Our eyes are usually closed when we sleep. However, a great deal of activity takes place under our closed eyelids: a team of researchers led by senior researchers Caroline Lustenberger, Sarah Meissner and Nicole Wenderoth from the Neuronal Movement Control Laboratory at ETH Zurich has observed that the size of the pupil fluctuates constantly during sleep.

The Pupil During Sleep

Sometimes it dilates, sometimes it constricts; sometimes these changes occur within seconds, sometimes only over the course of several minutes. “These dynamics reflect the state of arousal or the degree of brain activation in the regions responsible for sleep-wake regulation,” says Lustenberger. “These observations contradict the previous assumption that the level of arousal during sleep is generally low.”

Instead, these fluctuations in pupil size show that the brain constantly alternates between higher and lower levels of activation, even during sleep. These new findings confirm for humans what other research groups have recently discovered in studies on rodents, which also show slow fluctuations in the level of activation (known in the scientific community as arousal). The ETH researchers’ study was recently published in the journal Nature Communications.

Pupil Dynamics are Not Only Related to the Different Sleep Phases

The regions of the brain that control the activation state are located deep in the brain stem. This is why it has been difficult to directly measure these processes in humans during sleep. The existing methods are technically demanding and not yet established in this context. The ETH researchers’ study is therefore based on pupil measurements. It is well known that the pupils indicate the state of activation when a person is awake. They can therefore be used as markers for activity in deeper brain regions.

To examine the changes in the pupils of humans during sleep, the ETH researchers developed a new method: using a special adhesive technique and a transparent plaster, they were able to keep the subjects’ eyes open for several hours. “Our main concern was that the subjects would not be able to sleep with their eyes open. But in a dark room, most people forget that their eyes are still open and can sleep,” explains the lead author of the study, Manuel Carro Domínguez, who developed the technique.

Analysis of the data showed that pupil dynamics are associated not only with the different sleep phases but also with specific patterns of brain activity, such as sleep spindles and pronounced deep sleep waves – brain waves that are important for memory consolidation and sleep stability. The researchers also discovered that the brain reacts to sounds at different intensities depending on the level of activation, which is reflected in the size of the pupil.

A central regulator of the activation level is a small region in the brain stem called the locus coeruleus. In animals, scientists have shown that this is important for the regulation of sleep stages and wakefulness. In this study, the ETH researchers were unable to prove whether the locus coeruleus is actually directly responsible for the pupillary changes. The experts only observed pupillary changes that are related to the degree of brain activation and cardiac activity.

In a follow-up study, the researchers want to try to influence the activity of the locus coeruleus with medication to examine how this affects pupil dynamics. They hope to gain insights into whether this brain region is actually responsible for controlling the pupils during sleep and how changes in the level of activation affect sleep and its functions.

Using pupil Dynamics to Diagnose Diseases

Understanding pupil dynamics during sleep could also provide important insights for the diagnosis and treatment of sleep disorders and other diseases. The researchers therefore want to investigate whether changes in the pupil during sleep can provide clues to functional disorders of the arousal system. These include disorders such as insomnia, post-traumatic stress disorder and possibly Alzheimer’s disease.

Another goal is to make the technology usable outside of sleep laboratories, for example in hospitals, where it could help monitor the wakefulness of coma patients or more accurately diagnose sleep disorders. The pupil as a window to the brain could thus pave the way for new possibilities in sleep medicine and neuroscience.