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      Pupil Size Tracks Attentional Performance In Attention-Deficit/Hyperactivity Disorder

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          Abstract

          Attention-deficit/hyperactivity disorder (ADHD) diagnosis is based on reported symptoms, which carries the potential risk of over- or under-diagnosis. A biological marker that helps to objectively define the disorder, providing information about its pathophysiology, is needed. A promising marker of cognitive states in humans is pupil size, which reflects the activity of an ‘arousal’ network, related to the norepinephrine system. We monitored pupil size from ADHD and control subjects, during a visuo-spatial working memory task. A sub group of ADHD children performed the task twice, with and without methylphenidate, a norepinephrine–dopamine reuptake inhibitor. Off-medication patients showed a decreased pupil diameter during the task. This difference was no longer present when patients were on-medication. Pupil size correlated with the subjects’ performance and reaction time variability, two vastly studied indicators of attention. Furthermore, this effect was modulated by medication. Through pupil size, we provide evidence of an involvement of the noradrenergic system during an attentional task. Our results suggest that pupil size could serve as a biomarker in ADHD.

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          Attention deficit hyperactivity disorder.

          Attention deficit hyperactivity disorder (ADHD) is a childhood-onset neurodevelopmental disorder with a prevalence of 1·4-3·0%. It is more common in boys than girls. Comorbidity with childhood-onset neurodevelopmental disorders and psychiatric disorders is substantial. ADHD is highly heritable and multifactorial; multiple genes and non-inherited factors contribute to the disorder. Prenatal and perinatal factors have been implicated as risks, but definite causes remain unknown. Most guidelines recommend a stepwise approach to treatment, beginning with non-drug interventions and then moving to pharmacological treatment in those most severely affected. Randomised controlled trials show short-term benefits of stimulant medication and atomoxetine. Meta-analyses of blinded trials of non-drug treatments have not yet proven the efficacy of such interventions. Longitudinal studies of ADHD show heightened risk of multiple mental health and social difficulties as well as premature mortality in adult life.
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            Neuroscience of attention-deficit/hyperactivity disorder: the search for endophenotypes.

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              Pupil fluctuations track fast switching of cortical states during quiet wakefulness.

              Neural responses are modulated by brain state, which varies with arousal, attention, and behavior. In mice, running and whisking desynchronize the cortex and enhance sensory responses, but the quiescent periods between bouts of exploratory behaviors have not been well studied. We found that these periods of "quiet wakefulness" were characterized by state fluctuations on a timescale of 1-2 s. Small fluctuations in pupil diameter tracked these state transitions in multiple cortical areas. During dilation, the intracellular membrane potential was desynchronized, sensory responses were enhanced, and population activity was less correlated. In contrast, constriction was characterized by increased low-frequency oscillations and higher ensemble correlations. Specific subtypes of cortical interneurons were differentially activated during dilation and constriction, consistent with their participation in the observed state changes. Pupillometry has been used to index attention and mental effort in humans, but the intracellular dynamics and differences in population activity underlying this phenomenon were previously unknown.
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                Author and article information

                Contributors
                tossandonv@uc.cl
                Journal
                Sci Rep
                Sci Rep
                Scientific Reports
                Nature Publishing Group UK (London )
                2045-2322
                15 August 2017
                15 August 2017
                2017
                : 7
                : 8228
                Affiliations
                [1 ]ISNI 0000 0001 2157 0406, GRID grid.7870.8, Departamento de Psiquiatría, Escuela de Medicina and Centro Interdisciplinario de Neurociencia, , Pontificia Universidad Católica de Chile, ; Santiago, Chile
                [2 ]ISNI 0000 0001 2150 3115, GRID grid.412193.c, Laboratorio de Neurociencia Cognitiva y Social, Facultad de Psicología, , Universidad Diego Portales, ; Santiago, Chile
                [3 ]ISNI 0000 0001 2322 6764, GRID grid.13097.3c, Department of Psychosis Studies, Institute of Psychiatry, , Psychology and Neuroscience. King’s College London, ; London, UK
                [4 ]ISNI 0000 0004 0385 4466, GRID grid.443909.3, Servicio de Neurología y Psiquiatría, Hospital de Niños Dr. Luis Calvo Mackenna, , Facultad de Medicina, Universidad de Chile, ; Santiago, Chile
                Author information
                http://orcid.org/0000-0002-9517-5545
                Article
                8246
                10.1038/s41598-017-08246-w
                5557799
                28811624
                ee2962fa-d4bd-4577-8377-ecef6aba1c0c
                © The Author(s) 2017

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 20 April 2017
                : 10 July 2017
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