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Background: The atypical processing of eye contact is a characteristic hallmark of autism spectrum disorder (ASD). The severity of these symptoms, however, is thought to lie on a continuum that extends into the typical population. While behavioural evidence shows that differences in social cognitive tasks in typically developed (TD) adults are related to the levels of autistic-like traits, it remains unknown whether such a relation exists for the sensitivity to direct gaze. Methods: In two experiments, we measured reaction times to detect the faces with direct and averted gaze, suppressed from awareness, i.e. the access to awareness. In experiment 1, we tested N = 19 clinically diagnosed adults with ASD and N = 22 TD matched controls, while in experiment 2, we tested an independent sample of N = 20 TD adults. Results: In line with the literature, experiment 1 showed preferential processing of direct gaze in the TD group but not in the ASD group. Importantly, we found a linear relationship in both experiments between the levels of autistic traits within the groups of TD participants and their sensitivity to direct gaze: with increasing autistic characteristics, there was a decrease in sensitivity to direct gaze. Conclusion: These results provide the first evidence that differences in gaze processing and the sensitivity to direct gaze are already present in individuals with subclinical levels of autistic traits. Furthermore, they lend support to the continuum view of the disorder and could potentially help in an earlier diagnosis of individuals at high risk for autism. [ABSTRACT FROM AUTHOR]

Positive symptoms of schizophrenia such as delusions and hallucinations are thought to arise from an alteration in predictive mechanisms of the brain. Here, we empirically tested the hypothesis that schizophrenia is associated with an enhanced signalling of higher-level predictions that shape perception into conformity with acquired beliefs. Twenty-one patients with schizophrenia and twenty-eight healthy controls matched for age and gender took part in a functional magnetic resonance imaging (fMRI) experiment that assessed the effect of an experimental manipulation of cognitive beliefs on the perception of an ambiguous visual motion stimulus. At the behavioural level, there was a generally weaker effect of experimentally induced beliefs on perception in schizophrenia patients compared with controls, but a positive correlation between the effect of beliefs on perception and the severity of positive symptoms. At the neural level, belief-related connectivity between a region encoding beliefs in the orbitofrontal cortex (OFC) and a region encoding visual motion in the visual cortex (V5) was higher in patients compared with controls, indicating a stronger impact of cognitive beliefs on visual processing in schizophrenia. We suggest that schizophrenia might be associated with a generally weaker acquisition of externally generated beliefs and a compensatory increase in the effect of beliefs on sensory processing. Our current results are in line with the notion that enhanced signalling of higher-level predictions that shape perception into conformity with acquired beliefs might underlie positive symptoms in schizophrenia. Hum Brain Mapp 38:1767-1779, 2017. © 2017 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

According to current concepts, major depressive disorder is strongly related to dysfunctional neural processing of motivational information, entailing impairments in reinforcement learning. While computational modelling can reveal the precise nature of neural learning signals, it has not been used to study learning-related neural dysfunctions in unmedicated patients with major depressive disorder so far. We thus aimed at comparing the neural coding of reward and punishment prediction errors, representing indicators of neural learning-related processes, between unmedicated patients with major depressive disorder and healthy participants. To this end, a group of unmedicated patients with major depressive disorder (n = 28) and a group of age- and sex-matched healthy control participants (n = 30) completed an instrumental learning task involving monetary gains and losses during functional magnetic resonance imaging. The two groups did not differ in their learning performance. Patients and control participants showed the same level of prediction error-related activity in the ventral striatum and the anterior insula. In contrast, neural coding of reward prediction errors in the medial orbitofrontal cortex was reduced in patients. Moreover, neural reward prediction error signals in the medial orbitofrontal cortex and ventral striatum showed negative correlations with anhedonia severity. Using a standard instrumental learning paradigm we found no evidence for an overall impairment of reinforcement learning in medication-free patients with major depressive disorder. Importantly, however, the attenuated neural coding of reward in the medial orbitofrontal cortex and the relation between anhedonia and reduced reward prediction error-signalling in the medial orbitofrontal cortex and ventral striatum likely reflect an impairment in experiencing pleasure from rewarding events as a key mechanism of anhedonia in major depressive disorder. [ABSTRACT FROM AUTHOR]

