Neural circuitry underlying sustained attention in healthy adolescents and in ADHD symptomatology

Moment-to-moment reaction time variability on tasks of attention, often quantified by intra-individual response variability (IRV), provides a good indication of the degree to which an individual is vulnerable to lapses in sustained attention. Increased IRV is a hallmark of several disorders of attention, including Attention-Deficit/Hyperactivity Disorder (ADHD). Here, task-based fMRI was used to provide the first examination of how average brain activation and functional connectivity patterns in adolescents are related to individual differences in sustained attention as measured by IRV. We computed IRV in a large sample of adolescents (n=758) across 'Go' trials of a Stop Signal Task (SST). A data-driven, multi-step analysis approach was used to identify networks associated with low IRV (i.e., good sustained attention) and high IRV (i.e., poorer sustained attention). Low IRV was associated with greater functional segregation (i.e., stronger negative connectivity) amongst an array of brain networks, particularly between cerebellum and motor, cerebellum and prefrontal, and occipital and motor networks. In contrast, high IRV was associated with stronger positive connectivity within the motor network bilaterally and between motor and parietal, prefrontal, and limbic networks. Consistent with these observations, a separate sample of adolescents exhibiting elevated ADHD symptoms had increased fMRI activation and stronger positive connectivity within the same motor network denoting poorer sustained attention, compared to a matched asymptomatic control sample. With respect to the functional connectivity signature of low IRV, there were no statistically significant differences in networks denoting good sustained attention between the ADHD symptom group and asymptomatic control group. We propose that sustained attentional processes are facilitated by an array of neural networks working together, and provide an empirical account of how the functional role of the cerebellum extends to cognition in adolescents. This work highlights the involvement of motor cortex in the integrity of sustained attention, and suggests that atypically strong connectivity within motor networks characterizes poor attentional capacity in both typically developing and ADHD symptomatic adolescents

Neural Correlates of Polysubstance Use: Differential and Interactive Effects of Alcohol and Cannabis on the Adolescent Brain

Two of the most commonly used and abused substances by adolescents in the United States are alcohol and cannabis, which are associated with adverse medical and psychiatric outcomes. Alcohol use and cannabis use during adolescence is also associated with an increased risk of alcohol use disorder (AUD) and/or cannabis use disorder (CUD) in adulthood as well as increased likelihood of relapse after successful treatment. Despite this, much of the previous work on the neurobiology of substance use disorders has focused on adult substance use. This work has shown that individuals with AUD and/or CUD show dysfunction within reward processing, emotion processing, and executive functioning neuro-circuitries. In this dissertation, we have utilized the Monetary Incentive Delay (MID), Affective Stroop (aST), and Optimistic Bias (OB) tasks in order to examine dysfunction in these neuro-circuitries related to AUD and CUD symptomatology in a group of adolescents from a residential treatment facility and the surrounding community. The current data indicate that dysfunction in reward processing, emotion processing, and executive functioning neuro-circuitries is associated with AUD symptomatology, primarily within the MID and aST. However, dysfunction in emotion processing and executive functioning neuro-circuitries is associated with CUD neuro-circuitries across all three tasks. Moreover, there are interactive effects of AUD and CUD symptom severity on emotional processing and executive functioning neuro-circuitries within the aST and OB tasks. These data indicate differential and interactive effects of AUD and CUD on various neuro-circuitries within the adolescent brain

Social Cognition in Children with Attention-Deficit/Hyperactivity Disorder

Attention-Deficit/Hyperactivity Disorder (ADHD) is a neurodevelopmental disorder, which impacts behavioral outcomes, including social functioning. Children with ADHD demonstrate impairment across a number of social domains, including aggressive behavior, poor social skills, and higher rates of Oppositional Defiant Disorder compared to typically developing peers. However, the underlying neurocognitive underpinnings of these poor social outcomes are unclear. Furthermore, little is known regarding the impact of ADHD symptomatology on aspects of social cognition. Inattention, hyperactivity, and impulsivity may differentially impact components of social cognition. Determining whether performance on social cognition tasks is predictive of social skills and problem behaviors is also an area with limited research. Therefore, the current study investigated the relationship between behavioral outcomes, social cognition, and ADHD symptomatology. Children with ADHD performed significantly poorer than the control group on measures of affect recognition, pragmatic language, cognitive theory of mind (ToM), and cognitive empathy. Inattention was predictive of performance in these domains, but there was little improvement of the model with the addition of hyperactivity and impulsivity. Pragmatic language, cognitive ToM, and cognitive empathy were predictive of parent ratings of problem and prosocial behaviors. Findings indicate that children with ADHD have difficulty with cognitive, but not affective components of social cognition

