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, when outcomes were uncertain and salience was high, NAcc activation increased for both anticipated gain and loss.
Whole-brain analyses fit the findings of prior research. Salience activated a network of brain areas involved in arousal, attention, and uncertainty processing, including precuneus, parietal cortex, thalamus, amygdala, and insula (Huettel et al., 2005
; Simmons et al., 2004
). Salient trials also activated bilateral dorsal striatum, including caudate and globus pallidus, consistent with earlier studies investigating areas that support salience or contingency detection (Tricomi et al., 2004
; Zink et al., 2006
). By contrast, increasing valence activated a network of brain regions linked to reward representations, including mesial prefrontal cortex (Knutson et al., 2005
), orbitofrontal cortex (O’Doherty et al., 2001
; Rolls, 2004
), and inferior parietal cortex (Ernst et al., 2004
; Glimcher et al., 2005
). Only the ventral striatum, however, was significantly activated by the interaction of valence and salience, consistent with a unique role for this area in reward anticipation.
This study extends prior research by, for the first time, independently varying valence from negative to positive and salience from low to high within the same incentive modality. Independently manipulating these two factors allowed us to separately examine each factor’s influence on NAcc activation. Earlier studies that have focused on valence, using monetary incentives or aversive shock, have not independently varied salience (Abler et al., 2006
; Breiter et al., 2001
; Jensen et al., 2007
; Knutson et al., 2001
; Tobler et al., 2007
; Tom et al., 2007
), while studies that have varied salience have not independently varied valence across gains and losses (Bjork and Hommer, 2006
; Jensen et al., 2003
; Tricomi et al., 2004
; Zink et al., 2006
For the first time, we also used a real-time measure of the subjective impact of our incentive manipulations. These affect probes confirmed that participants were able to rate their arousal and positivity as uncorrelated factors. Varying outcome uncertainty had a significant impact on arousal (a possible index of salience, e.g., Zink et al., 2004
) but not positivity, while varying incentives between gains and losses had a significant impact on positivity but not arousal. This real-time method might not be without cost; although we examined neural activity only during trials without anticipatory affect probes, introspecting about emotions might be enough to influence affect or brain activation throughout the experiment. However, investigators who used continuous online ratings in an FMRI study to probe affect during film clips reported no effect of rating on either self-reported affect or brain areas associated with the affective response to films (Hutcherson et al, 2005
; although the NAcc was not one of these). The areas they and others (e.g., Phan et al., 2004
; Taylor et al., 2003
) have found to be associated with rating emotion (anterior cingulate, insula, and parietal cortex) were not the direct focus of this study, but further investigation of how online probes affect reward-related paradigms is needed.
The novel design of this study enabled a direct comparison of valence and salience accounts of NAcc activation--but neither account fully predicted the observed pattern of activation. The salience account suggests that NAcc activation should not differentiate between certain-gain and certain-loss trials, which were equally non-salient. They were equally arousing, and participants responded to them equally as often and as quickly, suggesting the conditions did not differentially recruit attention or motor preparation. Yet NAcc activation significantly distinguished between certain gain and loss, increasing prior to certain gains and decreasing prior to certain losses.
On the other hand, the valence account suggests that the NAcc activation should differentiate between uncertain-gain and uncertain-loss trials, since the former had positive expected value and elicited more positive affect. Yet NAcc activation did not distinguish between these trial types in this paradigm. Further, the valence account predicts that the NAcc should be more active for certain-gain than uncertain-gain or uncertain-loss trials, based on expected value and positive affect. Instead, NAcc activation did not distinguish between these conditions, despite obvious differences in their expected rewards.
Participants responded and hit more often in salient trials than non-salient trials, raising the possibility of a strategic difference between salient and non-salient. Salience is a stimulus-related feature that might be separate from, for example, effort induced by salience (Niv, 2007
). We attempted to control for the effects of reaction time, as an index of effort; reaction times were included in the whole-brain regression models, did not correlate with NAcc timecourses, and did not change systematically over time (Supplemental Results
). However, both the salience and valence accounts also make key predictions within salience levels that were not confirmed by the data. Certain-gain and certain-loss trials had identical salience and were matched in terms of elicited behavior, yet they induced significantly different NAcc activation, which the salience account cannot explain. On the other hand, uncertain-gain and uncertain-loss trials had differing valences and were matched in behavior, yet they were not significantly distinguished by NAcc activation, which the valence account cannot explain.
