Multimodal biomarker based on temporal complexity of eye movements and pupil diameter in attention-deficit/hyperactivity disorder

Attention-deficit/hyperactivity disorder (ADHD) is one of the most prevalent neurodevelopmental disorders without established biomarkers. Pupil diameter, regulated by the locus coeruleus-norepinephrine (LC-NE) system, and eye movements controlled by diverse brain regions exhibit specific patterns in patients with ADHD due to abnormal activity in these brain regions. Previous studies reported that patients with ADHD have larger pupil diameters and reduced temporal complexity. However, although the temporal complexity of eye movements has been associated with major movement disorders in previous studies, its relevance in conditions without primary movement disorders, such as ADHD, remains unclear. In this context, we hypothesized that the temporal complexity of eye movements would provide a more comprehensive understanding of eye movements in ADHD. This study aimed to analyze the temporal complexity of eye movements in patients with ADHD using multiscale entropy analysis and examine its diagnostic utility alongside pupil size. The results showed that patients with ADHD had lower temporal complexity in their eye movements and larger pupil diameters. Moreover, combining these features enhanced the accuracy of ADHD diagnosis. These findings support the potential of a multimodal approach for diagnosing adult ADHD, potentially improving clinical diagnostic accuracy.