Cumulative Effects of Resting-State Connectivity Across All Brain Networks Significantly Correlate with Attention-Deficit Hyperactivity Disorder Symptoms.

Identification of replicable neuroimaging correlates of attention-deficit hyperactivity disorder (ADHD) has been hindered by small sample sizes, small effects, and heterogeneity of methods. Given evidence that ADHD is associated with alterations in widely distributed brain networks and the small effects of individual brain features, a whole-brain perspective focusing on cumulative effects is warranted. The use of large, multisite samples is crucial for improving reproducibility and clinical utility of brain-wide MRI association studies. To address this, a polyneuro risk score (PNRS) representing cumulative, brain-wide, ADHD-associated resting-state functional connectivity was constructed and validated using data from the Adolescent Brain Cognitive Development (ABCD, N = 5,543, 51.5% female) study, and was further tested in the independent Oregon-ADHD-1000 case-control cohort (N = 553, 37.4% female). The ADHD PNRS was significantly associated with ADHD symptoms in both cohorts after accounting for relevant covariates (p < 0.001). The most predictive PNRS involved all brain networks, though the strongest effects were concentrated among the default mode and cingulo-opercular networks. In the longitudinal Oregon-ADHD-1000, non-ADHD youth had significantly lower PNRS (Cohen's d = -0.318, robust p = 5.5 × 10-4) than those with persistent ADHD (age 7-19). The PNRS, however, did not mediate polygenic risk for ADHD. Brain-wide connectivity was robustly associated with ADHD symptoms in two independent cohorts, providing further evidence of widespread dysconnectivity in ADHD. Evaluation in enriched samples demonstrates the promise of the PNRS approach for improving reproducibility in neuroimaging studies and unraveling the complex relationships between brain connectivity and behavioral disorders.

Joint polygenic and environmental risks for childhood attention-deficit/hyperactivity disorder (ADHD) and ADHD symptom dimensions.

Background: attention-deficit/hyperactivity disorder (ADHD) is associated with both polygenic liability and environmental exposures, both intrinsic to the family, such as family conflict, and extrinsic, such as air pollution. However, much less is known about the interplay between environmental and genetic risks relevant to ADHD-a better understanding of which could inform both mechanistic models and clinical prediction algorithms. Methods: Two independent data sets, the population-based Adolescent Brain Cognitive Development Study (ABCD) (N = 11,876) and the case-control Oregon-ADHD-1000 (N = 1449), were used to examine additive (G + E) and interactive (GxE) effects of selected polygenic risk scores (PRS) and environmental factors in a cross-sectional design. Genetic risk was measured using PRS for nine mental health disorders/traits. Exposures included family income, family conflict/negative sentiment, and geocoded measures of area deprivation, lead exposure risk, and air pollution exposure (nitrogen dioxide and fine particulate matter). Results: ADHD PRS and family conflict jointly predicted concurrent ADHD symptoms in both cohorts. Additive-effects models, including both genetic and environmental factors, explained significantly more variation in symptoms than any individual factor alone (joint R 2 = .091 for total symptoms in ABCD; joint R 2 = .173 in Oregon-ADHD-1000; all delta-R 2 p-values <2e-7). Significant effect size heterogeneity across ancestry groups was observed for genetic and environmental factors (e.g., Q = 9.01, p = .011 for major depressive disorder PRS; Q = 13.34, p = .001 for area deprivation). GxE interactions observed in the full ABCD cohort suggested stronger environmental effects when genetic risk is low, though they did not replicate. Conclusions: Reproducible additive effects of PRS and family environment on ADHD symptoms were found, but GxE interaction effects were not replicated and appeared confounded by ancestry. Results highlight the potential value of combining exposures and PRS in clinical prediction algorithms. The observed differences in risks across ancestry groups warrant further study to avoid health care disparities.

Youth Polygenic Scores, Youth ADHD Symptoms, and Parenting Dimensions: An Evocative Gene-Environment Correlation Study.

