ADHD is a complex condition with a heterogeneous presentation. Current diagnosis is primarily based on subjective experience and observer reports of behavioral symptoms – an approach that has significant limitations. Many studies show that individuals with ADHD exhibit poorer performance on cognitive tasks than neurotypical controls, and at least seven main functional domains appear implicated in ADHD. We discuss the underlying neural mechanisms of cognitive functions associated with ADHD with emphasis on the neural basis of selective attention, demonstrating the feasibility of basic research approaches for further understanding cognitive behavioral processes as they relate to human psychopathology. The study of circuit-level mechanisms underlying executive functions in nonhuman primates holds promise for advancing our understanding, and ultimately the treatment, of ADHD.

The processes of attention and working memory are conspicuously interlinked, suggesting that they may involve overlapping neural mechanisms. Working memory (WM) is the ability to maintain information in the absence of sensory input. Attention is the process by which a specific target is selected for further processing, and neural resources directed toward that target. The content of WM can be used to direct attention, and attention can in turn determine which information is encoded into WM. Here we discuss the similarities between attention and WM and the role prefrontal cortex (PFC) plays in each. First, at the theoretical level, we describe how attention and WM can both rely on models based on attractor states. Then we review the evidence for an overlap between the areas involved in both functions, especially the frontal eye field (FEF) portion of the prefrontal cortex. We also discuss similarities between the neural changes in visual areas observed during attention and WM. At the cellular level, we review the literature on the role of prefrontal DA in both attention and WM at the behavioral and neural levels. Finally, we summarize the anatomical evidence for an overlap between prefrontal mechanisms involved in attention and WM. Altogether, a summary of pharmacological, electrophysiological, behavioral, and anatomical evidence for a contribution of the FEF part of prefrontal cortex to attention and WM is provided.

Dopaminergic modulation of prefrontal cortex plays an important role in numerous cognitive processes, including attention. The frontal eye field (FEF) is modulated by dopamine and has an established role in visual attention, yet the underlying circuitry upon which dopamine acts is not known. We compared the expression of D1 and D2 dopamine receptors (D1Rs and D2Rs) across different classes of FEF neurons, including those projecting to dorsal or ventral extrastriate cortex. First, we found that both D1Rs and D2Rs are more prevalent on pyramidal neurons than on several classes of interneurons and are particularly prevalent on putatively long-range projecting pyramidals. Second, higher proportions of pyramidal neurons express D1Rs than D2Rs. Third, overall a higher proportion of inhibitory neurons expresses D2Rs than D1Rs. Fourth, among inhibitory interneurons, a significantly higher proportion of parvalbumin+ neurons expresses D2Rs than D1Rs, and a significantly higher proportion of calbindin+ neurons expresses D1Rs than D2Rs. Finally, compared with D2Rs, virtually all of the neurons with identified projections to both dorsal and ventral extrastriate visual cortex expressed D1Rs. Our results demonstrate that dopamine tends to act directly on the output of the FEF and that dopaminergic modulation of top-down projections to visual cortex is achieved predominately via D1Rs.