Differences in the functional brain architecture of sustained attention and working memory in youth and adults.

Sustained attention (SA) and working memory (WM) are critical processes, but the brain networks supporting these abilities in development are unknown. We characterized the functional brain architecture of SA and WM in 9- to 11-year-old children and adults. First, we found that adult network predictors of SA generalized to predict individual differences and fluctuations in SA in youth. A WM model predicted WM performance both across and within children-and captured individual differences in later recognition memory-but underperformed in youth relative to adults. We next characterized functional connections differentially related to SA and WM in youth compared to adults. Results revealed 2 network configurations: a dominant architecture predicting performance in both age groups and a secondary architecture, more prominent for WM than SA, predicting performance in each age group differently. Thus, functional connectivity (FC) predicts SA and WM in youth, with networks predicting WM performance differing more between youths and adults than those predicting SA.

Functional brain connectivity predicts sleep duration in youth and adults.

Sleep is critical to a variety of cognitive functions and insufficient sleep can have negative consequences for mood and behavior across the lifespan. An important open question is how sleep duration is related to functional brain organization which may in turn impact cognition. To characterize the functional brain networks related to sleep across youth and young adulthood, we analyzed data from the publicly available Human Connectome Project (HCP) dataset, which includes n-back task-based and resting-state fMRI data from adults aged 22-35 years (task n = 896; rest n = 898). We applied connectome-based predictive modeling (CPM) to predict participants' mean sleep duration from their functional connectivity patterns. Models trained and tested using 10-fold cross-validation predicted self-reported average sleep duration for the past month from n-back task and resting-state connectivity patterns. We replicated this finding in data from the 2-year follow-up study session of the Adolescent Brain Cognitive Development (ABCD) Study, which also includes n-back task and resting-state fMRI for adolescents aged 11-12 years (task n = 786; rest n = 1274) as well as Fitbit data reflecting average sleep duration per night over an average duration of 23.97 days. CPMs trained and tested with 10-fold cross-validation again predicted sleep duration from n-back task and resting-state functional connectivity patterns. Furthermore, demonstrating that predictive models are robust across independent datasets, CPMs trained on rest data from the HCP sample successfully generalized to predict sleep duration in the ABCD Study sample and vice versa. Thus, common resting-state functional brain connectivity patterns reflect sleep duration in youth and young adults.

Filtering respiratory motion artifact from resting state fMRI data in infant and toddler populations.

The importance of motion correction when processing resting state functional magnetic resonance imaging (rs-fMRI) data is well-established in adult cohorts. This includes adjustments based on self-limited, large amplitude subject head motion, as well as factitious rhythmic motion induced by respiration. In adults, such respiration artifact can be effectively removed by applying a notch filter to the motion trace, resulting in higher amounts of data retained after frame censoring (e.g., "scrubbing") and more reliable correlation values. Due to the unique physiological and behavioral characteristics of infants and toddlers, rs-fMRI processing pipelines, including methods to identify and remove colored noise due to subject motion, must be appropriately modified to accurately reflect true neuronal signal. These younger cohorts are characterized by higher respiration rates and lower-amplitude head movements than adults; thus, the presence and significance of comparable respiratory artifact and the subsequent necessity of applying similar techniques remain unknown. Herein, we identify and characterize the consistent presence of respiratory artifact in rs-fMRI data collected during natural sleep in infants and toddlers across two independent cohorts (aged 8-24 months) analyzed using different pipelines. We further demonstrate how removing this artifact using an age-specific notch filter allows for both improved data quality and data retention in measured results. Importantly, this work reveals the critical need to identify and address respiratory-driven head motion in fMRI data acquired in young populations through the use of age-specific motion filters as a mechanism to optimize the accuracy of measured results in this population.

Distinguishing cognitive effort and working memory load using scale-invariance and alpha suppression in EEG.

Despite being intuitive, cognitive effort has proven difficult to define quantitatively. Here, we proposed to study cognitive effort by investigating the degree to which the brain deviates from its default state, where brain activity is scale-invariant. Specifically, we measured such deviations by examining changes in scale-invariance of brain activity as a function of task difficulty and posited suppression of scale-invariance as a proxy for exertion of cognitive effort. While there is some fMRI evidence supporting this proposition, EEG investigations on the matter are scant, despite the EEG signal being more suitable for analysis of scale invariance (i.e., having a much broader frequency range). In the current study we validated the correspondence between scale-invariance (H) of cortical activity recorded by EEG and task load during two working memory (WM) experiments with varying set sizes. Then, we used this neural signature to disentangle cognitive effort from the number of items stored in WM within participants. Our results showed monotonic decreases in H with increased set size, even after set size exceeded WM capacity. This behavior of H contrasted with behavioral performance and an oscillatory indicator of WM load (i.e., alpha-band desynchronization), both of which showed a plateau at difficulty levels surpassing WM capacity. This is the first reported evidence for the suppression of scale-invariance in EEG due to task difficulty, and our work suggests that H suppression may be used to quantify changes in cognitive effort even when working memory load is at maximum capacity.

