Joel T. Nigg

Validity of the executive function theory of attention-deficit/ hyperactivity disorder: A meta-analytic review

One of the most prominent neuropsychologic theories of attention-deficit/hyperactivity disorder (ADHD) suggests that its symptoms arise from a primary deficit in executive functions (EF), defined as neurocognitive processes that maintain an appropriate problem-solving set to attain a later goal. To examine the validity of the EF theory, we conducted a meta-analysis of 83 studies that administered EF measures to groups with ADHD (total N = 3734) and without ADHD (N = 2969). Groups with ADHD exhibited significant impairment on all EF tasks. Effect sizes for all measures fell in the medium range (.46-.69), but the strongest and most consistent effects were obtained on measures of response inhibition, vigilance, working memory, and planning. Weaknesses in EF were significant in both clinic-referred and community samples and were not explained by group differences in intelligence, academic achievement, or symptoms of other disorders. ADHD is associated with significant weaknesses in several key EF domains. However, moderate effect sizes and lack of universality of EF deficits among individuals with ADHD suggest that EF weaknesses are neither necessary nor sufficient to cause all cases of ADHD. Difficulties with EF appear to be one important component of the complex neuropsychology of ADHD.

On inhibition/disinhibition in developmental psychopathology : Views from cognitive and personality psychology and a working inhibition taxonomy

Disinhibition is a common focus in psychopathology research. However, use of inhibition models often is piecemeal, lacking an overarching taxonomy of inhibitory processes. The author organizes key concepts and models pertaining to different kinds of inhibitory control from the cognitive and temperament/personality literatures. Within the rubrics of executive inhibitory processes, motivational inhibitory processes, and automatic attentional inhibition processes, 8 kinds of inhibition are distinguished. Three basic temperament traits may address key executive and motivational inhibitory processes. Future developmental psychopathology research should be based on a systematic conceptual taxonomy of the kinds of inhibitory function relevant to a given disorder. Such an approach can clarify which inhibition distinctions are correct and which inhibition deficits go with which disorders.

Is ADHD a disinhibitory disorder

Attention deficit hyperactivity disorder (ADHD) is widely theorized to stem from dysfunctional inhibitory processes. However, the definition of inhibition is imprecisely distinguished across theories. To clarify the evidence for this conception, the author relies on a heuristic distinction between inhibition that is under executive control and inhibition that is under motivational control (anxiety or fear). It is argued that ADHD is unlikely to be due to a motivational inhibitory control deficit, although suggestions are made for additional studies that could overturn that conclusion. Evidence for a deficit in an executive motor inhibition process for the ADHD combined type is more compelling but is not equally strong for all forms of executive inhibitory control. Remaining issues include specificity to ADHD, whether inhibitory problems are primary or secondary in causing ADHD, role of comorbid anxiety and conduct disorder, and functional deficits in the inattentive ADHD subtype.

The autism brain imaging data exchange: towards a large-scale evaluation of the intrinsic brain architecture in autism

Autism spectrum disorders (ASDs) represent a formidable challenge for psychiatry and neuroscience because of their high prevalence, lifelong nature, complexity and substantial heterogeneity. Facing these obstacles requires large-scale multidisciplinary efforts. Although the field of genetics has pioneered data sharing for these reasons, neuroimaging had not kept pace. In response, we introduce the Autism Brain Imaging Data Exchange (ABIDE)—a grassroots consortium aggregating and openly sharing 1112 existing resting-state functional magnetic resonance imaging (R-fMRI) data sets with corresponding structural MRI and phenotypic information from 539 individuals with ASDs and 573 age-matched typical controls (TCs; 7–64 years) (http://fcon_1000.projects.nitrc.org/indi/abide/). Here, we present this resource and demonstrate its suitability for advancing knowledge of ASD neurobiology based on analyses of 360 male subjects with ASDs and 403 male age-matched TCs. We focused on whole-brain intrinsic functional connectivity and also survey a range of voxel-wise measures of intrinsic functional brain architecture. Whole-brain analyses reconciled seemingly disparate themes of both hypo- and hyperconnectivity in the ASD literature; both were detected, although hypoconnectivity dominated, particularly for corticocortical and interhemispheric functional connectivity. Exploratory analyses using an array of regional metrics of intrinsic brain function converged on common loci of dysfunction in ASDs (mid- and posterior insula and posterior cingulate cortex), and highlighted less commonly explored regions such as the thalamus. The survey of the ABIDE R-fMRI data sets provides unprecedented demonstrations of both replication and novel discovery. By pooling multiple international data sets, ABIDE is expected to accelerate the pace of discovery setting the stage for the next generation of ASD studies.

