Levin et al. Neuropsychology of risky gains/losses FIGURE 1 | Illustration of the expanded neural model of decision-making under uncertainty. Processing of primary inducers, mediated by the amygdala, triggers the ventromedial prefrontal cortex (VMPFC) system, which, in turn, conducts a more deliberative analysis of uncertainty. However, decisions involving potential losses may trigger redundant neural responding from structures such as the insula (anterior, posterior, or both) and the adjacent primary and secondary somatosensory cortices (SI and SII), which are independent of the amygdala; these backup processes are represented here by dotted lines. risk1. We operationalize the “lure” of rewards as either the poten- tial for a relatively large gain in the gain domain (in comparison to the small sure gain from a riskless choice) or the potential for avoiding a loss altogether in the loss domain, and the “fear” of risk as arising from risking a relatively large loss in the loss domain (in comparison to the small sure loss from a riskless choice) or not winning anything in the gain domain. These two forces act in opposite directions in exciting or inhibiting risk-taking. We sug- gest that the VMPFC subregions, the amygdala, and the insula each contribute in different ways to the processing and utilization of these two critical pieces of emotional information. The mere pres- ence of uncertainty induces a primary “fear” response elicited by the amygdala, which has been associated speciﬁcally with fear pro- cessing and avoidance behavior (LeDoux, 2000; Trepel et al., 2005; Phelps, 2006). This fear response activates the VMPFC whose func- tion it is to mediate decision-making and allows for more careful deliberative processes by linking together working memory and emotional systems (Damasio, 1994). While the amygdala has been studied extensively and shown to be a key substrate for triggering emotional responses, especially in connection with fear (LeDoux, 2000), the fact remains that the triggering of emotional responses involves multiple neural regions, and not just the amygdala. Thus, structures such as the insula, which are independent of the amygdala, are also likely to impact decision-making under uncertainty (Kuhnen and Knutson, 2005; Clark et al., 2008; Weller et al., 2009). In particular, we propose that the insula and the amygdala provide complementary systems for dealing with potential losses, which we attribute to the evolu- tionary signiﬁcance of dealing with potential losses. Our ancestors 1Some deﬁnitions of risk include loss as a component. However, in order to incor- porate risk-taking for gains and losses, we use a more general deﬁnition of risky choice as involving choice options of differing outcome variability. In the typical task described here, the choice is between a “sure thing” or “riskless” option with ﬁxed outcome and a “risky” option with variable possible outcomes. learned to avoid situations that risked the loss of things essential for survival and it is reasonable to assume that our brains have been primed for avoiding losses. This account parallels the proposed dual systems approach of System 1 (experiential) and System 2 (deliberative) for decision-making (Kahneman, 2003). The neural underpinnings of these mechanisms have also been addressed in the “somatic marker” framework. According to the “somatic marker hypothe- sis” (Bechara and Damasio, 2005; Reimann and Bechara, 2010), after the amygdala triggers an automatic emotional response (or primary induction), the VMPFC subsequently prompts a more careful deliberative analysis that triggers secondary emotional responses (secondary induction) that help guide advantageous decision-making. Findings in support of the somatic marker hypothesis were key to new behavioral theories in which emo- tions play a pivotal role in decision-making (Mellers et al., 1999; Loewenstein et al., 2001; Slovic et al., 2002). In the following sections of this paper, we review the evidence for our model based on studies involving the VMPFC, amygdala, and insula, but we also include studies involving other areas that have implications for addressing the basic question of whether there is evidence at the neural level of a distinction between risky decision-making in the gain and loss domains. We will provide evidence that separate psychological processes are involved in risk- taking for gains and losses in terms of both behavioral and neuro- logical reactions that discriminate between risk-taking to achieve a gain and risk-taking to avoid a loss. We then address the more complex issue of whether distinct neural structures support these different reactions. In the case of fMRI studies, we will see that results depend on when during the decision-making process the recordings are made. We start, however, with some more straight- forward and well-known behavioral phenomena that motivate the search for neurological dissociations between risk-taking for gains and losses. It is typical to consider risk-taking as a uniﬁed behavioral con- cept when we talk about a person in terms such as “She is a risk-taker” or “He likes to play it safe.” However, it has been shown that risk-taking within the same individual varies across content domains such as monetary, health, and social risks (Weber et al., 2002). Within each of these domains, we may talk about an action as being “risky” because of the uncertainty of its outcome without differentiating between the potential for achieving beneﬁts ver- sus the potential for avoiding aversive consequences. Kahneman and Tversky (1979) demonstrated a fundamental principle that sparked decades of later research: individuals were more likely to take a risk to avoid a loss than to achieve a gain of the same magnitude2. Later work by the same authors revealed a fourfold pattern of risk-aversion for gains and risk-seeking for losses of 2Following Kahneman and Tversky (see Kahneman, 2003), most framing studies have employed between-subjects designs. However, it is important to note that reli- able risky choice framing effects have been reported in within-subject designs where procedural precautions have been taken to avoid recognition of repeated problems by using multiple problems and presenting gain and loss versions of the same prob- lem in separate sessions spaced widely apart (Levin et al., 2002). Emphasis in this paper will be on tasks involving actual gains and losses where separate gain and loss trials can be administered to the same decision makers without concern for consistency demands. Frontiers in Neuroscience | Decision Neuroscience February 2012 | Volume 6 | Article 15 | 2