BackgroundFaces play a key role in signaling social cues such as signals of trustworthiness. Although several studies identify the amygdala as a core brain region in social cognition, quantitative approaches evaluating its role are scarce.ObjectivesThis review aimed to assess the role of the amygdala in the processing of facial trustworthiness, by analyzing its amplitude BOLD response polarity to untrustworthy versus trustworthy facial signals under fMRI tasks through a Meta-analysis of effect sizes (MA). Activation Likelihood Estimation (ALE) analyses were also conducted.Data sourcesArticles were retrieved from MEDLINE, ScienceDirect and Web-of-Science in January 2016. Following the PRISMA statement guidelines, a systematic review of original research articles in English language using the search string “(face OR facial) AND (trustworthiness OR trustworthy OR untrustworthy OR trustee) AND fMRI” was conducted.Study selection and data extractionThe MA concerned amygdala responses to facial trustworthiness for the contrast Untrustworthy vs. trustworthy faces, and included whole-brain and ROI studies. To prevent potential bias, results were considered even when at the single study level they did not survive correction for multiple comparisons or provided non-significant results. ALE considered whole-brain studies, using the same methodology to prevent bias. A summary of the methodological options (design and analysis) described in the articles was finally used to get further insight into the characteristics of the studies and to perform a subgroup analysis. Data were extracted by two authors and checked independently.Data synthesisTwenty fMRI studies were considered for systematic review. An MA of effect sizes with 11 articles (12 studies) showed high heterogeneity between studies [Q(11) = 265.68, p < .0001; I2 = 95.86%, 94.20% to 97.05%, with 95% confidence interval, CI]. Random effects analysis [RE(183) = 0.851, .422 to .969, 95% CI] supported the evidence that the (right) amygdala responds preferentially to untrustworthy faces. Moreover, two ALE analyses performed with 6 articles (7 studies) identified the amygdala, insula and medial dorsal nuclei of thalamus as structures with negative correlation with trustworthiness. Six articles/studies showed that posterior cingulate and medial frontal gyrus present positive correlations with increasing facial trustworthiness levels. Significant effects considering subgroup analysis based on methodological criteria were found for experiments using spatial smoothing, categorization of trustworthiness in 2 or 3 categories and paradigms which involve both explicit and implicit tasks.LimitationsSignificant heterogeneity between studies was found in MA, which might have arisen from inclusion of studies with smaller sample sizes and differences in methodological options. Studies using ROI analysis / small volume correction methods were more often devoted specifically to the amygdala region, with some results reporting uncorrected p-values based on mainly clinical a priori evidence...

IntroductionVisual processing of ecologically relevant stimuli involves a central bias for stimuli demanding detailed processing (e.g., faces), whereas peripheral object processing is based on coarse identification. Fast detection of animal shapes holding a significant phylogenetic value, such as snakes, may benefit from peripheral vision. The amygdala together with the pulvinar and the superior colliculus are implicated in an ongoing debate regarding their role in automatic and deliberate spatial processing of threat signals.MethodsHere we tested twenty healthy participants in an fMRI task, and investigated the role of spatial demands (the main effect of central vs. peripheral vision) in the processing of fear-relevant ecological features. We controlled for stimulus dependence using true or false snakes; snake shapes or snake faces and for task constraints (implicit or explicit). The main idea justifying this double task is that amygdala and superior colliculus are involved in both automatic and controlled processes. Moreover the explicit/implicit instruction in the task with respect to emotion is not necessarily equivalent to explicit vs. implicit in the sense of endogenous vs. exogenous attention, or controlled vs. automatic processes.ResultsWe found that stimulus-driven processing led to increased amygdala responses specifically to true snake shapes presented in the centre or in the peripheral left hemifield (right hemisphere). Importantly, the superior colliculus showed significantly biased and explicit central responses to snake-related stimuli. Moreover, the pulvinar, which also contains foveal representations, also showed strong central responses, extending the results of a recent single cell pulvinar study in monkeys. Similar hemispheric specialization was found across structures: increased amygdala responses occurred to true snake shapes presented to the right hemisphere, with this pattern being closely followed by the superior colliculus and the pulvinar.ConclusionThese results show that subcortical structures containing foveal representations such as the amygdala, pulvinar and superior colliculus play distinct roles in the central and peripheral processing of snake shapes. Our findings suggest multiple phylogenetic fingerprints in the responses of subcortical structures to fear-relevant stimuli.

