Pain perception as hierarchical Bayesian inference: A test case for the theory of constructed emotion.

An intriguing perspective about human emotion, the theory of constructed emotion considers emotions as generative models according to the Bayesian brain hypothesis. This theory brings fresh insight to existing findings, but its complexity renders it challenging to test experimentally. We argue that laboratory studies of pain could support the theory because although some may not consider pain to be a genuine emotion, the theory must at minimum be able to explain pain perception and its dysfunction in pathology. We review emerging evidence that bear on this question. We cover behavioral and neural laboratory findings, computational models, placebo hyperalgesia, and chronic pain. We conclude that there is substantial evidence for a predictive processing account of painful experience, paving the way for a better understanding of neuronal and computational mechanisms of other emotions.

Test-retest reliability of Bayesian estimations of the effects of stimulation, prior information and individual traits on pain perception.

BACKGROUND: There is inter-individual variability in the influence of different components (e.g. nociception and expectations) on pain perception. Identifying the individual effect of these components could serve for patient stratification, but only if these influences are stable in time. METHODS: In this study, 30 healthy participants underwent a cognitive pain paradigm in which they rated pain after viewing a probabilistic cue informing of forthcoming pain intensity and then receiving electrical stimulation. The trial information was then used in a Bayesian probability model to compute the relative weight each participant put on stimulation, cue, cue uncertainty and trait-like bias. The same procedure was repeated 2 weeks later. Relative and absolute test-retest reliability of all measures was assessed. RESULTS: Intraclass correlation results showed good reliability for the effect of the stimulation (0.83), the effect of the cue (0.75) and the trait-like bias (0.75 and 0.75), and a moderate reliability for the effect of the cue uncertainty (0.55). Absolute reliability measures also supported the temporal stability of the results and indicated that a change in parameters corresponding to a difference in pain ratings ranging between 0.47 and 1.45 (depending on the parameters) would be needed to consider differences in outcomes significant. The comparison of these measures with the closest clinical data we possess supports the reliability of our results. CONCLUSIONS: These findings support the hypothesis that inter-individual differences in the weight placed on different pain factors are stable in time and could therefore be a possible target for patient stratification. SIGNIFICANCE: Our results demonstrate the temporal stability of the weight healthy individuals place on the different factors leading to the pain response. These findings give validity to the idea of using Bayesian estimations of the influence of different factors on pain as a way to stratify patients for treatment personalization.

Are multiple types of associative memory differently impacted by emotion?

The effect of emotion on associative memory is still an open question. Our aim was to test whether discrepant findings are due to differential impact of emotion on different types of associative memory or to differences in the way participants encoded stimuli across studies. We examined the effect of negative content on multiple forms of associative memory, using the same encoding task. Two registered experiments were conducted in parallel with random allocation of participants to experiments. Each experiment included 4 encoding blocks, in which participants read a neutral text comprised of 6 paragraphs, which were interleaved with neutral or negative images. Images were controlled for visual properties and semantic similarity. Memory tests included recognition memory, Remember/Know, order memory, temporal source memory and contextual memory. Analyses showed that emotion decreased contextual memory but not order memory or temporal source memory. We also found that temporal source memory and contextual memory were correlated. Recognition accuracy and subjective recollection were not impacted by emotion. In agreement with previous work, participants self-reported a reduced ability to integrate blocks containing negative images with paragraphs. In contrast to our hypothesis, results suggest that emotion does not impact all types of associative memory when stimuli are controlled.

Are We Any Closer to Understanding How Chronic Pain Develops? A Systematic Search and Critical Narrative Review of Existing Chronic Pain Vulnerability Models.

Identifying biopsychosocial factors underlying chronic pain vulnerability is essential for the design of preventative efforts. Multiple chronic pain vulnerability models exist, however, there is a lack of comprehensive evaluation of these models in the literature, potentially due to the lack of guidelines that specify the criteria by which these types of work should be assessed. In this work, we created evaluation criteria (based on the general goals of conceptual models), and we then used them to critically review the chronic pain vulnerability models available in the current peer-reviewed literature (identified through a systematic search). Particularly, we evaluated the models on the basis of conceptual clarity/specificity of measures, depth of description of aetiological and mechanistic factors, use of a whole system approach, and quality of the evidence associated with the models. We found nine conceptual models that have been explored in detail (eg, fear avoidance model, diathesis-stress model). These models excel at clarity and are supported mostly by self-report evidence of a psychological nature (anxiety sensitivity, pain catastrophizing, etc.), but provide little explanation of mechanistic and aetiological factors. In the future, models could be improved by complementing them with proposals from other models and exploring potential causal factors and mechanisms maintaining the condition. This task could be carried out through prospective cohort studies, and computational approaches, amongst others.

