Search

Flexible behavior is critical for everyday decision-making and has been implicated in restricted, repetitive behaviors (RRB) in autism spectrum disorder (ASD). However, how flexible behavior changes developmentally in ASD remains largely unknown. Here, we used a developmental approach and examined flexible behavior on a probabilistic reversal learning task in 572 children, adolescents, and adults (ASD N = 321; typical development [TD] N = 251). Using computational modeling, we quantified latent variables that index mechanisms underlying perseveration and feedback sensitivity. We then assessed these variables in relation to diagnosis, developmental stage, core autism symptomatology, and associated psychiatric symptoms. Autistic individuals showed on average more perseveration and less feedback sensitivity than TD individuals, and, across cases and controls, older age groups showed more feedback sensitivity than younger age groups. Computational modeling revealed that dominant learning mechanisms underpinning flexible behavior differed across developmental stages and reduced flexible behavior in ASD was driven by less optimal learning on average within each age group. In autistic children, perseverative errors were positively related to anxiety symptoms, and in autistic adults, perseveration (indexed by both task errors and model parameter estimates) was positively related to RRB. These findings provide novel insights into reduced flexible behavior in relation to clinical symptoms in ASD. Computational modeling of flexible choice behavior in autism spectrum disorder and typical development reveals comparable developmental shifts in dominant learning mechanisms and suggests that reduced flexible behavior in autism spectrum disorder is underpinned by less optimal probabilistic reversal learning. [ABSTRACT FROM AUTHOR]

How a child's brain develops specialization for print is poorly understood. One longstanding account is selective neuronal tuning to regularity of visual-orthographic features, which predicts a monotonically increased neural activation for inputs with higher regularity during development. However, we observed a robust interaction between a stimulus' orthographic regularity (bottom-up input) and children's lexical classification ability (top-down prediction): N1 response, which is the first negative component of the event-related potential (ERP) occurring at posterior electrodes, was stronger to lower-regularity stimuli, but only in children who were less efficient in lexically classifying these stimuli (high prediction error). In contrast, N1 responses were reduced to lower-regularity stimuli in children who showed high efficiency of lexical classification (low prediction error). The modulation of children's lexical classification efficiency on their neural responses to orthographic stimuli supports the predictive coding account of neural processes of reading. [ABSTRACT FROM AUTHOR]

Almost all attention and learning—in particular, most early learning—take place in social settings. But little is known of how our brains support dynamic social interactions. We recorded dual electroencephalography (EEG) from 12-month-old infants and parents during solo play and joint play. During solo play, fluctuations in infants’ theta power significantly forward-predicted their subsequent attentional behaviours. However, this forward-predictiveness was lower during joint play than solo play, suggesting that infants’ endogenous neural control over attention is greater during solo play. Overall, however, infants were more attentive to the objects during joint play. To understand why, we examined how adult brain activity related to infant attention. We found that parents’ theta power closely tracked and responded to changes in their infants’ attention. Further, instances in which parents showed greater neural responsivity were associated with longer sustained attention by infants. Our results offer new insights into how one partner influences another during social interaction. [ABSTRACT FROM AUTHOR]

Infiltrating monocyte-derived macrophages (MDMs) and resident microglia dominate central nervous system (CNS) injury sites. Differential roles for these cell populations after injury are beginning to be uncovered. Here, we show evidence that MDMs and microglia directly communicate with one another and differentially modulate each other’s functions. Importantly, microglia-mediated phagocytosis and inflammation are suppressed by infiltrating macrophages. In the context of spinal cord injury (SCI), preventing such communication increases microglial activation and worsens functional recovery. We suggest that macrophages entering the CNS provide a regulatory mechanism that controls acute and long-term microglia-mediated inflammation, which may drive damage in a variety of CNS conditions. [ABSTRACT FROM AUTHOR]

Altruistic behavior is considered a key feature of the human cooperative makeup, with deep ontogenetic roots. The tendency to engage in altruistic behavior varies between individuals and has been linked to differences in responding to fearful faces. The current study tests the hypothesis that this link exists from early in human ontogeny. Using eye tracking, we examined whether attentional responses to fear in others at 7 months of age predict altruistic behavior at 14 months of age. Our analysis revealed that altruistic behavior in toddlerhood was predicted by infants’ attention to fearful faces but not happy or angry faces. Specifically, infants who showed heightened initial attention to (i.e., prolonged first look) followed by greater disengagement (i.e., reduced attentional bias over 15 seconds) from fearful faces at 7 months displayed greater prosocial behavior at 14 months of age. Our data further show that infants’ attentional bias to fearful faces and their altruistic behavior was predicted by brain responses in the dorsolateral prefrontal cortex (dlPFC), measured through functional near-infrared spectroscopy (fNIRS). This suggests that, from early in ontogeny, variability in altruistic helping behavior is linked to our responsiveness to seeing others in distress and brain processes implicated in attentional control. These findings critically advance our understanding of the emergence of altruism in humans by identifying responsiveness to fear in others as an early precursor contributing to variability in prosocial behavior. [ABSTRACT FROM AUTHOR]

