Gray matter volume associations in youth with ADHD features of inattention and hyperactivity/impulsivity.

BACKGROUND: Prior research has shown smaller cortical and subcortical gray matter volumes among individuals with attention-deficit/hyperactivity disorder (ADHD). However, neuroimaging studies often do not differentiate between inattention and hyperactivity/impulsivity, which are distinct core features of ADHD. The present study uses an approach to disentangle overlapping variance to examine the neurostructural heterogeneity of inattention and hyperactivity/impulsivity dimensions. METHODS: We analyzed data from 10,692 9- to 10-year-old children from the Adolescent Brain Cognitive Development (ABCD) Study. Confirmatory factor analysis was used to derive factors representing inattentive and hyperactive/impulsive traits. We employed structural equation modeling to examine these factors' associations with gray matter volume while controlling for the shared variance between factors. RESULTS: Greater endorsement of inattentive traits was associated with smaller bilateral caudal anterior cingulate and left parahippocampal volumes. Greater endorsement of hyperactivity/impulsivity traits was associated with smaller bilateral caudate and left parahippocampal volumes. The results were similar when accounting for socioeconomic status, medication, and in-scanner motion. The magnitude of these findings increased when accounting for overall volume and intracranial volume, supporting a focal effect in our results. CONCLUSIONS: Inattentive and hyperactivity/impulsivity traits show common volume deficits in regions associated with visuospatial processing and memory while at the same time showing dissociable differences, with inattention showing differences in areas associated with attention and emotion regulation and hyperactivity/impulsivity associated with volume differences in motor activity regions. Uncovering such biological underpinnings within the broader disorder of ADHD allows us to refine our understanding of ADHD presentations.

Mapping potential pathways from polygenic liability through brain structure to psychological problems across the transition to adolescence.

BACKGROUND: We used a polygenic score for externalizing behavior (extPGS) and structural MRI to examine potential pathways from genetic liability to conduct problems via the brain across the adolescent transition. METHODS: Three annual assessments of child conduct problems, attention-deficit/hyperactivity problems, and internalizing problems were conducted across across 9-13 years of age among 4,475 children of European ancestry in the Adolescent Brain Cognitive DevelopmentSM Study (ABCD Study®). RESULTS: The extPGS predicted conduct problems in each wave (R2 = 2.0%-2.9%). Bifactor models revealed that the extPRS predicted variance specific to conduct problems (R2 = 1.7%-2.1%), but also variance that conduct problems shared with other measured problems (R2 = .8%-1.4%). Longitudinally, extPGS predicted levels of specific conduct problems (R2 = 2.0%), but not their slope of change across age. The extPGS was associated with total gray matter volume (TGMV; R2 = .4%) and lower TGMV predicted both specific conduct problems (R2 = 1.7%-2.1%) and the variance common to all problems in each wave (R2 = 1.6%-3.1%). A modest proportion of the polygenic liability specific to conduct problems in each wave was statistically mediated by TGMV. CONCLUSIONS: Across the adolescent transition, the extPGS predicted both variance specific to conduct problems and variance shared by all measured problems. The extPGS also was associated with TGMV, which robustly predicted conduct problems. Statistical mediation analyses suggested the hypothesis that polygenic variation influences individual differences in brain development that are related to the likelihood of conduct problems during the adolescent transition, justifying new research to test this causal hypothesis.

Psychosocial Characteristics of Women with a Delayed Diagnosis of Turner Syndrome.

OBJECTIVES: To characterize the psychosocial profiles of adult women diagnosed with Turner syndrome before (early diagnosis) and at or after (late diagnosis) 13 years of age. STUDY DESIGN: Women with Turner syndrome ages 22 and older at evaluation (n = 110) participated in a cross-sectional study at the National Institutes of Health. Researchers performed nonparametric and logistic regression analyses to assess early and late diagnosis cohorts on measures of depression, substance use, and perceptions of competence and identity. RESULTS: Of study participants, 47% received a Turner syndrome diagnosis at or after age 13 years. Median age at diagnosis was 12.0 years (range, 0-43). Covariate-adjusted models revealed that women with late diagnoses had an increased likelihood of developing mild to severe depressive symptoms (OR, 7.36) and a decreased likelihood of being perceived as competent (OR, 0.26). Women with a late diagnosis also exhibited more frequent substance use compared with women with early diagnoses. CONCLUSIONS: These data suggest that Turner syndrome diagnoses received at or after age 13 years may contribute to adverse outcomes related to depression, substance use, and perceptions of competence. Delayed Turner syndrome diagnoses may place women and girls at risk for negative psychosocial development extending into adulthood. These findings indicate it is important for pediatricians to evaluate psychosocial domains in girls with Turner syndrome regularly, particularly among those diagnosed at age 13 years or older. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00006334.

Early life stress and functional network topology in children.

