Katherine A. Johnson

Dissociation in performance of children with ADHD and high-functioning autism on a task of sustained attention.

Attention deficit hyperactivity disorder (ADHD) and autism are two neurodevelopmental disorders associated with prominent executive dysfunction, which may be underpinned by disruption within fronto-striatal and fronto-parietal circuits. We probed executive function in these disorders using a sustained attention task with a validated brain-behaviour basis. Twenty-three children with ADHD, 21 children with high-functioning autism (HFA) and 18 control children were tested on the Sustained Attention to Response Task (SART). In a fixed sequence version of the task, children were required to withhold their response to a predictably occurring no-go target (3) in a 1–9 digit sequence; in the random version the sequence was unpredictable. The ADHD group showed clear deficits in response inhibition and sustained attention, through higher errors of commission and omission on both SART versions. The HFA group showed no sustained attention deficits, through a normal number of omission errors on both SART versions. The HFA group showed dissociation in response inhibition performance, as indexed by commission errors. On the Fixed SART, a normal number of errors was made, however when the stimuli were randomised, the HFA group made as many commission errors as the ADHD group. Greater slow-frequency variability in response time and a slowing in mean response time by the ADHD group suggested impaired arousal processes. The ADHD group showed greater fast-frequency variability in response time, indicative of impaired top-down control, relative to the HFA and control groups. These data imply involvement of fronto-parietal attentional networks and sub-cortical arousal systems in the pathology of ADHD and prefrontal cortex dysfunction in children with HFA.

Separation of Cognitive Impairments in Attention-Deficit/Hyperactivity Disorder Into 2 Familial Factors

CONTEXT Attention-deficit/hyperactivity disorder (ADHD) is associated with widespread cognitive impairments, but it is not known whether the apparent multiple impairments share etiological roots or separate etiological pathways exist. A better understanding of the etiological pathways is important for the development of targeted interventions and for identification of suitable intermediate phenotypes for molecular genetic investigations. OBJECTIVES To determine, by using a multivariate familial factor analysis approach, whether 1 or more familial factors underlie the slow and variable reaction times, impaired response inhibition, and choice impulsivity associated with ADHD. DESIGN An ADHD and control sibling-pair design. SETTING Belgium, Germany, Ireland, Israel, Spain, Switzerland, and the United Kingdom. PARTICIPANTS A total of 1265 participants, aged 6 to 18 years: 464 probands with ADHD and 456 of their siblings (524 with combined-subtype ADHD), and 345 control participants. MAIN OUTCOME MEASURES Performance on a 4-choice reaction time task, a go/no-go inhibition task, and a choice-delay task. RESULTS The final model consisted of 2 familial factors. The larger factor, reflecting 85% of the familial variance of ADHD, captured 98% to 100% of the familial influences on mean reaction time and reaction time variability. The second, smaller factor, reflecting 13% of the familial variance of ADHD, captured 62% to 82% of the familial influences on commission and omission errors on the go/no-go task. Choice impulsivity was excluded in the final model because of poor fit. CONCLUSIONS The findings suggest the existence of 2 familial pathways to cognitive impairments in ADHD and indicate promising cognitive targets for future molecular genetic investigations. The familial distinction between the 2 cognitive impairments is consistent with recent theoretical models--a developmental model and an arousal-attention model--of 2 separable underlying processes in ADHD. Future research that tests the familial model within a developmental framework may inform developmentally sensitive interventions.

Sustained attention, attentional selectivity, and attentional capacity across the lifespan

Changes in sustained attention, attentional selectivity, and attentional capacity were examined in a sample of 113 participants between the ages of 12 and 75. To measure sustained attention, we employed the sustained-attention-to-response task (Robertson, Manly, Andrade, Baddeley, & Yiend, Neuropsychologia 35:747–58, 1997), a short continuous-performance test designed to capture fluctuations in sustained attention. To measure attentional selectivity and capacity, we employed a paradigm based on the theory of visual attention (Bundesen, Psychological Review 97:523–547, 1990), which enabled the estimation of parameters related to attentional selection, perceptual threshold, visual short-term memory capacity, and processing capacity. We found evidence of age-related decline in each of the measured variables, but the declines varied markedly in terms of magnitude and lifespan trajectory. Variables relating to attentional capacity showed declines of very large effect sizes, while variables relating to attentional selectivity and sustained attention showed declines of medium to large effect sizes, suggesting that attentional control is relatively preserved in older adults. The variables relating to sustained attention followed a U-shaped, curvilinear trend, and the variables relating to attentional selectivity and capacity showed linear decline from early adulthood, providing further support for the differentiation of attentional functions.