Overt attentional correlates of memorability of scene images and their relationships to scene semantics.

Computer vision-based research has shown that scene semantics (e.g., presence of meaningful objects in a scene) can predict memorability of scene images. Here, we investigated whether and to what extent overt attentional correlates, such as fixation map consistency (also called inter-observer congruency of fixation maps) and fixation counts, mediate the relationship between scene semantics and scene memorability. First, we confirmed that the higher the fixation map consistency of a scene, the higher its memorability. Moreover, both fixation map consistency and its correlation to scene memorability were the highest in the first 2 seconds of viewing, suggesting that meaningful scene features that contribute to producing more consistent fixation maps early in viewing, such as faces and humans, may also be important for scene encoding. Second, we found that the relationship between scene semantics and scene memorability was partially (but not fully) mediated by fixation map consistency and fixation counts, separately as well as together. Third, we found that fixation map consistency, fixation counts, and scene semantics significantly and additively contributed to scene memorability. Together, these results suggest that eye-tracking measurements can complement computer vision-based algorithms and improve overall scene memorability prediction.

Visual cues to fertility are in the eye (movements) of the beholder.

Past work demonstrates that humans behave differently towards women across their menstrual cycles, even after exclusively visual exposure to women's faces. People may look at women's faces differently as a function of women's menstrual cycles. Analyses of participants' scanpaths (eye movement patterns) while they looked at women at different phases of their menstrual cycles revealed that observers exhibit more consistent scanpaths when examining women's faces when women are in a menstrual cycle phase that typically corresponds with peak fertility, whereas they exhibit more variable patterns when looking at women's faces when they are in phases that do not correspond with fertility. A multivariate classifier on participants' scanpaths predicted whether they were looking at the face of a woman in a more typically fertile- versus non-fertile-phase of her menstrual cycle with above-chance accuracy. These findings demonstrate that people look at women's faces differently as a function of women's menstrual cycles, and suggest that people are sensitive to fluctuating visual cues associated with women's menstrual cycle phase.

To search or to like: Mapping fixations to differentiate two forms of incidental scene memory.

We employed eye-tracking to investigate how performing different tasks on scenes (e.g., intentionally memorizing them, searching for an object, evaluating aesthetic preference) can affect eye movements during encoding and subsequent scene memory. We found that scene memorability decreased after visual search (one incidental encoding task) compared to intentional memorization, and that preference evaluation (another incidental encoding task) produced better memory, similar to the incidental memory boost previously observed for words and faces. By analyzing fixation maps, we found that although fixation map similarity could explain how eye movements during visual search impairs incidental scene memory, it could not explain the incidental memory boost from aesthetic preference evaluation, implying that implicit mechanisms were at play. We conclude that not all incidental encoding tasks should be taken to be similar, as different mechanisms (e.g., explicit or implicit) lead to memory enhancements or decrements for different incidental encoding tasks.

Functional brain connectivity predictors of prospective substance use initiation and their environmental correlates.

Background: Early substance use initiation (SUI) places youth at substantially higher risk for later substance use disorders. Furthermore, adolescence is a critical period for the maturation of brain networks, the pace and magnitude of which are susceptible to environmental influences and may shape risk for SUI. Methods: We examined whether patterns of functional brain connectivity during rest (rsFC), measured longitudinally in pre-and-early adolescence, can predict future SUI. In an independent sub-sample, we also tested whether these patterns are associated with key environmental factors, specifically neighborhood pollution and socioeconomic dimensions. We utilized data from the Adolescent Brain Cognitive Development (ABCD) Study®. SUI was defined as first-time use of at least one full dose of alcohol, nicotine, cannabis, or other drugs. We created a control group (N = 228) of participants without SUI who were matched with the SUI group (N = 233) on age, sex, race/ethnicity, and parental income and education. Results: Multivariate analysis showed that whole-brain rsFC prior to SUI during 9-10 and 11-12 years of age successfully differentiated the prospective SUI and control groups. This rsFC signature was expressed more at older ages in both groups, suggesting a pattern of accelerated maturation in the SUI group in the years prior to SUI. In an independent sub-sample (N = 2,854) and adjusted for family socioeconomic factors, expression of this rsFC pattern was associated with higher pollution, but not neighborhood disadvantage. Conclusion: Brain functional connectivity patterns in early adolescence that are linked to accelerated maturation and environmental exposures can predict future SUI in youth.

