delivery.

Can speed be judged independent of direction?

The ability to judge speed is a fundamental aspect of visual motion processing. Speed judgments are generally assumed to depend on signals in motion-sensitive, directionally selective, neurons in areas such as V1 and MT. Speed comparisons might therefore be expected to be most accurate when they use information within a common set of directionally tuned neurons. However, there does not appear to be any published evidence on how well speeds can be compared for movements in different directions. We tested speed discrimination judgments between pairs of random-dot stimuli presented side-by-side in a series of four experiments (n = 65). Participants judged which appeared faster of a reference stimulus moving along the cardinal or oblique axis and a comparison stimulus moving either in the same direction or in a different direction. The bias (point of subjective equality) and sensitivity (Weber fraction) were estimated from individual psychometric functions fitted for each condition. There was considerable between-participants variability in psychophysical estimates across conditions. Nonetheless, participants generally made more acute comparisons between stimuli moving in the same direction than those moving in different directions, at least for conditions with an upwards reference (∼20% difference in Weber fractions). We also showed evidence for an oblique effect in speed discrimination when comparing stimuli moving in the same direction, and a bias whereby oblique motion tended to be perceived as moving faster than cardinal motion. These results demonstrate interactions between speed and direction processing, thus informing our understanding of how they are represented in the brain.

Children on the autism spectrum update their behaviour in response to a volatile environment.

Typical adults can track reward probabilities across trials to estimate the volatility of the environment and use this information to modify their learning rate (Behrens et al., 2007). In a stable environment, it is advantageous to take account of outcomes over many trials, whereas in a volatile environment, recent experience should be more strongly weighted than distant experience. Recent predictive coding accounts of autism propose that autistic individuals will demonstrate atypical updating of their behaviour in response to the statistics of the reward environment. To rigorously test this hypothesis, we administered a developmentally appropriate version of Behrens et al.'s (2007) task to 34 cognitively able children on the autism spectrum aged between 6 and 14 years, 32 age- and ability-matched typically developing children and 19 typical adults. Participants were required to choose between a green and a blue pirate chest, each associated with a randomly determined reward value between 0 and 100 points, with a combined total of 100 points. On each trial, the reward was given for one stimulus only. In the stable condition, the ratio of the blue or green response being rewarded was fixed at 75:25. In the volatile condition, the ratio alternated between 80:20 and 20:80 every 20 trials. We estimated the learning rate for each participant by fitting a delta rule model and compared this rate across conditions and groups. All groups increased their learning rate in the volatile condition compared to the stable condition. Unexpectedly, there was no effect of group and no interaction between group and condition. Thus, autistic children used information about the statistics of the reward environment to guide their decisions to a similar extent as typically developing children and adults. These results help constrain predictive coding accounts of autism by demonstrating that autism is not characterized by uniform differences in the weighting of prediction error.

Enhanced integration of motion information in children with autism.

To judge the overall direction of a shoal of fish or a crowd of people, observers must integrate motion signals across space and time. The limits on our ability to pool motion have largely been established using the motion coherence paradigm, in which observers report the direction of coherently moving dots amid randomly moving noise dots. Poor performance by autistic individuals on this task has widely been interpreted as evidence of disrupted integrative processes. Critically, however, motion coherence thresholds are not necessarily limited only by pooling. They could also be limited by imprecision in estimating the direction of individual elements or by difficulties segregating signal from noise. Here, 33 children with autism 6-13 years of age and 33 age- and ability-matched typical children performed a more robust task reporting mean dot direction both in the presence and the absence of directional variability alongside a standard motion coherence task. Children with autism were just as sensitive to directional differences as typical children when all elements moved in the same direction (no variability). However, remarkably, children with autism were more sensitive to the average direction in the presence of directional variability, providing the first evidence of enhanced motion integration in autism. Despite this improved averaging ability, children with autism performed comparably to typical children in the motion coherence task, suggesting that their motion coherence thresholds may be limited by reduced segregation of signal from noise. Although potentially advantageous under some conditions, increased integration may lead to feelings of "sensory overload" in children with autism.