Intrusive thoughts and compulsive urges to perform stereotyped behaviours are typical symptoms of obsessive-compulsive disorder. Emerging evidence suggests a cognitive bias towards habit formation at the expense of goal-directed performance in obsessive-compulsive disorder. In this study, we test this hypothesis using a novel individualized ecologically valid symptom provocation design: a live provocation functional magnetic resonance imaging paradigm with synchronous video-recording of behavioural avoidance responses. By pairing symptom provocation with online avoidance responses on a trial-by-trial basis, we sought to investigate the neural mechanisms leading to the compulsive avoidance response. In keeping with the model of habit formation in obsessive-compulsive disorder, we hypothesized that this disorder would be associated with lower activity in regions implicated in goal-directed behaviours and higher activity in regions implicated in habitual behaviours. Fifteen patients with obsessive-compulsive disorder and 15 healthy control volunteers participated in this functional magnetic resonance imaging study. Online stimuli were individually tailored to achieve effective symptom provocation at neutral, intermediate and strong intensity levels. During the symptom provocation block, the participant could choose to reject or terminate the provoking stimuli resulting in cessation of the symptom provocation. We thus separately analysed the neural correlates of symptom provocation, the urge to avoid, rejection and relief. Strongly symptom-provoking conditions evoked a dichotomous pattern of deactivation/activation in patients, which was not observed either in control conditions or in healthy subjects: a deactivation of caudate-prefrontal circuits accompanied by hyperactivation of subthalamic nucleus/putaminal regions. This finding suggests a dissociation between regions engaged in goal-directed and habitual behaviours. The putaminal hyperactivity during patients' symptom provocation preceded subsequent deactivation during avoidance and relief events, indicating a pivotal role of putamen in regulation of behaviour and habit formation in obsessive-compulsive disorder. Effective connectivity analysis identified the ventromedial prefrontal cortex/orbitofrontal cortex as the main structure in this circuitry involved in the modulation of compulsivity in obsessive-compulsive disorder. These findings suggest an imbalance in circuitry underlying habitual and goal-directed action control, which may represent a fundamental mechanism underlying compulsivity in obsessive-compulsive disorder. Our results complement current models of symptom generation in obsessive-compulsive disorder and may enable the development of future therapeutic approaches that aim to alleviate this imbalance.

Implicit contextual learning refers to the ability to memorize contextual information from our environment. This contextual information can then be used to guide our attention to a specific location. Although the medial temporal lobe is important for this type of learning, the basal ganglia might also be involved considering its role in many implicit learning processes. In order to understand the role of the basal ganglia in this top-down process, a group of non-demented early-stage Parkinson's patients were tested with a contextual cueing task. In this visual search task, subjects have to quickly locate a target among a number of distractors. To test implicit contextual learning, some of the configurations are repeated during the experiment, resulting in faster responses. A significant interaction effect was found between Group and Configuration, indicating that the control subjects responded faster when the spatial context was repeated, whereas Parkinson's patients failed to do so. These results, showing that the contextual cueing effect was significantly different for the patients than for the controls, suggest an important role for the basal ganglia in implicit contextual learning, thus extending previous findings of medial temporal lobe involvement. The basal ganglia are therefore not only involved in implicit motor learning, but may also have a role in purely visual implicit learning.

