Sex differences in trajectories of cortical development in autistic children from 2-13 years of age.

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.

Default mode and fronto-parietal network associations with IQ development across childhood in autism.

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.

Altered Development of Amygdala-Connected Brain Regions in Males and Females with Autism.

Altered amygdala development is implicated in the neurobiology of autism, but little is known about the coordinated development of the brain regions directly connected with the amygdala. Here we investigated the volumetric development of an amygdala-connected network, defined as the set of brain regions with monosynaptic connections with the amygdala, in autism from early to middle childhood. A total of 950 longitudinal structural MRI scans were acquired from 282 children (93 female) with autism and 128 children with typical development (61 female) at up to four time points (mean ages: 39, 52, 64, and 137 months, respectively). Volumes from 32 amygdala-connected brain regions were examined using mixed effects multivariate distance matrix regression. The Social Responsiveness Scale-2 was administered to assess degree of autistic traits and social impairments. The amygdala-connected network exhibited persistent diagnostic differences (p values ≤ 0.03) that increased over time (p values ≤ 0.02). These differences were most prominent in autistics with more impacted social functioning at baseline. This pattern was not observed across regions without monosynaptic amygdala connection. We observed qualitative sex differences. In males, the bilateral subgenual anterior cingulate cortices were most affected, while in females the left fusiform and superior temporal gyri were most affected. In conclusion, (1) autism is associated with widespread alterations to the development of brain regions connected with the amygdala, which were associated with autistic social behaviors; and (2) autistic males and females exhibited different patterns of alterations, adding to a growing body of evidence of sex differences in the neurobiology of autism.SIGNIFICANCE STATEMENT Global patterns of development across brain regions with monosynaptic connection to the amygdala differentiate autism from typical development, and are modulated by social functioning in early childhood. Alterations to brain regions within the amygdala-connected network differed in males and females with autism. Results also indicate larger volumetric differences in regions having monosynaptic connection with the amygdala than in regions without monosynaptic connection.

Sex-dependent structure of socioemotional salience, executive control, and default mode networks in preschool-aged children with 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.

Association of Amygdala Development With Different Forms of Anxiety in Autism Spectrum Disorder.

BACKGROUND: The amygdala is widely implicated in both anxiety and autism spectrum disorder. However, no studies have investigated the relationship between co-occurring anxiety and longitudinal amygdala development in autism. Here, the authors characterize amygdala development across childhood in autistic children with and without traditional DSM forms of anxiety and anxieties distinctly related to autism. METHODS: Longitudinal magnetic resonance imaging scans were acquired at up to four time points for 71 autistic and 55 typically developing (TD) children (∼2.5-12 years, 411 time points). Traditional DSM anxiety and anxieties distinctly related to autism were assessed at study time 4 (∼8-12 years) using a diagnostic interview tailored to autism: the Anxiety Disorders Interview Schedule-IV with the Autism Spectrum Addendum. Mixed-effects models were used to test group differences at study time 1 (3.18 years) and time 4 (11.36 years) and developmental differences (age-by-group interactions) in right and left amygdala volume between autistic children with and without DSM or autism-distinct anxieties and TD children. RESULTS: Autistic children with DSM anxiety had significantly larger right amygdala volumes than TD children at both study time 1 (5.10% increase) and time 4 (6.11% increase). Autistic children with autism-distinct anxieties had significantly slower right amygdala growth than TD, autism-no anxiety, and autism-DSM anxiety groups and smaller right amygdala volumes at time 4 than the autism-no anxiety (-8.13% decrease) and autism-DSM anxiety (-12.05% decrease) groups. CONCLUSIONS: Disparate amygdala volumes and developmental trajectories between DSM and autism-distinct forms of anxiety suggest different biological underpinnings for these common, co-occurring conditions in autism.

Altered Gray-White Matter Boundary Contrast in Toddlers at Risk for Autism Relates to Later Diagnosis of Autism Spectrum Disorder.

BACKGROUND: 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. MATERIALS AND METHODS: 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 (n = 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, n = 9; typical development, n = 8; non-typical development, n = 3). RESULTS: 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. LIMITATIONS: 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. CONCLUSION: 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.

Validation of a Virtual Reality Simulator for Percutaneous Pedicle Screw Insertion.

