Review
Linking ADHD to the Neural Circuitry of Attention

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Trends

Deficits in many different cognitive domains are associated with ADHD. Cognitive batteries that assess the performance of individuals within these different cognitive domains show that the disorder is very heterogeneous.

ADHD medication that improves performance in one cognitive measure does not necessarily improve it in others.

Studies in human and nonhuman primates have revealed much about the underlying mechanisms of endogenous, exogenous, and spatial- and feature-based selective attention.

The regions of the brain and the neuromodulators that influence selective attention and other cognitive domains implicated in ADHD are non-overlapping.

Attention deficit hyperactivity disorder (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 to be 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.

Section snippets

Bridging the Gap

ADHD is a complex condition affecting up to 10% of children worldwide [1] and comprises a heterogeneous set of behavioral dysfunctions. While prior work demonstrates validity of the ADHD construct in general, ongoing debate regarding subtype validity demonstrates the need for a more coherent model. An etiological basis for ADHD remains elusive, as have been efforts to subtype ADHD using biological indicators rather than solely relying on clinical assessments.

Decades of ADHD studies in humans

Diagnosis of ADHD

In current clinical practice, ADHD is diagnosed through observation and self-report of behavior. These are typically conducted through clinical interviews with the individual and family, and often use rating scales of ADHD symptoms. Consensus criteria for ADHD, as defined by the Diagnostic and Statistical Manual of Mental Disorders (DSM-5; http://www.psychiatry.org/psychiatrists/practice/dsm), require a persistent pattern of inattention and/or hyperactivity and impulsivity over a period greater

Cognitive Dysfunction in ADHD

Many studies show that individuals with ADHD exhibit poorer performance on cognitive tasks compared to neurotypical controls (reviewed in [11]). Meta-analyses indicate that populations of individuals with ADHD exhibit relatively consistent deficits in specific cognitive functions [12]. However, this is countered by substantial heterogeneity among the identified domains, leading to variable characterizations of ADHD as a predominant disorder of inhibition (e.g., [13]), delay aversion [14], or

Neural Mechanisms of Selective Attention

Selective attention is one cognitive domain implicated in ADHD (Box 2: Selective Attention Deficits in ADHD) for which there is significant insight into the underlying neural mechanisms. The term ‘attention’ is often used as shorthand for ‘selective attention’, which is the selective processing of specific stimuli over others (e.g., [25]). This is distinct from ‘sustained attention’, which refers more specifically to the maintenance of attention over a longer period of time, and may depend on

Neural Mechanisms of Other Cognitive Domains Associated with ADHD

Figure 4 summarizes the extensive literature describing the relationship between ADHD-related functional domains and the neural and neuromodulatory circuits that steer them. In addition to selective attention, described above, we provide a brief overview of current understanding of these other cognitive domains.

Utility of Nonhuman Primate Models

A fuller understanding of the neural circuits and neuromodulatory systems that underlie the cognitive diversity of individuals with ADHD will be key to improving their diagnosis and treatment. Indeed, recent research has shown that these systems are highly complex, and the ADHD phenotype cannot adequately be characterized as a dopaminergic deficit as previously thought. Instead, much more sophisticated and direct interrogation of these neuromodulatory circuits is needed. Indeed, it should be

Concluding Remarks

Many challenges currently face research and clinical paradigms for quantifying and specifying the symptoms and forms of ADHD (see Outstanding Questions). Use of more rigorous cognitive tests will help to characterize ADHD deficits, and the study of circuit-level mechanisms underlying executive functions in nonhuman primates holds promise for advancing our understanding, and ultimately the treatment, of ADHD.

To what extent are different populations of ADHD pathologies separable using

Glossary

Conners’ continuous performance task
a computer-based assessment of attention performance. It is not routinely used for diagnosis, but it is the most common test used in research on clinical populations.
Catecholamines
catecholamines are a class of neuromodulators that include dopamine and norepinephrine. Norepinephrine is a synonym for noradrenaline. Norepinephrine binds to noradrenergic receptors, and is released from noradrenergic neurons.
Disorder of delay aversion
the proposal that ADHD results

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