Single-component accounts invoking valence or salience do not fully explain NAcc activation in this paradigm. Since variation in either valence or salience correlates with NAcc activation, the data instead suggest that NAcc function may be better characterized with a two-component account involving both valence and salience. Several recent neuroimaging findings allude to a two-component account (Bjork and Hommer, 2006
; Dreher et al., 2006
; Knutson et al., 2005
; Preuschoff et al., 2006
; Tobler et al., 2007
; Yacubian et al., 2006
). Knutson et al. (2005)
and Yacubian et al. (2006)
varied anticipated reward magnitude and probability separately and found that NAcc activation represented magnitude independently of probability. Because these studies used a limited range of probability, the salience of the anticipated rewards may not have been as controlled as in the current paradigm. Bjork and Hommer (2006)
scanned participants in a reward-anticipation paradigm involving both certain and uncertain-gain trials, some of which required a motor response. Ventral striatal areas were active both for certain rewards requiring a motor response and for an interaction of uncertainty and response, when valence and salience were both high. Dreher et al. (2006)
varied reward probability in trials with longer anticipatory delays, and found that while early activation in the midbrain correlated with reward probability, ventral striatal activity during reward anticipation was greatest when rewards were maximally uncertain. Preuschoff et al. (2006)
varied reward probability across several levels (rather than merely certain or uncertain) and found that early ventral striatal activation correlated best with increasing reward probability, but later ventral striatal activation correlated best with maximal uncertainty. Tobler et al. (2007)
found that ventral striatal activation increased with both reward probability and magnitude. Although they found that ventral striatal activation for certain gains was greater than activation for uncertain gains, their design did not permit separate analysis of gain anticipation versus outcome or allow comparisons across different levels of motor demands.
These studies did not include loss anticipation overall, but all found that NAcc activation varied independently as a function of changes in anticipated reward valence or uncertainty. The current data are consistent with these findings and extend them into the domain of loss anticipation. NAcc activation correlated with valence when uncertainty was low, while NAcc activation correlated with primarily with uncertainty when uncertainty was high.
Valence and salience processing may additionally show distinct temporal profiles in the NAcc. Dreher et al. (2006)
and Preuschoff et al. (2006)
suggested that phasic, cue-related NAcc activation reflects the expected value of a reward, while tonic activation during anticipation reflects reward uncertainty. Electrophysiologists studying nonhuman primates responding to juice cues have found a similar pattern in midbrain dopamine neuron firing (Fiorillo et al., 2003
). Although our study’s design was not optimized to separate early from late anticipatory activation, we conducted post hoc analyses to examine whether the pattern of NAcc activation changed over time (Supplemental Results
, Figure S3
). At 4 s after cue onset, when cue-related hemodynamic activity would be expected to peak, NAcc activation was similarly elevated for both uncertain-gain and certain-gain trials. By 6 s after cue onset, however, when delay-related activity would be expected to peak, NAcc activation was more elevated for uncertain gain and loss trials than for all certain trials. (These later peaks were earlier than would be expected for hemodynamic activity related to the motor response, which occurred an average of 4.6 sec after the cue.) This pattern is consistent with a two-component account where valence-related activity at the cue signaled the presence of a potential reward and salience-related tonic activity continued to elevate NAcc activation for uncertain, but not certain, trials during anticipation.
The simplest two-component account suggests that NAcc activation codes for both valence and salience separately, perhaps separated in time. But other two-component accounts are possible. One such account is expected value (e.g., Tobler et al., 2007
), in which NAcc activation reflects the product of reward magnitude (correlated with valence) and probability (which has a quadratic relationship with salience). The current data do not support this account, since certain-gain and uncertain-gain trials have substantially larger expected values than uncertain-loss, but NAcc activation does not distinguish among them (and during anticipation, certain-gain activation is the lowest of the three).