A subset of brain regions within adult functional connectivity networks demonstrate high reliability across early development.

The human cerebral cortex contains groups of areas that support sensory, motor, cognitive, and affective functions, often categorized as functional networks. These areas show stronger internal and weaker external functional connectivity (FC) and exhibit similar FC profiles within rather than between networks. Previous studies have demonstrated the development of these networks from nascent forms present before birth to their mature, adult-like topography in childhood. However, analyses often still use definitions based on adult functional networks. We aim to assess how this might lead to the misidentification of functional networks and explore potential consequences and solutions. Our findings suggest that even though adult networks provide only a marginally better than-chance description of the infant FC organization, misidentification was largely driven by specific areas. By restricting functional networks to areas showing adult-like network clustering, we observed consistent within-network FC both within and across scans and throughout development. Additionally, these areas were spatially closer to locations with low variability in network identity among adults. Our analysis aids in understanding the potential consequences of using adult networks "as is" and provides guidance for future research on selecting and utilizing functional network models based on the research question and scenario. Highlights: Specialized functional networks in the human cerebral cortex, evident in resting-state fMRI, support sensory, motor, cognitive, and affective functions and evolve throughout the lifespan.Existing studies have focused on age-specific networks for infants, but less on to what extent adult networks can describe infant functional connectivity (FC).Analysis revealed a subset of areas in infants showing adult-like network organization, with within-network FC exhibiting less variation across age and higher reliability across scans.These areas are posited near locations with low variability in functional network identity in adults, suggestive of the relationship between developmental sequence and interindividual variability in functional network organization.

Neighborhood air pollution is negatively associated with neurocognitive maturation in early adolescence.

The ability to maintain focus and process task-relevant information continues developing during adolescence, but the specific physical environmental factors that influence this development remain poorly characterized. One candidate factor is air pollution. Evidence suggests that small particulate matter and NO2 concentrations in the air may negatively impact cognitive development in childhood. We assessed the relationship between neighborhood air pollution and the changes in performance on the n-back task, a test of attention and working memory, in the Adolescent Brain Cognitive Development (ABCD) Study's baseline (ages 9-10) and two-year-follow-up releases (Y2, ages 11-12; n = 5,256). In the behavioral domain, multiple linear regression showed that developmental change in n-back task performance was negatively associated with neighborhood air pollution (ß = -.044, t = -3.11, p = .002), adjusted for covariates capturing baseline cognitive performance of the child, their parental income and education, family conflicts, and their neighborhood's population density, crime rate, perceived safety, and Area Deprivation Index (ADI). The strength of the adjusted association for air pollution was similar to parental income, family conflict, and neighborhood ADI. In the neuroimaging domain, we evaluated a previously published youth cognitive composite Connectome-based Predictive Model (ccCPM), and again found that decreased developmental change in the strength of the ccCPM from pre- to early adolescence was associated with neighborhood air pollution (ß = -.110, t = -2.69, p = .007), adjusted for the covariates mentioned above and head motion. Finally, we found that the developmental change in ccCPM strength was predictive of the developmental change in n-back performance (r = .157, p < .001), and there was an indirect-only mediation where the effect of air pollution on change in n-back performance was mediated by the change in the ccCPM strength (ßindirect effect = -.013, p = .029). In conclusion, neighborhood air pollution is associated with lags in the maturation of youth cognitive performance and decreased strengthening of the brain networks supporting cognitive abilities over time.

Improvements in task performance after practice are associated with scale-free dynamics of brain activity.