Can neural correlates of encoding explain the context dependence of reward-enhanced memory?

Selective encoding can be studied by manipulating how valuable it is for participants to remember specific stimuli, for instance, by varying the monetary reward participants receive for recalling a particular stimulus in a subsequent memory test. It would be reasonable for participants to strategically attend more to high-reward items compared to low-reward items in mixed list contexts, but to attend both types of items equally in pure list contexts, where all items are of equal value. Reward-enhanced memory may be driven by automatic dopaminergic interactions between reward circuitry and the hippocampus and thus be insensitive to list context; or it may be driven by meta-cognitive strategies, and thus context-dependent. We contrasted these alternatives by manipulating list composition and tracked selective encoding through multiple EEG measures of attention and rehearsal. Behavioral results were context-dependent, such that recall of high-reward items was increased only in mixed lists. This result and aspects of the recall dynamics confirm predictions of the eCMR (emotional Context Maintenance and Retrieval) model. The power of ssVEPs was lower for high-reward items regardless of list composition, suggesting decreased visual processing of high-reward stimuli and that ssVEPs may index the modulation of context-to-item associations predicted by eCMR. By contrast, reward modulated the amplitude of Late Positive Potential and Frontal Slow Wave only in mixed lists. Taken together, the results provide evidence that reward-enhanced memory is caused by an interplay between strategic processes applied when high- and low-reward items compete for cognitive resources during encoding and context-dependent mechanisms operating during recall.

Adaptive coding of pain prediction error in the anterior insula.

BACKGROUND: Understanding the mechanisms behind the influence of expectation and context on pain perception is crucial for improving analgesic treatments. Prediction error (PE) signals how much a noxious stimulus deviates from expectation and is therefore crucial for our understanding of pain perception. It is thought that the brain engages in 'adaptive coding' of pain PE, such that sensitivity to unexpected outcomes is modulated by contextual information. While there is behavioural evidence that pain is coded adaptively, and evidence that reward PE signals are coded adaptively, controversy remains regarding the underlying neural mechanism of adaptively-coded pain PEs. METHODS: A cued-pain task was performed by 19 healthy adults while undergoing FMRI scanning. BOLD responses to the task were tested using an axiomatic approach to identify areas that may code pain PE adaptively. RESULTS: The left dorsal anterior insula demonstrated a pattern of response consistent with adaptively-coded pain PE. Signals from this area were sensitive to both predicted pain magnitudes on the instigation of expectation, and the unexpectedness of pain delivery. Crucially however, the response at pain delivery was consistent with the local context of the pain stimulation, rather than the absolute magnitude of delivered pain, a pattern suggestive of an adaptively-coded PE signal. CONCLUSIONS: The study advances our understanding of the neural basis of pain prediction. Alongside existing evidence that the periaqueductal grey codes pain PE and the posterior insula codes pain magnitude, the results highlight a distinct contribution of the left dorsal anterior insula in the processing of pain. SIGNIFICANCE: Although there is behavioural evidence that pain is coded adaptively, the neural mechanisms serving this process are not well understood. This study used functional MRI to provide the first evidence that the left dorsal anterior insula, an area associated with aversive learning, responds to pain in a manner consistent with the adaptive coding of pain prediction error. This study aids our understanding of the neural basis of subjective pain representation, and thus can contribute to the advancement of analgesic treatments.

Reward does not modulate forgetting in free recall tests.

Reward is thought to attenuate forgetting through the automatic effect of dopamine on hippocampal memory traces. Here we report a conceptual replication of previous results where we did not observe this effect of reward. Participants encoded eight lists of pictures and recalled picture content immediately or the next day. They were informed that they could gain monetary reward for recalling the pictures, with the level of reward indicated through the frame surrounding the picture. Reward was manipulated both within and across lists. Bayesian statistics found moderate evidence for the null hypothesis that reward does not modulate forgetting in human free recall.

An EEG study on the effect of being overweight on anticipatory and consummatory reward in response to pleasant taste stimuli.