A second account is the positive arousal (PA) account (Knutson et al., 2001
), in which NAcc activation reflects a combination of arousal and positivity proposed to constitute an underlying dimension of emotional experience (Watson et al., 1999
). Earlier studies using only uncertain trials found correlations between NAcc activation during gain anticipation and retrospective reports of PA (Bjork et al., 2004
; Knutson et al., 2001
). We calculated average online PA for each participant to compare it with NAcc activation (Supplemental Results
, Figure S4
). The current data do not fully support this account, since PA was significantly larger for uncertain-gain than uncertain-loss trials, but the NAcc does not distinguish between them. In other respects, however, the PA account matches NAcc activation more closely than either the valence or salience accounts, and thus the conditions under which PA might explain NAcc function deserve further investigation.
A third account proposes different incentive processing for gains and for losses. Economic behavior and brain activation both respond to incentive magnitude differently depending on whether the incentive is a gain or a loss relative to a reference point (De Martino et al., 2006
; Friedman and Savage, 1948
; Kahneman and Tversky, 1979
; Tom et al., 2007
). Tom et al. (2007)
recently found NAcc responses to mixed gambles decreased more steeply with loss magnitude than they increased with gain magnitude. Although their design did not permit separate analysis of anticipation or of salience, their findings might suggest a valence account with different response slopes between gains and losses. The current findings do not fully support such an account, since a valence account within gains alone would predict greater activation for certain-gain than uncertain-gain trials, while the current data demonstrate early NAcc activation does not distinguish the two (and later activation is greater for uncertain-gain trials). Potential strategic differences between certain and uncertain might well confound this comparison, however, and so we cannot rule out accounts with separate processing of gains and losses that take some aspect of salience or strategy into account. All of these accounts deserve further investigation with more specific paradigms.
The current data is thus most consistent with a simple two-component account that predicts anticipatory NAcc activation reflects changes in either valence or salience. The nature of the broad factors of “valence” and “salience,” though, remain to be fully clarified. We defined salience as a cued increase in the need for an important action, which we operationalized by manipulating reward certainty. Many cue features can increase salience, including outcome variance or uncertainty, outcome contingency, and subjective attention, all of which have been proposed to be specifically reflected in activation of various parts of the striatum. This paradigm was not intended to disentangle these features, and so these salience-related features all varied between uncertain and certain trials. Different effects of valence on NAcc activation within salience levels, however, suggests that recruitment of this region reflects at least two incentive features. Further studies will be needed to parse the concept of “salience” into a finer-grained set of features, and investigate how they may be separately represented in various parts of the striatum and elsewhere.
Questions also remain about how NAcc activation might reflect valence. NAcc activation in this study distinguished between anticipated gains and losses in certain but not uncertain trials. Both of these findings should be qualified by the small number of trials our design provided (eight per condition). The low percent signal change in the certain conditions especially calls for replication, although it is consistent with evidence for the valence account. The lack of distinction between uncertain-gain and uncertain-loss trials is less consistent with previous findings. Several studies using the MID task (e.g., Bjork et al., 2004
; Guyer et al., 2006
; Knutson et al., 2001
; Knutson et al., 2003
; Knutson et al., 2005
) have found greater NAcc activation for uncertain gain than loss (but not all; Juckel et al., 2006
). The current paradigm used smaller incentives ($3.00 vs. $5.00), which might be too small to elicit this difference. Accordingly, replications of the MID task have found the difference for large but not small incentives (i.e., $5.00, but not $1.00). Alternatively, this study’s novel mixture of certain and uncertain trials may have induced a framing effect in which participants considered both the chance to obtain gains and the chance to avoid losses in uncertain trials to be rewarding relative to certain losses (Ikemoto and Panksepp, 1999
; Nieuwenhuis et al., 2005
). Consistent with this possibility, participants’ positivity ratings were more negative for certain-loss than uncertain-loss trials and distinguished between gain and loss better in certain than uncertain trials. The current design did not allow analysis of outcomes, which might better distinguish these explanations. The framing account, however, predicts that NAcc activation reflects valence differently depending on other available incentives. The firing of monkey midbrain dopamine neurons appears susceptible to framing effects (Tobler et al., 2005
), but further human research will be necessary to determine whether NAcc activation shows such effects.