Although practicing a task generally benefits later performance on that same task, there are individual differences in practice effects. One avenue to model such differences comes from research showing that brain networks extract functional advantages from operating in the vicinity of criticality, a state in which brain network activity is more scale-free. We hypothesized that higher scale-free signal from fMRI data, measured with the Hurst exponent (H), indicates closer proximity to critical states. We tested whether individuals with higher H during repeated task performance would show greater practice effects. In Study 1, participants performed a dual-n-back task (DNB) twice during MRI (n = 56). In Study 2, we used two runs of n-back task (NBK) data from the Human Connectome Project sample (n = 599). In Study 3, participants performed a word completion task (CAST) across six runs (n = 44). In all three studies, multivariate analysis was used to test whether higher H was related to greater practice-related performance improvement. Supporting our hypothesis, we found patterns of higher H that reliably correlated with greater performance improvement across participants in all three studies. However, the predictive brain regions were distinct, suggesting that the specific spatial H↑ patterns are not task-general.

Socioeconomic resources in youth are linked to divergent patterns of network integration and segregation across the brain's transmodal axis.

Socioeconomic resources (SER) calibrate the developing brain to the current context, which can confer or attenuate risk for psychopathology across the lifespan. Recent multivariate work indicates that SER levels powerfully influence intrinsic functional connectivity patterns across the entire brain. Nevertheless, the neurobiological meaning of these widespread alterations remains poorly understood, despite its translational promise for early risk identification, targeted intervention, and policy reform. In the present study, we leverage the resources of graph theory to precisely characterize multivariate and univariate associations between household SER and the functional integration and segregation (i.e., participation coefficient, within-module degree) of brain regions across major cognitive, affective, and sensorimotor systems during the resting state in 5,821 youth (ages 9-10 years) from the Adolescent Brain Cognitive Development (ABCD) Study. First, we establish that decomposing the brain into profiles of integration and segregation captures more than half of the multivariate association between SER and functional connectivity with greater parsimony (100-fold reduction in number of features) and interpretability. Second, we show that the topological effects of SER are not uniform across the brain; rather, higher SER levels are related to greater integration of somatomotor and subcortical systems, but greater segregation of default mode, orbitofrontal, and cerebellar systems. Finally, we demonstrate that the effects of SER are spatially patterned along the unimodal-transmodal gradient of brain organization. These findings provide critical interpretive context for the established and widespread effects of SER on brain organization, indicating that SER levels differentially configure the intrinsic functional architecture of developing unimodal and transmodal systems. This study highlights both sensorimotor and higher-order networks that may serve as neural markers of environmental stress and opportunity, and which may guide efforts to scaffold healthy neurobehavioral development among disadvantaged communities of youth.

A pattern of cognitive resource disruptions in childhood psychopathology.

The Hurst exponent (H) isolated in fractal analyses of neuroimaging time series is implicated broadly in cognition. Within this literature, H is associated with multiple mental disorders, suggesting that H is transdimensionally associated with psychopathology. Here, we unify these results and demonstrate a pattern of decreased H with increased general psychopathology and attention-deficit/hyperactivity factor scores during a working memory task in 1,839 children. This pattern predicts current and future cognitive performance in children and some psychopathology in 703 adults. This pattern also defines psychological and functional axes associating psychopathology with an imbalance in resource allocation between fronto-parietal and sensorimotor regions, driven by reduced resource allocation to fronto-parietal regions. This suggests the hypothesis that impaired working memory function in psychopathology follows from a reduced cognitive resource pool and a reduction in resources allocated to the task at hand.

BIBSNet: A Deep Learning Baby Image Brain Segmentation Network for MRI Scans.

Objectives: Brain segmentation of infant magnetic resonance (MR) images is vitally important in studying developmental mental health and disease. The infant brain undergoes many changes throughout the first years of postnatal life, making tissue segmentation difficult for most existing algorithms. Here, we introduce a deep neural network BIBSNet (Baby and Infant Brain Segmentation Neural Network), an open-source, community-driven model that relies on data augmentation and a large sample size of manually annotated images to facilitate the production of robust and generalizable brain segmentations. Experimental Design: Included in model training and testing were MR brain images on 84 participants with an age range of 0-8 months (median postmenstrual ages of 13.57 months). Using manually annotated real and synthetic segmentation images, the model was trained using a 10-fold cross-validation procedure. Testing occurred on MRI data processed with the DCAN labs infant-ABCD-BIDS processing pipeline using segmentations produced from gold standard manual annotation, joint-label fusion (JLF), and BIBSNet to assess model performance. Principal Observations: Using group analyses, results suggest that cortical metrics produced using BIBSNet segmentations outperforms JLF segmentations. Additionally, when analyzing individual differences, BIBSNet segmentations perform even better. Conclusions: BIBSNet segmentation shows marked improvement over JLF segmentations across all age groups analyzed. The BIBSNet model is 600x faster compared to JLF and can be easily included in other processing pipelines.

