Rosemary Tannock

Neuroscience of attention-deficit/hyperactivity disorder: the search for endophenotypes

Research on attention-deficit/hyperactivity disorder (ADHD), a highly prevalent and controversial condition, has, for the most part, been descriptive and atheoretical. The imperative to discover the genetic and environmental risk factors for ADHD is motivating the search for quantifiable intermediate constructs, termed endophenotypes. In this selective review, we conclude that such endophenotypes should be solidly grounded in the neurosciences. We propose that three such endophenotypes — a specific abnormality in reward-related circuitry that leads to shortened delay gradients, deficits in temporal processing that result in high intrasubject intertrial variability, and deficits in working memory — are most amenable to integrative collaborative approaches that aim to uncover the causes of ADHD.

Impulsivity and Inhibitory Control

We report an experiment testing the hypothesis that impulsive behavior reflects a deficit in the ability to inhibit prepotent responses Specifically, we examined whether impulsive people respond more slowly to signals to inhibit (stop signals) than non-impulsive people In this experiment, 136 undergraduate students completed an impulsivity questionnaire and then participated in a stop-signal experiment, in which they performed a choice reaction time (go) task and were asked to inhibit their responses to the go task when they heard a stop signal The delay between the go signal and the stop signal was determined by a tracking procedure designed to allow subjects to inhibit on 50% of the stop-signal trials Reaction time to the go signal did not vary with impulsivity, but estimated stop-signal reaction time was longer in more impulsive subjects, consistent with the hypothesis and consistent with results from populations with pathological problems with impulse control

Attention Deficit Hyperactivity Disorder: Advances in Cognitive, Neurobiological, and Genetic Research

Conceptual and technological advances in cognitive neuroscience and molecular genetics have the potential to identify the pathogenesis of psychiatric disorders. This article reviews the application of these technologies to the scientific study of attention deficit hyperactivity disorder. It begins with a summary of shifts in conceptualization and scientific study of this common condition. This is followed by a critical review of findings from recent cognitive, neuroimaging, and genetic studies. The available data do not yet permit an integration across these different levels of enquiry, but implicate problems in response inhibition, dysfunction of frontostriatal networks, and genetic factors in the pathogenesis of this complex behavioral phenotype. The review closes with suggestions for future interdisciplinary research.

Development of inhibitory control across the life span.

The stop-signal procedure was used to examine the development of inhibitory control. A group of 275 participants, 6 to 81 years of age, performed a visual choice reaction time (go) task and attempted to inhibit their responses to the go task when they heard a stop signal. Reaction times to the stop and go signals were used to assess performance in inhibition and response execution, respectively. Results indicated the speed of stopping becomes faster with increasing age throughout childhood, with limited evidence of slowing across adulthood. By contrast, strong evidence was obtained for age-related speeding of go-signal reaction time throughout childhood, followed by marked slowing throughout adulthood. Hierarchical regression confirmed that the age-related change in inhibitory control could not be explained by general speeding or slowing of responses. Findings are discussed in regard to the contrast between the development of inhibition and response execution and the utility of the stop-signal procedure.

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).

Deficient inhibitory control in attention deficit hyperactivity disorder.

The purpose of this study was to examine two executive control processes — response inhibition and re-engagement of responses after inhibition in children with attention deficit hyperactivity disorder (ADHD). Thirty-three children with ADHD and 22 normal control children of similar age (7 to 11 years) and mean IQ (107) were tested with the change paradigm. ADHD subgroups were defined by the context in which the ADHD symptoms predominated (in the home only; at school only; and in both, i.e., pervasive ADHD). Children with marked oppositional defiant or conduct disorder were excluded. Children with ADHD exhibited deficits in inhibitory control and in response re-engagement. Deficits were greatest in pervasive ADHD and, to a lesser extent, in those with ADHD limited to the school context. ADHD limited to the home context showed the least deficit. These results replicate an earlier study that found deficient inhibitory control in pervasive ADHD and demonstrate that the deficit in ADHD involves a second aspect of executive control.

