{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,11]],"date-time":"2026-03-11T16:57:14Z","timestamp":1773248234365,"version":"3.50.1"},"reference-count":50,"publisher":"MIT Press","issue":"12","content-domain":{"domain":["direct.mit.edu"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2022,11,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Locus coeruleus (LC) overactivity, especially in the right hemisphere, is a recognized pathophysiology of attention-deficit\/hyperactivity disorder (ADHD) and may be related to inattention. LC activity synchronizes with the kinetics of the pupil diameter and reflects neural activity related to cognitive functions such as attention and arousal. Recent studies highlight the importance of the complexity of the temporal patterns of pupil diameter. Moreover, asymmetrical pupil diameter, which correlates with the severity of inattention, impulsivity, and hyperactivity in ADHD, might be attributed to a left-right imbalance in LC activity. We recently constructed a computational model of pupil diameter based on the newly discovered contralateral projection from the LC to the Edinger\u2013Westphal nucleus (EWN), which demonstrated mechanisms for the complex temporal patterns of pupil kinetics; however, it remains unclear how LC overactivity and its asymmetry affect pupil diameter. We hypothesized that a neural model of pupil diameter control featuring left-right differences in LC activity and projections onto two opponent sides may clarify the role of pupil behavior in ADHD studies. Therefore, we developed a pupil diameter control model reflecting LC overactivity in the right hemisphere by incorporating a contralateral projection from the LC to EWN and evaluated the complexity of the temporal patterns of pupil diameter generated by the model. Upon comparisons with experimentally measured pupil diameters in adult patients with ADHD, the parameter region of interest of the neural model was estimated, which was a region in the two-dimensional plot of complexity versus left-side LC baseline activity and that of the right. A region resulting in relatively high right-side complexity, which corresponded to the pathophysiological indexes, was identified. We anticipate that the discovery of lateralization of complexity in pupil diameter fluctuations will facilitate the development of biomarkers for accurate diagnosis of ADHD.<\/jats:p>","DOI":"10.1162\/neco_a_01545","type":"journal-article","created":{"date-parts":[[2022,10,25]],"date-time":"2022-10-25T19:42:23Z","timestamp":1666726943000},"page":"2388-2407","update-policy":"https:\/\/doi.org\/10.1162\/mitpressjournals.corrections.policy","source":"Crossref","is-referenced-by-count":10,"title":["Asymmetric Complexity in a Pupil Control Model With Laterally Imbalanced Neural Activity in the Locus Coeruleus: A Potential Biomarker for Attention-Deficit\/Hyperactivity Disorder"],"prefix":"10.1162","volume":"34","author":[{"given":"Hiraku","family":"Kumano","sequence":"first","affiliation":[{"name":"Graduate School of Information and Computer Science, Chiba Institute of Technology, Narashino, Chiba 275-0016, Japan"}]},{"given":"Sou","family":"Nobukawa","sequence":"additional","affiliation":[{"name":"Department of Computer Science\/Graduate School of Information and Computer Science, Chiba Institute of Technology, Narashino, Chiba 275-0016, Japan"},{"name":"Department of Preventive Intervention for Psychiatric Disorders, National Institute of Mental Health, National Center of Neurology and Psychiatry, Tokyo 187-8551, Japan nobukawa@cs.it-chiba.ac.jp"}]},{"given":"Aya","family":"Shirama","sequence":"additional","affiliation":[{"name":"Department of Preventive Intervention for Psychiatric Disorders, National Institute of Mental Health, National Center of Neurology and Psychiatry, Tokyo 187-8551, Japan shirama@ncnp.go.jp"}]},{"given":"Tetsuya","family":"Takahashi","sequence":"additional","affiliation":[{"name":"Research Center for Child Mental Development, Kanazawa University, Ishikawa 187-8551, Japan"},{"name":"Department of Neuropsychiatry, University of Fukui, Fukui 910-1193, Japan"},{"name":"Uozu Shinkei Sanatorium, Uozu 937-0017, Japan takahash@u-fukui.ac.jp"}]},{"given":"Toshinobu","family":"Takeda","sequence":"additional","affiliation":[{"name":"Faculty of Letters, Ryukoku University, Kyoto 612-8577, Japan t-tak@umin.ac.jp"}]},{"given":"Haruhisa","family":"Ohta","sequence":"additional","affiliation":[{"name":"Medical Institute of Developmental Disabilities Research, Showa University, Tokyo 157-8577, Japan haruhisap@gmail.com"}]},{"given":"Mitsuru","family":"Kikuchi","sequence":"additional","affiliation":[{"name":"Research Center for Child Mental Development and Department of Psychiatry and Behavioral Science, Kanazawa University, Ishikawa 920-8640, Japan mitsuruk@med.kanazawa-u.ac.jp"}]},{"given":"Akira","family":"Iwanami","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, School of Medicine, Showa University, Tokyo 157-8577, Japan iwanami@med.showa-u.ac.jp"}]},{"given":"Nobumasa","family":"Kato","sequence":"additional","affiliation":[{"name":"Medical Institute of Developmental Disabilities Research, Showa University, Tokyo 157-8577, Japan katon@med.showa-u.ac.jp"}]},{"given":"Shigenobu","family":"Toda","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Behavioral Science, Kanazawa University, Ishikawa 920-8640, Japan"},{"name":"Department of Psychiatry, Showa University East Hospital, Showa University, Tokyo 142-0054, Japan todashige@outlook.jp"}]}],"member":"281","published-online":{"date-parts":[[2022,11,8]]},"reference":[{"issue":"3","key":"2022110823085363700_B1","doi-asserted-by":"publisher","first-page":"336","DOI":"10.1097\/00004583-199503000-00020","article-title":"Six-year predictors of problems in a national sample of children and youth: I. 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