Scale invariance in fNIRS as a measurement of cognitive load.

Scale invariant neural dynamics are a relatively new but effective means of measuring changes in brain states as a result of varied cognitive load and task difficulty. This study tests whether scale invariance (as measured by the Hurst exponent, H) can be used with functional near-infrared spectroscopy (fNIRS) to quantify cognitive load, paving the way for scale-invariance to be measured in a variety of real-world settings. We analyzed H extracted from the fNIRS time series while participants completed an N-back working memory task. Consistent with what has been demonstrated in fMRI, the current results showed that scale-invariance analysis significantly differentiated between task and rest periods as calculated from both oxy- (HbO) and deoxy-hemoglobin (HbR) concentration changes. Results from both channel-averaged H and a multivariate partial least squares approach (Task PLS) demonstrated higher H during the 1-back task than the 2-back task. These results were stronger for H derived from HbR than from HbO. This suggests that scale-free brain states are a robust signature of cognitive load and not limited by the specific neuroimaging modality employed. Further, as fNIRS is relatively portable and robust to motion-related artifacts, these preliminary results shed light on the promising future of measuring cognitive load in real life settings.

Learning Strategies for Contrast-agnostic Segmentation via SynthSeg for Infant MRI data.

Longitudinal studies of infants' brains are essential for research and clinical detection of neurodevelopmental disorders. However, for infant brain MRI scans, effective deep learning-based segmentation frameworks exist only within small age intervals due to the large image intensity and contrast changes that take place in the early postnatal stages of development. However, using different segmentation frameworks or models at different age intervals within the same longitudinal data set would cause segmentation inconsistencies and age-specific biases. Thus, an age-agnostic segmentation model for infants' brains is needed. In this paper, we present "Infant-SynthSeg", an extension of the contrast-agnostic SynthSeg segmentation framework applicable to MRI data of infants at ages within the first year of life. Our work mainly focuses on extending learning strategies related to synthetic data generation and augmentation, with the aim of creating a method that employs training data capturing features unique to infants' brains during this early-stage development. Comparison across different learning strategy settings, as well as a more-traditional contrast-aware deep learning model (nnU-net) are presented. Our experiments show that our trained Infant-SynthSeg models show consistently high segmentation performance on MRI scans of infant brains throughout the first year of life. Furthermore, as the model is trained on ground truth labels at different ages, even labels that are not present at certain ages (such as cerebellar white matter at 1 month) can be appropriately segmented via Infant-SynthSeg across the whole age range. Finally, while Infant-SynthSeg shows consistent segmentation performance across the first year of life, it is outperformed by age-specific deep learning models trained for a specific narrow age range.

Resting-state functional connectivity identifies individuals and predicts age in 8-to-26-month-olds.

Resting-state functional connectivity (rsFC) measured with fMRI has been used to characterize functional brain maturation in typically and atypically developing children and adults. However, its reliability and utility for predicting development in infants and toddlers is less well understood. Here, we use fMRI data from the Baby Connectome Project study to measure the reliability and uniqueness of rsFC in infants and toddlers and predict age in this sample (8-to-26 months old; n = 170). We observed medium reliability for within-session infant rsFC in our sample, and found that individual infant and toddler's connectomes were sufficiently distinct for successful functional connectome fingerprinting. Next, we trained and tested support vector regression models to predict age-at-scan with rsFC. Models successfully predicted novel infants' age within ± 3.6 months error and a prediction R2 = .51. To characterize the anatomy of predictive networks, we grouped connections into 11 infant-specific resting-state functional networks defined in a data-driven manner. We found that connections between regions of the same network-i.e. within-network connections-predicted age significantly better than between-network connections. Looking ahead, these findings can help characterize changes in functional brain organization in infancy and toddlerhood and inform work predicting developmental outcome measures in this age range.

Visual features influence thought content in the absence of overt semantic information.

It has recently been shown that the perception of visual features of the environment can influence thought content. Both low-level (e.g., fractalness) and high-level (e.g., presence of water) visual features of the environment can influence thought content in real-world and experimental settings where these features can make people more reflective and contemplative in their thoughts. It remains to be seen, however, if these visual features retain their influence on thoughts in the absence of overt semantic content, which could indicate a more fundamental mechanism for this effect. In this study, we removed this limitation by creating scrambled edge versions of images, which maintain edge content from the original images but remove scene identification. Nonstraight edge density is one visual feature that has been shown to influence many judgements about objects and landscapes and has also been associated with thoughts of spirituality. We extend previous findings by showing that nonstraight edges retain their influence on the selection of a Spiritual & Life Journey topic after scene-identification removal. These results strengthen the implication of a causal role for the perception of low-level visual features on the influence of higher order cognitive function, by demonstrating that in the absence of overt semantic content, low-level features, such as edges, influence cognitive processes.

