cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.15154/1462947
title: Shared understanding of narratives is correlated with shared neural responses

description: Humans have a striking ability to infer meaning from even the sparsest and most abstract forms of narratives. At the same time, flexibility in the form of a narrative is matched by inherent ambiguity in its interpretation. How does the brain represent subtle, idiosyncratic differences in the interpretation of abstract and ambiguous narratives? In this fMRI study, subjects were scanned either watching a novel 7-min animation depicting a complex narrative through the movement of geometric shapes, or listening to a narration of the animation’s social story. Using an intersubject representational similarity analysis that compared interpretation similarity and neural similarity across subjects, we found that the more similar two people’s interpretations of the abstract shapes animation were, the more similar were their neural responses in regions of the default mode network (DMN) and fronto-parietal network. Moreover, these shared responses were modality invariant: the shapes movie and the verbal interpretation of the movie elicited shared responses in linguistic areas and a subset of the DMN when subjects shared interpretations. Together, these results suggest a network of high-level regions that are not only sensitive to subtle individual differences in narrative interpretation during naturalistic conditions, but also resilient to large differences in the modality of the narrative.
DOI: 10.15154/1464951
title: Do children with Autism Spectrum Disorder learn words differently?

description: Children with ASD often are late to start to produce words. However, despite the importance of language abilities for child outcomes in children with ASD, we still have only scratched the surface of understanding these children's early lexicons. Therefore, in the current study we examined the semantic networks of the words that children with ASD have been reported to produce and compared them to typically developing children.
DOI: 10.15154/1465389
title: Deviant vocabulary development in children with Autism Spectrum Disorder

description: Children diagnosed with autism spectrum disorder (ASD) have core impairments in social communication and have restricted interests and repetitive behaviors. Additionally, the majority of young children with ASD have early language delays. Although these early delays are well-documented, it is remains unclear whether language skills are simply delayed or if they are deviant. The current study aimed to expand on previous studies (e.g., Charman et al., 2003; Luyster, Lopez, & Lord, 2007; Rescorla & Safyer, 2012) to provide a large-scale comparison of early language profiles between typically developing (TD) toddlers and young children with ASD. Specifically, we sought to examine the composition of word classes (i.e., nouns, predicates, and close classed words) and semantic categories (i.e., games and routines, sound effects and animal noises) in the early TD and ASD language profiles. A series of linear regression analyses revealed that children with ASD produced a smaller percentage of nouns, and that the percentage of nouns in a vocabulary decreased as children learned more words, but that this reduction was less steep in the ASD group. When examining predicates, we found that children with ASD produced a significantly higher percentage of predicates. Also, as vocabulary size increased, the percentage of predicates increased; however, the slope was less steep for children with ASD. Lastly, children with SD produced a significantly higher percentage of closed class words and the trajectory of growth of the percentage of closed class words differed between groups. The current findings suggest that children with ASD may employ different word-learning strategies during early lexical development.
DOI: 10.15154/1475202
title: Evaluation of Differences in Temporal Synchrony Between Brain Regions in Individuals With Autism and Typical Development

