Dopaminergic Mechanisms Underlying Human Social Behavior

Early Phase 1

Completed

• Conditions: Decision Making; Executive Function; Dopamine
• Interventions: Drug: Tolcapone 200 MG; Other: Functional Magnetic Resonance Imaging (fMRI)

• Registration Number: NCT04205994
• Lead Sponsor: University of California, Berkeley

Brief Summary

Developing theoretical, quantitative models of the basic cognitive mechanisms underlying human social decision-making, and understanding the influence of neuromodulators such as dopamine on these mechanisms, has important ramifications for both healthy and patient populations. In this proposal the investigators combine quantitative social measures, computational models, neuroimaging, and a pharmacological intervention to define the mechanisms of social decision-making.

Detailed Description

A significant challenge for understanding social dysfunctions observed in mental illness is to link high-level theories of social behavior and cognition with the computations performed by brain circuits. Specifically, how does the brain translate social perception into social valuation, and how does such valuation influence social actions? Investigators propose to leverage recent developments in economic theory and cognitive neuroscience to bridge this divide using a computational, model-based approach. In this proposal, investigators hypothesize that social behavior is underpinned by brain mechanisms that are influenced by the neurotransmitter dopamine, and that these mechanisms can be captured by computational models that integrate internal representations of social experience, and parameters relevant to dopamine tone, to inform social actions. Social valuation thus critically, and quantitatively, depends upon both internal social representations and the neurochemistry of the actor within the social environment. To assess this hypothesis, investigators pursue two approaches to evaluate dopamine tone: one in which investigators use an FDA-approved medication, tolcapone, to influence dopamine metabolism, and one in which investigators perform Positron Emission Tomography (PET) imaging to measure dopamine release and baseline dopamine receptor D2/D3 occupancy. Investigators then apply a model of social valuation to subjects' behavior, and search for neural correlates of this valuation using functional MRI (fMRI). To this end, investigators bring together a group of experts in (1) the neuroeconomics and modeling of social and non-social decision-making, (2) cognitive neuroscience, (3) the pharmacology of frontostriatal circuits, and (4) neuroimaging. Investigators thus seek to broaden our understanding of the computations and circuits underlying social behavior. Moreover, investigators believe that a model-based understanding of these behaviors and neural circuits may guide more robust predictions of the effects of pharmacological manipulations on social valuation, and provide quantitative tools to assess the effects of such manipulations in patient populations, with possible therapeutic implications.

Study Timeline

• Study Start: 2019-12-01
• Study First Submitted: 2019-12-18
• Study First Submitted QC: 2019-12-18
• Study First Posted: 2019-12-20
• Primary Completion: 2023-12-31
• Study Completion: 2023-12-31
• Status Verified: 2024-05
• Last Update Submitted: 2024-05-14
• Last Update Posted: 2024-05-16

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 70

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Tolcapone	Functional Magnetic Resonance Imaging (fMRI)	Tolcapone is a brain penetrant catechol-O-methyltransferase (COMT) inhibitor. It will be administered in a single 200mg dosage once in randomized, double-blind, counterbalanced fashion with a placebo.
Placebo	Functional Magnetic Resonance Imaging (fMRI)	Placebo will be administered in a single pill once in randomized, double-blind, counterbalanced fashion with a placebo.
Tolcapone	Tolcapone 200 MG	Tolcapone is a brain penetrant catechol-O-methyltransferase (COMT) inhibitor. It will be administered in a single 200mg dosage once in randomized, double-blind, counterbalanced fashion with a placebo.

Primary Outcome Measures

Name	Time	Method
Behavioral responses in neuroeconomic tasks	Up to 4 weeks	Subjects will make financial decisions involving themselves and another person in the context of model-based neuroeconomic games.
Blood oxygen level dependent (BOLD) activity	Up to 4 weeks	BOLD activity represents an indirect measure of brain activity, and will be correlated with behavioral task performance.

Trial Locations

Locations (1)

University of California, Berkeley; 🇺🇸 Berkeley, California, United States