Brain networks are continuously modified throughout development, yet this plasticity can also make functional networks vulnerable to early life stress. Little is currently known about the effect of early life stress on the functional organization of the brain. The current study investigated the association between environmental stressors and network topology using data from the Adolescent Brain Cognitive DevelopmentSM (ABCD®) Study. Hierarchical modeling identified a general factor of environmental stress, representing the common variance across multiple stressors, as well as four subfactors including familial dynamics, interpersonal support, neighborhood SES deprivation, and urbanicity. Functional network topology metrics were obtained using graph theory at rest and during tasks of reward processing, inhibition, and affective working memory. The general factor of environmental stress was associated with less specialization of networks, represented by lower modularity at rest. Local metrics indicated that general environmental stress was also associated with less efficiency in the subcortical-cerebellar and visual networks while showing greater efficiency in the default mode network at rest. Subfactors of environmental stress were associated with differences in specialization and efficiency in select networks. The current study illustrates that a wide range of stressors in a child's environment are associated with differences in brain network topology.

Atypical Functional Network Properties and Associated Dimensions of Child Psychopathology During Rest and Task Performance.

Background: When brain networks deviate from typical development, this is thought to contribute to varying forms of psychopathology. However, research has been limited by the reliance on discrete diagnostic categories that overlook the potential for psychological comorbidity and the dimensional nature of symptoms. Methods: This study examined the topology of functional networks in association with 4 bifactor-defined psychopathology dimensions-general psychopathology, internalizing symptoms, conduct problems, and attention-deficit/hyperactivity disorder symptoms-via the Child Behavior Checklist in a sample of 3568 children from the ABCD (Adolescent Brain Cognitive Development) Study. Local and global graph theory metrics were calculated at rest and during tasks of reward processing, inhibition, and working memory. Results: Greater attention-deficit/hyperactivity disorder symptoms were associated with reduced modularity across rest and tasks as well as reduced local efficiency in motor networks at rest. Results survived sensitivity analyses for medication and socioeconomic status. Greater conduct problem symptoms were associated with reduced modularity on working memory and reward processing tasks; however, these results did not persist after sensitivity analyses. General psychopathology and internalizing symptoms showed no significant network associations. Conclusions: Our findings suggest reduced efficiency in topology in those with greater attention-deficit/hyperactivity disorder symptoms across 4 critical cognitive states, with conduct problems also showing network deficits, although less consistently. This may suggest that modularity deficits are a neurobiological marker of externalizing behavior in children. Such specificity has not been demonstrated before using graph theory metrics and has the potential to redefine our understanding of network deficits in children with psychopathology symptoms.

General and Specific Factors of Environmental Stress and Their Associations With Brain Structure and Dimensions of Psychopathology.

Background: Early-life stressors can adversely affect the developing brain. While hierarchical modeling has established the existence of a general factor of psychopathology, no studies have modeled a general factor of environmental stress and related this factor to brain development. Using a large sample of children from the ABCD (Adolescent Brain Cognitive Development) Study, the current study aimed to identify general and specific factors of environmental stress and test their associations with brain structure and psychopathology. Methods: In a sample of 11,878 children, bifactor modeling and higher-order (second-order) modeling identified general and specific factors of environmental stress: family dynamics, interpersonal support, neighborhood socioeconomic status deprivation, and urbanicity. Structural equation modeling was performed to examine associations between these factors and regional gray matter volume (GMV) and cortical thickness as well as general and specific factors of psychopathology. Results: The general environmental stress factor was associated with globally smaller cortical and subcortical GMV as well as thinner cortices across widespread regions. Family dynamics and neighborhood socioeconomic status deprivation were associated with smaller GMV in focal regions. Urbanicity was associated with larger cortical and subcortical GMV and thicker cortices in frontotemporal regions. The environmental factors were associated with psychopathology in the expected directions. The general factors of environmental stress and psychopathology were both predictors of smaller GMV in children, while remaining distinct from each other. Conclusions: This study reveals a unifying model of environmental influences that illustrates the inherent organization of environmental stressors and their relationship to brain structure and psychopathology.

Multivariate analytical approaches for investigating brain-behavior relationships.

Background: Many studies of brain-behavior relationships rely on univariate approaches where each variable of interest is tested independently, which does not allow for the simultaneous investigation of multiple correlated variables. Alternatively, multivariate approaches allow for examining relationships between psychopathology and neural substrates simultaneously. There are multiple multivariate methods to choose from that each have assumptions which can affect the results; however, many studies employ one method without a clear justification for its selection. Additionally, there are few studies illustrating how differences between methods manifest in examining brain-behavior relationships. The purpose of this study was to exemplify how the choice of multivariate approach can change brain-behavior interpretations. Method: We used data from 9,027 9- to 10-year-old children from the Adolescent Brain Cognitive DevelopmentSM Study (ABCD Study®) to examine brain-behavior relationships with three commonly used multivariate approaches: canonical correlation analysis (CCA), partial least squares correlation (PLSC), and partial least squares regression (PLSR). We examined the associations between psychopathology dimensions including general psychopathology, attention-deficit/hyperactivity symptoms, conduct problems, and internalizing symptoms with regional brain volumes. Results: The results of CCA, PLSC, and PLSR showed both consistencies and differences in the relationship between psychopathology symptoms and brain structure. The leading significant component yielded by each method demonstrated similar patterns of associations between regional brain volumes and psychopathology symptoms. However, the additional significant components yielded by each method demonstrated differential brain-behavior patterns that were not consistent across methods. Conclusion: Here we show that CCA, PLSC, and PLSR yield slightly different interpretations regarding the relationship between child psychopathology and brain volume. In demonstrating the divergence between these approaches, we exemplify the importance of carefully considering the method's underlying assumptions when choosing a multivariate approach to delineate brain-behavior relationships.

