4 General Discussion
4.2 Expectancy of Pain and Disgust on perceptual decisions
One of the main scope of Experiments 1-2 was to examine the case in which thermal and olfactory stimuli were at a fixed (medium) unpleasantness level but when preceded by different kinds of cue.
This allowed us to identify effects that were purely driven by expectancy, whilst minimizing any bottom-up confound. Our behavioral results from Experiments 1-2 accord with previous findings that the subjective pain experience evoked by identical thermal stimulus is strongly influenced by expectations87,91,490–492. Furthermore, here we found similar biases for olfactory stimuli. Such expectancy effect on olfaction add to studies showing that the subjective evaluation of odors may be biased by experimental manipulations of odor labels342–344, personal beliefs345,346, or social cues346,347. Our findings extend these data, not only by showing that comparable expectancy effects arise for both thermal and olfactory stimuli, but also by demonstrating for the first time the modality-specific nature of these effects, in addition to some cross-modal influence (found in Experiment 1 but not replicated in Experiment 2). Thus, trials with medium intensity stimuli revealed that the subjective affective evaluation of both thermal and olfactory events was biased by a cue predicting unpleasant events of the opposite modality, although such bias was weaker than that found in modality-consistent trials.
Crossmodal effects associated with pain, olfaction, or both have already been observed in other situations. For instance, olfaction can be modulated by gustation (possibly through integrated representations of flavor)567,568 or by vision569,570. A similar effect was documented between pain perception and vision417,382. Furthermore, pain unpleasantness can be affected by the valence of a simultaneously presented odour377,416. In line with these studies, our data suggest that pain and disgust might be processed at least partly through a representation that is not specific to a given modality, but encodes aversive meaning from different sensory channels, linked to different
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behavioral responses487,148,571. Most importantly, our results also extend previous work by suggesting that pain and disgust might be processed in a crossmodal fashion, not only during the stimulus delivery, but also during stimulus expectation. These subjective effects were paralleled by our SCR results which showed a general enhancement on medium trials whenever a cue of high (relative to low) unpleasantness was presented.
Most importantly, however, in both Experiments 1 and 2 the magnitude of cross-modal expectancy effects was significantly smaller than that associated with consistent trials (i.e. when cues predicted the correct stimulation modality). This within-modality enhancement suggests that the cues also elicited a representation of sensory-specific properties of the upcoming event. Moreover, this enhancement was weaker in participants who reported stronger conscious reliance on the cue during anticipation prior to stimulation (Experiment 1). A plausible interpretation is that individuals who admittedly considered the cues unreliable might have focused more on the unpleasant aspects of the events (unpleasantness was predictable at 100%) rather than on their modality-specific aspects (modality was predictable at 75%). Interestingly, in Experiment 2, almost all participants reported a strong reliance on the cue during the experimental session, which might explain why in this specific dataset we observed only modality-specific effects, at the expense of cross-modal modulations.
4.2.2 Neural Responses in Insula and MCC
In Experiment 2 we tested which brain structures mediated the modality-specific expectation effects observed behaviorally, and we found an involvement of dAI and MCC. The dAI and MCC are part of a well-known network repeatedly implicated in the experience of pain71,75,78,83,110,113,212,572,573,261, often called the “pain matrix”. Connectivity studies also demonstrated strong functional interactions between dAI and MCC, even at rest574, However, these two regions have been reported to respond to other emotional but painless experiences, such as disgust127,264,273,525,270,276,575 unpleasant touch or audition576–580, as well as to more general signals associated with prediction and risk73,92,94,320, error monitoring581–584, memory585–588, or social tasks589–592. This functional heterogeneity led some authors to argue that the insula and cingulate components of the pain matrix might in fact be part of a more general-purpose network for salience detection, according to which these regions respond to stimuli of any sensory modality whenever their features capture attention or call for adaptive behavioral changes122,496,497,564,593.
We believe that the results of our study cannot be explained in terms of salience only, but rather speak in favor of modality-specific processing within dAI and MCC. Although different definitions exist, the most common is that the salience of a stimulus is determined by how much it contrasts, along one or more physical dimensions, from its surrounding594–596.Salience is not determined only by stimulus
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intensity597, but also by its novelty598–600, as novel or unexpected stimuli contrast with the individual’s priors more than old or expected events. Hence, in our experimental design, a painful stimulus can be considered more salient when preceded by a cue predicting disgust (rather than when preceded by a cue predicting pain), because expectation and subsequent stimulation recruit mismatching (rather than matching) sensory channels. Our data, however, do not reveal any mismatch effect in dAI and MCC, thus suggesting that the functional properties of these regions cannot be interpreted exclusively in terms of salience.
