All cognitive operations including perceptual and motor processes unfold in time, and actions lead to successful outcomes only when they are executed at appropriate times. However, controlling multiple actions and monitoring their outcomes over a relatively long temporal interval poses challenging computational problems for the brain. Moreover, the ability to utilize temporal information is impaired in various psychiatric and neurological disorders, including attention-deficit/hyperactivity disorder (ADHD), Parkinson's disease, and substance abuse. Despite such broad theoretical and clinical significance, previous neurobiological studies on timing behavior and temporal decision-making have focused narrowly on the brain functions related to a single temporal interval or a unitary reward. The main goal of this proposal is to gain novel insights into the neural mechanisms capable of concurrently monitoring multiple temporal intervals and evaluating the value of multiple outcomes in a sequence. First, we will investigate the anatomical specificity of timing signals in the medial and lateral areas of the primate prefrontal cortex using a task that requires the animal to plan different actions according to two concurrent temporal intervals. We will test the hypothesis that the medial prefrontal cortex plays a special role in creating the internal timing signals from transient sensory events and transforming them into motor responses. Second, we will study the mechanism in the fronto-parietal network for integrating the values of multiple rewards in a sequence while the animal chooses between two separate temporally extended reward sequences. Specifically, we hypothesize that the flexible transformation of signals related to reward magnitude between the posterior parietal cortex and prefrontal cortex underlies the process of integrating the values of individual rewards into a single decision variable. The results from these two experiments will advance our knowledge about how the brain handles the timing information about multiple events efficiently, and lay the foundation for understanding the nature of clinical conditions with impaired abilities to process temporal information.

Public Health Relevance

Costs of mental illnesses to society are substantial, but the precise nature of underlying neural impairments responsible for cognitive and behavioral deficits remains unknown. In particular, many psychiatric disorders are characterized by impaired abilities to control behaviors temporally. Proposed studies will elucidate the cortical mechanisms for monitoring multiple temporal intervals and evaluating a sequence of multiple outcomes.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
5R01MH108629-04
Application #
9593030
Study Section
Mechanisms of Sensory, Perceptual, and Cognitive Processes Study Section (SPC)
Program Officer
Rossi, Andrew
Project Start
2015-12-15
Project End
2020-11-30
Budget Start
2018-12-01
Budget End
2019-11-30
Support Year
4
Fiscal Year
2019
Total Cost
Indirect Cost
Name
Yale University
Department
Neurosciences
Type
Schools of Medicine
DUNS #
043207562
City
New Haven
State
CT
Country
United States
Zip Code
06520
Constantinidis, Christos; Funahashi, Shintaro; Lee, Daeyeol et al. (2018) Persistent Spiking Activity Underlies Working Memory. J Neurosci 38:7020-7028
Massi, Bart; Donahue, Christopher H; Lee, Daeyeol (2018) Volatility Facilitates Value Updating in the Prefrontal Cortex. Neuron 99:598-608.e4
Farashahi, Shiva; Donahue, Christopher H; Khorsand, Peyman et al. (2017) Metaplasticity as a Neural Substrate for Adaptive Learning and Choice under Uncertainty. Neuron 94:401-414.e6
Farashahi, Shiva; Rowe, Katherine; Aslami, Zohra et al. (2017) Feature-based learning improves adaptability without compromising precision. Nat Commun 8:1768
Kleinman, Matthew R; Sohn, Hansem; Lee, Daeyeol (2016) A two-stage model of concurrent interval timing in monkeys. J Neurophysiol 116:1068-81