Attention-deficit/hyperactivity disorder: An integrated developmental psychopathology and Research Domain Criteria (RDoC) approach

Attention-deficit/hyperactivity disorder (ADHD) is characterized by heterogeneous behaviors and symptoms, developmental trajectories, and treatment response. Isolating intermediate phenotypes that are superior to current DSM-based nosology in order to explain such heterogeneity is integral to enhancing etiological theory, improving clinical assessment, predicting treatment response, and developing tailored treatments. To this end, this review provides an integrated developmental psychopathology and National Institute of Mental Health Research Domain Criteria (RDoC) approach to ADHD. In particular, associations between ADHD and RDoC domains of cognition (specifically working memory) and positive valence (reward anticipation/delay/receipt) are discussed. These domains are examined across behavioral and neurocircuitry levels of analysis and placed within a developmental context via examining associations among RDoC domains, relevant features of ADHD, and environmental correlates implicated across development. Limitations of the existing literature and proposed future directions are explored. Importantly, future work should focus on novel approaches that account for developmental shifts in functioning of relevant RDoC domains over time, as well as further examination of the interaction across RDoC domains and levels of analysis

An Executive Functioning Perspective in Neurofibromatosis Type 1: From ADHD and Autism Spectrum Disorder to Research Domains

Purpose: Neurofibromatosis type 1 (NF1) is a rare monogenic disorder associated with executive function (EF) deficits and heightened risk for attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD). The goal of this paper is to understand how EFs provide a common foundation to understand vulnerabilities for ADHD and ASD within NF1. Methods: A literature review and synthesis was conducted. Results: EF difficulties in working memory, inhibitory control, cognitive flexibility, and planning are evident in NF1, ADHD, and ASD. However, relatively little is known about the heterogeneity of EFs and ADHD and ASD outcomes in NF1. Assessment of ADHD and ASD in NF1 is based on behavioral symptoms without understanding neurobiological contributions. Recent efforts are promoting the use of dimensional and multidisciplinary methods to better understand normal and abnormal behavior, including integrating information from genetics to self-report measures. Conclusion: NF1 is a monogenic disease with well-developed molecular and phenotypic research as well as complementary animal models. NF1 presents an excellent opportunity to advance our understanding of the neurobiological impact of known pathogenic variation in normal and abnormal neural pathways implicated in human psychopathology. EFs are core features of NF1, ADHD, and ASD, and these neurodevelopmental outcomes are highly prevalent in NF1. We propose a multilevel approach for understanding EFs in patients with NF1.This is essential to advance targeted interventions for NF1 patients and to advance the exciting field of research in this condition

Possible Underlying Mechanisms of Hyperactivity in Children with ADHD

Conceptualizations of Attention-Deficit/Hyperactivity Disorder (ADHD) have evolved significantly over the years. Historically, early conceptualizations of ADHD described hyperactivity as the core symptom of the disorder. However, when the third version of the Diagnostic and Statistical Manual of Mental Disorders (DSM) was published (1980), hyperactivity became a specific qualifier of the disorder and was no longer necessary for a diagnosis. Despite this shift in conceptualization of the disorder, there is an abundance of empirical evidence, both recent and historical, supporting the fact that hyperactivity is an enduring and clinically impairing symptom domain in ADHD. Despite having numerous validated instruments available to measure hyperactive behavior, most current models of ADHD are purely neurocognitive in nature and fail to sufficiently account for hyperactive symptoms. The aim of this study was to gain a deeper, more nuanced understanding of hyperactivity in children with ADHD, as many questions remain about the relationships between neuropsychological constructs and hyperactivity. A total of 130 participants with ADHD were enrolled and completed working memory and behavioral inhibition tasks while wearing actigraphs. Results showed that unmedicated children with working memory deficits display significantly higher levels of activity than children without a deficit in this area; however, this relationship was no longer significant after controlling for basic attentional processes. There were no significant relationships between level of hyperactivity and behavioral inhibition. Implications of these findings will be discussed in detail

