Elsevier

NeuroImage

Volume 39, Issue 1, 1 January 2008, Pages 538-547
NeuroImage

Valence and salience contribute to nucleus accumbens activation

https://doi.org/10.1016/j.neuroimage.2007.08.009Get rights and content

Abstract

Different accounts of nucleus accumbens (NAcc) function have emphasized its role in representing either valence or salience during incentive anticipation. In an event-related FMRI experiment, we independently manipulated valence and salience by cuing participants to anticipate certain and uncertain monetary gains and losses. NAcc activation correlated with both valence and salience. On trials with certain outcomes, NAcc activation increased for anticipated gains and decreased for anticipated losses. On trials with uncertain outcomes, NAcc activation increased for both anticipated gains and losses but did not differ between them. These findings suggest that NAcc activation separately represents both valence and salience, consistent with its hypothesized role in appetitive motivation.

Introduction

A central goal of affective neuroscience is to understand how the brain generates emotional experience. Emotional states differ in many ways, but one of the most fundamental is valence, or how positive or negative an emotion feels (Russell, 1980, Wundt, 1896). Distinguishing between positive and negative has fundamental implications for both subjective experience and behavior. Positive emotions are linked to approach, while negative emotions are linked to avoidance (Schneirla, 1959). Despite the importance of this dimension, identifying neural correlates of valence with human brain imaging techniques has remained a challenge.

Several decades of comparative research on reward processing have identified a mesolimbic network that responds to anticipated or received positive incentives (Olds and Milner, 1954), and recent neuroimaging research suggests that these findings generalize to humans (Knutson and Cooper, 2005, Montague and Berns, 2002, O’Doherty, 2004). This research has implicated the midbrain (Schultz, 1998) and its projection areas in the ventral striatum (especially the nucleus accumbens [NAcc]; Knutson et al., 2001), dorsal striatum (Delgado et al., 2004, Zald et al., 2004), orbitofrontal cortex (Rolls, 2004), and other areas of mesial prefrontal cortex (Knutson et al., 2003, Ramnani et al., 2004), in anticipating or receiving rewards from money to attractive pictures to pleasant tastes. This network has been characterized as a “reward pathway” that responds to subjectively positive stimuli.

In both animal and human research, the NAcc in particular has been linked to anticipation of positive incentives (Ikemoto and Panksepp, 1999, Knutson et al., 2001). Dopamine infusion into this structure unconditionally elicits appetitive behavior (Ikemoto and Panksepp, 1999), and dopamine is released in it prior to delivery of primary or pharmacological rewards (Garris et al., 1999). The NAcc is a small structure nestled in the ventral parts of the striatum; it is not anatomically or cytoarchitectonically well-defined in humans nor is it explicitly identified in commonly used brain atlases (i.e., Talairach and Tournoux, 1988), but neuroimaging researchers have devised anatomical boundaries for studies of humans (Breiter et al., 1997). According to these specifications, an increasing number of studies have demonstrated NAcc activation in humans in anticipation of monetary and other rewards (Knutson and Cooper, 2005). Two theories have emerged to account for this activation.

One account suggests that the positive valence of anticipated rewards drives NAcc activation and that NAcc activation is key to distinguishing positive from negative valence (Ikemoto and Panksepp, 1999, Knutson et al., 2001, Schultz et al., 2000). Positive cues are those that predict fitness-increasing outcomes for an organism; a cue’s positive valence increases with reward magnitude, reward probability, or a particular motivational state (e.g., the sight of an oasis while thirsty). This account draws on imaging studies in humans that demonstrate increasing NAcc activation with increasing magnitude of anticipated rewards (Breiter et al., 2001, Knutson et al., 2001) and increasing self-reported positive arousal (Drevets et al., 2001), as well as decreasing NAcc activation with painful stimulation or increasing potential losses (Becerra et al., 2004, Tom et al., 2007). The valence account has historical roots in brain stimulation studies in rats (Olds and Milner, 1954), identifying electrical stimulation of the subcortex near the septum as a powerful positive reinforcer. More recently, this valence account has been revived by electrophysiological work in nonhuman primates linking reward anticipation to activation of midbrain dopamine neurons (Schultz et al., 1997, Tobler et al., 2005), some of which project to the NAcc. Computational models inspired by learning theory (Daw and Doya, 2006, Montague et al., 1996, Montague et al., 2006) have drawn on this data to suggest that dopaminergic inputs to the NAcc represent a predictive learning signal that can guide behavior toward rewards. The valence account makes the key predictions that anticipatory NAcc activation will correlate with positive emotional experience and so will predict approach behavior (Knutson et al., 2007).

