Working memory and inhibitory control deficits in children with ADHD: an experimental evaluation of competing model predictions.

Introduction: Children with ADHD demonstrate difficulties on many different neuropsychological tests. However, it remains unclear whether this pattern reflects a large number of distinct deficits or a small number of deficit(s) that broadly impact test performance. The current study is among the first experiments to systematically manipulate demands on both working memory and inhibition, with implications for competing conceptual models of ADHD pathogenesis. Method: A clinically evaluated, carefully phenotyped sample of 110 children with ADHD, anxiety disorders, or co-occurring ADHD+anxiety (Mage=10.35, 44 girls; 69% White Not Hispanic/Latino) completed a counterbalanced, double dissociation experiment, with two tasks each per inhibition (low vs. high) x working memory (low vs. high) condition. Results: Bayesian and frequentist models converged in indicating that both manipulations successfully increased demands on their target executive function (BF10>5.33x108, p<.001). Importantly, occupying children's limited capacity working memory system produced slower response times and reduced accuracy on inhibition tasks (BF10>317.42, p<.001, d=0.67-1.53). It also appeared to differentially reduce inhibition (and non-inhibition) accuracy for children with ADHD relative to children with anxiety (BF10=2.03, p=.02, d=0.50). In contrast, there was strong evidence against models that view working memory deficits as secondary outcomes of underlying inhibition deficits in ADHD (BF01=18.52, p=.85). Discussion: This pattern indicates that working memory broadly affects children's ability to inhibit prepotent tendencies and maintain fast/accurate performance, and may explain the errors that children with ADHD make on inhibition tests. These findings are broadly consistent with models describing working memory as a causal mechanism that gives rise to secondary impairments. In contrast, these findings provide evidence against models that view disinhibition as a cause of working memory difficulties or view working memory as a non-causal correlate or epiphenomenon in ADHD.

Does Anxiety Systematically Bias Estimates of Executive Functioning Deficits in Pediatric Attention-Deficit/Hyperactivity Disorder?

Growing evidence suggests that childhood ADHD is associated with larger impairments in working memory relative to inhibition. However, most studies have not considered the role of co-occurring anxiety on these estimates - a potentially significant confound given prior evidence that anxiety may increase working memory difficulties but decrease inhibition difficulties for these children. The current study extends prior work to examine the extent to which co-occurring anxiety may be systematically affecting recent estimates of the magnitude of working memory/inhibitory control deficits in ADHD. The carefully-phenotyped sample included 197 children with ADHD and 142 children without ADHD between the ages of 8 and 13 years (N = 339; Mage = 10.31, SD = 1.39; 144 female participants). Results demonstrated that ADHD diagnosis predicted small impairments in inhibitory control (d = 0.31) and large impairments in working memory (d = 0.99). However, child trait anxiety assessed dimensionally across multiple informants (child, parent, teacher) did not uniquely predict either executive function, nor did it moderate estimates of ADHD-related working memory/inhibition deficits. When evaluating anxiety categorically and controlling for ADHD, anxiety diagnosis predicted slightly better working memory (d = 0.19) but not inhibitory control for clinically evaluated children generally. Findings from the current study indicate that trait anxiety, measured dimensionally or categorically, does not differentially affect estimates of executive dysfunction in pediatric ADHD. Further, results suggest that trait anxiety is generally not associated with executive dysfunction above and beyond the impact of co-occurring ADHD. Future research is needed to further assess the role of anxiety in ADHD behavioral symptomatology, neurocognitive functioning, and mechanisms underlying these relations.

A preliminary 'shortlist' of individual, family, and social-community assets to promote resilience in pediatric ADHD.

