The amygdala and FFA track both social and non-social face dimensions

The amygdala is thought to perform a number of social functions, and has received much attention for its role in processing social properties of faces. In particular, it has been shown to respond more to facial expressions than to neutral faces, and more to positively valenced and negatively valenced faces than faces in the middle of the continuum. However, when these findings are viewed in the context of a multidimensional face space, an important question emerges. Face space is a vector space where every face can be represented as a point in the space. The origin of the space represents the average face. In this context, positively valenced and negatively valenced faces are further away from the average face than faces in the middle of the continuum. It is therefore unclear if the amygdala response to positively valenced and negatively valenced faces is due to their social properties or to their general distance from the average face. Here, we compared the amygdala response to a set of faces that varied along two dimensions centered around the average face but differing in social content. In both the amygdala and much of the posterior face network, we observed a similar response to both dimensions, with stronger responses to the extremes of the dimensions than to faces near the average face. These findings suggest that the responses in these regions to socially relevant faces may be partially due to general distance from the average face.     

The fusiform face area is not sufficient for face recognition: evidence from a patient with dense prosopagnosia and no occipital face area

We tested functional activation for faces in patient D.F., who following acquired brain damage has a profound deficit in object recognition based on form (visual form agnosia) and also prosopagnosia that is undocumented to date. Functional imaging demonstrated that like our control observers, D.F. shows significantly more activation when passively viewing face compared to scene images in an area that is consistent with the fusiform face area (FFA) (p < 0.01). Control observers also show occipital face area (OFA) activation; however, whereas D.F.'s lesions appear to overlap the OFA bilaterally. We asked, given that D.F. shows FFA activation for faces, to what extent is she able to recognize faces? D.F. demonstrated a severe impairment in higher level face processing--she could not recognize face identity, gender or emotional expression. In contrast, she performed relatively normally on many face categorization tasks. D.F. can differentiate faces from non-faces given sufficient texture information and processing time, and she can do this is independent of color and illumination information. D.F. can use configural information for categorizing faces when they are presented in an upright but not a sideways orientation and given that she also cannot discriminate half-faces she may rely on a spatially symmetric feature arrangement. Faces appear to be a unique category, which she can classify even when she has no advance knowledge that she will be shown face images. Together, these imaging and behavioral data support the importance of the integrity of a complex network of regions for face identification, including more than just the FFA--in particular the OFA, a region believed to be associated with low-level processing.     

Disconnection in prosopagnosia and face processing

Face perception is a function with significant complexity, reflected in cognitive models that propose a hierarchy of parallel and serial processing stages. Current neuroimaging data also show that face perception involves a core processing network of cortical modules, which are likely specialized for different functions involved in face processing. The core face processing network is further linked to an extended face processing network which is not solely involved in the perception of faces, but rather contains modules mediating the processing of semantic, biographic and emotional information about people. The segregation of these processes within discrete anatomic regions creates the potential for disconnection between regions to generate neuropsychological deficits involving faces. In this review we consider the types of disconnection possible both within the core face processing system and between the core and extended systems, the pattern of deficits that would be considered as evidence of such disconnections, the potential anatomy of lesions that would create them, and whether any cases exist that meet these criteria.     

Abnormal face identity coding in the middle fusiform gyrus of two brain-damaged prosopagnosic patients

We report a functional magnetic resonance imaging (fMRI) adaptation study of two well-described patients, DF and PS, who present face identity recognition impairments (prosopagnosia) following brain-damage. Comparing faces to non-face objects elicited activation in all visual areas of the cortical face processing network that were spared subsequent to brain damage. The common brain lesion in the two patients was in the right inferior occipital cortex, in the territory of the right “occipital face area” (‘OFA’), which strengthens the critical role of this region in processing faces. Despite the lesion to the right ‘OFA’, there was normal range of sensitivity to faces in the right “fusiform face area” (‘FFA’) in both patients, supporting a non-hierarchical model of face processing at the cortical level. At the same time, however, sensitivity to individual face representations, as indicated by release from adaptation to identity, was abnormal in the right ‘FFA’ of both patients. This suggests that the right ‘OFA’ is necessary to individualize faces, perhaps through reentrant interactions with other cortical face sensitive areas. The lateral occipital area (LO) is damaged bilaterally in patient DF, who also shows visual object agnosia. However, in patient PS, in whom LO was spared, sensitivity to individual representations of non-face objects was still found in this region, as in the normal brain, consistent with her preserved object recognition abilities. Taken together, these observations, which fruitfully combine functional imaging and neuropsychology, place strong constraints on the possible functional organization of the cortical areas mediating face processing in the human brain.     

