Data from animal models, both rodents and non-human primates, have shown a central role for the LC in selective attention 11, 23, 24, 25. Brain areas associated with attentional processing (e.g., parietal cortex, pulvinar nucleus, superior colliculus) receive particularly dense LC-NE innervations 12, 25. This system originates in the locus-coeruleus (LC) and projects throughout the cerebral cortex, hippocampus, thalamus and midbrain, among others 22, 23, 24, 27, 28, 29. Independent findings suggest that these fluctuations in pupil size reflect the state of the brain norepinephrine (NE) system 11, 22, 23, 24, 25, 26. After controlling for stimulus luminance, pupil size correlates with task difficulty, emotional valence, physical effort, motor output and arousal states 11, 16, 17, 18, 19, 20, 21. A biological marker that helps to objectively define the disorder, providing information about its pathophysiology and potential responses to medication, is needed 9, 10.Ī promising potential marker of cognitive states in humans is pupil size 11, 12, 13, 14, 15. These differences probably explain why some patients do not respond to medication 6, 7, 8, 9.

Like any complex disorder, ADHD patients display clear heterogeneities at the clinical and biological levels. This, together with evidence of a weak but consistent link between genetic polymorphisms associated to the catecholaminergic system and ADHD, prompted the widely accepted hypothesis that in this condition there is an underlying deficit in catecholaminergic neurotransmission 1, 7.Ĭurrently, diagnosis is being performed solely on the basis of observed behavior and reported symptoms, which carries the potential risk of over-diagnosis or under-diagnosis 6, 8. Both kinds of drugs increase the catecholamine availability at synapses. First-line treatment for ADHD is given by stimulants, mainly methylphenidate, and the usual second-line treatment is atomoxetine, a noradrenaline reuptake inhibitor 2, 6. Most of ADHD symptoms are related to problems in behavioral and cognitive control, and have been attributed to a deficient dopaminergic signaling 2, 4, 5. This condition is characterized by inattention, impulsiveness and hyperactivity, and is becoming increasingly recognized that many patients continue having these types of difficulties in adulthood 3. Similar content being viewed by othersĪttention-deficit/hyperactivity disorder (ADHD) is the most prevalent childhood neuropsychiatric disorder 1, 2. Our results suggest that pupil size could serve as a biomarker in ADHD. Through pupil size, we provide evidence of an involvement of the noradrenergic system during an attentional task.

Furthermore, this effect was modulated by medication. Pupil size correlated with the subjects’ performance and reaction time variability, two vastly studied indicators of attention. This difference was no longer present when patients were on-medication. Off-medication patients showed a decreased pupil diameter during the task. A sub group of ADHD children performed the task twice, with and without methylphenidate, a norepinephrine–dopamine reuptake inhibitor. We monitored pupil size from ADHD and control subjects, during a visuo-spatial working memory task. A promising marker of cognitive states in humans is pupil size, which reflects the activity of an ‘arousal’ network, related to the norepinephrine system.

A biological marker that helps to objectively define the disorder, providing information about its pathophysiology, is needed. Attention-deficit/hyperactivity disorder (ADHD) diagnosis is based on reported symptoms, which carries the potential risk of over- or under-diagnosis.

Normal pupils size chart