cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.15154/1503337
title: The Landscape of Somatic Mutation in Human Cerebral Cortex

description: Although roles of somatic mutations-- acquired post-fertilization and present in only a subset of an individual’s cells1-- in cancer and certain focal epilepsies are well established2, the extent to which such mutations shape the normally developing human brain or affect risk of neuropsychiatric disease is poorly understood3,4. Here we characterize the landscape of developmental somatic mutations in the human brain by identifying those somatic mutations present in ≥2-3% of cells using ultra-deep (~250X) whole-genome sequencing (WGS) of DNA isolated from the dorsolateral prefrontal cortex (PFC) of 60 postmortem brains of individuals with a diagnosis of autism spectrum disorder (ASD)—the largest such collection ever assembled—as well as 15 neurotypical brains. We identify on average 15 ± 7 somatic single nucleotide variants (sSNVs) per brain (range 3–34), detectable at mosaic fractions (percentage of mutant cells) of 4–83% (mean 18%). Our data reveal that ~5 sSNVs occur in the 1st cell generation after fertilization and ~3 sSNVs occur in each of the 2nd-4th generations, with enrichment of C&gt;T substitutions indicating evolving mutational mechanisms during early development. This mutation rate suggests that a typical individual possesses ~100 mosaic mutations present in ≥2% of cells, and the majority of individuals possess a function-altering sSNV present in ≥2% of cells somewhere in the cortex, levels associated with focal disease. Exons and open chromatin are relatively enriched for mutations, while sSNVs in active, brain-specific enhancers are more common in ASD cases than controls. This suggests that mosaic enhancer mutations contribute to ASD risk and reveals a mechanism of how transcriptional effects in the brain may occur without necessarily impairing non-CNS gene function. The high rate of damaging sSNV in humans suggests they are a routine feature of normal development, and deserve further exploration in other complex neuropsychiatric diseases.
DOI: 10.15154/1503347
title: Racial-Ethnic Disparities in First-Episode Psychosis Treatment Outcomes From the RAISE-ETP Study.

description: Abstract OBJECTIVE: This study examined racial and ethnic differences in treatment outcomes among participants in a randomized controlled trial of an intervention for first-episode psychosis called NAVIGATE. METHODS: Secondary data analyses were conducted for participants randomly assigned to usual community care (N=181) and NAVIGATE (N=223). Generalized estimating equations assessed whether race and ethnicity were associated with psychiatric symptoms and service use (medication management, family psychoeducation, and individual therapy) over a 24-month treatment period, accounting for baseline symptoms, duration of untreated psychosis, and insurance status. RESULTS: Among persons in usual community care, non-Hispanic blacks scored significantly higher throughout treatment on measures of positive symptoms (β=2.15, p=.010), disorganized thoughts (β=1.15, p=.033), and uncontrolled hostility (β=.74, p=.027), compared with non-Hispanic whites, and non-Hispanic blacks were less likely than non-Hispanic whites to receive individual therapy (OR=.45, p=.001). Families of Hispanic participants in usual community care were less likely than non-Hispanic white families to receive family psychoeducation (OR=.20, p=.01). For NAVIGATE participants, race and ethnicity were not associated with differences in psychiatric symptoms over time; families of non-Hispanic black participants were less likely than those of non-Hispanic white participants to receive family psychoeducation (OR=.53, p=.009). Hispanic participants in NAVIGATE were more likely than non-Hispanic white participants to receive medication management (OR=2.93, p=.001). CONCLUSIONS: In usual community care, non-Hispanic blacks scored higher on measures of psychiatric symptoms and were less likely to receive important services, compared with non-Hispanic whites. In NAVIGATE, racial and ethnic differences in psychiatric symptoms were not evident, although non-Hispanic blacks were less likely than non-Hispanic whites to receive family psychoeducation.
DOI: 10.15154/1503348
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: 10.15154/1503350
title: Relating Visual Production and Recognition of Objects in Human Visual Cortex

