Summary: The overall goal of the proposal is to determine the role of the medial temporal lobe (MTL) in visual perception and working memory. Although it is well established that the MTL is critical for long term episodic memory, recent work has indicated that it also plays a critical role in visual perception and working memory, and that damage or age-related changes to this brain region can disrupt our ability to accurately perceive the visual world around us, particularly when encountering complex scenes such as when driving a car. However, the specific role that the MTL plays in supporting visual perception is just beginning to be fully understood, and there is now a growing debate about when these deficits will be observed, and which underlying brain processes are responsible. Answering these questions will have a transformative effect on our understanding of visual cognition, and advance our knowledge about how various diseases influence the human brain. In addition, they have important translational implications for a variety of populations suffering from damage to different regions within the MTL such as patients with Alzheimer’s Disease, Schizophrenia, depression, and even in healthy aged individuals. The current proposal will address these questions using a unique combination of psychophysical methods, novel eye tracking approaches, studies of patients with focal MTL lesions, and high-resolution brain imaging methods in healthy subjects. Psychophysical methods will be used in ‘same/different’, ‘change-detection’ and ‘flicker’ visual discrimination tasks for scenes and objects in order to separate the processes involved during initial feature sampling and those involved in supporting subsequent change detection, as well as allowing us to track how these processes change as more information is sampled from the environment. The series of studies is designed to directly test the predictions of competing theories, and, when possible, we pit the predictions of these different accounts against one another. We will examine performance in healthy controls and in patients with focal MTL lesions in order to determine whether regions in the MTL such as the hippocampus play a critical role in various perception conditions. Moreover, we will utilize high-resolution functional magnetic resonance imaging to identify the role of hippocampal subfields as well as the broader brain networks involved in perception. Importantly, these methods will be combined with novel analytic approaches to quantifying eye movements to determine how the visual system samples information from the environment (e.g., examining saccadic dispersion, visual resampling, as well as meaning- and salience-sampling), and using novel fixation-related brain imaging methods to identify the neural circuitry that is critical for accurate visual perception.