The effects of grouping on speed discrimination thresholds in adults, typically developing children, and children with autism.

Adult observers show elevated speed discrimination thresholds when comparing the speeds of objects moving across a boundary compared to those moving parallel to a boundary (Verghese & McKee, 2006)-an effect that has been attributed to grouping processes in conjunction with a prior for smooth motion. Here, we extended Verghese and McKee's (2006) paradigm to typically developing children (n = 35) and children with autism (n = 26) and compared their performance with that of typical adults (n = 19). Speed discrimination thresholds were measured in three conditions: (a) with dots moving parallel to a boundary, (b) with dots moving perpendicular to a boundary, and (c) with dots in each stimulus half moving in orthogonal, oblique directions. As expected, participants had higher speed discrimination thresholds when dots appeared to cross a boundary compared to when dots moved parallel to the boundary. However, participants had even higher thresholds when dots moved in oblique, orthogonal directions, where grouping should be minimal. All groups of participants showed a similar pattern of performance across conditions although children had higher thresholds than adult participants overall. We consider various explanations for the pattern of performance obtained, including enhanced sensitivity for shearing motions and reduced sensitivity for discriminating different directions. Our results demonstrate that the speed discrimination judgments of typically developing children and children with autism are similarly affected by spatial configuration as those of typical adults and provide further evidence that speed discrimination is unimpaired in children with autism.

EXPRESS: Visual processing and decision-making in autism and dyslexia: Insights from cross-syndrome approaches.

Atypical visual processing has been reported in developmental conditions like autism and dyslexia, and some accounts propose a causal role for visual processing in the development of these conditions. However, few studies make direct comparisons between conditions, or use sufficiently sensitive methods, meaning that it is hard to say whether atypical visual processing tells us anything specific about these conditions, or whether it reflects a more general marker of atypical development. Here I review findings from two computational modelling approaches (equivalent noise and diffusion modelling) and related electroencephalography (EEG) indices which we have applied to data from autistic, dyslexic and typically developing children to reveal how the component processes involved in visual processing and decision-making are altered in autism and dyslexia. The results identify both areas of convergence and divergence in autistic and dyslexic children's visual processing and decision-making, with implications for influential theoretical accounts such as weak central coherence, increased internal noise and dorsal-stream vulnerability. In both sets of studies, we also see considerable variability across children in all three groups. To better understand this variability, and further understand the convergence and divergence identified between conditions, future studies would benefit from studying how the component processes reviewed here relate to transdiagnostic dimensions, which will also give insights into individual differences in visual processing and decision-making more generally.

Resolution of inflammation induces osteoblast function and regulates the Wnt signaling pathway.

OBJECTIVE: Inflammation in the bone microenvironment stimulates osteoclast differentiation, resulting in uncoupling of resorption and formation. Mechanisms contributing to the inhibition of osteoblast function in inflammatory diseases, however, have not been elucidated. Rheumatoid arthritis (RA) is a prototype of an inflammatory arthritis that results in focal loss of articular bone. The paucity of bone repair in inflammatory diseases such as RA raises compelling questions regarding the impact of inflammation on bone formation. The aim of this study was to establish the mechanisms by which inflammation regulates osteoblast activity. METHODS: We characterized an innovative variant of a murine model of arthritis in which inflammation is induced in C57BL/6J mice by transfer of arthritogenic K/BxN serum and allowed to resolve. RESULTS: In the setting of resolving inflammation, bone resorption ceased and appositional osteoblast-mediated bone formation was induced, resulting in repair of eroded bone. Resolution of inflammation was accompanied by striking changes in the expression of regulators of the Wnt/ß-catenin pathway, which is critical for osteoblast differentiation and function. Down-regulation of the Wnt antagonists secreted frizzled-related protein 1 (sFRP1) and sFRP2 during the resolution phase paralleled induction of the anabolic and pro-matrix mineralization factors Wnt10b and DKK2, demonstrating the role of inflammation in regulating Wnt signaling. CONCLUSION: Repair of articular bone erosion occurs in the setting of resolving inflammation, accompanied by alterations in the Wnt signaling pathway. These data imply that in inflammatory diseases that result in persistent articular bone loss, strict control of inflammation may not be achieved and may be essential for the generation of an anabolic microenvironment that supports bone formation and repair.