Two-thirds of adults in the United Kingdom currently suffer from overweight or obesity, making it one of the biggest contributors to health problems. Within the framework of the incentive sensitisation theory, it has been hypothesised that overweight people experience heightened reward anticipation when encountering cues that signal food, such as pictures and smells of food, but that they experience less reward from consuming food compared to normal-weight people. There is, however, little evidence for this prediction. Few studies test both anticipation and consumption in the same study, and even fewer with electroencephalography (EEG). This study sought to address this gap in the literature by measuring scalp activity when overweight and normal-weight people encountered cues signalling the imminent arrival of pleasant and neutral taste stimuli, and when they received these stimuli. The behavioural data showed that there was a smaller difference in valence ratings between the pleasant and neutral taste in the overweight than normal-weight group, in accordance with our hypothesis. However, contrary to our hypothesis, the groups did not differ in their electrophysiological response to taste stimuli. Instead, there was a reduction in N1 amplitude to both taste and picture cues in overweight relative to normal-weight participants. This suggests that reduced attention to cues may be a crucial factor in risk of overweight.

The Neural Representations of Emotional Experiences Are More Similar Than Those of Neutral Experiences.

Stimuli that evoke the same feelings can nevertheless look different and have different semantic meanings. Although we know much about the neural representation of emotion, the neural underpinnings of emotional similarity are unknown. One possibility is that the same brain regions represent similarity between emotional and neutral stimuli, perhaps with different strengths. Alternatively, emotional similarity could be coded in separate regions, possibly those sensitive to emotional valence and arousal. In behavior, the extent to which people consider similarity along emotional dimensions when they evaluate the overall similarity between stimuli has never been investigated. Although the emotional features of stimuli may dominate explicit ratings of similarity, it is also possible that people neglect emotional dimensions as irrelevant to that judgment. We contrasted these hypotheses in (male and female) healthy controls using two measures of similarity and two picture databases of complex negative and neutral scenes, the second of which provided exquisite control over semantic and visual attributes. The similarity between emotional stimuli was greater than between neutral stimuli in the inferior temporal cortex, the fusiform face area, and the precuneus. Additionally, only the similarity between emotional stimuli was significantly represented in early visual cortex, anterior insula and dorsal anterior cingulate cortex. Intriguingly, despite the stronger neural similarity between emotional stimuli, the same participants did not rate them as more similar to each other than neutral stimuli. These results contribute to our understanding of how emotion is represented within a general conceptual workspace and of the overgeneralization bias in anxiety disorders.SIGNIFICANCE STATEMENT We tested differences in similarity between emotional and neutral scenes. Arousal and negative valence did not increase similarity ratings. When conditions were equated on semantic similarity, participants rated emotional stimuli as similar to each other as neutral ones. Despite this equivalence, the similarity among the neural representations of emotional compared with neutral stimuli was higher in regions, which also expressed similarity between neutral stimuli and in unique regions. We report a striking difference between behavioral and neural similarity; strong neural similarity between emotional pictures did not influence similarity judgements in the same participants in the behavioral rating task after the scan. These findings may have an impact on research about the neural representations of emotional categories and the overgeneralization bias in anxiety disorders.

The effects of psychosocial stress on item, cued-pair and emotional memory.

Physical stress, such as from the cold-pressor test, has been robustly associated with altered memory retrieval, but it is less clear whether the same happens following psychosocial stress. Studies using psychosocial stressors report mixed effects on memory, leading to uncertainty about the common cognitive impact of both forms of stress. The current study uses a series of four carefully designed experiments, each differing by only a single critical factor to determine the effects of psychosocial stress on specific aspects of episodic memory. In three experiments, we induced psychosocial stress after participants encoded words, then assessed retrieval of those words after a prolonged delay. These experiments found no effect of post-encoding stress on recognition of neutral words or cued recall of word-pairs, but a small effect on recollection of semantically related words. There were, however, positive relationships within the stress group between measures of stress (cortisol in experiment 1 and self-reported-anxiety in experiment 3) and recollection of single word stimuli. In the fourth experiment, we found that psychosocial stress immediately before retrieval did not influence word recognition. Recollection, particularly for semantically related stimuli, may therefore be more susceptible to the effects of psychosocial stress, and future studies can assess how this relates to other forms of stress. Overall, our findings suggest that the effects of psychosocial stress on episodic memory may be more subtle than expected, warranting further exploration in larger studies.

Psychosocial stress has weaker than expected effects on episodic memory and related cognitive abilities: A meta-analysis.

