Relative valuation of pain in human orbitofrontal cortex

Abstract

The valuation of health-related states, including pain, is a critical issue in clinical practice, health economics, and pain neuroscience. Surprisingly the monetary value people associate with pain is highly context-dependent, with participants willing to pay more to avoid medium-level pain when presented in a context of low-intensity, rather than high-intensity, pain. Here, we ask whether context impacts upon the neural representation of pain itself, or alternatively the transformation of pain into valuation-driven behavior. While undergoing fMRI, human participants declared how much money they would be willing to pay to avoid repeated instances of painful cutaneous electrical stimuli delivered to the foot. We also implemented a contextual manipulation that involved presenting medium-level painful stimuli in blocks with either low- or high-level stimuli. We found no evidence of context-dependent activity within a conventional "pain matrix," where pain-evoked activity reflected absolute stimulus intensity. By contrast, in right lateral orbitofrontal cortex, a strong contextual dependency was evident, and here activity tracked the contextual rank of the pain. The findings are in keeping with an architecture where an absolute pain valuation system and a rank-dependent system interact to influence willing to pay to avoid pain, with context impacting value-based behavior high in a processing hierarchy. This segregated processing hints that distinct neural representations reflect sensory aspects of pain and components that are less directly nociceptive whose integration also guides pain-related actions. A dominance of the latter might account for puzzling phenomena seen in somatization disorders where perceived pain is a dominant driver of behavior.

Keywords: context sensitivity; neuroeconomics; pain; subjective health complaints; valuation.

Copyright © 2014 Winston et al.

Figures

Figure 1.

Task design, block structure, behavioral effects, and possible activation patterns. A, The components within a single trial are shown. The trial began with a warning crosshair and the endowment of 40p before a single electrical shock was delivered to inform the participant what pain level they were paying to avoid. Bids were then entered, followed by a variable delay before the market price (drawn from a uniform distribution) was announced. If participants bid more than the market price, they paid the market price and did not experience repeated shocks at the outcome phase (“pain relief”); if they bid less than the market price, they kept their entire 40p endowment but experienced the train of shocks at outcome. ITI, Intertrial interval. B, Example of block structure within a single run. Blocks constituted 10 trials but contained only two of the three pain intensity levels within the experiment. The end of a block was made explicit to participants with a short break, but the existence of structure within blocks was not. C, Mean bids across participants for the six conditions from our earlier behavioral study (left) and the current dataset. Data are normalized within subject to account for the fact that the 36 subjects in Vlaev et al. (2009) constituted two groups given endowments of either 40p or 80p. Bids revealed a significant effect of context (paired pain) for the medium-level pain (replicated across the two studies) but no clear effect for the low- or high-level pain. p values are different from those in the main text because of the normalization necessary for comparison across studies. Error bars indicate SEM. D, Illustrative theoretical patterns of BOLD activation for different cue-encoding mechanisms. Left, Pattern of responses encoding a pure signal of stimulus intensity. Right, Pattern that would be expected in a region encoding current stimulus rank.

Figure 2.

Responses to painful cue within pain-responsive regions are context-independent. SPM showing the main effect of pain (i.e., BOLD signal differences between the three pain levels) overlaid on the group average-normalized EPI. Threshold for display p < 0.001 uncorrected. Colored bar charts represent across-subject mean activity levels for all conditions (±SEM) for selected peak voxels (context refers to pain levels experienced within the current block: L, Low; M, medium; H, high). Bar heights are only readily interpretable relative to other conditions within the same region (see Materials and Methods). Gray bar chart represents Bayesian model selection result demonstrating that activity profiles in these regions are more consistent with intensity than rank responsiveness.

Figure 3.

OFC responses show encoding of cue stimulus rank and bid value. A, SPM showing the differential effects of medium-level pain depending upon context (greater activity to medium level pain when in a block with low level vs high level). Display as in Figure 2. B, Colored bars represent mean activity (±SEM) in peak OFC voxel for all conditions, illustrating the encoding of stimulus rank in this area. Gray bar represents results of Bayesian model selection showing that activity profile in peak OFC voxel is consistent with rank-based processing. C, Correlation of context-dependent differential OFC activity to medium-level pain (i.e., medium pain in the context of low to medium pain in the context of high) and propensity to report subjective health complaints (SHC) over the past month, indexed by the SHC questionnaire. D, More medially, OFC showed encoding of bid level at the time of choice as shown by SPM of significant linear relationship with bid value. Display as in Figure 2. E, Bid value (blue) and cue stimulus rank (red) encoding in lateral OFC are largely nonoverlapping with a single voxel of overlap (yellow). The area encoding bids is more medial and inferior to that encoding rank at the time of the cue. Activations thresholded at p < 0.001 uncorrected and displayed on the group average map of gray matter density. F, Illustrative plot of activity relating to bid value in peak OFC voxel from a supplementary model in which events were divided into quartiles based upon bid value and the GLM refitted.