INTRODUCTION: Working-hour restrictions, rota gaps and an increasing drive for theatre efficiency have resulted in challenges to surgical training. As a result, Virtual Reality (VR) has emerged as a popular tool to augment this training. Our aim was to evaluate the validity of a VR simulator for performing percutaneous pedicle screw guidewire insertion. MATERIALS AND METHODS: Twenty-four participants were divided into three equal groups depending on prior surgical experience: a novice group (<10 procedures), an intermediate group (10-50 procedures) and an expert group (>50 procedures). All subjects performed four guidewire insertions on a TraumaVision® simulator (Swemac Innovation AB, Linköping, Sweden) in a set order. Six outcome measures were recorded; total score, time, fluoroscopy exposure, wire depth, zone of placement and wall violations. RESULTS: There were statistically significant differences between the groups for time taken (p<0.001) and fluoroscopy exposure (p<0.001). The novice group performed the worst, and the expert group outperformed both intermediates and novices in both categories. Other outcome results were good and less variable. There was an observed learning effect in the novice and intermediate groups between each of the attempts for both time taken and fluoroscopy exposure. CONCLUSIONS: The study contributes constructive evidence to support the validity of the TraumaVision® simulator as a training tool for pedicle screw guidewire insertion. The simulator is less suitable as an assessment tool. The learning effect was evident in the less experienced groups, suggesting that VR may offer a greater benefit in the early stages of training. Further work is required to assess transferability to the clinical setting.

Longitudinal Evaluation of Cerebral Growth Across Childhood in Boys and Girls With Autism Spectrum Disorder.

BACKGROUND: Cerebral overgrowth is frequently reported in children but not in adults with autism spectrum disorder (ASD). This suggests that early cerebral overgrowth is followed by normalization of cerebral volumes. However, this notion is predicated on cross-sectional research that is vulnerable to sampling bias. For example, autistic individuals with disproportionate megalencephaly, a subgroup with higher rates of intellectual disability and larger cerebral volumes, may be underrepresented in studies of adolescents and adults. Furthermore, extant studies have cohorts that are predominately male, thus limiting knowledge of cerebral growth in females with ASD. METHODS: Growth of total cerebral volume, gray matter (GM) volume, and white matter volume as well as proportion of GM to total cerebral volume were examined in a longitudinal sample comprising 273 boys (199 with ASD) scanned at up to four time points (mean ages = 38, 50, 64, and 137 months, respectively) and 156 girls (95 with ASD) scanned at up to three time points (mean ages = 39, 53, and 65 months, respectively) using mixed-effects modeling. RESULTS: In boys with ASD, cerebral overgrowth in the ASD with disproportionate megalencephaly subgroup was predominately driven by increases in GM and persisted throughout childhood without evidence of volumetric regression or normalization. In girls with ASD, cerebral volumes were similar to those in typically developing girls, but growth trajectories of GM and white matter were slower throughout early childhood. The proportion of GM to total cerebral volume declined with age at a slower rate in autistic boys and girls relative to typically developing control subjects. CONCLUSIONS: Longitudinal evidence does not support the notion that early brain overgrowth is followed by volumetric regression, at least from early to late childhood.

A Longitudinal Study of White Matter Development in Relation to Changes in Autism Severity Across Early Childhood.

BACKGROUND: Cross-sectional diffusion-weighted magnetic resonance imaging studies suggest that young autistic children have alterations in white matter structure that differ from older autistic individuals. However, it is unclear whether these differences result from atypical neurodevelopment or sampling differences between young and older cohorts. Furthermore, the relationship between altered white matter development and longitudinal changes in autism symptoms is unknown. METHODS: Using longitudinal diffusion-weighted magnetic resonance imaging acquired over 2 to 3 time points between the ages of approximately 2.5 to 7.0 years in 125 autistic children and 69 typically developing control participants, we directly tested the hypothesis that autistic individuals have atypical white matter development across childhood. Additionally, we sought to determine whether changes in white matter diffusion parameters were associated with longitudinal changes in autism severity. RESULTS: Autistic children were found to have slower development of fractional anisotropy in the cingulum bundle, superior longitudinal fasciculus, internal capsule, and splenium of the corpus callosum. Furthermore, in the sagittal stratum, autistic individuals who increased in autism severity over time had a slower developmental trajectory of fractional anisotropy compared with individuals whose autism decreased in severity. In the uncinate fasciculus, autistic individuals who decreased in autism symptom severity also had greater increases in fractional anisotropy with age. CONCLUSIONS: These longitudinal findings indicate that previously reported differences in diffusion-weighted magnetic resonance imaging measures between younger and older autism cohorts are attributable to an atypical developmental trajectory of white matter. Differences in white matter development between individuals whose autism severity increased, remained stable, or decreased suggest that these functional differences are associated with fiber development in the autistic brain.

The Autism Phenome Project: Toward Identifying Clinically Meaningful Subgroups of Autism.