description: Drawing is a powerful tool that can be used to convey rich perceptual information about objects in the world. What are the neural mechanisms that enable us to produce a recognizable drawing of an object, and how does this visual production experience influence how this object is represented in the brain? Here we evaluate the hypothesis that producing and recognizing an object recruit a shared neural representation, such that repeatedly drawing the object can enhance its perceptual discriminability in the brain. We scanned human participants (N = 31; 11 male) using fMRI across three phases of a training study: during training, participants repeatedly drew two objects in an alternating sequence on an MR-compatible tablet; before and after training, they viewed these and two other control objects, allowing us to measure the neural representation of each object in visual cortex. We found that: (1) stimulus-evoked representations of objects in visual cortex are recruited during visually cued production of drawings of these objects, even throughout the period when the object cue is no longer present; (2) the object currently being drawn is prioritized in visual cortex during drawing production, while other repeatedly drawn objects are suppressed; and (3) patterns of connectivity between regions in occipital and parietal cortex supported enhanced decoding of the currently drawn object across the training phase, suggesting a potential neural substrate for learning how to transform perceptual representations into representational actions. Together, our study provides novel insight into the functional relationship between visual production and recognition in the brain. SIGNIFICANCE STATEMENT: Humans can produce simple line drawings that capture rich information about their perceptual experiences. However, the mechanisms that support this behavior are not well understood. Here we investigate how regions in visual cortex participate in the recognition of an object and the production of a drawing of it. We find that these regions carry diagnostic information about an object in a similar format both during recognition and production, and that practice drawing an object enhances transmission of information about it to downstream regions. Together, our study provides novel insight into the functional relationship between visual production and recognition in the brain.
DOI: 10.15154/1503351
title: Neural Correlates of Restricted Repetitive Behavior in Autism Spectrum Disorder

description: The objective of this study is to investigate relationships between restricted, repetitive behavior and neural circuitry alterations in autism spectrum disorder (ASD). The neural circuitry mediating restricted, repetitive behaviors is largely unknown, and consequently effective treatments are lacking. In order to perform these investigations we will use the National Database for Autism Research (NDA) to access questionnaires and assessments related to repetitive behavior as well as MRI, fMRI, and DTI scans from subjects with autism spectrum disorder (ASD) and typically developing controls. We will perform between-group morphological comparisons, as well as assessments of brain connectivity (e.g. diffusion tractography). For subjects with ASD, we will also correlate neuroimaging data to repetitive behavior scores. This study will help to better understand the link between restricted, repetitive behavior and specific brain alterations
DOI: 10.15154/1503352
title: Longitudinal trajectories of hippocampal and prefrontal contributions to episodic retrieval: Effects of age and puberty.

description: The current study investigated longitudinal change in hippocampal and prefrontal contribution to episodic retrieval. Functional neuroimaging data were collected during an item-context association memory task for children between the ages of 8 and 14 with individuals scanned 1-3 times over the course of 0.75-3.7 years (Timepoint 1 N = 90; Timepoint 2 N = 83, Timepoint 3 N = 75). We investigated developmental changes in functional activation associated with episodic retrieval (correct item-context &gt; incorrect item-context contrast) and asked whether pubertal changes contributed to developmental changes in pattern of activation. Non-linear developmental trajectories were observed. In the hippocampus, activation decreased with age during childhood and then increased into early adolescence. In the dorsolateral prefrontal cortex, activation was largely absent initially, but quickly accelerated over time. Independent of age, changes in pubertal status additionally predicted increases in item-context activation in initially older children, and decreases in initially younger children across both regions and two indicators of puberty: the Pubertal Development Scale and salivary testosterone. These findings suggest that changes in both age and pubertal status uniquely contribute to memory-related activation, and the timing of pubertal onset may play an important role in the neural mechanisms supporting memory retrieval.
DOI: 10.15154/1503353
title: Charting shared developmental trajectories of cortical thickness and structural connectivity in childhood and adolescence

description: XX
DOI: 10.15154/1503354
title: Familia Risk Factor of Childhood Psychopathology

description: Investigating the relationship of childhood psychopathology with familia risk factors, including parental psychopathology, recent substance use behaviors, and parenting behaviors.
DOI: 10.15154/1503402
title: Testing General Query adding Cohorts

description: This is a test to see how to add data to a cohort
DOI: 10.15154/1503430
title: An Examination of Heterogeneity in Treatment Response to Antipsychotic Medications

