Matthew R. Kleinman - US grants

DESCRIPTION (provided by applicant): Temporal information is used by humans and animals in a wide variety of situations, including learning action- outcome contingencies by understanding temporal proximity often implies causal relationships, planning a sequence of movements to achieve a goal, and interpreting a silence in a conversation as a short pause or an invitation to interject, depending on its duration. Furthermore, humans frequently must attend to many concurrent intervals; driving to work, a commuter can simultaneously estimate when the traffic light will turn green, whether they will be late to work, and how much longer until the weekend. Despite the importance of timing, the neurophysiological basis of temporal perception is largely unknown. Recent findings suggest prefrontal cortex may subserve some functions related to timing, but whether these same signals represent some other time-dependent task variable or also occur during other conditions, such as simultaneous timing, is unclear. The main aim of this research proposal is to pinpoint the single neuron activity underlying timing of concurrent intervals. First, I will use a novel behavioral paradigm to investigate whether non-human primates can accurately estimate multiple elapsing intervals simultaneously. Next, I will perform extracellular single unit electrophysiological recordings to determine how individual neurons in several prefrontal cortical regions encode elapsed duration (in addition to other variables) in the behavioral task. Finally, I will perform recordings after modifying the behaviora task to further isolate elapsed duration per se from other time-varying variables, such as reward expectation. Together, this set of experiments will directly answer the question of how time is represented at the neural level when there are multiple intervals being tracked behaviorally and will provide deep insight into the possible circuit-level implementations of a cognitive clock. PUBLIC HEALTH RELEVANCE: An accurate internal understanding of the passage of time is essential for many perceptual and cognitive mental processes. Disturbances in temporal perception are observed in a number of common disorders, ranging from attention-deficit hyperactivity disorder to substance abuse, and may underlie the deficits in planning and insensitivity to future outcomes that characterize these conditions. More fully understanding the cognitive and neural basis of the sense of time will lead to new understandings of, and potentially new treatments for, the timing-related symptoms of these disorders.