Confirmation of an Inhibitory Control Deficit in Attention-Deficit/Hyperactivity Disorder

The objective of this study was to determine whether deficient inhibitory control distinguishes children with a diagnosis of attention-deficit/hyperactivity (ADHD) disorder, conduct disorder (CD), and comorbid ADHD + CD from normally developing children. Participants were rigorously diagnosed children (age 7 to 12 years) with ADHD (N = 72), CD (N = 13) or ADHD + CD (N = 47) and 33 control children (NC). We studied inhibitory control using the stop-signal paradigm, a laboratory task that assessed the ability to inhibit an ongoing action. The ADHD group had significantly impaired inhibitory control compared to NC, CD, and ADHD + CD children. These results indicate that children with ADHD have deficient inhibition as measured in the stop-signal paradigm and that ADHD occurring in the presence of ADHD + CD may represent a phenocopy of CD rather than a variant of ADHD.

Neuropsychological profiles of adolescents with ADHD: effects of reading difficulties and gender

BACKGROUND Executive function, particularly behavioral inhibition, has been implicated as a core deficit specific to Attention-Deficit/Hyperactivity Disorder (ADHD) whereas rapid naming has been implicated as a core deficit specific to reading disabilities (RD). Females may be less impaired in executive function although adolescent females with ADHD have yet to be studied. METHOD Neuropsychological profiles of four adolescent groups aged 13-16 with equal female representation were investigated: 35 ADHD, 12 RD, 24 ADHD+RD, and 37 normal controls. A semi-structured interview (K-SADS-PL), the Conners Rating Scales and the Ontario Child Health Study Scales were used to diagnose ADHD. RD was defined as a standard score below 90 on at least one of the following: Reading or Spelling of the WRAT3 or Word Attack or Word Identification of the WRMT-R. The WISC-III, Rapid Automatized Naming, Stroop and Stop tasks were used as measures of cognitive and executive function. RESULTS The two ADHD groups (ADHD, ADHD+RD) showed deficits in processing speed, naming of objects, poor behavioral inhibition and greater variability in reaction times whereas the two RD groups (RD, RD+ADHD) showed verbal working memory deficits and slower verbal retrieval speed. Only the comorbid group was slower with naming of numbers and colors and had slower reaction times. Regression analyses indicated that incongruent color naming (Stroop) and variability in go reaction time were the best predictors of hyperactive/impulsive ADHD symptoms whereas variability in go reaction time and processing speed were the best predictors of inattentive ADHD symptoms. Speed of letter naming and verbal working memory accounted for the most variability in composite achievement scores. No gender differences were found on any of the cognitive tests. CONCLUSIONS This study challenges the importance of behavioral inhibition deficits in ADHD and that naming deficits are specific to RD. Further investigation into cognitive deficits in these groups is required.

Differential Effects of Methylphenidate on Working Memory in ADHD Children with and without Comorbid Anxiety

OBJECTIVE To examine the effects of methylphenidate (MPH) on working memory and behavior in anxious and nonanxious children with attention-deficit hyperactivity disorder (ADHD). METHOD A total of 40 ADHD children (22 nonanxious, 18 anxious) completed a randomized, double-blind, placebo-controlled, crossover trial with three doses (0.3, 0.6, 0.9 mg/kg) of MPH. A serial addition task was used to assess working memory; direct observation of motor activity indexed behavior. RESULTS MPH improved working memory in the nonanxious ADHD group but not in the comorbidity anxious group. By contrast, MPH reduced activity level in both groups. The presence of concurrent learning disabilities did not influence stimulant response. CONCLUSIONS The presence of comorbid anxiety in children with ADHD predicts a less robust response to stimulant treatment and suggests that ADHD with anxiety may constitute a distinct and clinically meaningful subtype of ADHD.

The Development of Selective Inhibitory Control Across the Life Span

A modification of the stop-signal task was used to investigate the development of selective inhibitory control. A group of 317 participants, age 6 to 82 years, performed a visual choice reaction time (go) task and attempted to selectively inhibit their response to the go task when hearing one of two randomly presented tones (1000 Hz, 250 Hz), each presented on 20% of trials. Measures of response execution and inhibition were assessed by using reaction times to the go signal (GoRT) and stop signal (SSRT), respectively. Results indicated that SSRT gets faster with increasing age throughout childhood, with pronounced slowing in older adulthood. In addition, strong evidence was obtained for age-related speeding in GoRT throughout childhood, with marked slowing throughout adulthood. Subsequent hierarchical regression analyses illustrated that the age-related changes in selective inhibitory control could not be explained simply by overall slowing or speeding of responses. Findings are discussed in regard to the decay and maturation of selective inhibitory control across the life span.