BACKGROUND: Understanding factors that promote resilience in pediatric ADHD is important though highly understudied. AIMS: The current study sought to provide a preliminary 'shortlist' of key individual, family, and social-community assets among children with ADHD. METHODS AND PROCEDURES: The study included well-characterized, clinically-evaluated samples of children with (n=108) and without ADHD (n=98) ages 8-13 years (M=10.31; 41.3% girls; 66.5% White/Non-Hispanic). All subsets regression and dominance analysis identified the subset of predictors that accounted for the most variance in broad-based resilience for children with ADHD and their relative importance. Findings were compared for children with versus without ADHD as preliminary evidence regarding the extent to which identified assets are promotive, protective, or conditionally helpful. OUTCOMES AND RESULTS: Higher levels of peer acceptance, social skills, and academic performance were top predictors of resilience among children with ADHD. Better child working memory, attention, higher levels of hyperactivity, older age, and fewer parent self-reported mental health concerns were also identified as predictors of resilience in ADHD. Both overlapping and unique factors were associated with resilience for children with versus without ADHD. Conclusions and Results: These results, if replicated, provide a strong preliminary basis for strength-based basic/applied research on key assets that promote resilience in ADHD.

The relation between executive functions, error-related brain activity, and ADHD symptoms in clinically evaluated school-aged children.

Two event-related potentials (ERPs) elicited following errors, the error-related negativity (ERN) and error positivity (Pe), have been proposed to reflect cognitive control, though the specific processes remain debated. Few studies have examined the ERN and Pe's relations with individual differences in cognitive control/executive functioning using well-validated tests administered separately from the inhibition tasks used to elicit the ERN/Pe. Additionally, neurocognitive tests of executive functions tend to strongly predict ADHD symptoms, but the extent to which task-based and EEG-based estimates of executive functioning/cognitive control account for the same variance in ADHD symptoms remains unclear. The current study addressed these limitations by examining relations between the ERN/Pe and three core executive functions (working memory, inhibitory control, set shifting) in a clinically-evaluated sample of 53 children ages 8-12 (Mage = 10.36, SD = 1.42; 77.4% White/Non-Hispanic; 16 girls) with and without ADHD. Results demonstrated that neither the ERN nor Pe were related to overall cognitive control/executive functioning, or to working memory or set shifting specifically (all 95%CIs include 0.0). In contrast, a larger Pe was associated with better-developed inhibitory control (ß=-.35, 95%CI excludes 0.0), but did not capture aspects of inhibitory control that are important for predicting ADHD symptoms. Neither the ERN nor Pe predicted ADHD symptoms (95%CIs include 0.0). Results were generally robust to control for age, sex, SES, ADHD symptom cluster, and anxiety, and emphasize the need for caution when interpreting the ERN/Pe as indices of broad-based cognitive control/executive functioning, as well as using the ERN/Pe to examine cognitive processes contributing to ADHD symptomatology.

[Formula: see text] Does training working memory or inhibitory control produce far-transfer improvements in set shifting for children with ADHD? A randomized controlled trial.

Children with ADHD show impairments in set shifting task performance. However, the limited available evidence suggests that directly training shifting may not improve shifting performance in this population. We hypothesized that this incongruence may be because impairments exhibited by children with ADHD during shifting tasks are due to deficits in other executive functions, as shifting tasks also engage children's working memory and/or inhibitory control abilities. This randomized controlled trial examined the extent to which neurocognitive training of working memory vs. inhibitory control can produce downstream (far-transfer) improvements in set shifting task performance. Children with ADHD ages 8-12 (M = 10.41, SD = 1.46; 12 girls; 74% White/Non-Hispanic) were randomized to either central executive training (CET; n = 25) or inhibitory control training (ICT; n = 29), two next-generation digital therapeutics previously shown to improve their intended neurocognitive targets. Two criterion set shifting tests were administered at pre- and post-treatment. Results indicated that ICT was superior to CET for improving shifting accuracy (treatmentxtime: p = .03, BF10 = 3.01, η2 = .09, d = 0.63). ICT was also superior to CET for improving shifting speed, albeit on only one of the two outcome tasks (p = .02, BF10 = 4.53, η2 = .08, d = 0.59). CET did not produce improvements in shifting speed or accuracy on either task (p > .52, BF01 > 2.62), but showed evidence for more general (non-shifting-specific) improvement in response times on one of the outcome tasks (shift trials, d = 0.70; non-shift trials, d = 0.68). Taken together, these findings confirm that inhibitory control is important for successful performance on shifting tests, and suggest that training inhibitory control may reflect a method for improving set shifting difficulties in children with ADHD.

