Many of our everyday choices require a cost-benefit analysis across a range of decision variables (e.g. likelihood of success, size or quality of the payoff, amount of work required to achieve outcome). A recent model of decision-making has proposed that the orbitofrontal cortex (OFC) contributes to choice behavior by integrating all of the variables necessary to make a decision. Damage to the frontal lobe, including the OFC and the anterior cingulate cortex (ACC), impairs the ability to make optimal choices in our everyday lives. Dysfunction of these regions has also been associated with many neuropsychiatric illnesses where choice behavior is impaired, particularly disorders involving impulsive or compulsive choice behavior. This includes disorders such as obsessive-compulsive disorder (OCD), attention-deficit hyperactivity disorder (ADHD), pathological aggression, phobic and anxiety disorder, addiction and compulsive gambling. In severe cases, removal of the ACC has even been used as a treatment for pathological aggression, anxiety disorders and OCD. Yet it remains unclear how these distinct cortical areas contribute to choice behavior. We will test the hypothesis that OFC neurons encode all the parameters necessary to make a decision, by deriving an abstract value signal. We will simultaneously record the activity of single neurons in four different frontal areas (ACC, OFC, ventrolateral prefrontal cortex and dorsolateral prefrontal cortex) in awake, behaving monkeys while they choose between two pictures associated with different values varied along three physically different valuation scales. Specifically, monkeys will choose between one group of pictures that differ in their association with reward magnitude, one group in their association with the amount of effort required to earn a fixed reward, and a third group in the probability that a reward would be delivered. Additional experiments will manipulate the parameters underlying the choice, to determine precisely on what the value signal is based. Finally, we will investigate the functional interaction of the frontal lobe with the midbrain dopaminergic system, known to at least partially underlie ADHD. We will test the hypothesis that dopamine serves as a teaching signal, training neurons in the frontal lobe as to which choices are more optimal. The experiments in this project will help elucidate the anatomy, neurophysiology and neuropharmacology that underpin choice behavior, and in doing so, determine avenues of research directed towards the development of improved interventions and treatments for these disorders. ? ? ?

National Institute of Health (NIH)
National Institute of Mental Health (NIMH)
Postdoctoral Individual National Research Service Award (F32)
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Special Emphasis Panel (ZRG1-F02B-G (20))
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Curvey, Mary F
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University of California Berkeley
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Cavanagh, Sean E; Wallis, Joni D; Kennerley, Steven W et al. (2016) Autocorrelation structure at rest predicts value correlates of single neurons during reward-guided choice. Elife 5:
Hunt, Laurence T; Behrens, Timothy E J; Hosokawa, Takayuki et al. (2015) Capturing the temporal evolution of choice across prefrontal cortex. Elife 4:
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
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
Kennerley, Steven W; Dahmubed, Aspandiar F; Lara, Antonio H et al. (2009) Neurons in the frontal lobe encode the value of multiple decision variables. J Cogn Neurosci 21:1162-78
Kennerley, Steven W; Wallis, Jonathan D (2009) Evaluating choices by single neurons in the frontal lobe: outcome value encoded across multiple decision variables. Eur J Neurosci 29:2061-73
Kennerley, Steven W; Wallis, Jonathan D (2009) Reward-dependent modulation of working memory in lateral prefrontal cortex. J Neurosci 29:3259-70

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