Understanding perceptual decisions by studying development and neurodiversity.

A cornerstone of human information processing is how we make decisions about incoming sensory percepts. Much of psychological science has focused on understanding how these judgements operate in skilled adult observers. While not typically the focus of this research, there is considerable variability in how adults make these judgements. Here, we review complementary computational modelling, electrophysiological data, eye-tracking and longitudinal approaches to the study of perceptual decisions across neurotypical development and in neurodivergent individuals. These data highlight multiple parameters and temporal dynamics feeding into how we become skilled adult perceptual decision makers, and which may help explain why we vary so much in how we make perceptual decisions.

"It Is a Big Spider Web of Things": Sensory Experiences of Autistic Adults in Public Spaces.

Background: Sensory processing differences are commonly experienced by autistic individuals, and some sensory experiences can greatly impact the mental health and quality of life of individuals. Previous research suggests that adapting the sensory nature of environments may improve individual experiences and engagement with these spaces. However, knowledge about which public places are particularly disabling is limited, especially from the perspective of autistic individuals. Little is also known about what in the sensory environment makes them particularly disabling. Methods: In this participatory research study, we investigated the sensory experiences of autistic adults in public spaces. We used an online focus group method, recruiting 24 autistic adults across 7 focus groups. We applied content analysis, reflexive thematic analysis, and case study analysis. Results: The results of the content analysis showed that supermarkets, eateries (i.e., restaurants, cafés, pubs), highstreets and city/town centers, public transport, health care settings (i.e., doctor's surgeries and hospitals), and retail shops and shopping centers are experienced to be commonly disabling sensory environments for autistic adults. However, outdoor spaces, retail shops, museums, concert venues/clubs, cinemas/theaters, and stadiums are identified to be commonly less disabling sensory environments. In addition, through reflexive thematic analysis we identified 6 key principles that underlie how disabling or enabling sensory environments are: Sensoryscape (sensory environment), Space, Predictability, Understanding, Adjustments, and Recovery. We represented these principles as a web to emphasize the interconnected, dimensional spectrum of the different themes. Lastly, we used case study analysis to evidence these principles in the commonly disabling sensory environments for richer detail and context and to provide credibility for the principles. Conclusions: Our findings have important implications for businesses, policy, and built environment designers to reduce the sensory impact of public places to make them more enabling for autistic people. By making public spaces more enabling, we may be able to improve quality of life for autistic individuals.

