Many types of decisions that are important in everyday life are driven by the gradual accumulation of evidence favoring one possible outcome over another. The long-term goal of this line of research is to understand how individual brain areas and their interactions process information related to evidence accumulation to reach decisions. Previous work from this laboratory has determined how regions in the brain's cortex encode such information and has determined their temporally precise causal role in a rat model of perceptual decisions. The proposed experiments will study the specific contributions of two subcortical brain areas, the striatum and the superior colliculus, to decision-making. The overall objective of this application is to understand how decision- related information is encoded in each of these areas, whether each representation is required for decision-making, and exactly when during a task trial this information is needed. In addition, we will distinguish the causal roles of neural connections from frontal cortex to each area individually. We will achieve this objective by recording neural activity to examine the moment-by-moment electrophysiological signatures of evidence accumulation in these subcortical areas and compare them directly to decision variables from behavioral data. Then we will inactivate each of these areas or the projections to them to define whether, and when, such neural activity is required for accumulation of evidence. The contribution is significant because it will resolve several important questions about the flow of information across time and space in this circuit. The approach is innovative because this laboratory has developed tools that allow continuous, single-trial estimates of decision behavior variables along with precisely timed interference with task-relevant signals within and between brain regions. The work proposed in this application will therefore advance knowledge of how the encoding of information and interactions among brain regions lead to decisions. In the long run, we expect this research to produce a detailed understanding of how information flows through this brain circuit to produce decisions.

Public Health Relevance

The proposed research is relevant to public health because our ability to diagnose and treat conditions that impair decision-making, including aging and addiction, is currently limited by a lack of information about the detailed function of brain circuts that control decisions driven by the accumulation of evidence. Because of the evolutionary conservation of brain structure and function, the study of model organisms such as the rat should yield fundamental concepts that contribute to understanding the human brain. This work is therefore relevant to the NIMH mission to use fundamental knowledge about the brain to reduce the burden of disease.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
5R01MH108358-03
Application #
9310143
Study Section
Special Emphasis Panel (ZRG1-IFCN-Q (02)M)
Program Officer
Rossi, Andrew
Project Start
2015-09-02
Project End
2020-05-31
Budget Start
2017-06-15
Budget End
2018-05-31
Support Year
3
Fiscal Year
2017
Total Cost
$398,800
Indirect Cost
$148,800
Name
Princeton University
Department
Biochemistry
Type
Schools of Arts and Sciences
DUNS #
002484665
City
Princeton
State
NJ
Country
United States
Zip Code
08543
Piet, Alex T; El Hady, Ahmed; Brody, Carlos D (2018) Rats adopt the optimal timescale for evidence integration in a dynamic environment. Nat Commun 9:4265
Piet, Alex T; Erlich, Jeffrey C; Kopec, Charles D et al. (2017) Rat Prefrontal Cortex Inactivations during Decision Making Are Explained by Bistable Attractor Dynamics. Neural Comput 29:2861-2886
Brody, Carlos D; Hanks, Timothy D (2016) Neural underpinnings of the evidence accumulator. Curr Opin Neurobiol 37:149-157