The benefit of directly comparing autism and schizophrenia for revealing mechanisms of social cognitive impairment

Autism and schizophrenia share a history of diagnostic conflation that was not definitively resolved until the publication of the DSM-III in 1980. Though now recognized as heterogeneous disorders with distinct developmental trajectories and dissociative features, much of the early nosological confusion stemmed from apparent overlap in certain areas of social dysfunction. In more recent years, separate but substantial literatures have accumulated for autism and schizophrenia demonstrating that abnormalities in social cognition directly contribute to the characteristic social deficits of both disorders. The current paper argues that direct comparison of social cognitive impairment can highlight shared and divergent mechanisms underlying pathways to social dysfunction, a process that can provide significant clinical benefit by informing the development of tailored treatment efforts. Thus, while the history of diagnostic conflation between autism and schizophrenia may have originated in similarities in social dysfunction, the goal of direct comparisons is not to conflate them once again but rather to reveal distinctions that illuminate disorder-specific mechanisms and pathways that contribute to social cognitive impairment.     

Representation of attitudinal knowledge: role of prefrontal cortex, amygdala and parahippocampal gyrus

It has been proposed that behavior is influenced by representations of different types of knowledge: action representations, event knowledge, attitudes and stereotypes. Attitudes (representations of a concept or object and its emotional evaluation) allow us to respond quickly to a given stimulus. In this study, we explored the representation and inhibition of attitudes. We show that right dorsolateral prefrontal cortex mediates negative attitudes whereas left ventrolateral prefrontal cortex mediates positive attitudes. Parahippocampal regions and amygdala mediate evaluative processing. Furthermore, anxiety modulates right dorsolateral prefrontal activation during negative attitude processing. Inhibition of negative attitudes activates left orbitofrontal cortex: a region that when damaged is associated with socially inappropriate behavior in patients. Inhibition of positive attitudes activates a brain system involving right inferior frontal gyrus and bilateral anterior cingulate. Thus, we show that there are dissociable networks for the representation and inhibition of attitudes.     

Effective connectivity between amygdala and orbitofrontal cortex differentiates the perception of facial expressions

Abstract

Emotion research is guided both by the view that emotions are points in a dimensional space, such as valence or approach–withdrawal, and by the view that emotions are discrete categories. We determined whether effective connectivity of amygdala with medial orbitofrontal cortex (MOFC) and lateral orbitofrontal cortex (LOFC) differentiates the perception of emotion faces in a manner consistent with the dimensional and/or categorical view. Greater effective connectivity from left MOFC to amygdala differentiated positive and neutral expressions from negatively valenced angry, disgust, and fear expressions. Greater effective connectivity from right LOFC to amygdala differentiated emotion expressions conducive to perceiver approach (happy, neutral, and fear) from angry expressions that elicit perceiver withdrawal. Finally, consistent with the categorical view, there were unique patterns of connectivity in response to fear, anger, and disgust, although not in response to happy expressions, which did not differ from neutral ones.     

The impact of neighborhood disadvantage on amygdala reactivity: Pathways through neighborhood social processes

Youth growing up in disadvantaged neighborhoods are more likely than their advantaged peers to face negative behavioral and mental health outcomes. Although studies have shown that adversity can undermine positive development via its impact on the developing brain, few studies have examined the association between neighborhood disadvantage and neural function, and no study has investigated potential social mechanisms within the neighborhood that might link neighborhood disadvantage to altered neural function. The current study evaluated the association between neighborhood disadvantage and amygdala reactivity during socioemotional face processing. We also assessed whether and which neighborhood-level social processes were related to amygdala reactivity, and whether these social processes mediated or moderated the association between neighborhood disadvantage and altered amygdala reactivity. We examined these aims in a registered report, using a sample of twins aged 7–19 years (N = 354 families, 708 twins) recruited from birth records with enrichment for neighborhood disadvantage. Twins completed a socioemotional face processing fMRI task and a sample of unrelated participants from the twins’ neighborhoods were also recruited to serve as informants on neighborhood social processes. We found that neighborhood disadvantage was associated with greater right amygdala reactivity to threat, but only when neighborhood informants perceived norms in the neighborhood to be more permissive regarding general safety and management. The findings from this research add to the growing literature highlighting the influence of neighborhood disadvantage on amygdala function and the ways that supportive social processes may buffer the impact of adversity on brain function.     