Animals live together with diverse bacteria that can impact their biology. In Drosophila melanogaster, gut-associated bacterial communities are relatively simple in composition but also have a strong impact on host development and physiology. It is generally assumed that gut bacteria in D. melanogaster are transient and their constant ingestion with food is required to maintain their presence in the gut. Here, we identify bacterial species from wild-caught D. melanogaster that stably associate with the host independently of continuous inoculation. Moreover, we show that specific Acetobacter wild isolates can proliferate in the gut. We further demonstrate that the interaction between D. melanogaster and the wild isolated Acetobacter thailandicus is mutually beneficial and that the stability of the gut association is key to this mutualism. The stable population in the gut of D. melanogaster allows continuous bacterial spreading into the environment, which is advantageous to the bacterium itself. The bacterial dissemination is in turn advantageous to the host because the next generation of flies develops in the presence of this particularly beneficial bacterium. A. thailandicus leads to a faster host development and higher fertility of emerging adults when compared to other bacteria isolated from wild-caught flies. Furthermore, A. thailandicus is sufficient and advantageous when D. melanogaster develops in axenic or freshly collected figs, respectively. This isolate of A. thailandicus colonizes several genotypes of D. melanogaster but not the closely related D. simulans, indicating that the stable association is host specific. This work establishes a new conceptual model to understand D. melanogaster–gut microbiota interactions in an ecological context; stable interactions can be mutualistic through microbial farming, a common strategy in insects. Moreover, these results develop the use of D. melanogaster as a model to study gut microbiota proliferation and colonization. [ABSTRACT FROM AUTHOR]

How does education affect cortical organization? All literate adults possess a region specialized for letter strings, the visual word form area (VWFA), within the mosaic of ventral regions involved in processing other visual categories such as objects, places, faces, or body parts. Therefore, the acquisition of literacy may induce a reorientation of cortical maps towards letters at the expense of other categories such as faces. To test this cortical recycling hypothesis, we studied how the visual cortex of individual children changes during the first months of reading acquisition. Ten 6-year-old children were scanned longitudinally 6 or 7 times with functional magnetic resonance imaging (fMRI) before and throughout the first year of school. Subjects were exposed to a variety of pictures (words, numbers, tools, houses, faces, and bodies) while performing an unrelated target-detection task. Behavioral assessment indicated a sharp rise in grapheme–phoneme knowledge and reading speed in the first trimester of school. Concurrently, voxels specific to written words and digits emerged at the VWFA location. The responses to other categories remained largely stable, although right-hemispheric face-related activity increased in proportion to reading scores. Retrospective examination of the VWFA voxels prior to reading acquisition showed that reading encroaches on voxels that are initially weakly specialized for tools and close to but distinct from those responsive to faces. Remarkably, those voxels appear to keep their initial category selectivity while acquiring an additional and stronger responsivity to words. We propose a revised model of the neuronal recycling process in which new visual categories invade weakly specified cortex while leaving previously stabilized cortical responses unchanged. [ABSTRACT FROM AUTHOR]

Reported values in the literature on the number of cells in the body differ by orders of magnitude and are very seldom supported by any measurements or calculations. Here, we integrate the most up-to-date information on the number of human and bacterial cells in the body. We estimate the total number of bacteria in the 70 kg "reference man" to be 3.8·1013. For human cells, we identify the dominant role of the hematopoietic lineage to the total count (≈90%) and revise past estimates to 3.0·1013 human cells. Our analysis also updates the widely-cited 10:1 ratio, showing that the number of bacteria in the body is actually of the same order as the number of human cells, and their total mass is about 0.2 kg. [ABSTRACT FROM AUTHOR]

Thymus is crucial for generation of a diverse repertoire of T cells essential for adaptive immunity. Although thymic epithelial cells (TECs) are crucial for thymopoiesis and T cell generation, how TEC development and function are controlled is poorly understood. We report here that mTOR complex 1 (mTORC1) in TECs plays critical roles in thymopoiesis and thymus function. Acute deletion of mTORC1 in adult mice caused severe thymic involution. TEC-specific deficiency of mTORC1 (mTORC1KO) impaired TEC maturation and function such as decreased expression of thymotropic chemokines, decreased medullary TEC to cortical TEC ratios, and altered thymic architecture, leading to severe thymic atrophy, reduced recruitment of early thymic progenitors, and impaired development of virtually all T-cell lineages. Strikingly, temporal control of IL-17-producing γδT (γδT17) cell differentiation and TCRVγ/δ recombination in fetal thymus is lost in mTORC1KO thymus, leading to elevated γδT17 differentiation and rearranging of fetal specific TCRVγ/δ in adulthood. Thus, mTORC1 is central for TEC development/function and establishment of thymic environment for proper T cell development, and modulating mTORC1 activity can be a strategy for preventing thymic involution/atrophy. [ABSTRACT FROM AUTHOR]