Pupil Changes During Sleep Reveal Brain Activity

For the first time, researchers have been able to observe how pupils react during sleep over an extended period, revealing surprising fluctuations in brain activity. A study published in Nature Communications by a team from ETH Zurich suggests that more happens in the brain during sleep than previously assumed, challenging long-standing beliefs about sleep-related brain activity.

Pupil Dynamics in Sleep: A Groundbreaking Discovery

Traditionally, sleep has been associated with minimal sensory activity, as eyes remain closed. However, the new study led by researchers Caroline Lustenberger, Sarah Meissner, and Nicole Wenderoth from ETH Zurich's Neural Control of Movement Lab has uncovered that pupil size fluctuates significantly during sleep. The findings suggest:

• Pupils exhibit constant changes in size during sleep, increasing and decreasing at varying speeds.

• These fluctuations are linked to shifts in brain activation levels responsible for sleep-wake regulation.

• The level of arousal during sleep is not static but instead alternates between higher and lower activation states.

These observations align with previous research on rodents, which also demonstrated slow fluctuations in arousal levels during sleep.

A New Method to Uncover Hidden Brain Activity

Studying deep brain activity during sleep has been technically challenging. The brainstem, which controls activation levels, is difficult to measure directly in sleeping humans. To bypass this challenge, ETH researchers used a novel method to examine pupil behavior:

• A specialized adhesive and transparent plaster technique allowed them to keep test subjects' eyes open for several hours.

• Subjects were able to fall asleep in dark rooms despite their eyes remaining open.

• Pupil size was recorded and analyzed in relation to sleep stages and brain wave activity.

The data showed a correlation between pupil size changes and specific sleep-related brain activities, such as:

• Sleep spindles – brief bursts of brain activity linked to memory consolidation.

• Deep sleep waves – associated with sleep stability and cognitive functions.

• Varied responses to external sounds, depending on brain activation levels.

The Role of the Locus Coeruleus and Future Research

A small brainstem region known as the locus coeruleus is believed to regulate arousal levels, but the ETH researchers could not directly confirm its role in controlling pupil dynamics. However, they plan to investigate this further by using medication to modulate its activity in future studies.

Understanding how the locus coeruleus influences pupil changes during sleep may provide deeper insights into:

• The mechanisms behind sleep regulation.

• The functional role of brain activation shifts in cognitive processes.

• How external stimuli interact with different sleep states.

Clinical Implications: Diagnosing Sleep Disorders Through Pupillary Analysis

Beyond neuroscience, this research holds promise for diagnosing and treating sleep-related disorders. By studying pupil changes during sleep, researchers aim to explore potential diagnostic markers for conditions such as:

• Insomnia

• Post-Traumatic Stress Disorder (PTSD)

• Alzheimer’s Disease

Future applications may also extend beyond sleep labs, including:

• Hospital Monitoring – Using pupil tracking to assess brain activity in coma patients.

• Sleep Disorder Diagnosis – Improving accuracy in identifying sleep disturbances.

• Neuroscience Research – Advancing knowledge of how sleep impacts overall brain health.

Conclusion

The pupil, often regarded as a mere responder to light, is emerging as a valuable indicator of brain activity during sleep. This breakthrough research from ETH Zurich could revolutionize the understanding of sleep mechanisms and pave the way for new medical applications in sleep medicine and neurology.

Reference:

Manuel Carro-Domínguez et al, Pupil size reveals arousal level fluctuations in human sleep, Nature Communications (2025). DOI: 10.1038/s41467-025-57289-5