From pupil to the brain: New insights for studying cortical plasticity through pupillometry

Pupil size variations have been associated with changes in brain activity patterns related with specific cognitive factors, such as arousal, attention, and mental effort. The locus coeruleus (LC), a key hub in the noradrenergic system of the brain, is considered to be a key regulator of cognitive control on pupil size, with changes in pupil diameter corresponding to the release of norepinephrine (NE). Advances in eye-tracking technology and open-source software have facilitated accurate pupil size measurement in various experimental settings, leading to increased interest in using pupillometry to track the nervous system activation state and as a potential biomarker for brain disorders. This review explores pupillometry as a non-invasive and fully translational tool for studying cortical plasticity starting from recent literature suggesting that pupillometry could be a promising technique for estimating the degree of residual plasticity in human subjects. Given that NE is known to be a critical mediator of cortical plasticity and arousal, the review includes data revealing the importance of the LC-NE system in modulating brain plasticity and pupil size. Finally, we will review data suggesting that pupillometry could provide a quantitative and complementary measure of cortical plasticity also in pre-clinical studies.