description: Objective: To examine treatment heterogeneity in the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE); a large RCT comparing effectiveness of several oral second-generation antipsychotics (SGAs) and a first-generation antipsychotic. We tested whether subgroup characteristics modified treatment effects on time to all-cause treatment discontinuation and change in neurocognition measured by the MATRICS Consensus Cognitive Battery (MCCB). Methods: Data is from the intent-to-treat cohort without tardive dyskinesia (N=1206). Participants aged 18-65 years, with a DSM-IV diagnosis of schizophrenia were randomly assigned to SGA olanzapine (OLAN), quetiapine (QUET), risperidone (RISP), or first-generation perphenazine (PERP) and followed for 18 months. For the primary analyses of overall time to all-cause treatment discontinuation and change in least squares mean (LSMean) MCCB composite Z-scores from baseline to month 2 between the four treatments (3 degrees of freedom, significance of p&lt;0.05), we tested the modification of assigned treatment by subgroup characteristics (i.e., age, sex, race, substance use disorder, baseline symptom severity (PANSS) and baseline adherence) using Kaplan-Meier curve estimation and cox proportional hazards regression models, and analysis of covariance, adjusted for treatment site and exacerbation of schizophrenia symptoms in the previous three months. Second, we tested the modification of bivariate pairs of SGAs versus PERP by subgroup characteristics on both outcomes. Results: The primary analysis of overall time to all-cause treatment discontinuation found no interactions, but bivariate analyses found longer time to all-cause treatment discontinuation in females assigned PERP versus QUET (χ2=5.93, p=0.02), and no difference in males. For the primary analysis of overall change in MCCB Z-score between the treatments, persons with PANSS ≥75 had the greatest LSMean increases when assigned PERP and RISP (increase=0.33 and 0.25 respectively) and the smallest increases when assigned QUET and OLAN (increase=0.10 and 0.14 respectively). Persons with PANSS &lt;75 at baseline had Z-score increases when assigned any treatment, but not significantly different between treatments (increases from 0.16-0.19). Bivariate analyses found persons with PANSS ≥75 had a greater increase when taking PERP versus QUET but the increase was not significantly different between QUET and PERP among persons with PANSS &lt;75 at baseline. Conclusions: In some comparisons, sex modified assigned treatments’ effects on time to all-cause treatment discontinuation and symptom severity modified assigned treatments’ effects on change in neurocognition. Although these analyses do not reach statistical significance after multiple comparisons adjustment, they are of potential clinical importance; further study is warranted. Examination of heterogeneity of treatment effects has the potential to lead to more personalized treatment choices.
DOI: 10.15154/1503440
title: Studying treatment-effect heterogeneity in precision medicine through induced subgroups

description: Precision medicine, in the sense of tailoring the choice of medical treatment to patients’ pretreatment characteristics, is nowadays gaining a lot of attention. Preferably, this tailoring should be realized in an evidencebased way, with key evidence in this regard pertaining to subgroups of patients that respond differentially to treatment (i.e., to subgroups involved in treatment–subgroup interactions). Often a-priori hypotheses on subgroups involved in treatment–subgroup interactions are lacking or are incomplete at best. Therefore, methods are needed that can induce such subgroups from empirical data on treatment effectiveness in a post hoc manner. Recently, quite a few such methods have been developed. So far, however, there is little empirical experience in their usage. This may be problematic for medical statisticians and statistically minded medical researchers, as many (nontrivial) choices have to be made during the dataanalytic process. The main purpose of this paper is to discuss the major concepts and considerations when using these methods. This discussion will be based on a systematic, conceptual, and technical analysis of the type of research questions at play, and of the type of data that the methods can
handle along with the available software, and a review of available empirical evidence. We will illustrate all this with the analysis of a dataset comparing several anti-depressant treatments.
DOI: 10.15154/1503524
title: ABCD

description: Using the distributions of the brain tissue to predict the fluid intelligence of children
DOI: 10.15154/1503533
title: Human Connectome Project-Aging (HCP-A) Release 1.0

description: Initial release of unprocessed data and preprocessed structural data for 100+ subjects.
DOI: 10.15154/1503677
title: Age attenuates noise and increases symmetry of head movements during sleep resting-state fMRI in healthy neonates, infants, and toddlers

