Processing of primary and secondary rewards: A quantitative meta-analysis and review of human functional neuroimaging studies

TL;DR: An activation likelihood estimation meta-analysis of 87 studies comparing the brain responses to monetary, erotic and food reward outcomes indicates that the computation of experienced reward value does not only recruit a core "reward system" but also reward type-dependent brain structures.

About: This article is published in Neuroscience & Biobehavioral Reviews.The article was published on 2013-05-01 and is currently open access. It has received 631 citations till now. The article focuses on the topics: Orbitofrontal cortex & Brain stimulation reward.

Summary

1. Introduction

• A classical distinction concerns primary rewards -i.e. food, sex and shelter- and secondary rewards -such as money or power.
• First, ALE provides a quantitative measure of cross-study consistency.
• Besides providing a synthetic overview of the literature, the use of a quantitative meta-analytic approach also has practical benefits.
• Moreover, for functionally defined brain regions such as the ventral striatum or medial OFC, current label-based reviews (e.g. Delgado, 2007; Haber and Knutson, 2010; Noonan et al., 2012) do not provide average stereotaxic coordinates from which to derive ROIs.

2.1. Selection of studies

• The authors conducted three independent searches in PubMed in order to identify fMRI and Positron Emission Tomography (PET) studies dealing with the processing of monetary, erotic and food reward outcomes.
• The lists of references cited in these studies were also scrutinized and relevant studies incorporated to their pool.
• 1) Only studies reporting whole-brain results were included.
• Talairach coordinates were transformed to MNI space using the Lancaster transform implemented in the GingerALE software (see below).
• Moreover, the results had to unambiguously reflect reward processing at the time of outcome, i.e. they had to be based on contrasts such as “reward > control condition”, “reward > omission of reward”, “reward > punishment” or “correlation with reward intensity”.

2.2. Data analysis

• Analyses were performed using the revised ALE method as implemented in the latest version of the GingerALE software (version 2.2, http://brainmap.org/ale), (Turkeltaub et al., 2002; Eickhoff et al., 2009).
• The width of this distribution, reflecting spatial uncertainty, is derived from an empirical model and weighted by the sample size of each experiment (Eickhoff et al., 2009).
• The statistical significance of the resulting p-values is determined using a false discovery rate (FDR) corrected threshold, which is applied to the ALE map along with a minimum cluster size.
• ALE scores for these two randomly assembled groups were calculated and the difference between these ALE scores was recorded for each voxel.
• In addition, “primary reward-specific” regions were defined as those stemming from the conjunction of erotic>money and food>money maps.

3. Results

• The first goal of this study was to identify a “common reward circuit” as defined by the regions of overlap between monetary, food and erotic reward outcomes.
• They show that a set of brain regions was consistently recruited by all three rewards, although with varying levels of significance and spatial extent.
• These regions included the bilateral striatum, mostly in its ventral part, the bilateral anterior insula/frontal operculum, the mediodorsal thalamus, the bilateral amygdala and the ventromedial prefrontal cortex extending into the pregenual anterior cingulate cortex .
• In contrast, the dorsal anterior insula and the somatosensory cortex appeared more likely to be activated by food compared to monetary and erotic rewards.

4. Discussion

• This meta-analysis provides a synthetic and objective overview of reward processing in the human brain, as provided by the paradigmatic examples of monetary, food and erotic rewards.
• As expected, the results confirmed the existence of a core set of brain regions processing reward outcomes in an indiscriminate fashion, in line with the idea of a centralized “reward circuit”.
• In addition, comparative analyses between rewards revealed that some regions were more specifically recruited by one type of reward compared to the others.
• Below the authors discuss those results in the light of current views on the putative functional role of these regions, and offer some tentative explanations to account for the observed differences between rewards.
• The discussion is organized by cerebral region, so that the reader can easily navigate from one sub-section to another.