Parenting practices and parental symptoms of attention-deficit/hyperactivity disorder (ADHD) have been linked to severity and course of youth ADHD. However, genetically influenced behaviors related to ADHD in youth may also influence parenting behaviors. Polygenic scores (PGS) have been widely used to quantify genetic vulnerability for ADHD but has rarely been used to examine gene-environment correlation effects. The current study examined the direct effects of youth ADHD PGS and its evocative effects on parenting behaviors via youth ADHD symptoms. 803 youth aged 6-18 years (58.5% male) completed a multistage, multi-informant assessment that included measures of parenting practices and youth and parental ADHD symptoms. A mediation model was used to evaluate direct and evocative effects. Furthermore, we examined if these evocative effects remain after controlling for parental ADHD symptoms. Sensitivity analyses across age, sex, and socioeconomic status (SES) as well as restricting ancestry groups to European only ancestry were also conducted. Results indicated that youth ADHD PGS reliably predicted youth ADHD symptoms across all models (ßs ranging from 0.18 to 0.26), including across age, sex, and SES and held even with ancestry restricted to the largest group (northern European). Evocative effects emerged such that higher youth PGS significantly predicted more youth ADHD symptoms, which in turn, significantly predicted lower levels of parental involvement and higher levels of poor supervision/monitoring and inconsistent discipline. These effects remained after controlling for parent ADHD symptoms.

Statistical word segmentation: Anchoring learning across contexts.

The present experiments were designed to assess infants' abilities to use syllable co-occurrence regularities to segment fluent speech across contexts. Specifically, we investigated whether 9-month-old infants could use statistical regularities in one speech context to support speech segmentation in a second context. Contexts were defined by different word sets representing contextual differences that might occur across conversations or utterances. This mimics the integration of information across multiple interactions within a single language, which is critical for language acquisition. In particular, we performed two experiments to assess whether a statistically segmented word could be used to anchor segmentation in a second, more challenging context, namely speech with variable word lengths. The results of Experiment 1 were consistent with past work suggesting that statistical learning may be hindered by speech with word-length variability, which is inherent to infants' natural speech environments. In Experiment 2, we found that infants could use a previously statistically segmented word to support word segmentation in a novel, challenging context. We also present findings suggesting that this ability was associated with infants' early word knowledge but not their performance on a cognitive development assessment.

Prospective prediction of developing internalizing disorders in ADHD.

BACKGROUND: Clinical course in attention-deficit/hyperactivity disorder (ADHD) is highly heterogeneous with respect to both core symptoms and associated features and impairment. Onset of comorbid anxiety and mood disorders during later childhood and adolescence is one critical aspect of divergent outcomes in ADHD. Characterizing heterogeneity in onset of anxiety and depression and identifying prospective predictors of these divergent courses may facilitate early identification of the children most at risk. METHODS: A total of 849 children recruited for a case-control study of ADHD development, aged 7-12 years at baseline, completed up to six annual waves of comprehensive clinical and cognitive assessment, including multi-informant behavior ratings, parent semi-structured clinical diagnostic interviews, and measures of executive function (EF). Latent class growth curve analyses (LCGAs) characterized patterns of anxiety and depression over time. Trajectories were predicted from baseline parent-rated child temperament, lab-measured child EF, coded parental criticism, and child-reported self-blame for inter-parental conflict. RESULTS: Latent class growth curve analyses separately identified three trajectories for anxiety and three for depression: persistently high, persistently low, and increasing. Temperamental fear/sadness and irritability were independent predictors that interacted with family characteristics. Baseline parental criticism and self-blame for inter-parental conflict exerted influence but only in the context of low temperamental risk. Better baseline child working memory was associated with delayed onset of depression. CONCLUSIONS: The interaction of baseline child emotional features with EF or family environment predicted divergent courses of both anxiety and depression from middle-childhood to mid-adolescence. Results suggest modifiable risk factors associated with prospective differences in long-term outcomes.

Temperament in middle childhood questionnaire: New data on factor structure and applicability in a child clinical sample.

The Temperament in Middle Childhood Questionnaire (TMCQ) is one of a family of instruments representing one of the major conceptual models of child temperament. The present study reports new psychometric information on the TMCQ using a larger sample than in prior factor-analytic studies of this instrument. Data from parent ratings of 1,418 children were utilized. The sample of community volunteers included 697 typically developing youth and 721 defined by research diagnostic procedures as having attention-deficit/hyperactivity disorder. Results failed to support the original proposed structure of the TMCQ, but found support for a structure with 12 subscales that confirmed a substantial portion of the lower order factor structure. However, the intended three-factor higher order structure was not able to be fully recovered. Two-group invariance was supported in the final model, supporting use in studies of typical and atypical development. In conclusion, with some modifications the TMCQ remains a useful research measure at the lower order factor level. The validity of the higher order structure is less clear, likely due to measure-specific limitations, and suggests a need for some refinement to the measure. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Attention-Deficit/Hyperactivity Disorder: Restricted Phenotypes Prevalence, Comorbidity, and Polygenic Risk Sensitivity in the ABCD Baseline Cohort.

