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Theses Doctoral

Characterization of the functional consequences of pupil-linked arousal during perceptual decision-making

Schriver, Brian James

The overarching purpose of this work is to expand the utility of pupillometry as a non-invasive index of pupil-linked neuromodulatory systems, which are correlated with behavior states and are integral in carrying out complex behaviors, such as decision-making. The work characterizes tonic pupil dynamics and their relation to brain state and behavior (B. J. Schriver, S. Bagdasarov, & Q. Wang, 2018), characterizes the mechanisms and functional consequences behind phasic arousal linked pupil dynamics, and examines the causal role of the locus coeruleus in mediating the relationship between pupil dynamics, arousal, and ultimately behavior.

For characterization of tonic pupil dynamics in the awake, behaving animal, rats were shown to be able to discriminate between directions of whisker deflections in a Go/No-Go behavioral paradigm with behavioral outcomes being associated with unique pupil dynamics. Furthermore, pupil baseline was inversely correlated with pupil dilation. Our work found that the behavior of rats performing the tactile discrimination task was highly dependent on pupil-indexed level of arousal. Pupil baseline exhibited an inverted U-shaped relationship with perceptual sensitivity and a U-shaped relationship with decision criterion. Shorter reaction times were also associated with higher perceptual sensitivity, more liberal decision criterion, and larger pupil baseline. We also found that behavioral outcomes influenced upcoming pupil dynamics and behavior. Altogether, we observed that there existed tight correlations between pupil dynamics, perceptual performance, and reaction time, all of which were influenced by fluctuating behavior state.

For characterization of the mechanisms and functional consequences behind phasic pupil dynamics in the awake, behaving animal, task-evoked pupil responses were first shown to differ according to their underlying cognitive processes. Task-evoked pupil responses are composed of a superposition of elementary components and this work showed that individual responses could be decomposed into the sum of their weighted, time-locked generalizable pupil-linked phasic arousal inputs. These phasic arousal inputs were separate from inputs controlling baseline related arousal fluctuations. We found distinct contributions to phasic arousal were made by stimulus encoding and decision-formation. Looking at these independently suggested differences in the underlying phasic arousal related mechanisms in driving the animals towards outcomes contingent on stimulus identity. Furthermore, drift-diffusion modeling revealed that interplay between phasic arousal evoked by both stimulus encoding and decision formation had important functional consequences on forming behavioral choice in perceptual decision-making.

We also observed a central role of the locus coeruleus-norepinephrine (LC-NE) system in modulating pupil-linked behavioral state. Both electrical and optogenetic activation of the LC-NE system mediated pupil dilation. Furthermore, trial-by-trial LC-NE system activation via channelrhodopsin-2 (ChR2) increased perceptual sensitivity in a difficulty dependent manner, with more pronounced improvement occurring when distracting stimuli were more similar to the target stimulus.

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More About This Work

Academic Units
Biomedical Engineering
Thesis Advisors
Wang, Qi
Degree
Ph.D., Columbia University
Published Here
January 30, 2020