In human cognition, most relevant stimuli, such as faces, are processed in central vision. However, it is widely believed that recognition of relevant stimuli (e.g. threatening animal faces) at peripheral locations is also important due to their survival value. Moreover, task instructions have been shown to modulate brain regions involved in threat recognition (e.g. the amygdala). In this respect it is also controversial whether tasks requiring explicit focus on stimulus threat content vs. implicit processing differently engage primitive subcortical structures involved in emotional appraisal. Here we have addressed the role of central vs. peripheral processing in the human amygdala using animal threatening vs. non-threatening face stimuli. First, a simple animal face recognition task with threatening and non-threatening animal faces, as well as non-face control stimuli, was employed in naïve subjects (implicit task). A subsequent task was then performed with the same stimulus categories (but different stimuli) in which subjects were told to explicitly detect threat signals. We found lateralized amygdala responses both to the spatial location of stimuli and to the threatening content of faces depending on the task performed: the right amygdala showed increased responses to central compared to left presented stimuli specifically during the threat detection task, while the left amygdala was better prone to discriminate threatening faces from non-facial displays during the animal face recognition task. Additionally, the right amygdala responded to faces during the threat detection task but only when centrally presented. Moreover, we have found no evidence for superior responses of the amygdala to peripheral stimuli. Importantly, we have found that striatal regions activate differentially depending on peripheral vs. central processing of threatening faces. Accordingly, peripheral processing of these stimuli activated more strongly the putaminal region, while central processing engaged mainly the caudate nucleus. We conclude that the human amygdala has a central bias for face stimuli, and that visual processing recruits different striatal regions, putaminal or caudate based, depending on the task and on whether peripheral or central visual processing is involved.

In the current study, we aimed to investigate the emotion recognition impairment in Huntington’s disease (HD) patients and define whether this deficit is caused by impaired scanning patterns of the face. To achieve this goal, we recorded eye movements during a two-alternative forced-choice emotion recognition task. HD patients in pre-symptomatic (n = 16) and symptomatic (n = 9) disease stages were tested and their performance was compared to a control group (n = 22). In our emotion recognition task, participants had to indicate whether a face reflected one of six basic emotions. In addition, and in order to define whether emotion recognition was altered when the participants were forced to look at a specific component of the face, we used a second task where only limited facial information was provided (eyes/mouth in partially masked faces). Behavioral results showed no differences in the ability to recognize emotions between pre-symptomatic gene carriers and controls. However, an emotion recognition deficit was found for all six basic emotion categories in early stage HD. Analysis of eye movement patterns showed that patient and controls used similar scanning strategies. Patterns of deficits were similar regardless of whether parts of the faces were masked or not, thereby confirming that selective attention to particular face parts is not underlying the deficits. These results suggest that the emotion recognition deficits in symptomatic HD patients cannot be explained by impaired scanning patterns of faces. Furthermore, no selective deficit for recognition of disgust was found in pre-symptomatic HD patients.

No abstract

Available evidence suggests that individuals can enhance their ability to modulate brain activity in target regions, within the Emotion Regulation network, using fMRI-based neurofeedback. However, there is no systematic review that investigates the effectiveness of this method on amygdala modulation, a core region within this network. The major goal of this study was to systematically review and analyze the effects of real-time fMRI-Neurofeedback concerning the neuromodulation of the amygdala during Emotion Regulation training. A search was performed in PubMed, Science Direct, and Web of Science with the following key terms: ≪(“neurofeedback” or “neuro feedback” or “neuro-feedback”) and (“emotion regulation”) and (fMRI OR “functional magnetic resonance”),≫ and afterwards two additional searches were performed, replacing the term “emotion regulation” for “amygdala” and “neurofeedback” for “feedback.” Of the 531 identified articles, only 19 articles reported results of amygdala modulation during Emotional Regulation training through rtfMRI-NF, using healthy participants or patients, in original research articles. The results, systematically reviewed here, provide evidence for amygdala's modulation during rtfMRI-NF training, although studies' heterogeneity precluded a quantitative meta-analysis—the included studies relied on different outcome measures to infer the success of neurofeedback intervention. Thus, a qualitative analysis was done instead. We identified critical features influencing inference on the quality of the intervention as: the inclusion of a Practice Run, a Transfer Run and a Control Group in the protocol, and to choose adequate Emotion Regulation strategies—in particular, the effective recall of autobiographic memories. Surprisingly, the Regulated vs. Control Condition was lacking in most of the studies, precluding valid inference of amygdala neuromodulation within Session. The best controlled studies nevertheless showed positive effects. The type of stimulus/interface did not seem critical for amygdala modulation. We also identified potential effects of lateralization of amygdala responses following Up- or Down-Regulation, and the impact of fMRI parameters for data acquisition and analysis. Despite qualitative evidence for amygdala modulation during rtfMRI-NF, there are still important limitations in the design of a clear conceptual framework of NF-training research. Future studies should focus on more homogeneous guidelines concerning design, protocol structure and, particularly, harmonized outcome measures to provide quantitative estimates of neuromodulatory effects in the amygdala.