Summary

for people ages 18-40 (full criteria)
healthy people welcome
at Berkeley, California
study started
estimated completion

Description

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 we combine quantitative social measures, computational models, neuroimaging, and a pharmacological intervention to define the mechanisms of social decision-making.

Official Title

Dopaminergic Mechanisms Underlying Human Social Behavior: A Multimodal Approach

Details

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? We propose to leverage recent developments in economic theory and cognitive neuroscience to bridge this divide using a computational, model-based approach. In this proposal, we 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, we pursue two approaches to evaluate dopamine tone: one in which we use an FDA-approved medication, tolcapone, to influence dopamine metabolism, and one in which we perform PET imaging to measure dopamine release and baseline dopamine receptor D2/D3 occupancy. We 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, we 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. We thus seek to broaden our understanding of the computations and circuits underlying social behavior. Moreover, we 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.

Keywords

Decision Making Executive Function Dopamine Tolcapone Dopamine Agonists Tolcapone 200 MG Functional Magnetic Resonance Imaging (fMRI)

Eligibility

You can join if…

Open to people ages 18-40

  • Ages 18-40 and right-handed
  • Able to provide written informed consent
  • Normal or corrected-to-normal visual acuity
  • General good health as determined for tolcapone studies by screening provider (Dr. Kayser, Dr.Jagust, or other approved, licensed clinician)

You CAN'T join if...

  • Regular and/or scheduled use of other neuro- or psycho-active medications
  • Severe low blood pressure or uncontrolled high blood pressure
  • IQ < 70 as assessed by the Wechsler Test of Adult Reading (WTAR)
  • History of mild, moderate, or severe traumatic brain injury
  • History of brain surgery (i.e. violating brain parenchyma) or penetrating brain injury
  • Active alcohol dependence or alcohol abuse by DSM-IV-TR criteria (within previous 30 days)
  • Active substance dependence or substance abuse by DSM-IV-TR criteria (excluding nicotine, but including marijuana, opiates, stimulants (cocaine, amphetamines), and hallucinogens within previous 30 days)
  • History of suicide attempt (last 5 years)
  • Clinically severe medical illness requiring treatment
  • History of brain tumor, stroke, demyelinating disease, encephalitis, or cerebral aneurysm rupture
  • Clinical diagnosis of Alzheimer's disease or other primary neurodegenerative disorder
  • Schizophrenia or other psychiatric disturbances

For Subjects Undergoing fMRI Scanning:

  • Contraindications to MRI (e.g. unremovable ferromagnetic metals, claustrophobia)
  • Inability to complete basic fMRI requirements (e.g. to make button presses and to minimize movement < 5mm)
  • Women of childbearing potential take a urine pregnancy test prior to scanning.

For Tolcapone Experiments:

  • Contraindications to tolcapone use, including liver function tests elevated more than 2.5 times above normal ranges, pregnancy, previous adverse reaction to tolcapone, significant liver or kidney impairment
  • Current use (within previous 30 days) of pharmacological agents with dopaminergic actions, including but not limited to levodopa/carbidopa, entacapone, tolcapone, amantadine, bromocriptine, pergolide, pramipexole, ropinirole, selegeline, isocarboxazid, phenelzine, tranylcypromine, clozapine, olanzapine, quetiapine, risperidone, ziprasidone, aripiprazole, fluphenazine, haloperidol, perphenazine, pimozide, thiothixene, trifluoperazine, loxapine, molindone, chlorpromazine, mesoridazine, thioridazine, promethazine, dextroamphetamine, dexmethylphenidate, dextroamphetamine, or methylphenidate

Location

  • University of California, Berkeley accepting new patients
    Berkeley California 94720 United States

Details

Status
accepting new patients
Start Date
Completion Date
(estimated)
Sponsor
University of California, Berkeley
ID
NCT04205994
Phase
Phase 1
Study Type
Interventional
Last Updated