description: Newborns produce spontaneous movements during sleep that are functionally important for their future development. This nuance has been previously studied using animal models and more recently using movement data from sleep resting-state fMRI (rs-fMRI) scans. Age-related trajectory of statistical features of spontaneous movements of the head is under-examined. This study quantitatively mapped a developmental trajectory of spontaneous head movements during an rs-fMRI scan acquired during natural sleep in 91 datasets from healthy children from ~birth to 3 years old, using the Open Science Infancy Research upcycling protocol. The youngest participants studied, 2-3 week-old neonates, showed increased noise-to-signal levels as well as lower symmetry features of their movements; noise-tosignal levels were attenuated and symmetry was increased in the older infants and toddlers (all Spearman’s rank-order correlations, P&lt; 0.05). Thus, statistical features of spontaneous head movements become more symmetrical and less noisy from birth to ~3 years in children. Because spontaneous movements during sleep in early life may trigger new neuronal activity in the cortex, the key outstanding question for in-vivo, non-invasive neuroimaging studies in young children is not “How can we correct head movement better?” but rather: How can we represent all important sources of neuronal activity that shape functional connections in the still-developing human central nervous system?
DOI: 10.15154/1503684
title: Brain structure, cognition and behavior in child and adolescent survivors of leukemia

description: Pediatric acute lymphoblastic leukemia (ALL) is the most common for of childhood cancer. It is successfully treated in ~90% of cases, primarily based on combination chemotherapy. Survivors of ALL are at elevated risk of cognitive or behavioral problems, which frequently include impairments in processing speed, working memory, attention, and executive function. These changes are accompanied by alterations in brain development, evident by changes in brain structure volume. In our study, data from the Pediatric MRI Data Repository was used as a secondary control data set (supplementing a control data set collected as part of the study). The results were shown as a collective, as well as in two groups matched on an individual basis to participants in the study (based on age, sex, and full-scale IQ).
DOI: 10.15154/1358268
title: The Diagnostic Efficacy of a Facial Recognition Screening Tool for Children with Autism Spectrum Disorder

description: Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by impairments in social communication and by restrictive and repetitive patterns of behavior. An important quantitative social deficit, which is oftentimes not discussed but seen in those with ASD is impaired facial recognition, or the ability to identify and discriminate faces based on memory of one’s unique facial features. Despite the absence of this impairment in the criteria of the Diagnostic and Statistical Manual of Mental Disorders, it is arguably a core deficit in those with ASD. Evidence of this impairment is seen across the board – in behavioral, neuroimaging and eye-tracking studies. The purpose of this study was to examine whether a standardized facial recognition tool, the Faces Immediate and Faces Delayed subtests of the Children’s Memory Scale (CMS; Cohen, 1997), could be used to distinguish between those with and without the disorder.
         Participants consisted of 26 children reliably diagnosed with ASD and 62 age-matched controls between the ages of five to sixteen. Data were utilized from the National Institute of Mental Health (NIMH)’s National Database for Autism Research (NDAR) as well as from the Psychological Evaluation Research and Counseling Clinic (PERCC) and the Diagnostic and Research Institute for Autism Spectrum Disorders at Hofstra University. Receiver operating characteristic (ROC) analysis was conducted to assess the diagnostic efficacy of this tool. Research questions were explored to consider whether areas of social functioning were associated with facial recognition scores. 
        The results of this study indicated that the CMS Faces Immediate subtest showed acceptable discrimination between those with and without ASD based on an area under the curve (AUC) of .706 (p &lt; .05). The sensitivity of the tool for the general sample ranged from 65% to 77% and the specificity ranged from above 50% to 61%. Upwards of 55 children were correctly identified based on a selected cut-point of 10. The CMS Faces Immediate subtest was also found in an acceptable range when discriminating between males and females with and without ASD with AUC’s that ranged from .738 to .735 (p &lt; .05). The CMS Faces Delayed subtest produced an AUC of .657 (p &lt; .05), which indicated that the CMS Faces Immediate was a more discriminative tool than the CMS Faces Delayed. Facial recognition scores were positively correlated with willingness to join group activities. The implications of these results for detection and for the use of a time and cost effective future screening tool are discussed. Based on these findings, the importance of facial recognition interventions for children with ASD is also explored.