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

Aya Shirama; Toshinobu Takeda; Haruhisa Ohta; Akira Iwanami; Shigenobu Toda; Nobumasa Kato

doi:10.1371/journal.pone.0244662

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

PLoS One. 2020 Dec 30;15(12):e0244662. doi: 10.1371/journal.pone.0244662. eCollection 2020.

Authors

Aya Shirama^{1

2}, Toshinobu Takeda^{1

3}, Haruhisa Ohta¹, Akira Iwanami⁴, Shigenobu Toda^{5

6}, Nobumasa Kato¹

Affiliations

¹ Medical Institute of Developmental Disabilities Research, Showa University, Tokyo, Japan.
² NTT Communication Science Laboratories, Nippon Telegraph and Telephone Corporation, Kanagawa, Japan.
³ Faculty of Letters Ryukoku University, Kyoto, Japan.
⁴ Department of Psychiatry, School of Medicine, Showa University, Tokyo, Japan.
⁵ Department of Psychiatry, Showa University East Hospital, Showa University, Tokyo, Japan.
⁶ Department of Psychiatry and Behavioral Science, Kanazawa University, Kanazawa, Japan.

Abstract

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adult
Attention Deficit Disorder with Hyperactivity / physiopathology
Attention Deficit Disorder with Hyperactivity / psychology*
Case-Control Studies
Female
Humans
Locus Coeruleus / physiopathology*
Male
Neurons / physiology
Neuropsychological Tests
Norepinephrine / metabolism*
Pupil / physiology*

Substances

Norepinephrine

Grants and funding

This work was supported by grants from JSPS KAKENHI [Grant Number JP19K24495] to AS and the Joint Usage/Research Program of the Medical Institute of Developmental Disabilities Research, Showa University to TT and ST. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.