The computational principles by which the brain creates a painful experience from nociception are still unknown. Classic theories suggest that cortical regions either reflect stimulus intensity or additive effects of intensity and expectations, respectively. By contrast, predictive coding theories provide a unified framework explaining how perception is shaped by the integration of beliefs about the world with mismatches resulting from the comparison of these beliefs against sensory input. Using functional magnetic resonance imaging during a probabilistic heat pain paradigm, we investigated which computations underlie pain perception. Skin conductance, pupil dilation, and anterior insula responses to cued pain stimuli strictly followed the response patterns hypothesized by the predictive coding model, whereas posterior insula encoded stimulus intensity. This novel functional dissociation of pain processing within the insula together with previously observed alterations in chronic pain offer a novel interpretation of aberrant pain processing as disturbed weighting of predictions and prediction errors.DOI: http://dx.doi.org/10.7554/eLife.24770.001

It has recently been suggested that learning signals in the amygdala might be best characterized by attentional theories of associative learning [such as Pearce-Hall (PH)] and more recent hybrid variants that combine Rescorla-Wagner and PH learning models. In these models, unsigned prediction errors (PEs) determine the associability of a cue, which is used in turn to control learning of outcome expectations dynamically and reflects a function of the reliability of prior outcome predictions. Here, we employed an aversive Pavlovian reversal-learning task to investigate computational signals derived from such a hybrid model. Unlike previous accounts, our paradigm allowed for the separate assessment of associability at the time of cue presentation and PEs at the time of outcome. We combined this approach with high-resolution functional magnetic resonance imaging to understand how different subregions of the human amygdala contribute to associative learning. Signal changes in the corticomedial amygdala and in the midbrain represented unsigned PEs at the time of outcome showing increased responses irrespective of whether a shock was unexpectedly administered or omitted. In contrast, activity in basolateral amygdala regions correlated negatively with associability at the time of cue presentation. Thus, whereas the corticomedial amygdala and the midbrain reflected immediate surprise, the basolateral amygdala represented predictiveness and displayed increased responses when outcome predictions became more reliable. These results extend previous findings on PH-like mechanisms in the amygdala and provide unique insights into human amygdala circuits during associative learning.

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Distractibility with auditory, visual, and bimodal stimulus changes was investigated using an audio-visual distraction paradigm. Participants were asked to discriminate between equiprobable short and long audio-visual stimuli. Infrequently, the auditory, the visual, or both parts of the stimuli changed. These rare deviations (deviants) were irrelevant for the actual task. The influence of the three types of deviant stimuli on the processing of task-relevant information was assessed with behavioral and event-related potential (ERP) measures assuming that bimodal deviants would lead to an increase in distraction. Behavioral and ERP results did not support this assumption, as reaction time (RT) prolongation and components amplitudes did not differ significantly for auditory and bimodal deviants. It is suggested that a maximal threshold of distraction accounts for these results. In addition, the processing of bimodal deviations was assessed. Audio-visual interactions were found following modality-specific deviance detection suggesting that integration only occurs with involuntary attention switching to task-irrelevant changes.

Background Previous eye-tracking studies provide preliminary evidence for a hypersensitivity to negative, potentially threatening interpersonal cues in borderline personality disorder (BPD). From an etiological point of view, such interpersonal threat hypersensitivity might be explained by a biological vulnerability along with a history of early life adversities. The objective of the current study was to investigate interpersonal threat hypersensitivity and its association with adverse childhood experiences (ACE) in patients with BPD employing eye-tracking technology. Methods We examined a sample of 46 unmedicated, adult female patients with BPD and 25 healthy female volunteers, matched on age and intelligence, with a well-established emotion classification paradigm with angry, fearful, happy, and neutral facial expressions. ACE were assessed retrospectively with the Childhood Trauma Questionnaire. Results Patients as compared to healthy volunteers reflexively directed their gaze more quickly towards the eyes of emotional and neutral faces and did not adapt their fixation patterns according to the facial expression presented. Misclassifying emotional and neutral faces as angry correlated positively with the patients’ self-reported ACE. Conclusions Building on and extending earlier findings, our results are likely to suggest a visual hypervigilance towards the eyes of emotional and neutral facial expressions and a childhood trauma-related anger bias in patients with BPD. Given the lack of a clinical control group, the question whether these findings are specific for BPD has to remain open. Thus, further research is needed to elucidate the specificity of altered visual attention allocation and the role of ACE in anger recognition in patients with BPD.

Individual genetic differences in the serotonin transporter-linked polymorphic region (5-HTTLPR) have been associated with variations in the sensitivity to social and emotional cues as well as altered amygdala reactivity to facial expressions of emotion. Amygdala activation has further been shown to trigger gaze changes toward diagnostically relevant facial features. The current study examined whether altered socio-emotional reactivity in variants of the 5-HTTLPR promoter polymorphism reflects individual differences in attending to diagnostic features of facial expressions. For this purpose, visual exploration of emotional facial expressions was compared between a low (n = 39) and a high (n = 40) 5-HTT expressing group of healthy human volunteers in an eye tracking paradigm. Emotional faces were presented while manipulating the initial fixation such that saccadic changes toward the eyes and toward the mouth could be identified. We found that the low vs. the high 5-HTT group demonstrated greater accuracy with regard to emotion classifications, particularly when faces were presented for a longer duration. No group differences in gaze orientation toward diagnostic facial features could be observed. However, participants in the low 5-HTT group exhibited more and faster fixation changes for certain emotions when faces were presented for a longer duration and overall face fixation times were reduced for this genotype group. These results suggest that the 5-HTT gene influences social perception by modulating the general vigilance to social cues rather than selectively affecting the pre-attentive detection of diagnostic facial features.

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