The relationship between ADHD and key cognitive phenotypes is not mediated by shared familial effects with IQ

BACKGROUND Twin and sibling studies have identified specific cognitive phenotypes that may mediate the association between genes and the clinical symptoms of attention deficit hyperactivity disorder (ADHD). ADHD is also associated with lower IQ scores. We aimed to investigate whether the familial association between measures of cognitive performance and the clinical diagnosis of ADHD is mediated through shared familial influences with IQ. METHOD Multivariate familial models were run on data from 1265 individuals aged 6-18 years, comprising 920 participants from ADHD sibling pairs and 345 control participants. Cognitive assessments included a four-choice reaction time (RT) task, a go/no-go task, a choice-delay task and an IQ assessment. The analyses focused on the cognitive variables of mean RT (MRT), RT variability (RTV), commission errors (CE), omission errors (OE) and choice impulsivity (CI). RESULTS Significant familial association (rF) was confirmed between cognitive performance and both ADHD (rF=0.41-0.71) and IQ (rF=-0.25 to -0.49). The association between ADHD and cognitive performance was largely independent (80-87%) of any contribution from etiological factors shared with IQ. The exception was for CI, where 49% of the overlap could be accounted for by the familial variance underlying IQ. CONCLUSIONS The aetiological factors underlying lower IQ in ADHD seem to be distinct from those between ADHD and RT/error measures. This suggests that lower IQ does not account for the key cognitive impairments observed in ADHD. The results have implications for molecular genetic studies designed to identify genes involved in ADHD.

Imaging the genetics of executive function

Recent advances in neuroimaging technologies have allowed ever more detailed studies of the human brain. The combination of neuroimaging techniques with genetics may provide a more sensitive measure of the influence of genetic variants on cognitive function than behavioural measures alone. Here we present a review of functional magnetic resonance imaging (fMRI) studies of genetic links to executive functions, focusing on sustained attention, working memory and response inhibition. In addition to studies in the normal population, we also address findings from three clinical populations: schizophrenia, ADHD and autism spectrum disorders. While the findings in the populations studied do not always converge, they all point to the usefulness of neuroimaging techniques such as fMRI as potential endophenotypes for parsing the genetic aetiology of executive function.

Attention Network Hypoconnectivity With Default and Affective Network Hyperconnectivity in Adults Diagnosed With Attention-Deficit/Hyperactivity Disorder in Childhood

IMPORTANCE The neurobiological underpinnings of attention-deficit/hyperactivity disorder (ADHD) and particularly those associated with the persistence of ADHD into adulthood are not yet well understood. The correlation patterns in spontaneous neural fluctuations at rest are known as resting-state functional connectivity (RSFC) and could characterize ADHD-specific connectivity changes. OBJECTIVE To determine the specific location of possible ADHD-related differences in RSFC between adults diagnosed as having ADHD in childhood and control subjects. DESIGN Using resting-state functional magnetic resonance imaging, we calculated and compared functional connectivity from attention, affective, default, and cognitive control networks involved in the psychopathology of ADHD between the ADHD and control groups. SETTING University psychiatric service and magnetic resonance imaging research center. PARTICIPANTS Sixteen drug-free adults (5 women and 11 men; mean age, 24.5 years) diagnosed with combined-type ADHD in childhood and 16 healthy controls matched for age (mean age, 24.4 years), sex, handedness, and educational level recruited from the community. INTERVENTION Functional magnetic resonance imaging. MAIN OUTCOMES AND MEASURES Connectivity data from ventral and dorsal attention, affective, default, and cognitive control networks and ADHD symptoms derived from ADHD-specific rating instruments. RESULTS Adults with ADHD showed significantly decreased RSFC within the attention networks and increased RSFC within the affective and default mode and the right lateralized cognitive control networks compared with healthy controls (P < .01, familywise error for whole-brain cluster correction). Lower RSFC in the ventral and dorsal attention network was significantly correlated with higher levels of ADHD symptoms (P < .001). CONCLUSIONS AND RELEVANCE These RSFC findings might underpin a biological basis for adult ADHD and are functionally related to persistent inattention, disturbance in cognitive control, and emotional dysregulation in adults with ADHD. These findings need to be understood in the context of all aspects of brain function in ADHD.