Does central executive training and/or inhibitory control training improve emotion regulation for children with attention-deficit/hyperactivity disorder? A randomized controlled trial.

Introduction: Approximately 48-54% of children with attention-deficit/hyperactivity disorder (ADHD) have impairing difficulties with emotion regulation, and these difficulties are not ameliorated by first-line ADHD treatments. Working memory and inhibitory control represent promising intervention targets given their functional, if not causal, links with ADHD-related emotion dysregulation. Methods: This preregistered randomized controlled trial tested whether two digital therapeutic training protocols that have been previously shown to improve working memory (Central Executive Training [CET]) and inhibitory control (Inhibitory Control Training [ICT]) can improve emotion regulation in a sample of 94 children with ADHD aged 8-13 years (M = 10.22, SD = 1.43; 76% White/non-Hispanic; 29 girls). Results: Results of Bayesian mixed model ANOVAs indicated both treatment groups demonstrated significant decreases in emotion dysregulation relative to pre-treatment at immediate post-treatment (parent report; d = 1.25, BF10 = 8.04 × 1013, p < 0.001), at 1-2 months after completing treatment (teacher report; d = 0.99, BF10 = 1.22 × 106, p < 0.001), and at 2-4-months follow-up (parent report; d = 1.22, BF10 = 1.15 × 1014, p < 0.001). Contrary to our hypotheses, the CET and ICT groups demonstrated equivalent reductions in emotion dysregulation and maintenance of effects. Exploratory analyses revealed that results were robust to control for informant expectancies, ADHD medication status/changes, in-person vs. at-home treatment, child age, and time from treatment completion to post-treatment ratings. Discussion: To determine whether working memory and inhibitory control are causally linked with ADHD-related emotion dysregulation, future studies should include active control conditions that do not train executive functions prior to making decisions about the clinical utility of CET/ICT for the treatment of emotion dysregulation in ADHD. Clinical trial registration: [https://clinicaltrials.gov/], identifier [NCT03324464].

Are There Resilient Children with ADHD?

OBJECTIVE: The adverse outcomes associated with ADHD are well known, but less is known about the minority of children with ADHD who may be flourishing despite this neurodevelopmental risk. The present multi-informant study is an initial step in this direction with the basic but unanswered question: Are there resilient children with ADHD? METHOD: Reliable change analysis of the BASC-3 Resiliency subscale for a clinically evaluated sample of 206 children with and without ADHD (ages 8-13; 81 girls; 66.5% White/Non-Hispanic). RESULTS: Most children with ADHD are perceived by their parents and teachers as resilient (52.8%-59.2%), with rates that did not differ from the comorbidity-matched Non-ADHD sample. CONCLUSION: Exploratory analyses highlighted the importance of identifying factors that promote resilience for children with ADHD specifically, such that some child characteristics were promotive (associated with resilience for both groups), some were protective (associated with resilience only for children with ADHD), and some were beneficial only for children without ADHD.

Executive Functioning and Emotion Regulation in Children with and without ADHD.

Difficulties with emotion regulation affect the majority of youth with attention-deficit/hyperactivity disorder (ADHD) and predict greater functional impairment than ADHD symptoms alone. Deficits in executive functioning are also present for most children with ADHD, and have been linked with emotion regulation difficulties in both clinical and neurotypical populations throughout development. The current study was the first to assess all three core executive functions (working memory, inhibitory control, set shifting) simultaneously in a clinically-diverse sample of children with and without ADHD and common comorbidities and investigate the extent to which they uniquely predict emotion dysregulation. A sample of 151 children ages 8-13 years (M = 10.36, SD = 1.52; 52 girls; 70.2% White/Non-Hispanic) were assessed using a criterion battery of executive functioning tasks, teacher-reported ADHD symptoms, and parent-reported emotion regulation. Results of the bias-corrected, bootstrapped conditional effects path model revealed that better-developed working memory predicted better emotion regulation (ß = 0.23) and fewer ADHD symptoms (ß = -0.21 to -0.37), that ADHD symptoms (ß = -0.18 to -0.20) independently predicted emotion dysregulation, and that working memory exerted indirect effects on emotion regulation through both inattention and hyperactivity/impulsivity (ß = 0.04-0.07). Sensitivity analyses indicated that these effects were generally robust to control for age, sex, executive function interrelations, and inclusion/exclusion of children with co-occurring ASD. These findings underscore the importance of working memory (relative to inhibitory control and set shifting) and its relations with ADHD symptoms for understanding children's emotion regulation skills, and may help explain the limited efficacy of first-line ADHD treatments, which do not target working memory, for improving emotion regulation skills.