Efficient threat detection from the environment is critical for survival. Accordingly, fear-conditioned stimuli receive prioritized processing and capture overt and covert attention. However, it is unknown whether eye movements are influenced by unconscious fear-conditioned stimuli. We performed a classical fear-conditioning procedure and subsequently recorded participants’ eye movements while they were exposed to fear-conditioned stimuli that were rendered invisible using interocular suppression. Chance-level performance in a forced-choice-task demonstrated unawareness of the stimuli. Differential skin conductance responses and a change in participants’ fearfulness ratings of the stimuli indicated the effectiveness of conditioning. However, eye movements were not biased towards the fear-conditioned stimulus. Preliminary evidence suggests a relation between the strength of conditioning and the saccadic bias to the fear-conditioned stimulus. Our findings provide no strong evidence for a saccadic bias towards unconscious fear-conditioned stimuli but tentative evidence suggests that such an effect may depend on the strength of the conditioned response. [ABSTRACT FROM AUTHOR]

Direct gaze is a potent non-verbal signal that establishes a communicative connection between two individuals, setting the course for further interactions. Although consciously perceived faces with direct gaze have been shown to capture attention, it is unknown whether an attentional preference for these socially meaningful stimuli exists even in the absence of awareness. In two experiments, we recorded participants’ eye movements while they were exposed to faces with direct and averted gaze rendered invisible by interocular suppression. Participants’ inability to correctly guess the occurrence of the faces in a manual forced-choice task demonstrated complete unawareness of the faces. However, eye movements were preferentially directed towards faces with direct compared to averted gaze, indicating a specific sensitivity to others’ gaze directions even without awareness. This oculomotor preference suggests that a rapid and automatic establishment of mutual eye contact constitutes a biological advantage, which could be mediated by fast subcortical pathways in the human brain. [ABSTRACT FROM AUTHOR]

Gaze direction and especially direct gaze is a powerful nonverbal cue that plays an important role in social interactions. Here we studied the neural mechanisms underlying the privileged access of direct gaze to visual awareness. We performed functional magnetic resonance imaging in healthy human volunteers who were exposed to faces with direct or averted gaze under continuous flash suppression, thereby manipulating their awareness of the faces. A gaze processing network comprising fusiform face area (FFA), superior temporal sulcus, amygdala, and intraparietal sulcus showed overall reduced neural responses when participants reported to be unaware of the faces. Interestingly, direct gaze elicited greater responses than averted gaze when participants were aware of the faces, but smaller responses when they were unaware. Additional between-subject correlation and single-trial analyses indicated that this pattern of results was due to a modulation of the relationship between neural responses and awareness by gaze direction: with increasing neural activation in the FFA, direct-gaze faces entered awareness more readily than averted-gaze faces. These findings suggest that for direct gaze, lower levels of neural activity are sufficient to give rise to awareness than for averted gaze, thus providing a neural basis for privileged access of direct gaze to awareness. [ABSTRACT FROM AUTHOR]

Cognitive theories of depression posit that perception is negatively biased in depressive disorder. Previous studies have provided empirical evidence for this notion, but left open the question whether the negative perceptual bias reflects a stable trait or the current depressive state. Here we investigated the stability of negatively biased perception over time. Emotion perception was examined in patients with major depressive disorder (MDD) and healthy control participants in two experiments. In the first experiment subjective biases in the recognition of facial emotional expressions were assessed. Participants were presented with faces that were morphed between sad and neutral and happy expressions and had to decide whether the face was sad or happy. The second experiment assessed automatic emotion processing by measuring the potency of emotional faces to gain access to awareness using interocular suppression. A follow-up investigation using the same tests was performed three months later. In the emotion recognition task, patients with major depression showed a shift in the criterion for the differentiation between sad and happy faces: In comparison to healthy controls, patients with MDD required a greater intensity of the happy expression to recognize a face as happy. After three months, this negative perceptual bias was reduced in comparison to the control group. The reduction in negative perceptual bias correlated with the reduction of depressive symptoms. In contrast to previous work, we found no evidence for preferential access to awareness of sad vs. happy faces. Taken together, our results indicate that MDD-related perceptual biases in emotion recognition reflect the current clinical state rather than a stable depressive trait. [ABSTRACT FROM AUTHOR]

