Anne-Claude Bedard, Ph.D.

Fellow in Child & Adolescent ADHD

Project Details

PROJECT TITLE

The Neural Correlates of Visual-Spatial Working Memory in Children and Adolescents with and without ADHD: An fMRI Study of Brain Activation

PROJECT SUMMARY

Working memory (WM) refers to the ability to temporarily hold and manipulate information in mind. Neuropsychological studies have consistently demonstrated that WM, and in particular visual-spatial WM (VSWM) as opposed to auditory-verbal WM, is impaired in a substantial portion of children with attention-deficit/hyperactivity disorder (ADHD). Deficits in WM have been linked to later psychopathology and academic difficulties, and, in turn, to long-term difficulty in both employment and quality-of-life.

The neural circuitry supporting VSWM, as delineated in studies in monkeys and human adults, includes the dorsolateral and ventrolateral prefrontal cortex (PFC), ventral occipital cortex, parietal cortex, and occipito-temporal structures , with α2A adrenoceptors in PFC playing a key role in modulating this system. It has been posited that VSWM deficits in ADHD are due to supersensitive postjunctional α2A adrenoceptors in the PFC, which in turn cause VSWM deficits that underlie the behavioral dysregulaton associated with the disorder. Testing this hypothesis would be best achieved by conducting a neuroimaging study in youth with and without ADHD. However, to date, no neuroimaging study has examined the neural substrates of VSWM in children with ADHD, and, to our knowledge, there has been no child-friendly VSWM task developed that is suitable for use during functional magnetic resonance imaging (fMRI). Yet, determining the neural correlates of VSWM deficits in children with ADHD would greatly advance our understanding of the pathophysiology of the disorder and potentially provide direction for advances in pharmacological and behavioral interventions. Interest in this area is heightened by the recent FDA approval of the α2A -adrenoceptor agonist guanfacine for the treatment of ADHD. Although extensive animal research indicates that the effects of guanfacine on VSWM are mediated via actions at postsynaptic receptors in the PFC, this purported mechanism of drug activity has yet to be studied in children with ADHD.

Thus, the primary goal of the proposed study is to devise a child-friendly VSWM task suitable for use in fMRI protocols, and to use this task to elucidate distinctions in the neural underpinnings of VSWM in children with ADHD vs. typically-developing children. A secondary aim is to gather preliminary data on the impact of guanfacine on the neural substrates of VSWM in children with ADHD, and to assess the degree to which pharmacologically-induced changes in this neural system are related to improvements in VSWM performance. The ultimate aim is to use these data to support an R01 application to test the effects of pharmacological and non-pharmacological treatments on VSWM in children with ADHD.

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