Atypical alert state control in adult patients with ADHD: A pupillometry study

Although behavioral studies have repeatedly demonstrated that individuals with attention-deficit/hyperactivity disorder (ADHD) have deficits in alertness, little is known about its underlying neural basis. It is hypothesized that pupil diameter reflects the firing of norepinephrine (NE) neurons in the locus coeruleus (LC), and that the LC-NE neuromodulatory system for regulating alertness may be dysfunctional in ADHD. To clinically and non-invasively examine this hypothesis, we monitored the kinetics of pupil diameter in response to stimuli and compared them between adults with ADHD (n = 17) and typically developing (TD) adults (n = 23) during an auditory continuous performance task. Individuals in the ADHD group exhibited a significantly larger tonic pupil diameter, and a suppressed stimulus-evoked phasic pupil dilation, compared to those in the TD group. These findings provide support for the idea that the aberrant regulatory control of pupil diameter in adults with ADHD may be consistent with a compromised state of alertness resulting from a hyperactivated LC-NE system.