Our data accord with those from previous pain expectancy studies, showing that the stimulus-induced activity of dAI and MCC is modulated by aversive information conveyed a preceding cue87,123. In the current study, we observed this effect not only for pain but also for disgust. However, it was reversed in the cross-modal conditions. These findings parallel those from a previous study127, where the right anterior insula disclosed shared, but nonetheless dissociable activity patterns for the experience of both pain and disgust. Our study extends these previous observations by suggesting that modality-specific neural responses are positively modulated by expectation of the same event type, but inhibited by expectation of a different sensory event.
More generally, our results provide new support to recent integrative accounts of insula function126,283, according to which dAI encodes prospective models of affective consequences of specific situations, which are then compared with the real outcomes for error-based learning. Interestingly, recent meta-analytical functional decoding analysis on brain imaging data601, suggests that activity in dAI is most
“diagnostic” of conditions involving pain discrimination or monitoring tasks, reward-based tasks, or Sternberg memory span tasks (in which participants assess whether a probe letter appeared in a previous group of letters). As in our study, all these tasks share a common requirement to assess whether an event outcome matches their predicted or desired representation, pointing to a major role of dAI in predictive coding also outside the domain of pain and disgust.
We note that in our and many previous studies, dAI and MCC were associated with similar effects, seemingly sharing the same functional properties. However, the role played by these two regions in the prediction and experience of painful or disgusting events might differ. For instance, it has been often highlighted that, unlike dAI, the involvement of MCC in pain and negative affect might reflect the monitoring and selection of optimal behavioral responses126,602. For instance, in their seminal meta-analysis, Shackman and colleagues602 revealed that the same portion of the cingulate cortex is involved in pain, negative affect, and cognitive control, suggesting that this region might constitute a key hub linking representations of outcomes (including pain) with goal-directed behavior.
Interestingly, the portion of the cingulate cortex highlighted by Shackman and colleagues602 (peak at
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the MNI-converted coordinates: x = 0, y = 10.20, z = 46.25) is very close (~7.5 mm) from the MCC cluster found in our study (x = 0, y = 10, z = 40), possibly implicating the same general monitoring mechanism.
4.2.3 Attention allocation and modality-switch
We also observed increased activity in bilateral TPJ, inferior PFC, and precuneus when the modality of the stimulus mismatched that of the cue. Instead, VMPFC and OFC activated when the stimulus matched the modality of the cue. Differently from dAI and MCC, these effects were unaffected by the predicted unpleasantness (similar modulations for low and high cues – see Figure 21), thus ruling out a role in the expectation of aversive events specifically, but suggesting a broader cognitive process instead. One interpretation for these effects is that they reflected modality switches (e.g., experiencing a thermal stimulation when expecting odorants), which led participants to re-orient from their current task set (“is the upcoming smell unpleasant?”) to a new one (“is this temperature-change unpleasant?”). In agreement, both the TPJ and inferior PFC are critically involved in the regulation of attentional allocation. The inferior PFC is activated by various tasks that make high demand in cognitive control459,603, such as the Stroop task604–606, task switching607,608, cognitive set shifting609, or reversals of stimulus-response mappings610. Furthermore, both the inferior PFC and TPJ have been implicated in expectancy violations611,612, for instance during cued perceptual decision tasks612 or reorienting attention after invalid cues towards task-relevant stimuli514,528,354. Likewise, the precuneus is frequently activated in task switching paradigms529,610,613,614. These areas therefore appear as key components of attention systems that promote the reconfiguration of current task set and contextual updating 615, which were specifically recruited by stimuli in the mismatching modality in our study.
The role played by VMPFC/OFC in response to predicted events is less clear, but this region displayed a functional profile opposite to the inferior PFC and TPJ, with increased activity during modality-consistent trials. One possibility is that this region may hold associations between predictive cues and their most likely outcome, as suggested by studies investigating predictive learning and decision making554,616–618. This region is consistently recruited by subjective evaluation processes619–622,348, as well as preference ratings and stimulus value tracking across a variety of sensory modalities621–626. VMPFC activity has also been associated with semantic labeling effects, whereby the subjective experience of gustatory624,627, olfactory622,348, nociceptive628, and even visual626,629 stimuli is biased by prior verbal descriptors. In this perspective, it is reasonable to assume that the VMPFC/OFC could subserve predictive learning and evaluative processes during modality-consistent trials, while it might be inhibited when the association between a cue and its associated outcome is broken.
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