description: Importance: Despite reports of widespread but heterogenous atypicality of functional connectivity in individuals with autism, little is known regarding the temporal dynamics of functional brain connections and how this relates to autistic traits. Objective: To investigate differences in temporal synchrony between brain regions in individuals with autism and typical development. Design: Cohort and replication sample study. The cohort includes data acquired between December 2016 and April 2018. Aggregate data included in the replication sample were released to the public in August 2012 (ABIDE I) and June 2016 (ABIDE II). Data were analyzed in April 2018. Setting: Population-based study conducted at the University of Utah. Participants: This cohort study, conducted at the University of Utah, included 90 adolescent and adult male participants. A larger sample from the multisite Autism Brain Imaging Data Exchange (ABIDE) was also used as a replication sample. Main Outcomes and Measures: Long duration (30 minutes per subject) of multiband, multi-echo functional magnetic resonance imaging was acquired in order to estimate functional connectivity between brain regions. Sustained connectivity, a measure of functional connectivity duration, as well as lagged temporal dynamics related to functional connectivity, were compared between groups for 361 gray matter regions of interest and a 17-network parcellation. Lagged findings were replicated in the larger ABIDE sample (n=1402). Sustained connectivity findings were also associated with behavioral and cognitive variables. Results: In 52 individuals with autism (mean [SD] age, 27.73 [8.66] years) and 38 controls (mean [SD] age, 27.09 [7.49] years), increases in both sustained connectivity and functional connectivity at several lags were found in individuals with autism compared to controls. Group differences in functional connectivity were replicated in the larger ABIDE dataset at a six second lag. Measures of symptom severity in individuals with autism were positively associated with sustained connectivity values. In controls, sustained connectivity was negatively associated with cognitive processing. Conclusions and Relevance: Whereas the magnitude of functional connectivity in autism is variable across brain regions, participant samples, and development, prolonged temporal synchrony of functional connections is reproducibly observed in autism, suggesting a potential mechanism for core symptoms.
DOI: 10.15154/1479202
title: Resting State Functional Connectivity and Psychotic-Like Experiences in Childhood: Results from the Adolescent Brain Cognitive Development Study

description: Background: Psychotic-like experiences (PLEs) during childhood are associated with greater risk of developing a psychotic disorder, highlighting the importance of identifying neural correlates of childhood PLEs. Three major cortical networks- the cingulo-opercular network (CON), default mode network (DMN), and fronto-parietal network (FPN)- are consistently implicated in psychosis as well as PLEs in adults. However, it is unclear whether variation in functional connectivity is associated with PLEs in school-aged children. Methods: Using hierarchical linear models, we examined the relationships between childhood PLEs and resting-state functional connectivity of the CON, DMN, and FPN, as well as the other networks using an a priori network parcellation, using data from 3,434 9-10-year-olds in the Adolescent Brain Cognitive Development (ABCD) study. We examined within-network, between-network, and subcortical connectivity. Results: Decreased CON and DMN connectivity, as well as cingulo-parietal (CPAR) network connectivity, were associated with greater PLEs, even after accounting for family history of psychotic disorders, internalizing symptoms, and cognitive performance. Decreased DMN network connectivity was more strongly associated with increased delusional ideation, whereas decreased CON connectivity was more strongly associated with increased perceptual distortions. Increased CON-cerebellar and decreased CPAR-cerebellar connectivity were also associated with increased PLEs, and CPAR-cerebellar connectivity was more strongly associated with increased perceptual distortions. Conclusion: Consistent with hypotheses about the dimensionality of psychosis, our results provide evidence that neural correlates of PLEs, such as reduced functional connectivity of higher-order cognitive networks, are present even in school-aged children. Therefore, the results provide further validation for continuity of PLEs across the lifespan.
DOI: 10.15154/1503425
title: Epigenetic marks of prenatal air pollution exposure found in multiple tissues relevant for child health

description: Background: Prenatal air pollution exposure has been linked to many adverse health conditions in the offspring. However, little is known about the mechanisms underlying these associations. Epigenetics may be one plausible biologic link. Here, we sought to identify site-specific and global DNA methylation (DNAm) changes, in developmentally relevant tissues, associated with prenatal exposure to nitrogen dioxide (NO2) and ozone (O3). Additionally, we assessed whether sex-specific changes in methylation exist and whether DNAm changes are consistently observed across tissues.