Why was this study done?: Autistic people often experience differences in sensory processing, such as finding bright lights and sounds overwhelming and painful. This has been linked to poorer quality of life and mental health. Not much is known about how public places could be changed to be less disabling for autistic adults. What was the purpose of this study?: We aimed to find out which public places are disabling for autistic adults due to the sensory environment, and what about these places makes them especially challenging. What did the researchers do?: We invited autistic adults to take part in online focus groups to tell us about their sensory experiences in public places. In total, 24 people took part across 7 focus groups. We analysed the data 3 ways: 1) we conducted content analysis, identifying categories of words or phrases that share meaning to find commonly disabling and enabling places; 2) we conducted reflexive thematic analysis, developing themes and sub-themes from trends in the data to understand how sensory environments can be experienced as disabling or enabling; and 3) we conducted case study analysis, to see if the themes and sub-themes were present in the commonly disabling environments. What were the results of the study?: We found that supermarkets, eateries (i.e., restaurants, cafés, pubs), highstreets and city/town centres, public transport, healthcare settings (i.e., doctor's surgeries and hospitals), and retail shops and shopping centres, were most often mentioned as being disabling sensory environments. But, outdoor spaces, retail shops, museums, concert venues/clubs, cinemas/theatres, and stadiums were most often talked about as being less disabling sensory environments. We also identified principles that can make these environments either disabling or enabling. These included Sensoryscape or the `sensory landscape' (sensory burden, sustained and inescapable input, uncontrollable environment), Space (busy and crowded, confined the built environment is), Predictably (lack of information, inconsistent and unfamiliar, and uncertainty), Understanding (unsupportive people, misunderstanding and judgement), Adjustments (suitable adjustments, pace pressures, inflexible communication), and Recovery (space to escape, unable to recover and prepare). Last, we showed in more detail what these principles look like in the different disabling public places. What do these findings add to what was already known?: Our findings add to our understanding about how autistic adults experience public places; particularly, that there are a range of external factors linked with sensory processing differences which can make public places disabling. What are potential weaknesses in the study?: Our study could have recruited a more diverse range of autistic individuals, such as those with cooccurring intellectual disability. It is important to understand experiences from a diverse range of autistic people to ensure that outcomes from research can improve the lives of all autistic people. How will these findings help autistic adults now or in the future?: Our findings provide insights into how public places could be improved so that they can become more enabling environments for autistic people. This is important for businesses, policy, and the design of spaces to make public places more accessible, improving mental wellbeing and quality of life for autistic individuals.

The reverse motion illusion in random dot motion displays and implications for understanding development.

Across two independent developmental labs, we have been puzzled by the observation that a small proportion of our child and adult participants consistently report perceiving motion in the direction opposite to that presented in random-dot motion displays, sometimes even when the motion is at 100% coherence. In this review, we first draw together existing reports of misperceptions of motion direction in random dot displays across observers in a small percentage of trials, before reporting evidence of consistent reverse motion perception in a minority of observers, including previously unreported observations from our own studies of visual development. We consider possible explanations for this reverse motion illusion, including motion induction, motion energy, correspondence noise and spatial undersampling. However, more work is required to understand the individual differences relating to this percept. We suggest that errors in perceived motion direction are likely to be more widespread than can be currently gleaned from the literature and explain why systematic study is needed, especially in children. Finally, we list some remaining open questions and call for collaborative efforts to document this phenomenon and stimulate future investigation.

Integration of visual motion and orientation signals in dyslexic children: an equivalent noise approach.

Dyslexic individuals have been reported to have reduced global motion sensitivity, which could be attributed to various causes including atypical magnocellular or dorsal stream function, impaired spatial integration, increased internal noise and/or reduced external noise exclusion. Here, we applied an equivalent noise experimental paradigm alongside a traditional motion-coherence task to determine what limits global motion processing in dyslexia. We also presented static analogues of the motion tasks (orientation tasks) to investigate whether perceptual differences in dyslexia were restricted to motion processing. We compared the performance of 48 dyslexic and 48 typically developing children aged 8 to 14 years in these tasks and used equivalent noise modelling to estimate levels of internal noise (the precision associated with estimating each element's direction/orientation) and sampling (the effective number of samples integrated to judge the overall direction/orientation). While group differences were subtle, dyslexic children had significantly higher internal noise estimates for motion discrimination, and higher orientation-coherence thresholds, than typical children. Thus, while perceptual differences in dyslexia do not appear to be restricted to motion tasks, motion and orientation processing seem to be affected differently. The pattern of results also differs from that previously reported in autistic children, suggesting perceptual processing differences are condition-specific.

Behavioural and neural indices of perceptual decision-making in autistic children during visual motion tasks.