Perceptual learning is the improvement in perceptual performance through training or exposure. Here, we used fMRI before and after extensive behavioral training to investigate the effects of perceptual learning on the recognition of objects under challenging viewing conditions. Objects belonged either to trained or untrained categories. Trained categories were further subdivided into trained and untrained exemplars and were coupled with high or low monetary rewards during training. After a 3-day training, object recognition was markedly improved. Although there was a considerable transfer of learning to untrained exemplars within categories, an enhancing effect of reward reinforcement was specific to trained exemplars. fMRI showed that hippocampus responses to both trained and untrained exemplars of trained categories were enhanced by perceptual learning and correlated with the effect of reward reinforcement. Our results suggest a key role of hippocampus in object recognition after perceptual learning. [ABSTRACT FROM AUTHOR]

Although neural signals of reward anticipation have been studied extensively, the functional relationship between reward and attention has remained unclear: Neural signals implicated in reward processing could either reflect attentional biases towards motivationally salient stimuli, or proceed independently of attentional processes. Here, we sought to disentangle reward and attention-related neural processes by independently modulating reward value and attentional task demands in a functional magnetic resonance imaging study in healthy human participants. During presentation of a visual reward cue that indicated whether monetary reward could be obtained in a subsequent reaction time task, participants either attended to the reward cue or performed an unrelated attention-demanding task at two different levels of difficulty. In ventral striatum and ventral tegmental area, neural responses were modulated by reward anticipation irrespective of attentional demands, thus indicating attention-independent processing of reward cues. By contrast, additive effects of reward and attention were observed in visual cortex. Critically, reward-related activations in right anterior insula strongly depended on attention to the reward cue. Dynamic causal modelling revealed that the attentional modulation of reward processing in insular cortex was mediated by enhanced effective connectivity from ventral striatum to anterior insula. Our results provide evidence for distinct functional roles of the brain regions involved in the processing of reward-indicating information: While subcortical structures signal the motivational salience of reward cues even when attention is fully engaged elsewhere, reward-related responses in anterior insula depend on available attentional resources, likely reflecting the conscious evaluation of sensory information with respect to motivational value. Hum Brain Mapp 35:3036-3051, 2014. © 2013 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Eye movements provide a direct link to study the allocation of overt attention to stimuli in the visual field. The initiation of saccades towards visual stimuli is known to be influenced by the bottom-up salience of stimuli as well as the motivational context of the task. Here, we asked whether the initiation of saccades is also influenced by the intrinsic motivational salience of a stimulus. Face stimuli were first associated with positive or negative motivational salience through instrumental learning. The same faces served as target stimuli in a subsequent saccade task, in which their motivational salience was no longer task-relevant. Participants performed either voluntary saccades, which required the selection of the saccade target out of two simultaneously presented stimuli (experiment 1), or reactive saccades, where only the target stimulus was presented (experiment 2). We found a specific effect of learned positive stimulus value on the latencies of voluntary saccades: For faces with high versus low positive motivational salience, saccadic latencies were significantly reduced. No such difference was observed for previously punished faces. In contrast, reactive saccades to both previously rewarded and punished faces were unaffected by learned stimulus value. Our findings show for the first time that saccadic preparation is susceptible to the acquired intrinsic motivational salience of visual stimuli. Based on the observation that only voluntary saccades but not reactive saccades were modulated, we conclude that the recruitment of neural processes for target identification is required to allow for an influence of motivational stimulus salience on saccadic preparation. [ABSTRACT FROM AUTHOR]

