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This research investigated whether episodic memory development can be explained by improvements in relational binding processes, involved in forming novel associations between events and the context in which they occurred. Memory for item–space, item–time, and item–item relations was assessed in an ethnically diverse sample of 151 children aged 7–11 years and 28 young adults. Item–space memory reached adult performance by 9½ years, whereas item–time and item–item memory improved into adulthood. In path analysis, item– space, but not item–time best explained item–item memory. Across age groups, relational binding related to source memory and performance on standardized memory assessments. In conclusion, relational binding development depends on relation type, but relational binding overall supports episodic memory development.

Previous studies have reported alterations in cortical thickness in autism. However, few have included enough autistic females to determine if there are sex specific differences in cortical structure in autism. This longitudinal study aimed to investigate autistic sex differences in cortical thickness and trajectory of cortical thinning across childhood. Participants included 290 autistic (88 females) and 139 nonautistic (60 females) individuals assessed at up to 4 timepoints spanning ~2–13 years of age (918 total MRI timepoints). Estimates of cortical thickness in early and late childhood as well as the trajectory of cortical thinning were modeled using spatiotemporal linear mixed effects models of age-by-sex-by-diagnosis. Additionally, the spatial correspondence between cortical maps of sex-by-diagnosis differences and neurotypical sex differences were evaluated. Relative to their nonautistic peers, autistic females had more extensive cortical differences than autistic males. These differences involved multiple functional networks, and were mainly characterized by thicker cortex at ~3 years of age and faster cortical thinning in autistic females. Cortical regions in which autistic alterations were different between the sexes significantly overlapped with regions that differed by sex in neurotypical development. Autistic females and males demonstrated some shared differences in cortical thickness and rate of cortical thinning across childhood relative to their nonautistic peers, however these areas were relatively small compared to the widespread differences observed across the sexes. These results support evidence of sex-specific neurobiology in autism and suggest that processes that regulate sex differentiation in the neurotypical brain contribute to sex differences in the etiology of autism.

The structure of large-scale intrinsic connectivity networks is atypical in adolescents diagnosed with autism spectrum disorder (ASD or autism). However, the degree to which alterations occur in younger children, and whether these differences vary by sex, is unknown. We utilized structural magnetic resonance imaging (MRI) data from a sex- and age- matched sample of 122 autistic and 122 typically developing (TD) children (2–4 years old) to investigate differences in underlying network structure in preschool-aged autistic children within three large scale intrinsic connectivity networks implicated in ASD: the Socioemotional Salience, Executive Control, and Default Mode Networks. Utilizing structural covariance MRI (scMRI), we report network-level differences in autistic versus TD children, and further report preliminary findings of sex-dependent differences within network topology.

One of the most universally accepted facts about autism is that it is heterogenous. Individuals diagnosed with autism spectrum disorder have a wide range of behavioral presentations and a variety of co-occurring medical and mental health conditions. The identification of more homogenous subgroups is likely to lead to a better understanding of etiologies as well as more targeted interventions and treatments. In 2006, we initiated the UC Davis MIND Institute Autism Phenome Project (APP) with the overarching goal of identifying clinically meaningful subtypes of autism. This ongoing longitudinal multidisciplinary study now includes over 400 children and involves comprehensive medical, behavioral, and neuroimaging assessments from early childhood through adolescence (2 to 19 years of age). We have employed several strategies to identify sub-populations within autistic individuals: subgrouping by neural, biological, behavioral or clinical characteristics as well as by developmental trajectories. In this Mini Review, we summarize findings to date from the APP cohort and describe progress made towards identifying meaningful subgroups of autism.

Using multi‐decadal simulations, we investigate the relationship between the quasi‐biennial oscillation (QBO) and the Madden–Julian oscillation (MJO) in the Global Ocean Mixed Layer configuration of the Met Office Unified Model (MetUM‐GOML1) at two horizontal resolutions (approximately 200 and 90 km at the equator). MetUM‐GOML1 produces a weak and insignificant correlation between QBO winds and mean MJO amplitude in boreal winter, in contrast to the significant anti‐correlation in reanalysis. While reanalysis shows the easterly QBO favors stronger Maritime Continent MJO activity, MetUM‐GOML1 displays stronger West Pacific MJO activity. The biased QBO–MJO relationship in MetUM‐GOML1 may be due to weak QBO‐induced temperature anomalies in the tropical tropopause layer, or to errors in MJO vertical structure. MetUM‐GOML1 produces a weak and insignificant correlation between QBO winds and mean MJO amplitude in boreal winter, in contrast to the significant anti‐correlation in reanalysis. While reanalysis shows the easterly QBO favors stronger Maritime Continent MJO activity, MetUM‐GOML1 displays stronger West Pacific MJO activity. The biased QBO–MJO relationship in MetUM‐GOML1 may be due to weak QBO‐induced temperature anomalies in the tropical tropopause layer, or to errors in MJO vertical structure.