The human amygdala is necessary for developing and expressing normal interpersonal trust

The human amygdala is known to be involved in processing social, emotional, and reward-related information. Previous reports have indicated that the amygdala is involved in extracting trustworthiness information from faces. Interestingly, functional neuroimaging research using economic tasks that presumably require developing and/or expressing interpersonal trust, such as the Trust Game (TG), have not routinely identified involvement of the amygdala. The present study sought to explore the role of the amygdala in developing and expressing interpersonal trust, via a multi-round, multiplayer economic exchange, a version of the TG, in a large sample of participants with focal brain damage. Participants with unilateral damage to the amygdala displayed increased benevolent behavior in the TG, and specifically, they tended to increase trust in response to betrayals. On the other hand, neurologically normal adults tended to repay trust in kind, i.e., they decreased interpersonal trust in response to betrayals or increased trust in response to increases from others. Comparison participants, with brain damage that does not include the amygdala, ventromedial prefrontal or insular cortices, tended to behave ambivalently to the expressed trust or betrayal of others. Our data suggest that the amygdala is necessary for developing and expressing normal interpersonal trust. This increased tendency to behave benevolently in response to defections from others may be related to the abnormal social behavior observed in this group. Moreover, increased benevolence may increase the likelihood or opportunity to be taken advantage of by others.     

fMRI activation of the fusiform gyrus and amygdala to cartoon characters but not to faces in a boy with autism

Abnormal hypoactivation in the amygdala and fusiform gyrus, brain areas that participate in face processing and social cognition, has consistently been demonstrated in persons with autism. We investigated activity in these areas in a boy with autism, DD, who had a special interest in "Digimon" cartoon characters. DD individuates Digimon faster than familiar faces and objects, but he individuates familiar faces no faster than objects. In contrast, a typically developing boy with an interest in "Pokemon" cartoon characters is equally fast at individuating faces and Pokemon and faster at individuating faces and Pokemon than objects and Digimon. In addition, using functional magnetic resonance imaging (fMRI), we show that DD activates his amygdala and fusiform gyrus for perceptual discriminations involving Digimon but not for those involving familiar or unfamiliar faces. This pattern of activation is not seen in the typically developing control with an interest in Pokemon or in a second comparison case who has autism but no interest in Digimon. These results have important implications for our understanding of autism, cortical face specialization, and the possible role of the amygdala in the development of perceptual expertise.     

Early visual ERP sensitivity to the species and animacy of faces

Assessing the agency of potential actors in the visual world is a critically important aspect of social cognition. Adult observers are generally capable of distinguishing real faces from artificial faces (even allowing for recent advances in graphics technology and motion capture); even small deviations from real facial appearance can lead to profound effects on face recognition. Presently, we examined how early components of visual event-related potentials (ERPs) are affected by the “life” in human faces and animal faces. We presented participants with real and artificial faces of humans and dogs, and analyzed the response properties of the P100 and the N170 as a function of stimulus appearance and task (species categorization vs. animacy categorization). The P100 exhibited sensitivity to face species and animacy. We found that the N170’s differential responses to human faces vs. dog faces depended on the task participants’ performed. Also, the effect of species was only evident for real faces of humans and dogs, failing to obtain with artificial faces. These results suggest that face animacy does modulate early components of visual ERPs—the N170 is not merely a crude face detector, but reflects the tuning of the visual system to natural face appearance.     

