Pupillometry in Vision, Arousal and Cognition: an Integrated Approach Using Oculomotor and Autonomic Responses, Brain Stimulation, and Computational Modeling(5/5)

Developing an effective low-cost method for understanding human brain functions in health and disease is one of the most pressing challenges in psychology and neuroscience. Although pupil size is becoming one of the most promising indices for cognitive and neural processing, neural mechanisms underlying these pupil size modulations remain unclear. Pupil size controlled by the sympathetic and parasympathetic nervous systems changes mainly in response to luminance levels of the environment with larger pupil sizes for lower luminance levels. This illumination-dependent pupil modulation is thought to balance the trade-off between sensitivity and sharpness for the optimization of image quality. However, research that directly examines this assumption is surprisingly limited. The influence of physical pupil size on visual detection or discrimination is largely unknown. Moreover, cumulative evidence has documented that pupil size is also intertwined with not only changes in arousal but also demanding in cognition. Although both arousal and cognitive processes evoke pupil dilation, the resulted behavioral consequences and their underlying neural mechanisms could be different. The locus coeruleus (LC), a subcortical structure arguably underlying relationships between pupil size and arousal, is also importantly involved in cognitive aging brain. LC neuronal loss is considered one of the characteristic pathologies for early-stage Alzheimer's disease (AD). However, how the arousal-related pupil modulation is affected in AD is yet to be explored. The goal of the proposal is 1) to investigate the functional role of pupil size in visual processing with simultaneous recording of autonomic responses to differentiate pupil size from arousal effects (in collaboration with Prof. MUNOZ at Queen’s University to perform parallel experiments with neuronal recording in the superior colliculus (SC) and V1 on behaving monkeys); 2) to understand the resulted processing consequences from increasing arousal level or cognitive demand (in collaboration with Prof. ITTI at University of Southern California to build a computational model for these two pupil modulations); 3) to understand the neural mechanisms (LC-centered and SC-centered pathways) and the sympathetic and parasympathetic contributions on the arousal- and cognitionrelated pupil modulations using a pharmacological method and transcranial direct current stimulation; 4) to understand the link between the arousal-related pupil modulation and LC pathology for early diagnosis of Alzheimer’s disease using AD animal models with classifier computational model (in collaboration with Profs. FERREIRA and DEFELICE at Federal University and Prof. ITTI). Through a combination of causal and correlational methodologies, I will build an integrated framework on the complex and dynamic interaction between vision, cognition, arousal, autonomic, and oculomotor functions. These research questions will be addressed by multidisciplinary approaches that utilize the insights from psychology, physiology, neuroscience, biology, and computer science.