Background The core symptoms of autism spectrum disorder (ASD) are widely theorized to result from altered brain connectivity. Diffusion-weighted magnetic resonance imaging (DWI) has been a versatile method for investigating underlying microstructural properties of white matter (WM) in ASD. Despite phenotypic and etiological heterogeneity, DWI studies in majority male samples of older children, adolescents, and adults with ASD have largely reported findings of decreased fractional anisotropy (FA) across several commissural, projection, and association fiber tracts. However, studies in preschool-aged children (i.e., < 30–40 months) suggest individuals with ASD have increased measures of WM FA earlier in development. Methods We analyzed 127 individuals with ASD (85♂, 42♀) and 54 typically developing (TD) controls (42♂, 26♀), aged 25.1–49.6 months. Voxel-wise effects of ASD diagnosis, sex, age, and their interaction on DWI measures of FA, mean diffusivity (MD), radial diffusivity (RD), and axial diffusivity (AD) were investigated using tract-based spatial statistics (TBSS) while controlling mean absolute and relative motion. Results Compared to TD controls, males and females with ASD had significantly increased measures of FA in eight clusters (threshold-free cluster enhancement p < 0.05) that incorporated several WM tracts including regions of the genu, body, and splenium of the corpus callosum, inferior frontal-occipital fasciculi, inferior and superior longitudinal fasciculi, middle and superior cerebellar peduncles, and corticospinal tract. A diagnosis by sex interaction was observed in measures of AD across six significant clusters incorporating areas of the body, genu, and splenium of the corpus collosum. In these tracts, females with ASD showed increased AD compared to TD females, while males with ASD showed decreased AD compared to TD males. Conclusions The current findings support growing evidence that preschool-aged children with ASD have atypical measures of WM microstructure that appear to differ in directionality from alterations observed in older individuals with the condition. To our knowledge, this study represents the largest sample of preschool-aged females with ASD to be evaluated using DWI. Microstructural differences associated with ASD largely overlapped between sexes. However, differential relationships of AD measures indicate that sex likely modulates ASD neuroanatomical phenotypes. Further longitudinal study is needed to confirm and quantify the developmental relationship of WM structure in ASD.

Recent neuroimaging studies have highlighted differences in cerebral maturation in individuals with autism spectrum disorder (ASD) in comparison to typical development. For instance, the contrast of the gray-white matter boundary is decreased in adults with ASD. To determine how gray-white matter boundary integrity relates to early ASD phenotypes, we used a regional structural MRI index of gray-white matter contrast (GWC) on a sample of toddlers with a hereditary high risk for ASD. We used a surface-based approach to compute vertex-wise GWC in a longitudinal cohort of toddlers at high-risk for ASD imaged twice between 12 and 24 months ( = 20). A full clinical assessment of ASD-related symptoms was performed in conjunction with imaging and again at 3 years of age for diagnostic outcome. Three outcome groups were defined (ASD, = 9; typical development, = 8; non-typical development, = 3). ASD diagnostic outcome at age 3 was associated with widespread increases in GWC between age 12 and 24 months. Many cortical regions were affected, including regions implicated in social processing and language acquisition. In parallel, we found that early onset of ASD symptoms (i.e., prior to 18-months) was specifically associated with slower GWC rates of change during the second year of life. These alterations were found in areas mainly belonging to the central executive network. Our study is the first to measure maturational changes in GWC in toddlers who developed autism, but given the limited size of our sample results should be considered exploratory and warrant further replication in independent and larger samples. These preliminary results suggest that ASD is linked to early alterations of the gray-white matter boundary in widespread brain regions. Early onset of ASD diagnosis constitutes an independent clinical parameter associated with a specific corresponding neurobiological developmental trajectory. Altered neural migration and/or altered myelination processes potentially explain these findings.

