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

Front Neural Circuits. 2023 Mar 31:17:1151847. doi: 10.3389/fncir.2023.1151847. eCollection 2023.

Abstract

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.

Keywords: cortical plasticity; locus coeruleus; neuromodulation; noradrenaline; norepinephrine; pupil size; pupillometry.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Arousal
  • Attention / physiology
  • Brain*
  • Humans
  • Locus Coeruleus
  • Pupil* / physiology

Grants and funding

This work was partially supported by AIRETT Associazione Italiana per la Sindrome di Rett Project “Validation of pupillometry as a biomarker for Rett syndrome and related disorders: longitudinal assessment and relationship with disease,” Orphan Disease Center University of Pennsylvania grant MDBR-19-103-CDKL5, Associazione “CDKL5–Insieme verso la cura,” AI4Media– A European Excellence Centre for Media, Society and Democracy (EC, H2020 n. 951911), the “CRONOLAB” project of the PRO3 joint program, and the Tuscany Health Ecosystem (THE) Project (CUP I53C22000780001), funded by the National Recovery and Resilience Plan (NRPP), within the NextGeneration Europe (NGEU) Program. RM was supported by Fondazione Umberto Veronesi. This work was supported by the Open Access Publishing Fund of the Scuola Normale Superiore.