Abstract: Recent studies have shown that motivational stimulus information is represented in the brain even in situations where the individual is not actively engaged in stimulus evaluation. However, it has remained unclear whether neural representations of such implicit motivational information reflect the motivational value or motivational salience of stimuli. While motivational values correspond to the desirability of stimuli, motivational salience is related to the arousal elicited by the stimulus. Here we aimed at disentangling the neural representation of both motivational dimensions. In the first part, participants learned the association of face stimuli with monetary reward and punishment. The same face stimuli were presented in a subsequent fMRI experiment, during which participants either performed a gender discrimination task on the faces or an orientation discrimination task on two simultaneously presented bars. Importantly, faces only differed regarding their implicit motivational information as acquired in the previous learning task, as participants neither received monetary reinforcement during the fMRI experiment nor were they asked to explicitly judge their face preferences. We found that neural responses in lateral OFC were modulated by implicit motivational value, whereas the faces'' implicit motivational salience was coded in medial OFC. While the value-related responses in lateral OFC decreased over time, the salience-related modulation of medial OFC activity remained stable over the duration of the fMRI experiment. Neural responses to both motivational dimensions were observed independent of whether participants'' attention was directed to the faces or to the surrounding bars, suggesting an automatic processing of implicit motivational value and salience. The functional dissociation within the OFC suggests that this region is critically involved in distinct motivation-related processes: In medial OFC, a representation of salient items may be maintained in order to facilitate responses towards behaviourally relevant stimuli in the future; in contrast the temporary value effect in lateral OFC might reflect decreasing stimulus valuation in the absence of explicit motivational stimulus differences. [Copyright &y& Elsevier]

Abstract: A fundamental challenge for organisms is how to focus on perceptual information relevant to current goals while remaining able to respond to goal-irrelevant stimuli that signal potential threat. Here, we studied how visual threat signals influence the effects of goal-directed spatial attention on the retinotopic distribution of processing resources in early visual cortex. We used a combined blocked and event-related functional magnetic resonance imaging paradigm with target displays comprising diagonal pairs of intact and scrambled faces presented simultaneously in the four visual field quadrants. Faces were male or female and had fearful or neutral emotional expressions. Participants attended covertly to a pair of two diagonally opposite stimuli and performed a gender-discrimination task on the attended intact face. In contrast to the fusiform face area, where attention and fearful emotional expression had additive effects, neural responses to attended and unattended fearful faces were indistinguishable in early retinotopic visual areas: When attended, fearful face expression did not further enhance responses, whereas when unattended, fearful expression increased responses to the level of attended face stimuli. Remarkably, the presence of fearful stimuli augmented the enhancing effect of attention on retinotopic responses to neutral faces in remote visual field locations. We conclude that this redistribution of neural activity in retinotopic visual cortex may serve the purpose of allocating processing resources to task-irrelevant threat-signaling stimuli while at the same time increasing resources for task-relevant stimuli as required for the maintenance of goal-directed behavior. [Copyright &y& Elsevier]

It is well-established that increased sensory uncertainty impairs perceptual decision-making and leads to degraded neural stimulus representations. Recently, we also showed that providing unreliable feedback to choices leads to changes in perceptual decision-making similar to those of increased stimulus noise: A deterioration in objective task performance, a decrease in subjective confidence and a lower reliance on sensory information for perceptual inference. To investigate the neural basis of such feedback-based changes in perceptual decision-making, in the present study, two groups of healthy human participants (n = 15 each) performed a challenging visual orientation discrimination task while undergoing functional magnetic resonance imaging (fMRI). Critically, one group received reliable feedback regarding their task performance in an intervention phase, whereas the other group correspondingly received unreliable feedback – thereby keeping stimulus information constant. The effects of feedback reliability on performance and stimulus representation in the primary visual cortex (V1) were studied by comparing the pre- and post-intervention test phases between the groups. Compared to participants who received reliable feedback, those receiving unreliable feedback showed a decline in task performance that was paralleled by reduced distinctness of fMRI response patterns in V1. These results show that environmental uncertainty can affect perceptual inference at the earliest cortical processing stages. • Past studies suggest that manipulated feedback increases sensory uncertainty. • We probed effects of unreliable feedback on visual discrimination and fMRI responses. • Results show that such feedback impairs accuracy and stimulus representations in V1. • Thus, beliefs about environmental uncertainty can affect early visual processing. [ABSTRACT FROM AUTHOR]

