Elsevier

Biological Psychiatry

Volume 57, Issue 11, 1 June 2005, Pages 1416-1423
Biological Psychiatry

Advancing the neuroscience of ADHD
Varieties of Attention-Deficit/Hyperactivity Disorder-Related Intra-Individual Variability

https://doi.org/10.1016/j.biopsych.2004.12.005Get rights and content

Intra-individual variability in behavior and functioning is ubiquitous among children with attention-deficit/hyperactivity disorder (ADHD), but it has not been systematically examined or integrated within causal models. This article seeks to provide a conceptual, methodologic, and analytic framework as a foundation for future research. We first identify five key research questions and methodologic issues. For illustration, we examine the periodic structure of Eriksen Flanker task reaction time (RT) data obtained from 24 boys with ADHD and 18 age-matched comparison boys. Reaction time variability in ADHD differed quantitatively from control subjects, particularly at a modal frequency around .05 Hz (cycle length approximately 20 sec). These oscillations in RT were unaffected by double-blind placebo and were suppressed by double-blind methylphenidate. Together with converging lines of basic and clinical evidence, these secondary data analyses support the speculative hypothesis that the increased power of multisecond oscillations in ADHD RT data, and by inference, in attentional performance, represents a catecholaminergic deficit in the ability to appropriately modulate such oscillations in neuronal activity. These results highlight the importance of retaining time-series data and quantitatively examining intra-subject measures of variability as a putative endophenotype for ADHD.

Section snippets

Conceptual Issues and Foundational Research Questions

In this section, we draw a number of conceptual distinctions regarding ARV that lead us to frame a program of basic research around five key questions.

Issues of Measurement and Analysis

In the previous section, we proposed questions that provide the framework for a program of research into ARV; however, a prerequisite is the development of methods to quantify and characterize important features of variability. This raises issues of data capture, data characterization, and the use of inferential statistical methods to determine the extent to which children with ADHD differ from typically developing children. In this section, we address each of these conditions in turn.

An Illustrative Comparison: From Standard Deviations to Fourier Analyses

Supported by overwhelming evidence that, as a group, children with ADHD consistently exhibit deficits in multiple versions of the continuous performance task (Corkum and Siegel 1993), early accounts of the neuropsychology of ADHD posited a central deficit of sustained attention or vigilance, which worsens as test sessions are prolonged (Sykes et al 1971). The straightforward prediction in ADHD was that performance relative to comparison subjects should also worsen over time, but this was not

Implications of Quantitative Analyses of Variability in ADHD

Before considering the results of our analyses, we must first acknowledge that the form of the Eriksen Flanker task used here could itself entrain oscillations based on the rhythmic presentation of trials every 3 sec (i.e., at .33 Hz). The main RT oscillation we encountered reflected a cycle length approximately seven times the ITI, and harmonics from such a presumed artifact were not observed. This possibility could be definitively excluded in the future by varying the ITI for this and other

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