Effects of exercise on cognitive performance in children and adolescents with ADHD:Potential mechanisms and evidence-based recommendations

Attention Deficit Hyperactivity Disorder (ADHD) is a neurodevelopmental disorder with a complex symptomatology, and core symptoms as well as functional impairment often persist into adulthood. Recent investigations estimate the worldwide prevalence of ADHD in children and adolescents to be ~7%, which is a substantial increase compared to a decade ago. Conventional treatment most often includes pharmacotherapy with central nervous stimulants, but the number of non-responders and adverse effects call for treatment alternatives. Exercise has been suggested as a safe and low-cost adjunctive therapy for ADHD and is reported to be accompanied by positive effects on several aspects of cognitive functions in the general child population. Here we review existing evidence that exercise affects cognitive functions in children with and without ADHD and present likely neurophysiological mechanisms of action. We find well-described associations between physical activity and ADHD, as well as causal evidence in the form of small to moderate beneficial effects following acute aerobic exercise on executive functions in children with ADHD. Despite large heterogeneity, meta-analyses find small positive effects of exercise in population-based control (PBC) children, and our extracted effect sizes from long-term interventions suggest consistent positive effects in children and adolescents with ADHD. Paucity of studies probing the effect of different exercise parameters impedes finite conclusions in this regard. Large-scale clinical trials with appropriately timed exercise are needed. In summary, the existing preliminary evidence suggests that exercise can improve cognitive performance intimately linked to ADHD presentations in children with and without an ADHD diagnosis. Based on the findings from both PBC and ADHD children, we cautiously provide recommendations for parameters of exercise

A Randomized Controlled Trial of an Integrated Brain, Body, and Social Intervention for Children With ADHD

Objective: This study evaluated the efficacy of an Integrated Brain, Body, and Social (IBBS) intervention for children with ADHD. Treatment consisted of computerized cognitive remediation training, physical exercises, and a behavior management strategy. Method: Ninety-two children aged 5 to 9 years with ADHD were randomly assigned to 15 weeks of IBBS or to treatment-as-usual. Primary outcome measures included blinded clinician ratings of ADHD symptoms and global clinical functioning. Secondary outcome measures consisted of parent and teacher ratings of ADHD and neurocognitive tests. Results: No significant treatment effects were found on any of our primary outcome measures. In terms of secondary outcome measures, the IBBS group showed significant improvement on a verbal working memory task; however, this result did not survive correction for multiple group comparisons. Conclusion: These results suggest that expanding cognitive training to multiple domains by means of two training modalities does not lead to generalized improvement of ADHD symptomatology

Boys with conduct problems and callous-unemotional traits: Neural response to reward and punishment and associations with treatment response

abstract: Abnormalities in reward and punishment processing are implicated in the development of conduct problems (CP), particularly among youth with callous-unemotional (CU) traits. However, no studies have examined whether CP children with high versus low CU traits exhibit differences in the neural response to reward and punishment. A clinic-referred sample of CP boys with high versus low CU traits (ages 8–11; n = 37) and healthy controls (HC; n = 27) completed a fMRI task assessing reward and punishment processing. CP boys also completed a randomized control trial examining the effectiveness of an empirically-supported intervention (i.e., Stop-Now-And-Plan; SNAP). Primary analyses examined pre-treatment differences in neural activation to reward and punishment, and exploratory analyses assessed whether these differences predicted treatment outcome. Results demonstrated associations between CP and reduced amygdala activation to punishment independent of age, race, IQ and co-occurring ADHD and internalizing symptoms. CU traits were not associated with reward or punishment processing after accounting for covariates and no differences were found between CP boys with high versus low CU traits. While boys assigned to SNAP showed a greater reduction in CP, differences in neural activation were not associated with treatment response. Findings suggest that reduced sensitivity to punishment is associated with early-onset CP in boys regardless of the level of CU traits