According to the reward deficiency syndrome and allostatic hypotheses, hyposensitivity of mesocorticolimbic regions to non–alcohol-related stimuli predisposes to dependence or is long-lastingly enhanced by chronic substance use. To date, no study has directly compared mesocorticolimbic brain activity during non–drug reward anticipation between alcohol-dependent, at risk, and healthy subjects. Seventy-five abstinent alcohol-dependent human subjects (mean abstinence duration 957.66 days), 62 healthy first-degree relatives of alcohol-dependent individuals, and 76 healthy control subjects without family history of alcohol dependence performed a monetary incentive delay task. Functional magnetic resonance imaging data of the anticipation phase were analyzed, during which visual cues predicted that fast response to a target would result in monetary gain, avoidance of monetary loss, or a neutral outcome. During gain anticipation, there were no significant group differences. During loss anticipation, abstinent alcohol-dependent subjects showed lower activity in the left anterior insula compared with healthy control subjects without family history of alcohol dependence only (Montreal Neurological Institute [MNI] −25 19 –5; t 206 = 4.17, familywise error corrected p =.009). However, this effect was no longer significant when age was included as a covariate. There were no group differences between abstinent alcohol-dependent subjects and healthy first-degree relatives or between healthy first-degree relatives and healthy control subjects during loss anticipation, respectively. Neither the neural reward deficiency syndrome nor the allostatic hypotheses are supported by the results. Future studies should investigate whether the incentive salience hypothesis allows for more accurate predictions regarding mesocorticolimbic brain activity of subjects with alcohol dependence and healthy individuals during reward and loss anticipation and further examine the neural substrates underlying a predisposition to dependence. [ABSTRACT FROM AUTHOR]

Summary: Intuitively, it would seem that we need to be aware of an object to locate it in our visual environment. Occasionally, however, we experience our actions as guided by the unconscious use of visual information. For example, most tennis players would agree that they sometimes hit a ball without even having seen it. Can we thus locate visual information without awareness? It may appear straightforward to adopt subjects'' reports about their conscious experience as the benchmark for visual awareness: a dissociation between awareness and the ability to locate a stimulus would be demonstrated when subjects deny seeing the stimulus while correctly guessing its location. This approach, however, suffers from potential response biases: Subjects may claim not to see a stimulus despite being partially or even fully aware of it . We report that observers are biased to look at stimuli even when objectively unaware of them; that is, even when at chance level in guessing stimulus location. This demonstrates that the human visual system can control goal-directed oculomotor behavior towards invisible stimuli in the objective absence of awareness. [Copyright &y& Elsevier]