4.1.1. Modality-independent activations

• The striatum, essentially in its ventral part, was found to be consistently activated by monetary, food and erotic outcomes in their meta-analysis.
• Importantly, recent studies using large-scale reverse inferences have suggested that the ventral striatum has a relatively specific role in reward processing, as compared to other cognitive processes (Cauda et al., 2011; Yarkoni et al., 2011).
• The ventral part, centred on the nucleus accumbens, is part of the limbic loop and receives many projections from the OFC, ACC, amygdala and midbrain.
• It is hence in an ideal place to integrate cognitive, motor and affective information and influence goal-directed behaviour independently of reward modality (Haber and Knutson, 2010; Delgado, 2007).
• Besides, two studies that have explicitly tried to disentangle reward value from prediction error have reported a better correlation with the latter (Hare et al., 2008; Rohe et al., 2012).

4.1.2. Modality-dependent activations

• The authors results indicate that monetary rewards activate the ventral striatum more reliably than do erotic and food rewards.
• Instead, the authors think that the present result stems from at least two important differences in how monetary and non-monetary rewards are usually delivered.
• First, the protocols used in monetary studies often involve learning of probabilistic stimulusreward associations, whereas most erotic and food studies use passive stimulation tasks with fully predictable rewards (see Table 1).
• Supporting this idea, several studies show that erotic and food rewards elicit higher ventral striatal activity when they are unexpected compared to when they are expected (Sescousse et al., 2010; McClure et al., 2003; D'Ardenne et al., 2008; Veldhuizen et al., 2011).
• The authors results did not confirm a previous hypothesis suggesting that primary rewards such as juice might recruit more lateral portions of the striatum (i.e. the putamen) compared to secondary rewards such as money (Delgado, 2007).

4.2. Ventromedial prefrontal / orbitofrontal cortex

• The orbitofrontal cortex is a vast and heterogeneous region, which can be broadly divided into three main sections based on anatomical and cytoarchitectonic considerations: a posterior OFC region, an anterior OFC region and a vmPFC region (Haber and Knutson, 2010).
• The authors meta-analysis revealed different patterns of activation in these regions depending on reward type.

4.2.1. Modality-independent activations in the vmPFC

• In concert with the ventral striatum, the vmPFC responded to all three tested rewards.
• The present meta-analysis confirms that the vmPFC is equally important for the computation of experienced reward values.
• Importantly, the vmPFC seems to be sensitive to the subjective value of rewards rather than to their mere intensity.
• One might further note that the activations observed in their meta-analysis spread over the pregenual ACC, which has strong connections with both the ventral striatum and medial OFC, and has been shown to be involved in reward and emotion processing in two other meta-analyses (Beckmann et al., 2009; Fujiwara et al., 2009).

4.2.2. Modality-dependent activations in the lateral OFC

• The authors results further revealed money-specific activations in the right anterior OFC.
• Such a dissociation is in line with the cytoarchitectonic properties of the OFC, showing that the anterior part, characterized by a granular cell layer, is phylogenetically more recent than the posterior part consisting in agranular and dysgranular cortices (Ongür and Price, 2000; Wise, 2008).
• Furthermore, this hypothesis can be integrated in a broader perspective on frontal lobe organization, suggesting a trend in complexity and abstraction along a posterior-anterior axis with the frontopolar cortex at the apex (Badre and D'Esposito, 2009).
• In accordance with the above hypothesis and previous results from their group (Sescousse et al., 2010), one would have expected primary rewards (i.e. food and erotic stimuli) to specifically recruit the posterior portion of the OFC in comparison to monetary rewards.
• This is consistent with a recent report showing that aesthetic appraisal across diverse sensory modalities primarily recruits the OFC in its posterior part (Brown et al., 2011).

4.3.1. Modality-independent activations

• The amygdala receives projections from a number of cortical regions, but is most strongly connected to the ventral striatum and OFC (Haber and Knutson, 2010; Murray, 2007).
• These results shed light on the debate opposing valence and salience coding in the amygdala.
• Yet, the results from the present meta-analysis provide strong evidence that the amygdala is equally sensitive to rewarding stimuli, as confirmed by a wealth of animal studies (Sugase-Miyamoto and Richmond, 2005; Tye and Janak, 2007; Bermudez et al., 2012).
• This emotional tagging would further participate in the updating of current reward value and the flexible adaptation of behavior, as illustrated by the decrease in amygdala activity following reinforcer devaluation (Baxter and Murray, 2002; Gottfried et al., 2003).
• The authors meta-analysis also revealed that the amygdala, and possibly its centro-medial nucleus, was more reliably activated by erotic than by monetary and food rewards.