OBJECTIVE: To evaluate the prevalence and major comorbidities of ADHD using different operational definitions in a newly available national dataset and to test the utility of operational definitions against genetic and cognitive correlates. METHOD: The US Adolescent Brain Cognitive Development (ABCD) Study enrolled 11,878 children aged 9-10 years at baseline. ADHD prevalence, comorbidity, and association with polygenic risk score and laboratory-assessed executive functions were calculated at 4 thresholds of ADHD phenotype restrictiveness. Bias from missingness, sampling, and nesting were addressed statistically. RESULTS: Prevalence of current ADHD for 9- to 10-year old children was 3.53% (95% CI 3.14%-3.92%) when Computerized Schedule for Affective Disorders and Schizophrenia for School-Age Children (K-SADS-COMP) score and parent and teacher ratings were required to converge. Of ADHD cases so defined, 70% had a comorbid psychiatric disorder. After control for overlapping comorbidity and ruling out for psychosis or low IQ, 30.9% (95% CI 25.7%-36.7%) had a comorbid disruptive behavior disorder, 27.4% (95% CI 22.3%-33.1%) had an anxiety or fear disorder, and 2.1% (95% CI 1.2%-3.8%) had a mood disorder. Children in the top decile of polygenic load incurred a 63% increased chance of having ADHD vs the bottom half of polygenic load (p < .01)-an effect detected only with a stringent phenotype definition. Dimensional latent variables for irritability, externalizing, and ADHD yielded convergent results for cognitive correlates. CONCLUSION: This fresh estimate of national prevalence of ADHD in the United States suggests that the DSM-5 definition requiring multiple informants yields a prevalence of about 3.5%. Results may inform further ADHD studies in the ABCD sample.

Electroencephalogram aperiodic power spectral slope can be reliably measured and predicts ADHD risk in early development.

The aperiodic exponent of the electroencephalogram (EEG) power spectrum has received growing attention as a physiological marker of neurodevelopmental psychopathology, including attention-deficit/hyperactivity disorder (ADHD). However, its use as a marker of ADHD risk across development, and particularly in very young children, is limited by unknown reliability, difficulty in aligning canonical band-based measures across development periods, and unclear effects of treatment in later development. Here, we investigate the internal consistency of the aperiodic EEG power spectrum slope and its association with ADHD risk in both infants (n = 69, 1-month-old) and adolescents (n = 262, ages 11-17 years). Results confirm good to excellent internal consistency in infancy and adolescence. In infancy, a larger aperiodic exponent was associated with greater family history of ADHD. In contrast, in adolescence, ADHD diagnosis was associated with a smaller aperiodic exponent, but only in children with ADHD who had not received stimulant medication treatment. Results suggest that disruptions in cortical development associated with ADHD risk may be detectable shortly after birth via this approach. Together, findings imply a dynamic developmental shift in which the developmentally normative flattening of the EEG power spectrum is exaggerated in ADHD, potentially reflecting imbalances in cortical excitation and inhibition that could contribute to long-lasting differences in brain connectivity.

Longitudinal network model of the co-development of temperament, executive functioning, and psychopathology symptoms in youth with and without ADHD.

Attention Deficit Hyperactivity Disorder (ADHD) is a common, chronic, and impairing disorder, yet presentations of ADHD and clinical course are highly heterogeneous. Despite substantial research efforts, both (a) the secondary co-occurrence of ADHD and complicating additional clinical problems and (b) the developmental pathways leading toward or away from recovery through adolescence remain poorly understood. Resolving these requires accounting for transactional influences of a large number of features across development. Here, we applied a longitudinal cross-lagged panel network model to a multimodal, multilevel dataset in a well-characterized sample of 488 children (nADHD=296) to test Research Domain Criteria initiative-inspired hypotheses about transdiagnostic risk. Network features included DSM symptoms, trait-based ratings of emotional functioning (temperament), and performance-based measures of cognition. Results confirmed that ADHD symptom domains, temperamental Irritability, and Working Memory are independent transdiagnostic risk factors for psychopathology based on their direct associations with other features across time. ADHD symptoms and working memory each had direct, independent associations with depression. Results also demonstrated tightly linked co-development of ADHD symptoms and temperamental Irritability, consistent with the possibility that this type of anger dysregulation is a core feature that is co-expressed as part of the ADHD phenotype for some children.