Methods: Genome-scale DNAm measurements were obtained using the Infinium HumanMethylation450k platform for 133 placenta and 175 cord blood specimens from Early Autism Risk Longitudinal Investigation (EARLI) neonates. Ambient NO2 and O3 exposure levels were based on prenatal address locations of EARLI mothers and the Environmental Protection Agency’s AirNOW monitoring network using inverse distance weighting. We computed sample-level aggregate methylation measures for each of 5 types of genomic regions including genome-wide, open sea, shelf, shore, and island regions. Linear regression was performed for each genomic region; per-sample aggregate methylation measures were modeled as a function of quantitative exposure level with covariate adjustment. In addition, bumphunting was performed to identify differentially methylated regions (DMRs) associated with prenatal O3 and NO2 exposures in each tissue and by sex, with adjustment for technical and biological sources of variation.

Results: We identified global and locus-specific changes in DNA methylation related to prenatal exposure to NO2 and O3 in 2 developmentally relevant tissues. Neonates with increased prenatal O3 exposure had lower aggregate levels of DNAm at CpGs located in open sea and shelf regions of the genome. We identified 6 DMRs associated with prenatal NO2 exposure, including 3 sex-specific. An additional 3 sex-specific DMRs were associated with prenatal O3 exposure levels. DMRs initially detected in cord blood samples (n=4) showed consistent exposure-related changes in DNAm in placenta. However, the DMRs initially detected in placenta (n=5) did not show DNAm differences in cord blood and, thus, they appear to be tissue-specific.

Conclusions: We observed global, locus, and sex-specific methylation changes associated with prenatal NO2 and O3 exposures. Our findings support DNAm is a biologic target of prenatal air pollutant exposures and highlight epigenetic involvement in sex-specific differential susceptibility to environmental exposure effects in 2 developmentally relevant tissues.
DOI: 10.15154/1503452
title: Estimating patient-specific treatment advantages in the ‘Treatment for Adolescents with Depression Study’

description: The ‘Treatment for Adolescents with Depression Study’ (TADS, ClinicalTrials.gov, identifier: NCT00006286) was a cornerstone, randomized controlled trial evaluating the effectiveness of standard treatment options for major depression in adolescents. Whereas previous TADS analyses examined primarily effect modifications of treatment-placebo differences by various patient characteristics, less is known about the modification of inter-treatment differences, and hence, patient characteristics that might guide treatment selection. We sought to fill this gap by estimating patient-specific inter-treatment differences as a function of patients’ baseline characteristics. We did so by applying the ‘model-based random forest’, a recently-introduced machine learning-based method for evaluating effect heterogeneity that allows for the estimation of patient-specific treatment effects as a function of arbitrary baseline characteristics. Treatment conditions were cognitive-behavioural therapy (CBT) alone, fluoxetine (FLX) alone, and the combination of CBT and fluoxetine (COMB). All inter-treatment differences (CBT vs. FLX; CBT vs. COMB; FLX vs. COMB) were evaluated across 23 potential effect modifiers extracted from previous studies. Overall, FLX was superior to CBT, while COMB was superior to both CBT and FLX. Evidence for effect heterogeneity was found for the CBT-FLX difference and the FLX-COMB difference, but not for the CBT-COMB difference. Baseline depression severity modified the CBT-FLX difference; whereas baseline depression severity, patients’ treatment expectations, and childhood trauma modified the FLX-COMB difference. All modifications were quantitative rather than qualitative, however, meaning that the differences varied only in magnitude, but not direction. These findings imply that combining CBT with fluoxetine may be superior to either therapy used alone across a broad range of patients.
DOI: 10.15154/1503519
title: The relationship between functional brain organization and self-reported digital screen engagement in late childhood