The impact of stress on episodic memory and related cognitive abilities is well documented in both animal and human literature. However, it is unclear whether the same cognitive effects result from all forms of stress - in particular psychosocial stress. This review systematically explored the effects of psychosocial stress on episodic memory and associated cognitive abilities. PubMed, PsycInfo, and Web of Science databases were searched. Fifty-one studies were identified and compared based on the timing of stress induction. A small positive effect of post-learning psychosocial stress with a long retention interval was shown. No other effects of psychosocial stress were seen. Re-analysis of previous meta-analyses also showed no significant effect of psychosocial stress on episodic memory, highlighting potentially different effects between stressor types. Psychosocial stress also had a moderately different effect when emotional vs. neutral stimuli were compared. Finally, psychosocial stress also decreased performance on executive function, but not working memory tasks. Our findings demonstrate that psychosocial stress may not have the clear effects on episodic memory previously ascribed to it.

In for a penny, in for a pound: examining motivated memory through the lens of retrieved context models.

When people encounter items that they believe will help them gain reward, they later remember them better than others. A recent model of emotional memory, the emotional context maintenance and retrieval model (eCMR), predicts that these effects would be stronger when stimuli that predict high and low reward can compete with each other during both encoding and retrieval. We tested this prediction in two experiments. Participants were promised £1 for remembering some pictures, but only a few pence for remembering others. Their recall of the content of the pictures they saw was tested after 1 min and, in experiment 2, also after 24 h. Memory at the immediate test showed effects of list composition. Recall of stimuli that predicted high reward was greater than of stimuli that predicted lower reward, but only when high- and low-reward items were studied and recalled together, not when they were studied and recalled separately. More high-reward items in mixed lists were forgotten over a 24-h retention interval compared with items studied in other conditions, but reward did not modulate the forgetting rate, a null effect that should be replicated in a larger sample. These results confirm eCMR's predictions, although further research is required to compare that model against alternatives.

The use of 'artificial saliva' as a neutral control condition in gustatory research: Artificial saliva is not a neutral gustatory stimulus.

Distilled water with NaHCO3 and KCl is a solution often referred to as 'artificial saliva' because its chemical composition mimics human saliva. It is often used as a control stimulus in gustatory research, especially in neuroimaging, owing to the claim that it does not produce a response in primary gustatory cortex Yet evidence that human research volunteers perceive this liquid as affectively neutral is lacking. Unpublished data from our lab suggested that this solution might be perceived as aversive. This study set out to systematically test the parameters influencing taste neutrality. We used two different concentrations of distilled water with NaHCO3 and KCl, as well as bottled water as a control stimulus. Healthy adults rated all stimuli on two separate scales to rule out an interpretation based on the specifics of a single scale. Our participants rated artificial saliva as aversive on both scales. The bottled water was rated as neutral in valence on both scales, and as significantly less intense in sensation than both concentrations of the artificial saliva. This is the first study to have directly tested the subjective feelings that accompany the ingestion of these oft-used solutions on a trial-by-trial basis. We found that these stimuli, which were previously assumed to be neutral, may not be perceived as such by research participants. Therefore, future gustatory studies should take care when using this solution as a neutral baseline. It is advised that trial-by-trial ratings are collected. Also, depending on the nature of future studies, bottled water may be considered as a preferable neutral baseline.

Priming recognition memory test cues: No evidence for an attributional basis of recollection.

We argue that while the proposed memory model by Bastin et al. can explain familiarity-based memory judgements through the interaction of a core representation system and an attribution system, recollection-based memory judgements are not based on non-mnemonic signals being attributed to memory.

Quantifying how much attention rodents allocate to motivationally-salient objects with a novel object preference test.

The allocation of attention can be modulated by the emotional value of a stimulus. In order to understand the biasing influence of emotion on attention allocation further, we require an animal test of how motivational salience modulates attention. In mice, female odour triggers arousal and elicits emotional responses in males. Here, we determined the extent to which objects labelled with female odour modulated the attention of C57BL/6J male mice. Seven experiments were conducted, using a modified version of the spontaneous Novel Object Recognition task. Attention was operationalised as differential exploration time of identical objects that were labelled with either female mouse odour (O+), a non-social odour, almond odour (Oa) or not labelled with any odour (O-). In some experiments we tested trial unique (novel) objects than never carried an odour (X-). Using this novel object preference test we found that when single objects were presented, as well as when two objects were presented simultaneously (so competed with each other for attention), O+ received preferential attention compared to O-. This result was independent of whether O+ was at a novel or familiar location. When compared with Oa at a novel location, O+ at a familiar location attracted more attention. Compared to X-, O+ received more exploration only when placed at a novel location, but attention to O+ and X- was equivalent when they were placed in a familiar location. These results suggest that C57BL/6J male mice weigh up aspects of odour, object novelty and special novelty for motivational salience, and that, in some instances, female odour elicits more attention (object exploration) compared to other object properties. The findings of this study pave the way to using motivationally-significant odours to modulate the cognitive processes that give rise to differential attention to objects.

