Phase of pupillary unrest corresponds with perceptual sensitivity, MEG, and whole brain fMRI signals

2468 

Abstract Submission 

Victoria Gobo¹, Javier Gonzalez-Castillo¹, Joshua Teves¹, Micah Holness¹, Peter Bandettini¹, Sharif Kronemer¹

¹National Institute of Mental Health, Bethesda, MD

Victoria Gobo  
National Institute of Mental Health
Bethesda, MD

Javier Gonzalez-Castillo, PhD  
National Institute of Mental Health
Bethesda, MD

Joshua Teves  
National Institute of Mental Health
Bethesda, MD

Micah Holness  
National Institute of Mental Health
Bethesda, MD

Peter Bandettini, Ph.D.  
National Institute of Mental Health
Bethesda, MD

Sharif Kronemer  
National Institute of Mental Health
Bethesda, MD

Perceptual sensitivity – the likelihood of perceiving a sensory event – is closely linked to arousal state that is regulated by neuromodulatory activity from the thalamus and brainstem (Setzer, B. et al. 2022). A practical challenge is that these subcortical, arousal network foci are difficult to record from in humans. Therefore, an accessible, proxy measure of arousal would have numerous clinical and experimental benefits. One possible candidate is the spontaneous fluctuations in pupil size – pupillary unrest – independent of light stimulation. Previous research finds that changes in pupil size correspond to widespread subcortical and cortical activity across species (e.g., Bradshaw, J. 1967; Kronemer et al. 2022). To evaluate the relationship between the phase of pupillary unrest and perception sensitivity and brain activity, we aimed to: (1) examine how perceptual sensitivity changes are linked with the phase of pupillary unrest and (2) track and map the brain activity associated with the phase of pupillary unrest.

Healthy, adult participants (N = 4; Target N = 35) completed closed-loop auditory and visual perception tasks coupled with concurrent pupillometry (EyeLink 1000 Plus; SR Research, Inc.) and magnetoencephalography (MEG; 275-channel system; CTF Systems, Inc., Canada). The perception tasks involved a novel algorithm that detected four pupil phase events in real time: (1) local minima (troughs), (2) local maxima (peaks), (3) dilation, and (4) constriction periods. When a pupil phase event was detected, a near-perceptual threshold auditory tone was played in the left or right ear (auditory paradigm) or a near-perceptual threshold image was shown on the left or right side of the screen (visual paradigm). The participants were prompted to respond with a button press if they perceived the stimuli and indicate its location (either ear or screen side). In addition, a pupil phase independent stimulus condition presented stimuli at random, which served as a control. To map the brain networks linked with pupil phase, including subcortical regions inaccessible with MEG we analyzed a large (N > 100) healthy, adult human resting state fMRI dataset with concurrent pupillometry (7T; Human Connectome Project [HCP]). HCP pupillometry timecourses were analyzed retroactively to detect the pupil phase events. The whole brain fMRI signal preceding and following the pupil phase events were examined.

Preliminary results demonstrate that the phase of pupillary unrest predicts perceptual sensitivity in audition and vision: decreased perception rate relative to baseline (i.e., random condition) perceptual sensitivity during constriction pupil phases (Figure 1). This result corresponds with MEG findings that show field potential divergences preceding pupil phase events. Particularly, field potential increases in parietal-occipital areas of the scalp are associated with pupil dilation and decreases with pupil constriction (Figure 2A). Finally, fMRI signals suggest that the areas most correlated with pupil phase are among sensory and arousal networks sites, including primary visual cortex and thalamus (Figure 2B).

The phase of pupillary unrest may offer a real time readout of arousal state that previous research finds linked with behavior, cognition, and perception. Preliminary results demonstrate that pupil phase predicts perceptual sensitivity for auditory and visual stimuli. These perception state changes can be linked with field potentials in parietal-occipital scalp areas. In addition, fMRI signal divergences in sensory and arousal networks were observed according to the pupil phase. These results have the potential to elucidate the timecourse and neural origin of conscious state in healthy neurophysiology.

EEG/MEG Modeling and Analysis

Consciousness and Awareness ¹

Perception: Auditory/ Vestibular

Perception: Multisensory and Crossmodal ²

Perception: Visual

FUNCTIONAL MRI

MEG

Perception

Vision

Other - Arousal, Closed-loop