A mechanism known as Pavlovian-to-instrumental transfer (PIT) describes a phenomenon by which the values of environmental cues acquired through Pavlovian conditioning can motivate instrumental behavior. PIT may be one basic mechanism of action control that can characterize mental disorders on a dimensional level beyond current classification systems. Therefore, we review human PIT studies investigating subclinical and clinical mental syndromes. The literature prevails an inhomogeneous picture concerning PIT. While enhanced PIT effects seem to be present in non-substance-related disorders, overweight people, and most studies with AUD patients, no altered PIT effects were reported in tobacco use disorder and obesity. Regarding AUD and relapsing alcohol-dependent patients, there is mixed evidence of enhanced or no PIT effects. Additionally, there is evidence for aberrant corticostriatal activation and genetic risk, e.g., in association with high-risk alcohol consumption and relapse after alcohol detoxification. In patients with anorexia nervosa, stronger PIT effects elicited by low caloric stimuli were associated with increased disease severity. In patients with depression, enhanced aversive PIT effects and a loss of action-specificity associated with poorer treatment outcomes were reported. Schizophrenic patients showed disrupted specific but intact general PIT effects. Patients with chronic back pain showed reduced PIT effects. We provide possible reasons to understand heterogeneity in PIT effects within and across mental disorders. Further, we strengthen the importance of reliable experimental tasks and provide test-retest data of a PIT task showing moderate to good reliability. Finally, we point toward stress as a possible underlying factor that may explain stronger PIT effects in mental disorders, as there is some evidence that stress per se interacts with the impact of environmental cues on behavior by selectively increasing cue-triggered wanting. To conclude, we discuss the results of the literature review in the light of Research Domain Criteria, suggesting future studies that comprehensively assess PIT across psychopathological dimensions. [ABSTRACT FROM AUTHOR]

Delusions are unfounded yet tenacious beliefs and asymptomof psychotic disorder. Varying degrees of delusional ideation are also found in the healthy population. Here, we empirically validated a neurocognitive model that explains both the formation and the persistence of delusional beliefs in terms of altered perceptual inference. In a combined behavioral and functional neuroimaging study in healthy participants, we used ambiguous visual stimulation to probe the relationship between delusion-proneness and the effect of learned predictions on perception. Delusional ideation was associated with less perceptual stability, but a stronger belief-induced bias on perception, paralleled by enhanced functional connectivity between frontal areas that encoded beliefs and sensory areas that encoded perception. These findings suggest that weakened lower-level predictions that result in perceptual instability are implicated in the emergence of delusional beliefs. In contrast, stronger higher-level predictions that sculpt perception into conformity with beliefs might contribute to the tenacious persistence of delusional beliefs. [ABSTRACT FROM AUTHOR]

Appetitive Pavlovian conditioning is a learning mechanism of fundamental biological and pathophysiological significance. Nonetheless, its exploration in humans remains sparse, which is partly attributed to the lack of an established psychophysiological parameter that aptly represents conditioned responding. This study evaluated pupil diameter and other ocular response measures (gaze dwelling time, blink duration and count) as indices of conditioning. Additionally, a learning model was used to infer participants' learning progress on the basis of their pupil dilation. Twenty‐nine healthy volunteers completed an appetitive differential delay conditioning paradigm with a primary reward, while the ocular response measures along with other psychophysiological (heart rate, electrodermal activity, postauricular and eyeblink reflex) and behavioral (ratings, contingency awareness) parameters were obtained to examine the relation among different measures. A significantly stronger increase in pupil diameter, longer gaze duration and shorter eyeblink duration was observed in response to the reward‐predicting cue compared to the control cue. The Pearce‐Hall attention model best predicted the trial‐by‐trial pupil diameter. This conditioned response was corroborated by a pronounced heart rate deceleration to the reward‐predicting cue, while no conditioning effect was observed in the electrodermal activity or startle responses. There was no discernible correlation between the psychophysiological response measures. These results highlight the potential value of ocular response measures as sensitive indices for representing appetitive conditioning. Despite its central biological and pathophysiological significance, exploration of human appetitive Pavlovian conditioning remains sparse. This is commonly ascribed to the lack of a suitable measure that aptly reflects conditioned learning. In this study, we show that pupil diameter not only constitutes a sensitive and robust index for representing appetitive learning, but also precisely predicts individual trial‐by‐trial learning mechanisms in a Pearce‐Hall attention‐weighted learning model. Successful conditioning was confirmed by additional psychophysiological measures. These findings highlight the potential value of pupil diameter when exploring human appetitive conditioning and may help expedite research of this fundamental learning mechanism. [ABSTRACT FROM AUTHOR]