Many studies report atypical responses to sensory information in autistic individuals, yet it is not clear which stages of processing are affected, with little consideration given to decision-making processes. We combined diffusion modelling with high-density EEG to identify which processing stages differ between 50 autistic and 50 typically developing children aged 6-14 years during two visual motion tasks. Our pre-registered hypotheses were that autistic children would show task-dependent differences in sensory evidence accumulation, alongside a more cautious decision-making style and longer non-decision time across tasks. We tested these hypotheses using hierarchical Bayesian diffusion models with a rigorous blind modelling approach, finding no conclusive evidence for our hypotheses. Using a data-driven method, we identified a response-locked centro-parietal component previously linked to the decision-making process. The build-up in this component did not consistently relate to evidence accumulation in autistic children. This suggests that the relationship between the EEG measure and diffusion-modelling is not straightforward in autistic children. Compared to a related study of children with dyslexia, motion processing differences appear less pronounced in autistic children. Exploratory analyses also suggest weak evidence that ADHD symptoms moderate perceptual decision-making in autistic children.

Prior information use and response caution in perceptual decision-making: No evidence for a relationship with autistic-like traits.

Interpreting the world around us requires integrating incoming sensory signals with prior information. Autistic individuals have been proposed to rely less on prior information and make more cautious responses than non-autistic individuals. Here, we investigated whether these purported features of autistic perception vary as a function of autistic-like traits in the general population. We used a diffusion model framework, whereby decisions are modelled as noisy evidence accumulation processes towards one of two bounds. Within this framework, prior information can bias the starting point of the evidence accumulation process. Our pre-registered hypotheses were that higher autistic-like traits would relate to reduced starting point bias caused by prior information and increased response caution (wider boundary separation). 222 participants discriminated the direction of coherent motion stimuli as quickly and accurately as possible. Stimuli were preceded with a neutral cue (square) or a directional cue (arrow). 80% of the directional cues validly predicted the upcoming motion direction. We modelled accuracy and response time data using a hierarchical Bayesian model in which starting point varied with cue condition. We found no evidence for our hypotheses, with starting point bias and response caution seemingly unrelated to Adult Autism Spectrum Quotient (AQ) scores. Alongside future research applying this paradigm to autistic individuals, our findings will help refine theories regarding the role of prior information and altered decision-making strategies in autistic perception. Our study also has implications for models of bias in perceptual decision-making, as the most plausible model was one that incorporated bias in both decision-making and sensory processing.

Global motion evoked potentials in autistic and dyslexic children: A cross-syndrome approach.

Atypicalities in psychophysical thresholds for global motion processing have been reported in many neurodevelopmental conditions, including autism and dyslexia. Cross-syndrome comparisons of neural dynamics may help determine whether altered motion processing is a general marker of atypical development or condition-specific. Here, we assessed group differences in N2 peak amplitude (previously proposed as a marker of motion-specific processing) in typically developing (n = 57), autistic (n = 29) and dyslexic children (n = 44) aged 6-14 years, in two global motion tasks. High-density EEG data were collected while children judged the direction of global motion stimuli as quickly and accurately as possible, following a period of random motion. Using a data-driven component decomposition technique, we identified a reliable component that was maximal over occipital electrodes and had an N2-like peak at ~160 msec. We found no group differences in N2 peak amplitude, in either task. However, for both autistic and dyslexic children, there was evidence of atypicalities in later stages of processing that require follow up in future research. Our results suggest that early sensory encoding of motion information is unimpaired in dyslexic and autistic children. Group differences in later processing stages could reflect sustained global motion responses, decision-making, metacognitive processes and/or response generation, which may also distinguish between autistic and dyslexic individuals.

Perceptual Decision-Making in Children: Age-Related Differences and EEG Correlates.