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 (2-19 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 toward identifying meaningful subgroups of autism.

High Psychopathology Subgroup in Young Children With Autism: Associations With Biological Sex and Amygdala Volume.

OBJECTIVE: The aims of this study were to identify a subset of children with autism spectrum disorder (ASD) and co-occurring symptoms of psychopathology, and to evaluate associations between this subgroup and biological sex and amygdala volume. METHOD: Participants included 420 children (ASD: 91 girls, 209 boys; typically developing controls: 57 girls, 63 boys). Latent profile analysis was used to identify ASD subgroups based on symptoms of psychopathology, adaptive functioning, cognitive development, and autism severity. Differences in the proportions of girls and boys across subgroups were evaluated. Magnetic resonance imaging scans were acquired (346 children); amygdala volumes were evaluated in relation to subgroups and problem behavior scores. RESULTS: Three ASD subgroups were identified. One group was characterized by high levels of psychopathology and moderate impairment on other measures (High Psychopathology Moderate Impairments [HPMI], comprising 27% of the sample). The other two subgroups had lower symptoms of psychopathology but were differentiated by high and low levels of impairment on other measures. A higher proportion of girls were classified into the HPMI subgroup (40% of girls versus 22% of boys). Relative to controls, amygdala volumes were enlarged only in the HPMI subgroup. There was a positive association between right amygdala volume and internalizing behaviors in girls but not in boys with ASD. CONCLUSION: A higher proportion of girls with ASD faced greater challenges with psychopathology, suggesting a need for closer evaluation and potentially earlier intervention to help improve outcomes. Amygdala enlargement was associated with co-occurring symptoms of psychopathology, and sex-specific correlations with symptoms were observed.

Changes in anterior and posterior hippocampus differentially predict item-space, item-time, and item-item memory improvement.

Relational memory improves during middle childhood and adolescence, yet the neural correlates underlying those improvements are debated. Although memory for spatial, temporal, and other associative relations requires the hippocampus, it is not established whether within-individual changes in hippocampal structure contribute to memory improvements from middle childhood into adolescence. Here, we investigated how structural changes in hippocampal head, body, and tail subregions predict improvements in the capacity to remember item-space, item-time, and item-item relations. Memory for each relation and volumes of hippocampal subregions were assessed longitudinally in 171 participants across 3 time points (Mage at T1 = 9.45 years; Mage at T2 = 10.86 years, Mage at T3 = 12.12 years; comprising 393 behavioral assessments and 362 structural scans). Among older children, volumetric growth in: (a) head and body predicted improvements in item-time memory, (b) head predicted improvements in item-item memory; and (c) right tail predicted improvements in item-space memory. The present research establishes that changes in hippocampal structure are related to improvements in relational memory, and that sub-regional changes in hippocampal volume differentially predict changes in different aspects of relational memory. These findings underscore a division of labor along the anterior-posterior axis of the hippocampus during child development.

Sex Differences in the Amygdala Resting-State Connectome of Children With Autism Spectrum Disorder.

BACKGROUND: Multifactorial liability models predict greater dissimilarity in the neural phenotype of autism spectrum disorder (ASD) in female individuals than in male individuals, while gender incoherence and extreme male brain models predict attenuated sex differences in ASD. The amygdala is an informative target to explore these models because it is implicated in both the neurobiology of ASD and sex differences in typical development. METHODS: This study investigated amygdala resting-state functional connectivity in a cohort of 116 children with ASD (36 female) and 58 typically developing children (27 female) 2 to 7 years of age during natural sleep. First, multivariate distance matrix regression assessed global sex and diagnostic differences across the amygdala connectome. Second, univariate general linear models identified regions with mean connectivity differences. RESULTS: Multivariate distance matrix regression revealed greater differences between typically developing children and those with ASD in females than in males, consistent with multifactorial liability models, and attenuated sex differences in the left amygdala connectome of children with ASD in a pattern consistent with the gender incoherence model. Univariate analysis identified similar sex differences in dorsomedial and ventral prefrontal cortices, lingual gyrus, and posterior cingulate cortex, but also noted that lower amygdala connectivity with superior temporal sulcus is observed across sexes. CONCLUSIONS: This study provides evidence that compared with sex-matched control subjects, ASD manifests differently in the brain at the time of diagnosis and prior to the influence of compensatory mechanisms in male and female children, consistent with multifactorial liability models, and that ASD is associated with reduced sex differences in a pattern consistent with gender incoherence models.

A diffusion-weighted imaging tract-based spatial statistics study of autism spectrum disorder in preschool-aged children.

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.

Progress update from the hippocampal subfields group.