Selectivity in bilingual nonspeech label learning.

This research investigates selectivity in word learning for bilingual infants. Previous work demonstrated that bilingual infants show greater openness to non-native language sounds in object labels than monolinguals (Hay et al., 2015; Singh, 2018). It remains unclear whether bilingual openness extends to nonspeech sounds. We presented 14- and 19-month-old bilinguals with object labels consisting of nonspeech tones. Monolinguals recently displayed learning of the same labels at 14 months, but not 19 months (Graf Estes et al., 2018). In contrast, bilinguals failed to learn the labels. We propose that hearing phonological variation across two languages helps bilinguals reject nonspeech word forms.

One language or two? Navigating cross-language conflict in statistical word segmentation.

Bilingual infants must navigate the similarities and differences between their languages to achieve native proficiency in childhood. Bilinguals learning to find individual words in fluent speech face the possibility of conflicting cues to word boundaries across their languages. Despite this challenge, bilingual infants typically begin to segment and learn words in both languages around the same time as monolinguals. It is possible that early bilingual experience may support infants' abilities to track regularities relevant for word segmentation separately across their languages. In a dual speech stream statistical word segmentation task, we assessed whether 16-month-old infants could track syllable co-occurrence regularities in two artificial languages despite conflicting information across the languages. We found that bilingual, but not monolingual, infants were able to segment the dual speech streams using statistical regularities. Although the two language groups did not differ on secondary measures of cognitive and linguistic development, bilingual infants' real-world experience with bilingual speakers was predictive of their performance in the dual language statistical segmentation task.

Specificity of representations in infants' visual statistical learning.

Past work has demonstrated infants' robust statistical learning across visual and auditory modalities. However, the specificity of representations produced via visual statistical learning has not been fully explored. The current study addressed this by investigating infants' abilities to identify previously learned object sequences when some object features (e.g., shape, face) aligned with prior learning and other features did not. Experiment 1 replicated past work demonstrating that infants can learn statistical regularities across sequentially presented objects and extended this finding to 16-month-olds. In Experiment 2, infants viewed test sequences in which one object feature (e.g., face) had been removed but the other feature (e.g., shape) was maintained, resulting in failure to identify familiar sequences. We further probed learning specificity by assessing infants' recognition of sequences when one feature was altered rather than removed (Experiment 3) and when one feature was uncorrelated with the original sequence structure (Experiment 4). In both cases, infants failed to identify sequences in which object features were not identical between learning and test. These findings suggest that infants are limited in their ability to generalize the statistical structure of an object sequence when the objects' features do not align between learning and test.

Learning across languages: bilingual experience supports dual language statistical word segmentation.

Bilingual acquisition presents learning challenges beyond those found in monolingual environments, including the need to segment speech in two languages. Infants may use statistical cues, such as syllable-level transitional probabilities, to segment words from fluent speech. In the present study we assessed monolingual and bilingual 14-month-olds' abilities to segment two artificial languages using transitional probability cues. In Experiment 1, monolingual infants successfully segmented the speech streams when the languages were presented individually. However, monolinguals did not segment the same language stimuli when they were presented together in interleaved segments, mimicking the language switches inherent to bilingual speech. To assess the effect of real-world bilingual experience on dual language speech segmentation, Experiment 2 tested infants with regular exposure to two languages using the same interleaved language stimuli as Experiment 1. The bilingual infants in Experiment 2 successfully segmented the languages, indicating that early exposure to two languages supports infants' abilities to segment dual language speech using transitional probability cues. These findings support the notion that early bilingual exposure prepares infants to navigate challenging aspects of dual language environments as they begin to acquire two languages.

Intersecting Constraints on Label Learning: Effects of Age, Label Properties, and Referential Context.

This research investigates the development of constraints in word learning. Previous experiments have shown that as infants gain more knowledge of native language structure, they become more selective about the forms that they accept as labels. However, the developmental pattern exhibited depends greatly on the way that infants are introduced to the labels and tested. In a series of experiments, we examined how providing referential context in the form of familiar objects and familiar object names affects how infants learn labels that they would otherwise reject, nonspeech sounds. We found evidence of the development of intersecting constraints: Younger infants (14-month-olds) were more open to learning nonspeech tone labels than older infants (19-month-olds), and younger infants were more open to the influence of referential context. These findings suggest that infants form expectations about labels and labeling contexts as they become more sophisticated learners.