Background Intellectual disability affects approximately one third of individuals with autism spectrum disorder (autism). Yet, a major unresolved neurobiological question is what differentiates autistic individuals with and without intellectual disability. Intelligence quotients (IQs) are highly variable during childhood. We previously identified three subgroups of autistic children with different trajectories of intellectual development from early (2–3½ years) to middle childhood (9–12 years): (a) persistently high: individuals whose IQs remained in the normal range; (b) persistently low: individuals whose IQs remained in the range of intellectual disability (IQ < 70); and (c) changers: individuals whose IQs began in the range of intellectual disability but increased to the normal IQ range. The frontoparietal (FPN) and default mode (DMN) networks have established links to intellectual functioning. Here, we tested whether brain regions within the FPN and DMN differed volumetrically between these IQ trajectory groups in early childhood. Methods We conducted multivariate distance matrix regression to examine the brain regions within the FPN (11 regions x 2 hemispheres) and the DMN (12 regions x 2 hemispheres) in 48 persistently high (18 female), 108 persistently low (32 female), and 109 changers (39 female) using structural MRI acquired at baseline. FPN and DMN regions were defined using networks identified in Smith et al. (Proc Natl Acad Sci U S A 106:13040–5, 2009). IQ trajectory groups were defined by IQ measurements from up to three time points spanning early to middle childhood (mean age time 1: 3.2 years; time 2: 5.4 years; time 3: 11.3 years). Results The changers group exhibited volumetric differences in the DMN compared to both the persistently low and persistently high groups at time 1. However, the persistently high group did not differ from the persistently low group, suggesting that DMN structure may be an early predictor for change in IQ trajectory. In contrast, the persistently high group exhibited differences in the FPN compared to both the persistently low and changers groups, suggesting differences related more to concurrent IQ and the absence of intellectual disability. Conclusions Within autism, volumetric differences of brain regions within the DMN in early childhood may differentiate individuals with persistently low IQ from those with low IQ that improves through childhood. Structural differences in brain networks between these three IQ-based subgroups highlight distinct neural underpinnings of these autism sub-phenotypes.

Episodic memory critically depends on the hippocampus to bind the features of an experience into memory. Episodic memory develops in childhood and adolescence, and hippocampal changes during this period may contribute to this development. Little is known, however, about how the hippocampus contributes to episodic memory development. The hippocampus is comprised of several cytoarchitectural subfields with functional significance for episodic memory. However, hippocampal subfields have not been assessed in vivo during child development, nor has their relation with episodic memory been assessed during this period. In the present study, high-resolution T2-weighted images of the hippocampus were acquired in 39 children and adolescents aged 8 to 14years (M=11.30, SD=2.38), and hippocampal subfields were segmented using a protocol previously validated in adult populations. We first validated the method in children and adolescents and examined age-related differences in hippocampal subfields and correlations between subfield volumes and episodic memory. Significant age-related increases in the subfield volume were observed into early adolescence in the right CA3/DG and CA1. The right CA3/DG subfield volumes were positively correlated with accurate episodic memory for item–color relations, and the right CA3/DG and subiculum were negatively correlated with item false alarm rates. Subfield development appears to follow a protracted developmental trajectory, and likely plays a pivotal role in episodic memory development. •Validates a hippocampal subfield segmentation protocol in pediatric sample.•Age-related differences are observed in right CA1 and CA3/DG subfields.•CA3/DG volume is positively related with episodic memory performance in childhood.•CA3/DG volume is negatively related with item false-alarm rates in childhood.

The third version of the Regional Atmosphere and Land (RAL3) science configuration is documented. Developed through international partnerships, RAL configurations define settings for the Unified Model atmosphere and Joint UK Land Environment Simulator (JULES) when applied across timescales with kilometre and sub-kilometre-scale model grids. The RAL3 configuration represents a major advance compared to previous versions by delivering a common science definition suitable for application to tropical and mid-latitude regions. Developments within RAL3 include the introduction of a double-moment microphysics scheme and a bimodal cloud scheme, replacing use of a single-moment scheme and different cloud schemes for mid-latitudes and tropics in previous versions. Updates have been implemented to the boundary layer scheme and a consolidation of land model settings to be more consistent with global atmosphere and land (GAL) science configurations. Physics developments aimed to address priorities for model performance improvement identified by users. This paper documents the RAL3 science configuration, including a series of iterative revisions delivered since its first release, and their characteristics. Evidence is provided from the variety of assessments of RAL3, relative to the previous version (RAL2). Collaborative development and evaluation across organizations have enabled evaluation across a range of domains, grid spacing and timescales. The analysis indicates more realistic precipitation distributions, improved representation of clouds and of visibility, a continued trend to more realistic representation of convection, and reduced near-surface wind speeds but a persistent cold-temperature bias. Overall the convective-scale verification scores and climatological model distributions relative to observations improve for the majority of variables. Ensemble results show improvements to the spread–error relationship. User feedback from subjective assessment activities has also been positive. Differences between RAL3 revisions and RAL2 are further illustrated through a process-based analysis of a convective system over the UK. The latest RAL3 configuration (RAL3.3) is therefore recommended for research, operational numerical weather prediction, and climate production at kilometre and sub-kilometre scales.