4.4.1. Modality-independent activations

• The authors meta-analysis showed that the anterior insula bordering the frontal operculum was consistently activated by monetary, food and erotic rewards.
• Surprisingly, this structure has been relatively overlooked in the reward literature, and most often associated with aversive events such as monetary losses (Knutson and Bossaerts, 2007; Knutson and Greer, 2008; Petrovic et al., 2008b).
• This mapping then leads to an explicit emotional feeling, after being integrated with the events originally eliciting those bodily states (Bechara and Damasio, 2005; Critchley, 2005).
• Indeed, a number of neuroimaging studies have shown that it is involved in the representation of a wide variety of subjective feelings, and not just those arising from bodily states, as well as in many other cognitive processes such as attention, time perception or perceptual decision-making (Craig, 2009).
• It is further consistent with the idea that the anterior insula tracks the salience of outcomes, regardless of their valence (Rutledge et al., 2010) Thus, in the context of reward processing, the anterior insula might be in charge of tracking both expected and experienced risk, a mechanism that would participate more broadly in emotional appraisal.

4.4.2. Modality-dependent activations

• Finally, although their results unambiguously support a role of the anterior insula in the processing of both primary and secondary rewards, they suggest a stronger involvement in the processing of primary rewards.
• This could reflect the higher autonomic arousal induced by primary rewards: in line with their prominent role in homeostasis and survival, erotic and food rewards are known to generate acute changes in bodily states and autonomic arousal, as evidenced by changes in heart beat, skin conductance, sexual drive or satiety levels.
• Such changes are in turn often correlated with activity in the anterior insula, shown to be critically involved in autonomic conditioning (Critchley et al., 2002; Kuhn and Gallinat, 2011).
• Based on the role of the ventral insula in emotional appraisal and its frequent coactivation with the amygdala (Deen et al., 2010; Mutschler et al., 2009), the present result might reflect the particularly strong emotional impact of erotic rewards.
• This is further consistent with the food-specific activation observed in the somatosensory cortex and adjacent middle insula, known to be involved in the processing of the physical properties of food and the mapping of bodily states (Bechara and Damasio, 2005).

4.5. Mediodorsal thalamus

• The authors meta-analysis revealed that the mediodorsal thalamus, a structure which is rarely discussed in the reward literature, was consistently activated by monetary, erotic and food rewards.
• Importantly, the present results demonstrate that the mediodorsal thalamus also plays an important role in processing the experienced value of rewards.
• These results can be interpreted within the previous framework, i.e. as reflecting increased arousal, but could alternatively be seen as reflecting reward value coding.
• The hypothalamus is part of the limbic system and plays a general role in homeostatic control and autonomic responses, essentially by means of its neuroendocrine function.
• This suggests that the extrastriate body area is mainly sensitive to the visual features of erotic stimuli, rather than to their rewarding properties.

4.7. Limitations and strengths

• The present meta-analysis is not free of limitations, demanding to treat the results with some caution.
• Note however that the difference in block versus eventrelated designs does not seem to impact reward-related activations, at least for erotic stimuli (Buhler et al., 2008).
• Finally, it could be argued that the differential activation patterns presently observed between rewards are confounded by differences in reward intensity.
• It should be noted that since this is a coordinate-based meta-analysis, the authors are not comparing the amplitude of brain activity between conditions (as would be done by contrasting Betas within a regular GLM analysis), but the spatial consistency of reported peaks of activity between groups of studies (regardless of peak t-values).
• In fact, the authors had to exclude a surprisingly high number of ROI-based studies, which is somehow paradoxical considering the only recent availability of objective reference (such as the present meta-analysis) for these studies in the literature.

4.8. Conclusions

• This meta-analysis first reveals that there is ample support in the neuroimaging literature for a “common reward circuit” in the brain (Fig. 3).
• Their results offer an objective and quantitative demonstration.
• Strongly connected to the vmPFC, the ventral striatum is thought to primarily reflect prediction error and to contribute to learning and motivation, although its pattern of activation is also compatible with the computation of experienced value.
• Addressing previously stated methodological limitations will be another challenge.
• The present meta-analysis was focused on the identification of reward-related regions, and studied how the engagement of these regions varies with reward type.