Children make faster and more accurate decisions about perceptual information as they get older, but it is unclear how different aspects of the decision-making process change with age. Here, we used hierarchical Bayesian diffusion models to decompose performance in a perceptual task into separate processing components, testing age-related differences in model parameters and links to neural data. We collected behavioural and EEG data from 96 6- to 12-year-old children and 20 adults completing a motion discrimination task. We used a component decomposition technique to identify two response-locked EEG components with ramping activity preceding the response in children and adults: one with activity that was maximal over centro-parietal electrodes and one that was maximal over occipital electrodes. Younger children had lower drift rates (reduced sensitivity), wider boundary separation (increased response caution) and longer non-decision times than older children and adults. Yet, model comparisons suggested that the best model of children's data included age effects only on drift rate and boundary separation (not non-decision time). Next, we extracted the slope of ramping activity in our EEG components and covaried these with drift rate. The slopes of both EEG components related positively to drift rate, but the best model with EEG covariates included only the centro-parietal component. By decomposing performance into distinct components and relating them to neural markers, diffusion models have the potential to identify the reasons why children with developmental conditions perform differently to typically developing children and to uncover processing differences inapparent in the response time and accuracy data alone.

Interplay of Cyclic GMP-AMP Synthase/Stimulator of IFN Genes and Toll-Like Receptor Nucleic Acid Sensing Pathways in Autoinflammation and Abnormal Bone Formation due to DNaseII-Deficiency.

Nucleic acid (NA) sensing receptors were first described in the context of host defense. We now know that some endosomal NA sensors play a critical role in the development of systemic autoimmune diseases such as systemic lupus erythematosus, whereas cytosolic Cyclic GMP-AMP Synthase/Stimulator of IFN Genes (cGAS/STING) DNA-detecting pathway has been associated with monogenic autoinflammatory interferonopathies such as Aicardi-Goutieres and Education; collaboration; communication STING-associated vasculopathy with onset in infancy (SAVI). DNaseII hypomorphic patients and DNase-/- IFNaR-/- (double knockout [DKO]) mice also develop an autoinflammatory syndrome associated with an interferon signature. We now add to the description of an unusual clinical manifestation of DKO mice that involves the accrual of trabecular bone in long bone marrow and the formation of ectopic bone within the spleen. This aberrant bone formation is lost not only in STING-deficient but also in Unc93b1-deficient mice and, therefore, depends on the interplay of cells expressing cytosolic and endosomal NA sensing receptors.

Global Motion Perception in Autism Spectrum Disorder: A Meta-Analysis.

Visual perception in individuals with autism spectrum disorder (ASD) is often debated in terms of enhanced local and impaired global perception. Deficits in global motion perception seem to support this characterization, although the evidence is inconsistent. We conducted a large meta-analysis on global motion, combining 48 articles on biological and coherent motion. Results provide evidence for a small global motion processing deficit in individuals with ASD compared to controls in both biological and coherent motion. This deficit appears to be present independent of the paradigm, task, dependent variable, age or IQ of the groups. Results indicate that individuals with ASD are less sensitive to these types of global motion, although the difference in neural mechanisms underlying this behavioral difference remains unclear.

Neural dynamics underlying coherent motion perception in children and adults.

Motion sensitivity increases during childhood, but little is known about the neural correlates. Most studies investigating children's evoked responses have not dissociated direction-specific and non-direction-specific responses. To isolate direction-specific responses, we presented coherently moving dot stimuli preceded by incoherent motion, to 6- to 7-year-olds (n = 34), 8- to 10-year-olds (n = 34), 10- to 12-year-olds (n = 34) and adults (n = 20). Participants reported the coherent motion direction while high-density EEG was recorded. Using a data-driven approach, we identified two stimulus-locked EEG components with distinct topographies: an early component with an occipital topography likely reflecting sensory encoding and a later, sustained positive component over centro-parietal electrodes that we attribute to decision-related processes. The component waveforms showed clear age-related differences. In the early, occipital component, all groups showed a negativity peaking at ˜300 ms, like the previously reported coherent-motion N2. However, the children, unlike adults, showed an additional positive peak at ˜200 ms, suggesting differential stimulus encoding. The later positivity in the centro-parietal component rose more steeply for adults than for the youngest children, likely reflecting age-related speeding of decision-making. We conclude that children's protracted development of coherent motion sensitivity is associated with maturation of both early sensory and later decision-related processes.