Gauging facial feature viewing preference as a stable individual trait in autism spectrum disorder.

Eye tracking provides insights into social processing deficits in autism spectrum disorder (ASD), especially in conjunction with dynamic, naturalistic free-viewing stimuli. However, the question remains whether gaze characteristics, such as preference for specific facial features, can be considered a stable individual trait, particularly in those with ASD. If so, how much data are needed for consistent estimations? To address these questions, we assessed the stability and robustness of gaze preference for facial features as incremental amounts of movie data were introduced for analysis. We trained an artificial neural network to create an object-based segmentation of naturalistic movie clips (14 s each, 7410 frames total). Thirty-three high-functioning individuals with ASD and 36 age- and IQ-equated typically developing individuals (age range: 12-30 years) viewed 22 Hollywood movie clips, each depicting a social interaction. As we evaluated combinations of one, three, five, eight, and 11 movie clips, gaze dwell times on core facial features became increasingly stable at within-subject, within-group, and between-group levels. Using a number of movie clips deemed sufficient by our analysis, we found that individuals with ASD displayed significantly less face-centered gaze (centralized on the nose; p < 0.001) but did not significantly differ from typically developing participants in eye or mouth looking times. Our findings validate gaze preference for specific facial features as a stable individual trait and highlight the possibility of misinterpretation with insufficient data. Additionally, we propose the use of a machine learning approach to stimuli segmentation to quickly and flexibly prepare dynamic stimuli for analysis. LAY SUMMARY: Using a data-driven approach to segmenting movie stimuli, we examined varying amounts of data to assess the stability of social gaze in individuals with autism spectrum disorder (ASD). We found a reduction in social fixations in participants with ASD, driven by decreased attention to the center of the face. Our findings further support the validity of gaze preference for face features as a stable individual trait when sufficient data are used.

Cognitive Functioning in Turner Syndrome: Addressing Deficits Through Academic Accommodation.

Background: The cognitive profile of Turner syndrome, a genetic disorder resulting from partial or complete X-chromosome deletion, presents characteristic deficits. Despite this, studies have yet to evaluate how deficits translate into and are compensated for in academic settings. This study seeks to explore cognitive functioning, as well as the accessibility and development of academic accommodations in females with Turner syndrome from adolescence to adulthood. Materials and Methods: This cross-sectional study took place at the National Institutes of Health. Females with Turner syndrome (age range: 10-68; n = 142) were evaluated on need for and procurement of academic accommodations. Cognitive functioning was evaluated in participants aged 20 years and older (n = 101), as per the age validation of the Repeatable Battery for the Assessment of Neuropsychological Status. Data were analyzed using descriptive statistics, one-sample comparisons, and analyses of variance. Results: Females with Turner syndrome scored significantly lower than the normative population on visuospatial (p < 0.001), delayed memory (p < 0.001), and overall (p < 0.001) functioning. About 25.9% of participants reported that accommodations were not needed, despite displaying one or more cognitive deficits. Approximately 12.7% reported needing but not receiving accommodations, however, this is only reported by females 30 years and older; no females aged 10-29 years indicated this discrepancy. Conclusions: Findings suggest that procurement of academic accommodations has increased within recent decades. Still, there is a discrepancy between those displaying cognitive deficits and those receiving academic accommodations. We highlight frequently received accommodations so that students and professionals can target deficits with appropriate accommodations.

Fertility-Dependent Acoustic Variation in Women's Voices Previously Shown to Affect Listener Physiology and Perception.

Previous research demonstrates that listeners perceive women's voices as more attractive when recorded at high compared to low fertility phases of the menstrual cycle. This effect has been repeated with multiple voice recording samples, but one stimuli set has shown particularly robust replications. First collected by Pipitone and Gallup (2008), women were recorded counting from 1-10 on approximately the same day and time once a week for 4 weeks. Repeatedly, studies using these recordings have shown that naturally cycling women recorded at high fertility are rated as more attractive compared to voices of the same women at low fertility. Additionally, these stimuli have been shown to elicit autonomic nervous system arousal and precipitate a rise in testosterone levels among listeners. Although previous studies have examined the acoustic properties of voices across the menstrual cycle, they reach little consensus. The current study evaluates Pipitone and Gallup's voice stimuli from an acoustic perspective, analyzing specific vocal characteristics of both naturally cycling women and women taking hormonal contraceptives. Results show that among naturally cycling women, variation in vocal amplitude (shimmer) was significantly lower in high fertility recordings compared to the women's voices at low fertility. Harmonics-to-noise ratio and variation in voice pitch (jitter) also fluctuated systematically across voices sampled at different times during the menstrual cycle, though these effects were not statistically significant. It is possible that these acoustic changes could account for some of the replicated perceptual, hormonal, and physiological changes documented in prior literature using these voice stimuli.