From genes to behavior: placing cognitive models in the context of biological pathways.

Connecting neural mechanisms of behavior to their underlying molecular and genetic substrates has important scientific and clinical implications. However, despite rapid growth in our knowledge of the functions and computational properties of neural circuitry underlying behavior in a number of important domains, there has been much less progress in extending this understanding to their molecular and genetic substrates, even in an age marked by exploding availability of genomic data. Here we describe recent advances in analytical strategies that aim to overcome two important challenges associated with studying the complex relationship between genes and behavior: (i) reducing distal behavioral phenotypes to a set of molecular, physiological, and neural processes that render them closer to the actions of genetic forces, and (ii) striking a balance between the competing demands of discovery and interpretability when dealing with genomic data containing up to millions of markers. Our proposed approach involves linking, on one hand, models of neural computations and circuits hypothesized to underlie behavior, and on the other hand, the set of the genes carrying out biochemical processes related to the functioning of these neural systems. In particular, we focus on the specific example of value-based decision-making, and discuss how such a combination allows researchers to leverage existing biological knowledge at both neural and genetic levels to advance our understanding of the neurogenetic mechanisms underlying behavior

Three perspectives on social decision-making

The three essays herein explore social decision-making at various scopes and for various ends. At the biological level, substantial progress has been made at the neural level in characterizing the dopaminergic and frontostriatal mechanisms mediating how we learn to adapt in such settings. Chapter \ref{chap:learning} describes research in which we combined computational modeling of strategic learning with a pathway approach to characterize association of strategic behavior with variations in the dopamine pathway. Our findings highlight dissociable roles of frontostriatal systems in strategic learning and support the notion that genetic variation, organized along specific pathways, forms an important source of variation in complex phenotypes such as strategic behavior. Even crudely biased information may be persuasive when people are not fully rational. For Chapter \ref{chap:persuasion}, using novel sender-receiver experiments, I evaluate 78 individuals' cognitive susceptibility to persuasion by comparing the relative influences of truthful strategic and non-strategic signals. The main finding is that people underestimate and undercorrect for bias. Consistent with an anchor-and-adjust heuristic, higher cognitive cost negatively affects the size of bias correction. Finally, for the research in Chapter \ref{chap:collusion} I studied the role of social preferences in inciting collusion by asking 282 online participants how they might behave in a sequential game of chance (a hidden die game) with hypothetical partners and possible cheating. Extending previous findings, I found evidence of types that are predicted by a measure of social preferences. Many people are willing to collude, given the chance. Some always refuse, even disrupting attempts at collusion. And a sizable middle are honest when only one other person colludes, but dishonest when two other people collude prior to the subject. This last group tend to prefer more altruistic options in a dictator game

Three perspectives on social decision-making

The three essays herein explore social decision-making at various scopes and for various ends. At the biological level, substantial progress has been made at the neural level in characterizing the dopaminergic and frontostriatal mechanisms mediating how we learn to adapt in such settings. Chapter \ref{chap:learning} describes research in which we combined computational modeling of strategic learning with a pathway approach to characterize association of strategic behavior with variations in the dopamine pathway. Our findings highlight dissociable roles of frontostriatal systems in strategic learning and support the notion that genetic variation, organized along specific pathways, forms an important source of variation in complex phenotypes such as strategic behavior. Even crudely biased information may be persuasive when people are not fully rational. For Chapter \ref{chap:persuasion}, using novel sender-receiver experiments, I evaluate 78 individuals' cognitive susceptibility to persuasion by comparing the relative influences of truthful strategic and non-strategic signals. The main finding is that people underestimate and undercorrect for bias. Consistent with an anchor-and-adjust heuristic, higher cognitive cost negatively affects the size of bias correction. Finally, for the research in Chapter \ref{chap:collusion} I studied the role of social preferences in inciting collusion by asking 282 online participants how they might behave in a sequential game of chance (a hidden die game) with hypothetical partners and possible cheating. Extending previous findings, I found evidence of types that are predicted by a measure of social preferences. Many people are willing to collude, given the chance. Some always refuse, even disrupting attempts at collusion. And a sizable middle are honest when only one other person colludes, but dishonest when two other people collude prior to the subject. This last group tend to prefer more altruistic options in a dictator game.U of I OnlyAuthor requested U of Illinois access only (OA after 2yrs) in Vireo ETD syste

Dopamine modulates egalitarian behavior in humans.