An integrative theory of attention-deficit/ hyperactivity disorder based on the cognitive and affective neurosciences

Attention-deficit/hyperactivity disorder (ADHD) is a behavioral syndrome that arises in early childhood, often co-occurs with conduct disorder and leads, developmentally, to antisocial behavior and substance abuse. Models from cognitive and affective neuroscience have been invoked in an effort to understand the development of ADHD, leading to a broad array of interrelated theories and hypothesized mechanisms. In this paper, we highlight core mechanisms that may cut across several theories and constructs, and thus provide some leverage for further study and conceptualization from a neuroscience perspective. We emphasize the joint operations of frontostriatal and frontocerebellar neural loops in detecting and predicting what and when important events in the environment will occur and their interaction with frontoamygdala loops in assigning emotional significance to these events. We note that weaknesses in the development of these basic operations could lead to decrement in the development of cognitive and affective control and other mental operations mediated by prefrontal cortex during development. In turn, such decrement could lead to many of the phenotypic cognitive and neuropsychological features seen in children with ADHD.

Neuropsychologic Theory and Findings in Attention-Deficit/Hyperactivity Disorder: The State of the Field and Salient Challenges for the Coming Decade

The past decade has witnessed the establishment of several now well-replicated findings in the neuropsychology of attention-deficit/hyperactivity disorder (ADHD), which have been confirmed by meta-analyses. Progress has been notable from the importing of cognitive science and neuroscience paradigms. Yet these findings point to many neural networks being involved in the syndrome and to modest effect sizes suggesting that any one neuropsychologic deficit will not be able to explain the disorder. In this article, leading theories and key findings are briefly reviewed in four key domains: attention, executive functions, state regulation and motivation, and temporal information processing. Key issues facing the field of neuropsychologic research and theory in ADHD include 1) the need for more integrative developmental accounts that address both multiple neural systems and the socialization processes that assure their development; 2) consideration of multiple models/measures in the same study so as to examine relative contributions, within-group heterogeneity, and differential deficit; and 3) better integration of cognitive process models with affective and temperament theories so that early precursors to ADHD can be better understood. Overall, the field has witnessed notable progress as it converges on an understanding of ADHD in relation to disruption of a multicomponent self-regulatory system. The next era must articulate multipathway, multilevel developmental accounts of ADHD that incorporate neuropsychologic effects.

Etiologic Subtypes of Attention-Deficit/Hyperactivity Disorder: Brain Imaging, Molecular Genetic and Environmental Factors and the Dopamine Hypothesis

Multiple theories of Attention-Deficit/Hyper- activity Disorder (ADHD) have been proposed, but one that has stood the test of time is the dopamine deficit theory. We review the narrow literature from recent brain imaging and molecular genetic studies that has improved our understanding of the role of dopamine in manifestation of symptoms of ADHD, performance deficits on neuropsychological tasks, and response to stimulant medication that constitutes the most common treatment of this disorder. First, we consider evidence of the presence of dopamine deficits based on the recent literature that (1) confirms abnormalities in dopamine-modulated frontal-striatal circuits, reflected by size (smaller-than-average components) and function (hypoactivation); (2) clarifies the agonist effects of stimulant medication on dopaminergic mechanisms at the synaptic and circuit level of analysis; and (3) challenges the most-widely accepted ADHD-related neural abnormality in the dopamine system (higher-than-normal dopamine transporter [DAT] density). Second, we discuss possible genetic etiologies of dopamine deficits based on recent molecular genetic literature, including (1) multiple replications that confirm the association of ADHD with candidate genes related to the dopamine receptor D4 (DRD4) and the DAT; (2) replication of differences in performance of neuropsychological tasks as a function of the DRD4 genotype; and (3) multiple genome-wide linkage scans that demonstrate the limitations of this method when applied to complex disorders but implicate additional genes that may contribute to the genetic basis of ADHD. Third, we review possible environmental etiologies of dopamine deficits based on recent studies of (1) toxic substances that may affect the dopamine system in early development and contribute substantially to the etiology of ADHD; (2) fetal adaptations in dopamine systems in response to stress that may alter early development with lasting effects, as proposed by the developmental origins of health and disease hypothesis; and (3) gene-environment interactions that may moderate selective damage or adaptation of dopamine neurons. Based on these reviews, we identify critical issues about etiologic subtypes of ADHD that may involve dopamine, discuss methods that could be used to address these issues, and review old and new theories that may direct research in this area in the future.