Correction to Moore et al. (2020).

Reports an error in "Criterion validity and relationships between alternative hierarchical dimensional models of general and specific psychopathology" by Tyler M. Moore, Antonia N. Kaczkurkin, E. Leighton Durham, Hee Jung Jeong, Malerie G. McDowell, Randolph M. Dupont, Brooks Applegate, Jennifer L. Tackett, Carlos Cardenas-Iniguez, Omid Kardan, Gaby N. Akcelik, Andrew J. Stier, Monica D. Rosenberg, Donald Hedeker, Marc G. Berman and Benjamin B. Lahey (Journal of Abnormal Psychology, Advanced Online Publication, Jul 16, 2020, np). In the article (http://dx.doi.org/10.1037/abn0000601), an acknowledgment is missing from the author note. The missing acknowledgement is included in the erratum. (The following abstract of the original article appeared in record 2020-50590-001.) Psychopathology can be viewed as a hierarchy of correlated dimensions. Many studies have supported this conceptualization, but they have used alternative statistical models with differing interpretations. In bifactor models, every symptom loads on both the general factor and 1 specific factor (e.g., internalizing), which partitions the total explained variance in each symptom between these orthogonal factors. In second-order models, symptoms load on one of several correlated lower-order factors. These lower-order factors load on a second-order general factor, which is defined by the variance shared by the lower-order factors. Thus, the factors in second-order models are not orthogonal. Choosing between these valid statistical models depends on the hypothesis being tested. Because bifactor models define orthogonal phenotypes with distinct sources of variance, they are optimal for studies of shared and unique associations of the dimensions of psychopathology with external variables putatively relevant to etiology and mechanisms. Concerns have been raised, however, about the reliability of the orthogonal specific factors in bifactor models. We evaluated this concern using parent symptom ratings of 9-10 year olds in the ABCD Study. Psychometric indices indicated that all factors in both bifactor and second-order models exhibited at least adequate construct reliability and estimated replicability. The factors defined in bifactor and second-order models were highly to moderately correlated across models, but have different interpretations. All factors in both models demonstrated significant associations with external criterion variables of theoretical and clinical importance, but the interpretation of such associations in second-order models was ambiguous due to shared variance among factors. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Criterion validity and relationships between alternative hierarchical dimensional models of general and specific psychopathology.

[Correction Notice: An Erratum for this article was reported in Vol 129(7) of Journal of Abnormal Psychology (see record 2020-72912-001). In the article (http://dx.doi.org/10.1037/abn0000601), an acknowledgment is missing from the author note. The missing acknowledgement is included in the erratum.] Psychopathology can be viewed as a hierarchy of correlated dimensions. Many studies have supported this conceptualization, but they have used alternative statistical models with differing interpretations. In bifactor models, every symptom loads on both the general factor and 1 specific factor (e.g., internalizing), which partitions the total explained variance in each symptom between these orthogonal factors. In second-order models, symptoms load on one of several correlated lower-order factors. These lower-order factors load on a second-order general factor, which is defined by the variance shared by the lower-order factors. Thus, the factors in second-order models are not orthogonal. Choosing between these valid statistical models depends on the hypothesis being tested. Because bifactor models define orthogonal phenotypes with distinct sources of variance, they are optimal for studies of shared and unique associations of the dimensions of psychopathology with external variables putatively relevant to etiology and mechanisms. Concerns have been raised, however, about the reliability of the orthogonal specific factors in bifactor models. We evaluated this concern using parent symptom ratings of 9-10 year olds in the ABCD Study. Psychometric indices indicated that all factors in both bifactor and second-order models exhibited at least adequate construct reliability and estimated replicability. The factors defined in bifactor and second-order models were highly to moderately correlated across models, but have different interpretations. All factors in both models demonstrated significant associations with external criterion variables of theoretical and clinical importance, but the interpretation of such associations in second-order models was ambiguous due to shared variance among factors. (PsycInfo Database Record (c) 2020 APA, all rights reserved).