description: The idea that the increased ubiquity of digital devices negatively impacts neurodevelopment is as compelling as it is disturbing. The proposed study will investigate this concern by systematically evaluating how different profiles of screen-based engagement relate to functional brain organization in late childhood. Participants will be drawn from a large and representative sample of young people participating in the first wave of the ABCD study (ages 9-12 years). Of interest are the relations between self-reported use of various digital screen technologies and functional brain organization. These relationships will then be related to functional outcomes associated with mental health and cognition. The corresponding analytic plan was designed and executed using the first released sample of the initial wave of ABCD data (baseline n=4521). We will then test the replicability of our results on those participants included in the second release of the initial wave of ABCD data. Of principle interest are two hypotheses: First, that functional brain organization (assessed through resting state functional connectivity MRI; rs-fcMRI) is related to digital screen engagement; and second, that children with higher rates of engagement will have functional brain organization profiles related to maladaptive functioning. Results will be interpreted in light of the ongoing scientific, policy, and public debate concerning digital devices and their effect on children’s cognitive development. We will extend our findings to ultimately inform professional screen time recommendations, our understanding of brain development, and empirical investigations of child functioning in the age of open science.
DOI: 10.15154/1503722
title: Human Connectome Project for Early Psychosis
DOI: 10.15154/1503728
title: Failure to attune to language predicts autism in high risk infants

description: Young humans are typically sensitive to evolutionarily important aspects of information in the surrounding environment in a way that makes us thrive. Seeking to probe the putative disruptions of this process in infancy, I examined the statistical character of head movements in 52 9–10 mo-old infants, half at high familial risk (HR) for Autism Spectrum Disorders (ASD), who underwent an fMRI scan while listening to words spoken with alternating stress patterns on syllables. Relative to low risk (LR) infants, HR infants, in particular those showing the least rapid receptive language progress, had significantly lower noise-to-signal levels and increased symmetry. A comparison of patterns during a native language and a sleep scan revealed the most atypical ordering of signatures on the 3 tasks in a subset of HR infants, suggesting that the biological mechanism of language development is least acquisitive in those HR infants who go on to develop ASD in toddlerhood.
DOI: 10.15154/1503840
title: When does the youthfulness of the female brain emerge?

description: Goyal et al., report in the February issue of PNAS that the female adult
brain has a persistently lower metabolic brain age compared with the male brain
at the same chronological age (1). In interpreting this remarkable finding, the
authors propose that sex-related differences in brain development may in part
play a role in “setting” the female brain at a younger initial brain age at puberty,
allowing them to maintain a younger brain throughout adulthood. We argue that
may not be the case and provide evidence to show that, in fact, the opposite may
be true during childhood and adolescence.
First, according to the Figure 2A in Goyal et al, surprisingly, the predicted
age between 35-50 y were under-estimated for both males and females. It is
unclear if the bias in this age range could have affected the overall findings or
played a role in only the result from training on males and testing on females
surviving a two-sided t-test. Moreover, it is unclear which age range was
determinative of the significant difference between predicted and chronological
age.
Second, we used cortical thickness, which i) has been validated as a
reliable biomarker for brain age (2, 3) and ii) has shown strong association with
sex hormones during puberty maturation (4, 5) from 265 healthy children and
youth (118 boys, 147 girls) between the ages of 5 and 18 from the NIH MRI
Study of Normal Brain Development (6) and estimated the difference between
brain age and actual chronological age. Similar to Goyal et al., we first trained the
ML algorithm (support vector regression with default parameters, implemented
using LIBSVM toolbox) on the male cohort only and then tested it on the female
cohort, and vice versa. We found that while cortical-thickness-based brain age
correlated strongly with actual chronological age in both cohorts (training on boys
and testing on girls: r = 0.75, p&lt;0.001; training on girls and testing on boys: r =
0.71, p &lt; 0.001; Figure 1A), the mean cortical thickness brain age was on
average 0.42 y older for girls compared with boys (p = 0.02, two-sided t-test;
Figure 1B) when the male data was used as the training set and 0.47 y younger
for boys compared with girls (p = 0.03, two-sided t-test; Figure 1B) when the
female data was used as the training set. In other words, while per Goyal and
colleagues’ investigation adult females may have a younger brain than adult
males during development, this pattern is not the same and in fact seems to be in
the opposite direction during puberty.
While cortical thinning as a biomarker for aging may reflect a different
aspect of aging than what metabolic changes may reflect, given that they are
both strongly predictive of chronological age, it is likely that they may also be
correlated. Therefore, given our finding, we propose that the mechanisms that
are involved in keeping the female brain younger in adulthood may get engaged
at a later point in life and not during puberty.
DOI: 10.15154/1503881
title: Demographic, Psychological, Behavioral, and Cognitive Correlates of BMI in Youth: Findings from the Adolescent Brain Cognitive Development (ABCD) Study

