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1.  How Costs Influence Decision Values for Mixed Outcomes 
The things that we hold dearest often require a sacrifice, as epitomized in the maxim “no pain, no gain.” But how is the subjective value of outcomes established when they consist of mixtures of costs and benefits? We describe theoretical models for the integration of costs and benefits into a single value, drawing on both the economic and the empirical literatures, with the goal of rendering them accessible to the neuroscience community. We propose two key assays that go beyond goodness of fit for deciding between the dominant additive model and four varieties of interactive models. First, how they model decisions between costs when reward is not on offer; and second, whether they predict changes in reward sensitivity when costs are added to outcomes, and in what direction. We provide a selective review of relevant neurobiological work from a computational perspective, focusing on those studies that illuminate the underlying valuation mechanisms. Cognitive neuroscience has great potential to decide which of the theoretical models is actually employed by our brains, but empirical work has yet to fully embrace this challenge. We hope that future research improves our understanding of how our brain decides whether mixed outcomes are worthwhile.
PMCID: PMC3481112  PMID: 23112758
cost-benefit analysis; decision-making; decision-making and neuroeconomics; economic models; reward; punishment; aversive decision-making
2.  Dopamine, Time, and Impulsivity in Humans 
Disordered dopamine neurotransmission is implicated in mediating impulsiveness across a range of behaviors and disorders including addiction, compulsive gambling, attention-deficit/hyperactivity disorder, and dopamine dysregulation syndrome. Whereas existing theories of dopamine function highlight mechanisms based on aberrant reward learning or behavioral disinhibition, they do not offer an adequate account of the pathological hypersensitivity to temporal delay that forms a crucial behavioral phenotype seen in these disorders. Here we provide evidence that a role for dopamine in controlling the relationship between the timing of future rewards and their subjective value can bridge this explanatory gap. Using an intertemporal choice task, we demonstrate that pharmacologically enhancing dopamine activity increases impulsivity by enhancing the diminutive influence of increasing delay on reward value (temporal discounting) and its corresponding neural representation in the striatum. This leads to a state of excessive discounting of temporally distant, relative to sooner, rewards. Thus our findings reveal a novel mechanism by which dopamine influences human decision-making that can account for behavioral aberrations associated with a hyperfunctioning dopamine system.
PMCID: PMC3059485  PMID: 20592211
3.  Encoding of marginal utility across time in the human brain 
Marginal utility theory prescribes the relationship between the objective property of the magnitude of rewards and their subjective value. Despite its pervasive influence, however, there is remarkably little direct empirical evidence for such a theory of value, let alone of its neurobiological basis. We show that human preferences in an inter-temporal choice task are best described by a model that integrates marginally diminishing utility with temporal discounting. Using functional magnetic resonance imaging (fMRI), we show that activity in the dorsal striatum encodes both the marginal utility of rewards, over and above that which can be described by their magnitude alone, and the discounting associated with increasing time. In addition, our data show that dorsal striatum may be involved in integrating subjective valuation systems inherent to time and magnitude, thereby providing an overall metric of value used to guide choice behaviour. Furthermore, during choice we show that anterior cingulate activity correlates with the degree of difficulty associated with dissonance between value and time. Our data support an integrative architecture for decision-making, revealing the neural representation of distinct subcomponents of value that may contribute to impulsivity and decisiveness.
PMCID: PMC2816907  PMID: 19641120
Utility; Intertemporal; fMRI; striatum; decision-making; impulsivity
4.  BioNetBuilder2.0: bringing systems biology to chicken and other model organisms 
BMC Genomics  2009;10(Suppl 2):S6.
Systems Biology research tools, such as Cytoscape, have greatly extended the reach of genomic research. By providing platforms to integrate data with molecular interaction networks, researchers can more rapidly begin interpretation of large data sets collected for a system of interest. BioNetBuilder is an open-source client-server Cytoscape plugin that automatically integrates molecular interactions from all major public interaction databases and serves them directly to the user's Cytoscape environment. Until recently however, chicken and other eukaryotic model systems had little interaction data available.
Version 2.0 of BioNetBuilder includes a redesigned synonyms resolution engine that enables transfer and integration of interactions across species; this engine translates between alternate gene names as well as between orthologs in multiple species. Additionally, BioNetBuilder is now implemented to be part of the Gaggle, thereby allowing seamless communication of interaction data to any software implementing the widely used Gaggle software. Using BioNetBuilder, we constructed a chicken interactome possessing 72,000 interactions among 8,140 genes directly in the Cytoscape environment. In this paper, we present a tutorial on how to do so and analysis of a specific use case.
BioNetBuilder 2.0 provides numerous user-friendly systems biology tools that were otherwise inaccessible to researchers in chicken genomics, as well as other model systems. We provide a detailed tutorial spanning all required steps in the analysis. BioNetBuilder 2.0, the tools for maintaining its data bases, standard operating procedures for creating local copies of its back-end data bases, as well as all of the Gaggle and Cytoscape codes required, are open-source and freely available at
PMCID: PMC2966329  PMID: 19607657

Results 1-4 (4)