. The brain systems that control our motivation, emotions, and decisions rely at their most fundamental level on predicting the future: learning what rewards and punishments to expect, when they will arrive, and how valuable they will be. It is only natural that we are strongly motivated to seek information that will reduce our uncertainty about future events. Indeed, not only do humans and other animals choose to observe cues that inform them about future motivational outcomes, they are willing to pay for the privilege ? and remarkably, they pay for information even when they cannot use it to influence the outcome, effectively treating the knowledge itself as a reward. Despite its importance in everyday decision making and clinical settings, little is known about how this information seeking behavior is generated and governed ? how the brain anticipates information, endows it with value, and sends it to motivational circuits to drive behavior. We identified set of anatomically connected cortical and subcortical brain areas, including the anterior cingulate cortex and specific subregions of the basal ganglia (BG), that encode the quantitative level of reward uncertainty. Does this set of brain areas mediate the drive to seek advance information to reduce uncertainty, and if so, how? Aim 1 will first test whether and how uncertainty-selective neurons in the cortico-BG network anticipate the arrival of information about future rewards and punishments. Preliminary data suggest that the cortico-BG network anticipates information that resolves reward uncertainty (as dissociated from simple anticipation of valuable and/or uncertain rewards). Next, aim 1 will transiently disrupt specific uncertainty- sensitive subregions in the cortico-BG network to assess their contributions to information seeking, and to neuronal activity in other subregions of the network. Preliminary data suggest that the information-anticipation signals in the BG play an active role in mediating information seeking.
Aim 2 will use a carefully designed decision-making paradigm in which primates pay to obtain information under different levels of reward uncertainty, combined with computational modelling, to quantitatively determine how information, uncertainty, and value signals in the cortico-BG network contribute to motivated decision making, including the evaluation of information, risk, and value. Next, aim 2 will use the same paradigm to elucidate information and reward value processing in the lateral habenula (LHb), a key structure for the control of motivation. Preliminary data indicate that BG information signals track the subjective value of obtaining information and that the LHb is a prime candidate for receiving these signals and generating information-seeking behavior.
The Aims represent crucial steps for our understanding of the neurobiology of motivated behavior, will broaden our understanding of the mechanisms of information seeking and uncertainty reduction, and will shed light on how brain areas known to be crucially involved in human psychiatric disorders, but that have not been commonly studied in the primate, contribute to our decisions and actions.

Public Health Relevance

. The control of behavior, at its most fundamental level, relies on the motivation to seek information about the future, so that we can make good predictions and adaptively adjust our expectations. Malfunctions in these processes are associated with psychiatric disorders and maladaptive behavioral states, such as anxiety, persistent risk-seeking, obsessive compulsive disorder, and drug-addiction. This project aims to discover how the brain controls information seeking, how it anticipates when new information will arrive and what it will tell us, and how it uses this information to help us make adaptive decisions about the future.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
5R01MH116937-03
Application #
10088480
Study Section
Neurobiology of Motivated Behavior Study Section (NMB)
Program Officer
Rossi, Andrew
Project Start
2019-04-10
Project End
2024-01-31
Budget Start
2021-02-01
Budget End
2022-01-31
Support Year
3
Fiscal Year
2021
Total Cost
Indirect Cost
Name
Washington University
Department
Neurosciences
Type
Schools of Medicine
DUNS #
068552207
City
Saint Louis
State
MO
Country
United States
Zip Code
63130