Figures

Table 2. Overview of the erotic reward studies included in our meta-analysis. For each study, the column “n” indicates the number of participants, the column “Foci” indicates the number of foci included in our meta-analysis, and the column “Task” provides a description of the type of paradigm used. In the column “Contrast”, “Omission” refers to a null outcome when a potential erotic stimulus was expected, and “Baseline” refers to any low-level condition such as a fixation cross. When multiple thresholds are reported for one study, “&” means that these thresholds were applied simultaneously to every foci, while “|” means that these thresholds were applied to different foci.

Table 3. Overview of the food reward studies included in our meta-analysis. For each study, the column “n” indicates the number of participants, the column “Foci” indicates the number of foci included in our meta-analysis, and the column “Task” provides a description of the type of paradigm used. In the column “Contrast”, “Omission” refers to a null outcome when a potential food stimulus was expected, and “Baseline” refers to any low-level condition such as a fixation cross. * The study by Green and Murphy (2012) was split into two studies since results are reported separately for two distinct groups of healthy participants (diet soda drinkers and non-diet soda drinkers). When multiple thresholds are reported for one study, “&” means that these thresholds were applied simultaneously to every foci, while “|” means that these thresholds were applied to different foci.

Frequently asked questions

Q1. What are the contributions in "Processing of primary and secondary rewards: a quantitative meta-analysis and review of human functional neuroimaging studies" ?

In this paper, the authors show that a core set of brain regions, including the ventral tegmental area, nucleus accumbens, amygdala and ventromedial prefrontal cortex, are sensitive to various types of rewards. 

Q2. What have the authors stated for future works in "Processing of primary and secondary rewards: a quantitative meta-analysis and review of human functional neuroimaging studies" ?

First, it will be instructive to extend the present work in the future, when enough data has been accumulated to run meta-analyses on other types of rewards, such as beautiful faces, pleasant odors or positive social feedback. Image-based metaanalyses, which make use of crucial information such as activation magnitude and spatial extent of clusters, but require access to the original data, seem like a promising avenue ( Salimi-Khorshidi et al., 2009 ; Poldrack, 2008 ). 

Q3. What is the role of the ventral striatum in the computation of experienced value?

Strongly connected to the vmPFC, the ventral striatum is thought to primarily reflect prediction error and to contribute to learning and motivation, although its pattern of activation is also compatible with the computation of experienced value. 

Q4. What is the role of the vmPFC in the computation of reward values?

During reward anticipation, the vmPFC has been shown to be sensitive to various generic properties of rewards such as magnitude, probability or delay (Haber and Knutson, 2010). 

Q5. What is the role of the vmPFC in the reward-related circuit?

Within this circuit, the vmPFC appears to be directly responsible for computing the experienced value of rewards on a common scale. 

Q6. What are the likely regions to be activated by erotic rewards?

the bilateral amygdala, the ventral anterior insula and the extrastriate body area were more robustly activated by erotic than by monetary and food rewards. 

Q7. How did the authors make sure that all cerebral regions have an equal chance of being represented?

in order to provide anobjective view of reward processing in the brain, it is important to make sure that all cerebral regions have an equal chance of being represented, by specifically excluding studies reporting partial (and inherently biased) results. 

Q8. What is the role of the ventral striatum in reward learning?

As for the amygdala, even though its involvement in reward learning is still a matter of debate, considerable evidence shows that it plays a major role in assigning emotional value to rewards. 

Q9. What was the FDR-corrected threshold for the contrast analysis?

The authors employed an FDR-corrected threshold of p<0.05, along with a minimum cluster size of 600 mm3 (a less stringent p-value was used because contrast analyses are more conservative). 

Q10. What type of reward was more likely to activate the right anterior insula?

The results showed that the bilateral ventral striatum and the right anterior OFC were more likely to be activated by monetary compared to food and erotic rewards. 

Q11. Where was the only brain area more reliably activated by primary versus secondary rewards?

The only brain area more reliably activated by primary (i.e. erotic and food) compared to secondary (i.e. monetary) rewards was located in the middle insula.