Functional developmental changes underlying response inhibition and error-detection processes

This study examined the developmental trajectories associated with response inhibition and error processing as exemplar executive processes. We present fMRI data showing developmental changes to the functional networks underlying response inhibition and error-monitoring, comparing activation between adults and young adolescents performing the sustained attention to response task (SART). During successful inhibitions, we observed greater activation for the young adolescents than for the adults, in a widely distributed network including frontal, parietal and medial regions. When inhibition failed, however, adults showed increased activation compared to young adolescents in a number of regions, including bilateral parahippocampal gyrus, left and right lingual gyri, the right insula, and cerebellar regions. These differences largely remained even when the two groups were matched for performance, suggesting that performance differences are unlikely to be the driving factor behind these developmental differences. Instead, the neurodevelopmental trajectory of these important executive functions may reveal the basis for the immature executive functioning of the young adolescent.

Dopaminergic genotype biases spatial attention in healthy children

In everyday life, our sensory system is bombarded with visual input and we rely upon attention to select only those inputs that are relevant to behavioural goals. Typically, humans can shift their attention from one visual field to the other with little cost to perception. In cases of ‘unilateral neglect’, however, there is a persistent bias of spatial attention towards the same side as the damaged cerebral hemisphere. We used a visual orienting task to examine the influence of functional polymorphisms of the dopamine transporter gene (DAT1) on individual differences in spatial attention in normally developing children. DAT1 genotype significantly influenced spatial bias. Healthy children who were homozygous for alleles that influence the expression of dopamine transporters in the brain displayed inattention for left-sided stimuli, whereas heterozygotes did not. Our data provide the first evidence in healthy individuals of a genetically mediated bias in spatial attention that is related to dopamine signalling.

Dissociation in response to methylphenidate on response variability in a group of medication naïve children with ADHD

Increased variability in reaction time (RT) has been proposed as a cardinal feature of attention deficit hyperactivity disorder (ADHD). Increased variability during sustained attention tasks may reflect inefficient fronto-striatal and fronto-parietal circuitry; activity within these circuits is modulated by the catecholamines. A disruption to dopamine signaling is suggested in ADHD that may be ameliorated by methylphenidate (MPH). This study investigated the effects of MPH administration on the variability in RT and error performance on a sustained attention task of a group of 31 medication naïve children with ADHD, compared with 22 non-ADHD, non-medicated, control children. All children performed the fixed-sequence sustained attention to response task (SART) at two time-points: at baseline and after six weeks. The children with ADHD were tested when medication naive at baseline and after six weeks of treatment with MPH and whilst on medication. The medication naïve children with ADHD performed the SART with greater errors of commission and omission when compared with the control group. They demonstrated greater standard deviation of RT and fast moment-to-moment variability. They did not differ significantly from the control group in terms of slow variability in RT. MPH administration resulted in reduced and normalised levels of commission errors and fast, moment-to-moment variability in RT. MPH did not affect the rate of omission errors, standard deviation of RT or slow frequency variability in RT. MPH administration may have a specific effect on those performance components that reflect sustained attention and top-down control rather than arousal.

What would Karl Popper say - Are current psychological theories of ADHD falsifiable?

Attention Deficit Hyperactivity Disorder (ADHD) is a common and highly heritable neurodevelopmental psychiatric disorder. Here, we critically review four major psychological theories of ADHD – the Executive Dysfunction, the State Regulation, the Delay Aversion and the Dynamic Developmental – on their abilities to explain all the symptoms of ADHD, their testability and their openness to falsification. We conclude that theoreticians should focus, to a greater extent than currently practiced, on developing refutable theories of ADHD.