description: Background: Previous research has implicated demographic, psychological, behavioral, and cognitive variables in the onset and maintenance of pediatric overweight/obesity. No adequately-powered study has simultaneously modeled these variables to assess their relative associations with body mass index (BMI; kg/m2) in a nationally representative sample of youth. 
Methods: Multiple machine learning regression approaches were employed to estimate the relative importance of 43 demographic, psychological, behavioral, and cognitive variables previously associated with BMI in youth to elucidate the associations of both fixed (e.g., demographics) and potentially modifiable (e.g., psychological/behavioral) variables with BMI in a diverse representative sample of youth. The primary analyses consisted of 9-10 year olds divided into a training (n = 2724) and test (n = 1123) sets. Secondary analyses were conducted by sex, ethnicity, and race.
Results: The full sample model captured 12% of the variance in both the training and test sets, suggesting good generalizability. Stimulant medications and demographic factors were most strongly associated with BMI. Lower attention problems and matrix reasoning (i.e., nonverbal abstract problem solving and inductive reasoning) and higher social problems and screen time were robust positive correlates in the primary analyses and in analyses separated by sex. 
Conclusions: Beyond demographics and stimulant use, this study highlights abstract reasoning as an important cognitive variable and reaffirms social problems and screen time as significant correlates of BMI and as modifiable therapeutic targets. Prospective data are needed to understand the predictive power of these variables for BMI gain.
DOI: 10.15154/1503887
title: Investigating Vocabulary Profiles in Preverbal and Minimally Verbal Children with Autism Spectrum Disorder

description: The majority of children with autism spectrum disorder (ASD) are delayed in producing their first words and approximately 30% continue to be minimally verbal across childhood. The current study examined the syntactic and semantic features of the early words that 64 preverbal and minimally verbal children with ASD produced and compared them to 682 typically developing (TD) toddlers who produced 1-10 words. Word-level responses that were reported on the MacArthur-Bates Communicative Development Inventory were examined. Children with ASD produced a greater proportion of predicates, relative to the TD group. Also, there were group differences in the following semantic categories: action words, people, sound effects, and animals. Of these, children with ASD produced more action words. We further examined the action words by assigning them social scores, with action words that typically involve people having higher social scores. TD toddlers produced action words that were slightly more social than children with ASD. These findings suggest that future studies should examine early verb learning and processing in children with ASD.
DOI: 10.15154/1503900
title: Distinguishing Remitted Bipolar Disorder from Remitted Unipolar Depression in Pre-Adolescent Children: A Neural Reward Processing Perspective

description: Bipolar disorder (BD) is often misdiagnosed as unipolar depression (UD), highlighting the need to identify clinically useful markers to differentiate them. To provide insights into this endeavor, the current study will employ functional magnetic resonance imaging and conduct region-of-interest (ROI; ventral striatum and orbitofrontal cortex), whole-brain, and connectivity analyses to examine the similarities and differences between children with BD, children with UD, and healthy controls (HCs) in brain activation patterns and functional coupling between brain regions within the context of reward processing, as evoked by the Monetary Incentive Delay task. The current study represents the first examination of neural reward processing in preadolescent children with remitted BD or UD. We aim to (a) test whether preadolescent children with remitted BD or UD display abnormal patterns of neural activation and connectivity in response to reward, relative to HCs and (b) compare remitted UD and BD directly with each other to evaluate whether they can be distinguished by neural activation and connectivity during reward processing