An event-related brain potential study of explicit face recognition

To determine the time course of face recognition and its links to face-sensitive event-related potential (ERP) components, ERPs elicited by faces of famous individuals and ERPs to non-famous control faces were compared in a task that required explicit judgements of facial identity. As expected, the face-selective N170 component was unaffected by the difference between famous and non-famous faces. In contrast, the occipito-temporal N250 component was linked to face recognition, as it was selectively triggered by famous faces. Importantly, this component was present for famous faces that were judged to be definitely known relative to famous faces that just appeared familiar, demonstrating that it is associated with the explicit identification of a particular face. The N250 is likely to reflect early perceptual stages of face recognition where long-term memory traces of familiar faces in ventral visual cortex are activated by matching on-line face representations. Famous faces also triggered a broadly distributed longer-latency positivity (P600f) that showed a left-hemisphere bias and was larger for definitely known faces, suggesting links between this component and name generation. These results show that successful face recognition is predicted by ERP components over face-specific visual areas that emerge within 230 ms after stimulus onset.     

Reprint of: Fear-enhanced visual search persists after amygdala lesions

Previous research has indicated that the amygdala is a critical neural substrate of the emotional modulation of attention. However, a recent case study suggests that the amygdala may not be essential for all types of emotion-attention interactions. In order to test this hypothesis, we assessed the visual-search performance of patients with unilateral amygdala lesions, matched controls, and medication-matched epilepsy patients with intact amygdalae. All participants completed a visual-search task consisting of trials in which (1) an emotional target was embedded among neutral distractors, (2) a neutral target was embedded among emotional distractors, or (3) a neutral target was embedded among neutral distractors. All participant groups, including those with amygdala lesions, detected emotional targets more efficiently than neutral targets. These data indicate that the amygdala is not necessary for emotion-guided visual search and suggest that other mechanisms beyond the amygdala help guide attention toward threatening stimuli.     

Developmental deficits in social perception in autism: the role of the amygdala and fusiform face area

Autism is a severe developmental disorder marked by a triad of deficits, including impairments in reciprocal social interaction, delays in early language and communication, and the presence of restrictive, repetitive and stereotyped behaviors. In this review, it is argued that the search for the neurobiological bases of the autism spectrum disorders should focus on the social deficits, as they alone are specific to autism and they are likely to be most informative with respect to modeling the pathophysiology of the disorder. Many recent studies have documented the difficulties persons with an autism spectrum disorder have accurately perceiving facial identity and facial expressions. This behavioral literature on face perception abnormalities in autism is reviewed and integrated with the functional magnetic resonance imaging (fMRI) literature in this area, and a heuristic model of the pathophysiology of autism is presented. This model posits an early developmental failure in autism involving the amygdala, with a cascading influence on the development of cortical areas that mediate social perception in the visual domain, specifically the fusiform "face area" of the ventral temporal lobe. Moreover, there are now some provocative data to suggest that visual perceptual areas of the ventral temporal pathway are also involved in important ways in representations of the semantic attributes of people, social knowledge and social cognition. Social perception and social cognition are postulated as normally linked during development such that growth in social perceptual skills during childhood provides important scaffolding for social skill development. It is argued that the development of face perception and social cognitive skills are supported by the amygdala-fusiform system, and that deficits in this network are instrumental in causing autism.     

Test‐retest reliability of effective connectivity in the face perception network

Computational approaches have great potential for moving neuroscience toward mechanistic models of the functional integration among brain regions. Dynamic causal modeling (DCM) offers a promising framework for inferring the effective connectivity among brain regions and thus unraveling the neural mechanisms of both normal cognitive function and psychiatric disorders. While the benefit of such approaches depends heavily on their reliability, systematic analyses of the within‐subject stability are rare. Here, we present a thorough investigation of the test‐retest reliability of an fMRI paradigm for DCM analysis dedicated to unraveling intra‐ and interhemispheric integration among the core regions of the face perception network. First, we examined the reliability of face‐specific BOLD activity in 25 healthy volunteers, who performed a face perception paradigm in two separate sessions. We found good to excellent reliability of BOLD activity within the DCM‐relevant regions. Second, we assessed the stability of effective connectivity among these regions by analyzing the reliability of Bayesian model selection and model parameter estimation in DCM. Reliability was excellent for the negative free energy and good for model parameter estimation, when restricting the analysis to parameters with substantial effect sizes. Third, even when the experiment was shortened, reliability of BOLD activity and DCM results dropped only slightly as a function of the length of the experiment. This suggests that the face perception paradigm presented here provides reliable estimates for both conventional activation and effective connectivity measures. We conclude this paper with an outlook on potential clinical applications of the paradigm for studying psychiatric disorders. Hum Brain Mapp 37:730–744, 2016. © 2015 Wiley Periodicals, Inc.     