Assessing Irritability in Children with Autism Spectrum Disorder Using the Affective Reactivity Index.

Irritability is an impairing problem in children with ASD that may be associated with other behavioral and emotional concerns. The Affective Reactivity Index (ARI) is a parent-rated measure of irritability widely used in children with mood disorders, however, its utility in children with ASD remains unclear. In this study, we examined ARI parent ratings in children with ASD and contributions of parent-rated anxiety and noncompliance to irritability measured by the ARI. Participants included 81 children with ASD, aged 8-16 years. Results suggest that both anxiety and noncompliance contribute to irritability, but that anxiety only contributes to irritability in the absence of noncompliance. Further, the ARI is likely to be a useful measure of irritability in children with ASD.

Discrepancies between parent and child ratings of anxiety in children with autism spectrum disorder.

Co-occurring anxiety is common in children with autism spectrum disorder (ASD). However, inconsistencies across parent and child reports of anxiety may complicate the assessment of anxiety in this population. The present study examined parent and child anxiety ratings in children with ASD with and without anxiety disorders and tested the association between parent-child anxiety rating discrepancy and ASD symptom severity. Participants included children aged 8-16 years in three diagnostic groups: ASD with co-occurring anxiety disorders (ASD + Anxiety; n = 34), ASD without co-occurring anxiety disorders (ASD; n = 18), and typically developing healthy controls (TD; n = 50). Parents and children completed ratings of child anxiety using the Multidimensional Anxiety Rating Scale. Patterns of parent and child anxiety ratings differed among the three groups, with parent ratings exceeding child ratings only in the ASD + Anxiety group. Parents reported higher levels of child anxiety in the ASD + Anxiety versus ASD group, whereas children reported comparable levels of anxiety in the two groups. Among children with ASD, ASD symptom severity was positively associated with the degree to which parent ratings exceeded child ratings. Results suggest that children with ASD and co-occurring anxiety disorders endorse some anxiety symptoms but may underreport overall levels of anxiety. In addition, ASD symptom severity might increase discrepancies in parent-child anxiety ratings. These findings suggest a unique and valuable role of child anxiety ratings and suggest that both parent and child anxiety ratings should be considered in light of children's ASD symptom severity and used to guide further assessment. Autism Res 2020, 13: 93-103. © 2019 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: Children with autism spectrum disorder (ASD) commonly experience anxiety; yet, their perceptions of their anxiety might differ from their parents' perceptions. This study found that, while children with ASD and anxiety disorders acknowledge some anxiety, their parents report them as having higher levels of anxiety. Also, child and parent perceptions of anxiety may differ more for children with more severe ASD symptoms. How these findings may guide research and clinical practice is discussed.

Anger Rumination is Associated with Restricted and Repetitive Behaviors in Children with Autism Spectrum Disorder.

Children with autism spectrum disorder (ASD) are reported to have greater levels of anger rumination than typically developing children. This study examined anger rumination in children with ASD in comparison to children with disruptive behavior disorder without ASD. We also tested if anger rumination is associated with aggression and the core ASD symptoms of restricted and repetitive behaviors (RRBs). This study included three groups of children aged 8-16 years: 63 had ASD (ASD group), 79 had disruptive behavior disorder (DB group), and 40 healthy controls (HC). ASD and DB groups showed greater anger rumination relative to the HC group. Anger rumination was associated with RRBs in children with ASD, suggesting the link to core ASD symptoms.