Egalitarian motives form a powerful force in promoting prosocial behavior and enabling large-scale cooperation in the human species [1]. At the neural level, there is substantial, albeit correlational, evidence suggesting a link between dopamine and such behavior [2, 3]. However, important questions remain about the specific role of dopamine in setting or modulating behavioral sensitivity to prosocial concerns. Here, using a combination of pharmacological tools and economic games, we provide critical evidence for a causal involvement of dopamine in human egalitarian tendencies. Specifically, using the brain penetrant catechol-O-methyl transferase (COMT) inhibitor tolcapone [4, 5], we investigated the causal relationship between dopaminergic mechanisms and two prosocial concerns at the core of a number of widely used economic games: (1) the extent to which individuals directly value the material payoffs of others, i.e., generosity, and (2) the extent to which they are averse to differences between their own payoffs and those of others, i.e., inequity. We found that dopaminergic augmentation via COMT inhibition increased egalitarian tendencies in participants who played an extended version of the dictator game [6]. Strikingly, computational modeling of choice behavior [7] revealed that tolcapone exerted selective effects on inequity aversion, and not on other computational components such as the extent to which individuals directly value the material payoffs of others. Together, these data shed light on the causal relationship between neurochemical systems and human prosocial behavior and have potential implications for our understanding of the complex array of social impairments accompanying neuropsychiatric disorders involving dopaminergic dysregulation

Dissociable contribution of prefrontal and striatal dopaminergic genes to learning in economic games

The article of record as published may be found at http://dx.doi.org/10.1073/pnas.1316259111This article contains supporting information online at www.pnas.org/lookup/suppl/doi:10. 1073/pnas.1316259111/-/DCSupplemental.Game theory describes strategic interactions where success of players’ actions depends on those of coplayers. In humans, substantial progress has been made at the neural level in characterizing the dopaminergic and frontostriatal mechanisms mediating such behavior. Here we combined computational modeling of strategic learning with a pathway approach to characterize association of strategic behavior with variations in the dopamine pathway. Specifically, using gene-set analysis, we systematically examined contribution of different dopamine genes to variation in a multi-strategy competitive game captured by (i) the degree players anticipate and respond to actions of others (belief learning) and (ii) the speed with which such adaptations take place (learning rate). We found that variation in genes that primarily regulate prefrontal dopamine clearance—catechol-O-methyl transferase (COMT) and two isoforms of monoamine oxidase—modulated degree of belief learning across individuals. In contrast, we did not find significant association for other genes in the dopamine pathway. Furthermore, variation in genes that primarily regulate striatal dopamine function— dopamine transporter and D2 receptors—was significantly associated with the learning rate. We found that this was also the case with COMT, but not for other dopaminergic genes. Together, these findings highlight dissociable roles of frontostriatal systems in strategic learning and support the notion that genetic variation, organized along specific pathways, forms an important source of variation in complex phenotypes such as strategic behavior.National Institute of Mental Health Grant R01 MH098023Ministry of Education, SingaporeAXA Research Fun

Damage to dorsolateral prefrontal cortex affects tradeoffs between honesty and self-interest.

Substantial correlational evidence suggests that prefrontal regions are critical to honest and dishonest behavior, but causal evidence specifying the nature of this involvement remains absent. We found that lesions of the human dorsolateral prefrontal cortex (DLPFC) decreased the effect of honesty concerns on behavior in economic games that pit honesty motives against self-interest, but did not affect decisions when honesty concerns were absent. These results point to a causal role for DLPFC in honest behavior

The heritability of attitude toward economic risk

10.1375/twin.12.1.103Twin Research and Human Genetics121103-10