Brain Networks Underlying Eye’s Pupil Dynamics

Abstract

Phasic changes in eye’s pupil diameter have been repeatedly observed during cognitive, emotional and behavioral activity in mammals. Although pupil diameter is known to be associated with noradrenergic firing in the pontine Locus Coeruleus (LC), thus far the causal chain coupling spontaneous pupil dynamics to specific cortical brain networks remains unknown. In the present study, we acquired steady-state blood oxygenation level-dependent (BOLD) functional magnetic resonance imaging (fMRI) data combined with eye-tracking pupillometry from fifteen healthy subjects that were trained to maintain a constant attentional load. Regression analysis revealed widespread visual and sensorimotor BOLD-fMRI deactivations correlated with pupil diameter. Furthermore, we found BOLD-fMRI activations correlated with pupil diameter change rate within a set of brain regions known to be implicated in selective attention, salience, error-detection and decision-making. These regions included LC, thalamus, posterior cingulate cortex (PCC), dorsal anterior cingulate and paracingulate cortex (dACC/PaCC), orbitofrontal cortex (OFC), and right anterior insular cortex (rAIC). Granger-causality analysis performed on these regions yielded a complex pattern of interdependence, wherein LC and pupil dynamics were far apart in the network and separated by several cortical stages. Functional connectivity (FC) analysis revealed the ubiquitous presence of the superior frontal gyrus (SFG) in the networks identified by the brain regions correlated to the pupil diameter change rate. No significant correlations were observed between pupil dynamics, regional activation and behavioral performance. Based on the involved brain regions, we speculate that pupil dynamics reflects brain processing implicated in changes between self- and environment-directed awareness.

Vigilance Effects in Resting-State fMRI

“…Using pupilometry, Schneider et al (2016) found that spontaneous pupil dilations were associated with increased BOLD activity in the salience network, thalamus, and frontoparietal regions, whereas spontaneous pupil constrictions were associated with increased BOLD activity in the visual and sensoriomotor areas. Similarly, several studies have reported a positive correlation between pupil size and the rsfMRI BOLD signal in regions comprising cingulo-opercular, default mode, and fronto-parietal networks and a negative correlation in the visual and sensorimotor regions (Yellin et al, 2015;Breeden et al, 2017;DiNuzzo et al, 2019). To first order, the spatial pattern of correlations observed with pupilometry are roughly consistent with those reported using simultaneous EEG fMRI studies.…”

“…To first order, the spatial pattern of correlations observed with pupilometry are roughly consistent with those reported using simultaneous EEG fMRI studies. In addition, a positive correlation has been demonstrated between pupil size and BOLD activity in the locus coeruleus (Murphy et al, 2014;DiNuzzo et al, 2019), a nucleus in the brainstem that contains norepinephrine neurons that are thought to modulate pupil size (Joshi et al, 2016).…”

Locus Coeruleus Norepinephrine in Learned Behavior: Anatomical Modularity and Spatiotemporal Integration in Targets

“…The link between LC-NE activity and arousal is likely relevant for explaining the role of LC-NE in learned behaviors during wakefulness. LC activation tightly correlates with pupil size and arousal level in mice ( Reimer et al, 2016 ; Breton-Provencher and Sur, 2019 ), monkeys ( Joshi et al, 2016 ), and humans ( Murphy et al, 2014 ; Elman et al, 2017 ; DiNuzzo et al, 2019 ). This activity of LC-NE neurons alone is sufficient to promote global arousal in mice, as photo-activation or -inhibition of LC-NE neurons during wakefulness increases or reduces arousal levels, respectively ( Carter et al, 2010 ; Lovett-Barron et al, 2017 ; Breton-Provencher and Sur, 2019 ; Hayat et al, 2020 ).…”

Beyond MRI: on the scientific value of combining non-human primate neuroimaging with metadata

“…Pupil size positively correlates with BOLD activations in the Locus Coeruleus, thalamus, posterior cingulate cortex, dorsal anterior cingulate and paracingulate cortex, orbitofrontal cortex, and right anterior insular cortex, i.e. in brain regions associated with selective attention, salience, error-detection and decision-making ( Yellin et al., 2015 , DiNuzzo et al., 2019 ).…”