The neural mechanisms underlying choice behavior are important for understanding addiction, a characteristic of which is a failure to exert control over choices. The frontal lobe is critical to choice behavior since damage to this region produces specific impairments in decision-making. Two areas of the frontal lobe are of particular interest: anterior cingulate cortex (ACC) and orbitofrontal cortex (OFC). Tasks that require decision-making and choice behavior consistently activate both areas, and both areas contain neurons that encode various aspects related to the value of choice alternatives. In addition, both ACC and OFC are involved in addiction: addicts show structural and functional changes in the two areas. However, we have little understanding about what each area independently contributes to the process of choice behavior. To determine this, we will use neurophysiological techniques to record simultaneously from both areas while subjects are engaged in tasks designed to involve either ACC or OFC. We will compare and contrast the functional properties of ACC and OFC neurons.
Our aim i s to dissociate the functions of the two areas based on their neurophysiological properties there by providing a deeper understanding of the role that they play in addiction. Theoretical frameworks of choice behavior highlight two processes that must occur. First, the individual must predict the likely outcome of selecting either alternative. Second, the individual must evaluate the predicted outcomes in order to determine which is more valuable. The anatomy of ACC and OFC suggests the differential contribution that the two areas may make to these processes. ACC and OFC both connect with areas responsible for processing reward-related information. However, ACC strongly connects with motor areas and only weakly with sensory areas, while OFC shows the opposite pattern. Thus, the first hypothesis we will test is that ACC neurons predict outcomes associated with different behavioral responses whereas OFC neurons predict outcomes associated with environmental stimuli. We will test this hypothesis by recording the activity of ACC and OFC neurons during tasks where the subject has to base choices on response- outcome or stimulus-outcome associations. The second hypothesis we will test is that ACC, but not OFC, evaluates the amount of effort necessary to earn a payoff. We will test this hypothesis by contrasting the encoding of ACC and OFC neurons during a task that requires our subject to integrate an outcome's value (which we manipulate by varying the magnitude of a juice reward) with the effort required to obtain the outcome (which we manipulate using a torque adjustable lever that the subject must press to earn the reward). To summarize, our specific aims are as follows: 1. Determine the contribution of ACC and OFC to the process of predicting outcomes associated with responses or stimuli respectively 2. Determine the contribution of ACC and OFC to the evaluation of effort-based choices

Public Health Relevance

This project focuses on the anterior cingulate cortex (ACC) and orbitofrontal cortex (OFC), two areas of the brain that show structural and functional changes in people addicted to drugs. We will record the electrical activity from neurons in both areas during two tasks designed to tax different aspects of choice behavior. Addiction is characterized by a difficulty in exerting control over choice behavior, and so understanding the physiological underpinnings of this process could allow us to develop novel therapeutic strategies for the treatment of addictive behavior.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Research Project (R01)
Project #
5R01DA019028-09
Application #
8490320
Study Section
Neurobiology of Motivated Behavior Study Section (NMB)
Program Officer
Volman, Susan
Project Start
2004-12-01
Project End
2015-06-30
Budget Start
2013-07-01
Budget End
2014-06-30
Support Year
9
Fiscal Year
2013
Total Cost
$349,898
Indirect Cost
$117,098
Name
University of California Berkeley
Department
Neurosciences
Type
Organized Research Units
DUNS #
124726725
City
Berkeley
State
CA
Country
United States
Zip Code
94704
Lara, Antonio H; Wallis, Jonathan D (2014) Executive control processes underlying multi-item working memory. Nat Neurosci 17:876-83
Rich, Erin L; Wallis, Jonathan D (2014) Medial-lateral organization of the orbitofrontal cortex. J Cogn Neurosci 26:1347-62
Hosokawa, Takayuki; Kennerley, Steven W; Sloan, Jennifer et al. (2013) Single-neuron mechanisms underlying cost-benefit analysis in frontal cortex. J Neurosci 33:17385-97
Lara, Antonio H; Wallis, Jonathan D (2012) Capacity and precision in an animal model of visual short-term memory. J Vis 12:
Wallis, Jonathan D (2012) Cross-species studies of orbitofrontal cortex and value-based decision-making. Nat Neurosci 15:13-9
Wallis, Jonathan D; Kennerley, Steven W (2011) Contrasting reward signals in the orbitofrontal cortex and anterior cingulate cortex. Ann N Y Acad Sci 1239:33-42
Kennerley, Steven W; Behrens, Timothy E J; Wallis, Jonathan D (2011) Double dissociation of value computations in orbitofrontal and anterior cingulate neurons. Nat Neurosci 14:1581-9
Canolty, Ryan T; Ganguly, Karunesh; Kennerley, Steven W et al. (2010) Oscillatory phase coupling coordinates anatomically dispersed functional cell assemblies. Proc Natl Acad Sci U S A 107:17356-61
Wallis, Jonathan D; Kennerley, Steven W (2010) Heterogeneous reward signals in prefrontal cortex. Curr Opin Neurobiol 20:191-8
Luk, Chung-Hay; Wallis, Jonathan D (2009) Dynamic encoding of responses and outcomes by neurons in medial prefrontal cortex. J Neurosci 29:7526-39

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