However, a second account suggests that the salience of an incentive cue, not its valence, drives NAcc activation, and thus that NAcc activation does not necessarily distinguish positive from negative. We define salience behaviorally: a salient cue is one that increases the chance an organism will need to make an important behavioral response in the near future. Crucially, this action might involve either approach or withdrawal; cues predicting danger or a need for escape will hold as much (if not more) salience as cues predicting reward. According to this account, the NAcc promotes attention towards important or unexpected events, rather than promotes approach behavior (Berridge and Robinson, 1998, Redgrave et al., 1999). Cue salience might increase with absolute incentive magnitude (good or bad), incentive uncertainty or the contingency of the response (i.e., how important an organism’s response is to the outcome). The salience account references evidence that NAcc activation increases with behavioral demands or interference (Tricomi et al., 2004, Zink et al., 2004, Zink et al., 2006), in response to novel nonrewarded events (Zink et al., 2003), or in anticipation of painful stimulation (Berridge and Robinson, 1998, Jensen et al., 2003). At least two studies have reported NAcc activation correlated with salience prediction error models of conditioning for painful stimuli that included decreases during unpredicted avoidance of painful stimuli (Jensen et al., 2007, Seymour et al., 2004). The salience account, like the valence account, pertains primarily to anticipation. Incentive outcomes (especially unpredicted) may recruit attention or arousal, but they do not necessarily require further action. Existing studies have yielded conflicting evidence as to whether all salient outcomes increase NAcc activation (e.g., O’Doherty et al., 2003, Pagnoni et al., 2002). In the case of anticipation, however, the salience account clearly makes predictions in contrast to the valence account. Specifically, the salience account predicts that NAcc activation will correlate with orienting and subjective arousal, but not preferentially with positive experience or approach behavior.

Earlier studies have not independently varied both valence and salience in the same incentive modality, creating an opportunity to test these opposing predictions in a single experiment. This study aimed to compare these accounts by independently varying valence and salience in the context of a monetary incentive delay task (Knutson et al., 2001) and by comparing anticipatory NAcc activation across different conditions. While earlier studies have often focused only on gains, we used both gain and loss to manipulate valence and varied the certainty of the outcome to manipulate salience. We also examined the connection between NAcc activation and subjective experience by including self-reported affect probes in real time for a subset of the task trials.

This design enabled us to contrast specific conflicting predictions. Both valence and salience accounts predict increased NAcc activation during anticipation of uncertain (i.e., salient) gains and unchanged or decreased activation during anticipation of certain (i.e., nonsalient) losses. However, the valence account predicts increased NAcc activation during anticipation of certain gains but the salience account does not. Additionally, the salience account predicts increased NAcc activation during anticipation of uncertain losses but the valence account does not.

Given prior experimental support for both valence and salience accounts, we also considered the possibility that NAcc activation may correlate with multiple factors. Several recent studies found that midbrain dopamine neurons and ventral striatal activation represent different reward features during anticipation of a single reward (Dreher et al., 2006, Fiorillo et al., 2003, Knutson et al., 2005, Preuschoff et al., 2006). In these studies, early dopamine firing or NAcc activation increased with anticipated reward magnitude or probability, but continued dopamine firing or NAcc activation during anticipation increased with reward variance. These findings suggest that any single-factor theory of the NAcc’s role may not fully account for its activation. We therefore predicted that NAcc activation might increase during anticipation of both certain gains and uncertain gains and losses.

Section snippets

Participants

Twelve right-handed healthy volunteers (6 women; ages 19–25) participated. Participants had no history of neurological or psychiatric disorder and gave informed consent for a protocol approved by the Institutional Review Board of the Stanford University School of Medicine. Participants were screened for excessive head motion in the scanner (> 1 mm across sequential acquisitions) and none were excluded based on this criterion.

Experimental design and task

We used a variant of the monetary incentive delay (MID) task previously

Behavioral

Participants responded on almost all trials; mean response rate was 93.3% (SEM 1.4%). There were no main effects or linear interactions of certainty or valence on response rate, but there was a significant effect of salience (F(1,11) = 5.75, p < 0.05). Paired t-tests revealed that uncertain-gain and uncertain-loss trials had significantly higher response rates than all other trials (Table 1). No other trial types differed. In all conditions, however, average response rates exceeded 90%, and no

Discussion

Combining event-related FMRI with a novel variant of the monetary incentive delay (MID) task (Knutson et al., 2001), we directly compared valence and salience accounts of NAcc activation. We found that both the valence and salience of anticipated incentives correlated with NAcc activation and further found a significant interaction between these factors. When outcomes were certain and salience was low, NAcc activation increased for anticipated gain and decreased for anticipated loss. However,

Conclusion

These findings are consistent with a two-component account in which anticipatory NAcc activation reflects both valence and salience. Valence and salience each partially account for NAcc activation during incentive processing, but neither provides a complete account. Furthermore, findings from this and other studies are consistent with the possibility of a temporal separation between processing of valence and salience. If NAcc activation is proportional to a spatiotemporal summation of local

Acknowledgments

We thank Jamil Bhanji and G. Elliott Wimmer for assistance at all stages of this study and many helpful comments and discussions, Antonio Rangel for insightful comments on salience, and the anonymous reviewers whose comments greatly improved this study. This research was supported by seed grant AG024957-02 from the National Institute on Aging to B. K. and a Stanford Graduate Fellowship in Science and Engineering to J. C. C.

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