INTRODUCTION: Heterogeneity of segmentation protocols for medial temporal lobe regions and hippocampal subfields on in vivo magnetic resonance imaging hinders the ability to integrate findings across studies. We aim to develop a harmonized protocol based on expert consensus and histological evidence. METHODS: Our international working group, funded by the EU Joint Programme-Neurodegenerative Disease Research (JPND), is working toward the production of a reliable, validated, harmonized protocol for segmentation of medial temporal lobe regions. The working group uses a novel postmortem data set and online consensus procedures to ensure validity and facilitate adoption. RESULTS: This progress report describes the initial results and milestones that we have achieved to date, including the development of a draft protocol and results from the initial reliability tests and consensus procedures. DISCUSSION: A harmonized protocol will enable the standardization of segmentation methods across laboratories interested in medial temporal lobe research worldwide.

The Importance of Knowing When You Don't Remember: Neural Signaling of Retrieval Failure Predicts Memory Improvement Over Time.

Just as the ability to remember prior events is critical for guiding our decision-making, so too is the ability to recognize the limitations of our memory. Indeed, we hypothesize that neural signaling of retrieval failure promotes more accurate memory judgments over time. To test this hypothesis, we collected longitudinal functional magnetic resonance imaging data from 8 to 9 years olds, 10 to 12 years olds, and adults, with two time points spaced approximately 1.4 years apart (198 scan sessions in total). Participants performed an episodic memory retrieval task in which they could either select a response or report uncertainty about the target memory detail. Children who engaged anterior insula more strongly during inaccurate or uncertain responses exhibited greater longitudinal increases in anterior prefrontal cortex activation for decisions to report uncertainty; both of these neural variables predicted improvements in episodic memory. Together, the results suggest that the brain processes supporting effective cognitive control and decision-making continue to develop in middle childhood and play an important role for memory development.

Age- and performance-related differences in hippocampal contributions to episodic retrieval.

The goal of the present study was to investigate whether hippocampal contribution to episodic memory retrieval varies as a function of age (8-9 versus 10-11 versus adults), performance levels (high versus low) and hippocampal sub-region (head, body, tail). We examined fMRI data collected during episodic retrieval from a large sample (N=126). Participants judged whether a stimulus had been encoded previously, and, if so, which of three scenes it had been paired with (i.e., source judgment). For 8- to 9-years-olds as well as low-performing 10- to 11-year-olds, hippocampal activations did not reliably differentiate between trials on which item-scene associations were correctly recalled (correct source), incorrectly recalled (incorrect source), or trials on which the item was forgotten (miss trials). For high-performing 10-11-year olds and low-performing adults, selective hippocampal activation was observed for correct source relative to incorrect source and miss trials; this effect was observed across the entire hippocampus. For high-performing adults, hippocampal activation also distinguished between correct and incorrect source trialsl, but only in the hippocampal head, suggesting that good performance in adults is associated with more focal hippocampal recruitment. Thus, both age and performance are important factors for understanding the development of memory and hippocampal function.

A Time and Place for Everything: Developmental Differences in the Building Blocks of Episodic Memory.

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.

Assessing hippocampal development and language in early childhood: Evidence from a new application of the Automatic Segmentation Adapter Tool.

Volumetric assessments of the hippocampus and other brain structures during childhood provide useful indices of brain development and correlates of cognitive functioning in typically and atypically developing children. Automated methods such as FreeSurfer promise efficient and replicable segmentation, but may include errors which are avoided by trained manual tracers. A recently devised automated correction tool that uses a machine learning algorithm to remove systematic errors, the Automatic Segmentation Adapter Tool (ASAT), was capable of substantially improving the accuracy of FreeSurfer segmentations in an adult sample [Wang et al., 2011], but the utility of ASAT has not been examined in pediatric samples. In Study 1, the validity of FreeSurfer and ASAT corrected hippocampal segmentations were examined in 20 typically developing children and 20 children with autism spectrum disorder aged 2 and 3 years. We showed that while neither FreeSurfer nor ASAT accuracy differed by disorder or age, the accuracy of ASAT corrected segmentations were substantially better than FreeSurfer segmentations in every case, using as few as 10 training examples. In Study 2, we applied ASAT to 89 typically developing children aged 2 to 4 years to examine relations between hippocampal volume, age, sex, and expressive language. Girls had smaller hippocampi overall, and in left hippocampus this difference was larger in older than younger girls. Expressive language ability was greater in older children, and this difference was larger in those with larger hippocampi, bilaterally. Overall, this research shows that ASAT is highly reliable and useful to examinations relating behavior to hippocampal structure.