Decoding the brain state-dependent relationship between pupil dynamics and resting state fMRI signal fluctuation

Abstract

Pupil dynamics serve as a physiological indicator of cognitive processes and arousal states of the brain across a diverse range of behavioral experiments. Pupil diameter changes reflect brain state fluctuations driven by neuromodulatory systems. Resting state fMRI (rs-fMRI) has been used to identify global patterns of neuronal correlation with pupil diameter changes, however, the linkage between distinct brain state-dependent activation patterns of neuromodulatory nuclei with pupil dynamics remains to be explored. Here, we identified four clusters of trials with unique activity patterns related to pupil diameter changes in anesthetized rat brains. Going beyond the typical rs-fMRI correlation analysis with pupil dynamics, we decomposed spatiotemporal patterns of rs-fMRI with principal components analysis (PCA) and characterized the cluster-specific pupil-fMRI relationships by optimizing the PCA component weighting via decoding methods. This work shows that pupil dynamics are tightly coupled with different neuromodulatory centers in different trials, presenting a novel PCA-based decoding method to study the brain state-dependent pupil-fMRI relationship.

Decoding the brain state-dependent relationship between pupil dynamics and resting state fMRI signal fluctuation

“…The PCA time courses were variance normalized before the optimization of linear regression and GRU weights. The functional and anatomical data are available online (84).…”

Relating pupil diameter and blinking to cortical activity and hemodynamics across arousal states

“…As head-fixed mice frequently sleep with their eyes open (Karimi Abadchi et al, 2020;Turner et al, 2020;Yuzgec et al, 2018), it has been observed that pupil diameter is lower during sleep and can be used detect sleep events minute-to-minute timescale (Karimi Abadchi et al, 2020;Yuzgec et al, 2018). Changes in pupil diameter are tightly coupled with BOLD fMRI signals seen neuromodulatory centers (Pais-Roldan et al, 2020;Sobczak et al, 2021). In addition to noradrenergic effects on neurons, noradrenergic input from the locus coeruleus causes vasoconstriction of cortical arteries (Bekar et al, 2012), coupling cortical hemodynamics to arousal.…”

“…In addition to its effects on neurons, noradrenergic input from the LC causes vasoconstriction of cortical arteries (Bekar et al, 2012). LC activity and noradrenergic tone provides a potential mechanism for coupling arousal to cortical hemodynamics (Pisauro et al, 2016), as changes in pupil diameter are also correlated with blood-oxygen-level-dependent (BOLD) signals seen in neuromodulatory centers during functional magnetic resonance imaging (fMRI) (Pais-Roldan et al, 2020;Sobczak et al, 2021). Both head-fixed and freely behaving mice frequently sleep with their eyes open (Karimi Abadchi et al, 2020;Senzai and Scanziani, 2022;Turner et al, 2020;Yuzgec et al, 2018).…”