The Emotional Facet of Subjective and Neural Indices of Similarity.

Emotional similarity refers to the tendency to group stimuli together because they evoke the same feelings in us. The majority of research on similarity perception that has been conducted to date has focused on non-emotional stimuli. Different models have been proposed to explain how we represent semantic concepts, and judge the similarity among them. They are supported from behavioural and neural evidence, often combined by using Multivariate Pattern Analyses. By contrast, less is known about the cognitive and neural mechanisms underlying the judgement of similarity between real-life emotional experiences. This review summarizes the major findings, debates and limitations in the semantic similarity literature. They will serve as background to the emotional facet of similarity that will be the focus of this review. A multi-modal and overarching approach, which relates different levels of neuroscientific explanation (i.e., computational, algorithmic and implementation), would be the key to further unveil what makes emotional experiences similar to each other.

Patterns of Neural Oscillations in Emotional Memory Discrimination.

An exciting experiment by Zheng et al. (2019) in this issue of Neuron identifies neural signatures of successful and unsuccessful emotional memory discrimination. By examining human intracranial recordings with high spatial and temporal resolution, this study provides a novel link between rodent and human research on pattern separation.

A retrieved context model of the emotional modulation of memory.

Emotion enhances episodic memory, an effect thought to be an adaptation to prioritize the memories that best serve evolutionary fitness. However, viewing this effect largely in terms of prioritizing what to encode or consolidate neglects broader rational considerations about what sorts of associations should be formed at encoding, and which should be retrieved later. Although neurobiological investigations have provided many mechanistic clues about how emotional arousal modulates item memory, these effects have not been wholly integrated with the cognitive and computational neuroscience of memory more generally. Here we apply the Context Maintenance and Retrieval Model (CMR; Polyn, Norman, & Kahana, 2009) to this problem by extending it to describe the way people may represent and process emotional information. A number of ways to operationalize the effect of emotion were tested. The winning emotional CMR (eCMR) model conceptualizes emotional memory effects as arising from the modulation of a process by which memories become bound to ever-changing temporal and emotional contexts. eCMR provides a good qualitative fit for the emotional list-composition effect and the emotional oddball effect, illuminating how these effects are jointly determined by the interplay of encoding and retrieval processes. eCMR can account for the increased advantage of emotional memories in delayed memory tests by assuming a limited ability to reinstate the temporal context of encoding after a delay. By leveraging the rich tradition of temporal context models, eCMR helps integrate existing effects of emotion and provides a powerful tool to test mechanisms by which emotion affects memory in a broad range of paradigms. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Testing the Possibility of Model-based Pavlovian Control of Attention to Threat.

Signals for reward or punishment attract attention preferentially, a principle termed value-modulated attention capture (VMAC). The mechanisms that govern the allocation of attention can be described with a terminology that is more often applied to the control of overt behaviors, namely, the distinction between instrumental and Pavlovian control, and between model-free and model-based control. Although instrumental control of VMAC can be either model-free or model-based, it is not known whether Pavlovian control of VMAC can be model-based. To decide whether this is possible, we measured steady-state visual evoked potentials (SSVEPs) while 20 healthy adults took part in a novel task. During the learning stage, participants underwent aversive threat conditioning with two conditioned stimuli (CSs): one that predicted pain (CS+) and one that predicted safety (CS-). Instructions given before the test stage allowed participants to infer whether novel, ambiguous CSs (new_CS+/new_CS-) were threatening or safe. Correct inference required combining stored internal representations and new propositional information, the hallmark of model-based control. SSVEP amplitudes quantified the amount of attention allocated to novel CSs on their very first presentation, before they were ever reinforced. We found that SSVEPs were higher for new_CS+ than new_CS-. This result is potentially indicative of model-based Pavlovian control of VMAC, but additional controls are necessary to verify this conclusively. This result underlines the potential transformative role of information and inference in emotion regulation.