Identification of attention-deficit hyperactivity disorder based on the complexity and symmetricity of pupil diameter

Abstract

Adult attention-deficit/hyperactivity disorder (ADHD) frequently leads to psychological/social dysfunction if unaddressed. Identifying a reliable biomarker would assist the diagnosis of adult ADHD and ensure that adults with ADHD receive treatment. Pupil diameter can reflect inherent neural activity and deficits of attention or arousal characteristic of ADHD. Furthermore, distinct profiles of the complexity and symmetricity of neural activity are associated with some psychiatric disorders. We hypothesized that analysing the relationship between the size, complexity of temporal patterns, and asymmetricity of pupil diameters will help characterize the nervous systems of adults with ADHD and that an identification method combining these features would ease the diagnosis of adult ADHD. To validate this hypothesis, we evaluated the resting state hippus in adult participants with or without ADHD by examining the pupil diameter and its temporal complexity using sample entropy and the asymmetricity of the left and right pupils using transfer entropy. We found that large pupil diameters and low temporal complexity and symmetry were associated with ADHD. Moreover, the combination of these factors by the classifier enhanced the accuracy of ADHD identification. These findings may contribute to the development of tools to diagnose adult ADHD.

Pupil dilation as a marker of dysfunctional arousal regulation during sustained attention in children and adolescents with ADHD

“…Therefore, we expected reduced performance in the ADHD group compared to the control group. We expected increased tonic pupil diameter in ADHD compared to control group since this was reported by attention studies with adults with ADHD and was interpreted as overactivity of the LC-NE system [40,41]. Due to a postulated regulation deficit in ADHD [7,10] a different course of the pupil diameter throughout the task was expected between groups.…”

“…Some studies reported decreased phasic (stimulus-related) pupil dilation responses in off-medication children with ADHD compared to controls [37], for descriptive effects in the same direction see [38,39]. However, in sustained attention tasks two recent studies with adults with ADHD reported increased tonic pupil diameter in the ADHD group than in the control group [40,41]. Shirama and colleagues (2020) conducted an auditory CPT and reported increased tonic and reduced phasic pupil dilation responses in adults with ADHD compared to controls.…”

“…The authors interpreted their results as hyperarousal state in which compromised phasic responses to target stimuli in the ADHD group are due to a hyperactivated LC-NE system. A study by Nobukawa et al [41], that investigates several features of PD in adults with ADHD, reported increased tonic pupil dilation during the fixation of a steady cross in adults with ADHD compared to a control group. Similar to Shirama et al [40], they discussed their findings in the framework of an overactivity of the LC system [41].…”

“…Recent studies investigating pupil diameter (PD) in children with ADHD used mainly cognitive tasks that do not specifically measure sustained attention [36][37][38][39]. However, recent studies with adults who were asked to perform a sustained attention task or to fixate a visual stimulus for two minutes, showed an increased tonic PD and reduced phasic PD in ADHD patients [40,41].…”

“…This was interpreted as an overactivity of the LC-NE system [40,41]. Thus, the changes in PD during task performance could be an important indirect marker of the adaptation of arousal to the requirements of an attention task.…”