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.
Highlights
Consensual changes in eye’s pupil size are strongly associated with neuromodulatory tone
The results found in animal models might not directly translate to the human brain, the relationship between pupil dynamics and locus coeruleus (LC) has been indirectly confirmed in humans using pupillometry and functional magnetic resonance imaging (Alnaes et al, 2014; Murphy et al, 2014; Yellin et al, 2015; Schneider et al, 2016; Elman et al, 2017)
We found that the rAICseed Functional connectivity (FC) network and the posterior cingulate cortex (PCC)-seed FC network exhibited the lowest between-map correlation (Figure 4B), both right anterior insular cortex (rAIC) and PCC were strongly correlated with the pupil diameter change rate (Figure 2 and Table 2)
Summary
Consensual changes in eye’s pupil size are strongly associated with neuromodulatory tone. Pupil dilations after activation of LC occur on a relatively slow time-scale (500–1000 ms) (Larsen and Waters, 2018) These findings strongly support the possibility to track pupil-related brain activity using neurovascular coupling through the fMRI blood oxygenation level-dependent (BOLD) signals, as evidenced by several experiments. It was found that it is not pupil size per se but the change rate of pupil diameter to be correlated with the BOLD signals in LC and other subcortical and cortical areas during resting state (Schneider et al, 2016) This notion is consistent with electrophysiological measurements in mice showing that, during both quiet waking and locomotion, pupil size is correlated with the cholinergic system, while its time derivative is correlated with the noradrenergic LC (Reimer et al, 2016). It is important to remark that fMRI is not able to resolve these dependencies, especially the correlations between regional brain activity and the highfrequency components of pupil dynamics
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