The Frequency and State-Dependent Relationship between Pupil Size and Respiration

Arousal reflects our level of alertness and impacts our readiness to engage with our environment. When arousal is low, such as when we are drowsy, we are less likely to detect a knock at the door compared with when arousal is higher, such as after drinking coffee. In the literature, arousal is a broad term used to describe cognitive states that influence perception and behavior, bodily states that are associated with affective experience, and feedback loops that connect these processes. In the cognitive domain, arousal level has been heavily linked with the norepinephrine-producing locus ceruleus (LC) in the brainstem (Aston-Jones et al., 1999). Measuring neural activity directly from the LC to estimate arousal level is technically challenging, however, and it is not always practical. Instead, systemic physiology is often used as a marker of arousal since physiological processes have been found to covary with arousal and in some cases have been specifically linked with LC activity. Although the pupil's main role is to regulate the amount of light that enters the eye, pupil diameter is a common surrogate of arousal because of the relationship between the pupil and LC. An increase in LC activity leads to pupil dilation by inhibiting the Edinger–Westphal nucleus (EWN), which provides parasympathetic inputs to the pupil, and by exciting the superior cervical ganglion (SCG), which provides sympathetic inputs to the pupil (Joshi et al., 2016; Liu et al., 2017). As a result, a larger pupil is interpreted as a sign of elevated LC-linked arousal. Periodic fluctuations in pupil diameter have also emerged as a potential indicator of arousal state. These fluctuations, called pupillary hippus, are most prominent at rest, so their presence is considered an indicator of low arousal level. The exact frequency of hippus is variable across lighting conditions, experimental contexts, and species … Correspondence should be addressed to Deepa Issar at deepaissar{at}cmu.edu.