Neuropsychological executive functions and DSM-IV ADHD subtypes.

OBJECTIVE To evaluate and compare a focused set of component neuropsychological executive functions in the DSM-IV attention-deficit/hyperactivity disorder combined (ADHD-C) and inattentive (ADHD-I) subtypes. METHOD The Stop task, Tower of London, Stroop task, Trailmaking Test, and output speed measures were completed by 105 boys and girls aged 7-12 classified as either DSM-IV ADHD-C (n = 46), ADHD-I (n = 18), or community control (n = 41). RESULTS Both subtypes had deficits on output speed. A group x gender interaction was observed on the Stop task: boys with ADHD-C were impaired versus boys with ADHD-I, whereas girls in the two subtypes did not differ. The ADHD-C type had a deficit in planning. Neither ADHD group had a deficit in interference control per se, although they were slower than controls on the Stroop tasks. CONCLUSIONS ADHD-I shares neuropsychological deficits with ADHD-C in the domain of output speed; on most domains the subtypes did not differ. Neuropsychological distinctions between these ADHD subtypes may be few, depending on which domain of executive functioning is assessed, and these distinctions differ by gender. In the case of boys, the two subtypes may be distinguished by the specificity of motor inhibition deficits to ADHD-C.

Validity of DSM-IV attention deficit/hyperactivity disorder symptom dimensions and subtypes.

Diagnostic and Statistical Manual of Mental Disorders, 4th Edition (DSM-IV) criteria for attention deficit/hyperactivity disorder (ADHD) specify two dimensions of inattention and hyperactivity-impulsivity symptoms that are used to define three nominal subtypes: predominantly hyperactive-impulsive type (ADHD-H), predominantly inattentive type (ADHD-I), and combined type (ADHD-C). To aid decision making for DSM-5 and other future diagnostic systems, a comprehensive literature review and meta-analysis of 546 studies was completed to evaluate the validity of the DSM-IV model of ADHD. Results indicated that DSM-IV criteria identify individuals with significant and persistent impairment in social, academic, occupational, and adaptive functioning when intelligence, demographic factors, and concurrent psychopathology are controlled. Available data overwhelmingly support the concurrent, predictive, and discriminant validity of the distinction between inattention and hyperactivity-impulsivity symptoms, and indicate that nearly all differences among the nominal subtypes are consistent with the relative levels of inattention and hyperactivity-impulsivity symptoms that define the subtypes. In contrast, the DSM-IV subtype model is compromised by weak evidence for the validity of ADHD-H after first grade, minimal support for the distinction between ADHD-I and ADHD-C in studies of etiological influences, academic and cognitive functioning, and treatment response, and the marked longitudinal instability of all three subtypes. Overall, we conclude that the DSM-IV ADHD subtypes provide a convenient clinical shorthand to describe the functional and behavioral correlates of current levels of inattention and hyperactivity-impulsivity symptoms, but do not identify discrete subgroups with sufficient long-term stability to justify the classification of distinct forms of the disorder. Empirical support is stronger for an alternative model that would replace the subtypes with dimensional modifiers that reflect the number of inattention and hyperactivity-impulsivity symptoms at the time of assessment. (PsycINFO Database Record (c) 2012 APA, all rights reserved).

Temperament and attention deficit hyperactivity disorder: the development of a multiple pathway model.

This article outlines the parallels between major theories of attention deficit hyperactivity disorder (ADHD) and relevant temperament domains, summarizing recent research from our laboratories on (a) child temperament and (b) adult personality traits related to ADHD symptoms. These data are convergent in suggesting a role of effortful control and regulation in the core symptoms of ADHD. Negative approach and anger is also associated with ADHD, but this may be due to the overlap of ADHD and antisocial behavior. Positive approach may be involved in an alternate pathway to ADHD. The involvement of effortful control is congruent with experimental findings of executive functioning deficits in children with ADHD. We hypothesize that, whereas regulation problems may occur in most children with ADHD, a subgroup also may be characterized by positive approach problems and another subgroup by negative approach problems. We conclude with a theorized multiple process developmental model outlining alternate pathways to ADHD that warrant empirical investigation to better resolve etiological heterogeneity in ADHD.