Characterising cerebrovascular reactivity and the pupillary light response-a comparative study

Introduction: Smooth muscle is integral to multiple autonomic systems, including cerebrovascular dynamics through vascular smooth muscle cells and in ocular muscle dynamics, by regulating pupil size. In the brain, smooth muscle function plays a role in cerebrovascular reactivity (CVR) that describes changes in blood vessel calibre in response to vasoactive stimuli. Similarly, pupil size regulation can be measured using the pupillary light response (PLR), the pupil's reaction to changes in light levels. The primary aim of this study was to explore the interplay between cerebral blood flow and pupil dynamics, evaluated using CVR and PLR, respectively.

Methods: A total of 20 healthy adults took part in a CVR gas stimulus protocol and a light and dark flash PLR protocol. CVR was calculated as the blood flow velocity change in the middle cerebral artery, measured using transcranial Doppler ultrasound in response to a 5% increase in CO₂. Multiple PLR metrics were evaluated with a clinical pupillometer.

Results: CVR and PLR metrics were all within the expected physiological ranges for healthy adults. Nine different PLR metrics, assessed through the light and dark flash protocols, were compared against CVR. A significant negative relationship was observed between the latency of the PLR in the dark flash protocol and CVR. No statistically significant relationships were found between CVR and other PLR metrics.

Conclusion: This is the first study to investigate the relationship between cerebral blood flow and pupil dynamics. A significant relationship between dark flash latency and CVR was observed. Future work includes evaluating these relationships using more robust CVR and PLR measurement techniques in a larger, more diverse cohort. Notably, more research is warranted into the PLR using a dark flash protocol and its connection to cerebrovascular function.