Reprint of: Aspects of neuroticism and the amygdala: chronic tuning from motivational styles

Recent research and theory has highlighted the dynamic nature of amygdala activation. Rather than simply being sensitive to a few limited stimulus categories, amygdala activation appears to be dependent on the goals of the perceiver. In this study, we extend this line of work by demonstrating that the means by which a person seeks to accomplish a goal also modulates the amygdala response. Specifically, we examine the modulatory effects of the aspects of neuroticism (volatility/withdrawal), a personality variable that has been linked to both generalized anxiety and differences in amygdala sensitivity. Whereas Neuroticism-Volatility is proposed to be associated with the fight-flight-freeze system (FFFS) and a sensitivity for any cues of negativity, Neuroticism-Withdrawal is proposed to be associated with the behavioral inhibition system (BIS) and a generalized tendency toward passive avoidance. During fMRI scanning, participants were presented with positive, negative, and neutral images and were required to approach (move perceptually closer) or avoid (move perceptually farther away) stimuli in different blocks of trials. Consistent with hypotheses proposing a dissociation between these two aspects of neuroticism, participants higher in Neuroticism-Volatility had increased amygdala activation to negative stimuli (regardless of whether they were approached or avoided), whereas participants higher in Neuroticism-Withdrawal had increased amygdala activation to all approached stimuli (regardless of stimulus valence). These data provide further support for the motivational salience hypothesis of amygdala function, and demonstrate that both the ends and means of goal pursuit are important for shaping a response.     

Defining the face processing network: optimization of the functional localizer in fMRI

Functional localizers that contrast brain signal when viewing faces versus objects are commonly used in functional magnetic resonance imaging studies of face processing. However, current protocols do not reliably show all regions of the core system for face processing in all subjects when conservative statistical thresholds are used, which is problematic in the study of single subjects. Furthermore, arbitrary variations in the applied thresholds are associated with inconsistent estimates of the size of face-selective regions-of-interest (ROIs). We hypothesized that the use of more natural dynamic facial images in localizers might increase the likelihood of identifying face-selective ROIs in individual subjects, and we also investigated the use of a method to derive the statistically optimal ROI cluster size independent of thresholds. We found that dynamic facial stimuli were more effective than static stimuli, identifying 98% (versus 72% for static) of ROIs in the core face processing system and 69% (versus 39% for static) of ROIs in the extended face processing system. We then determined for each core face processing ROI, the cluster size associated with maximum statistical face-selectivity, which on average was approximately 50 mm(3) for the fusiform face area, the occipital face area, and the posterior superior temporal sulcus. We suggest that the combination of (a) more robust face-related activity induced by a dynamic face localizer and (b) a cluster-size determination based on maximum face-selectivity increases both the sensitivity and the specificity of the characterization of face-related ROIs in individual subjects.     

Cerebral lateralization of face-sensitive areas in left-handers: Only the FFA does not get it right

Face perception is highly lateralized to the right hemisphere (RH) in humans, as supported originally by observations of face recognition impairment (prosopagnosia) following brain damage. Divided visual field presentations, neuroimaging and event-related potential studies have supported this view. While the latter studies are typically performed in right-handers, the few reported cases of prosopagnosia with unilateral left damage were left-handers, suggesting that handedness may shift or qualify the lateralization of face perception. We tested this hypothesis by recording the whole set of face-sensitive areas in 11 left-handers, using a face-localizer paradigm in functional magnetic resonance imaging (fMRI) (faces, cars, and their phase-scrambled versions). All face-sensitive areas identified (superior temporal sulcus, inferior occipital cortex, anterior infero-temporal cortex, amygdala) were strongly right-lateralized in left-handers, this right lateralization bias being as large as in a population of right-handers (40) tested with the same paradigm (Rossion et al., 2012). The notable exception was the so-called ‘Fusiform face area’ (FFA), an area that was slightly left lateralized in the population of left-handers. Since the left FFA is localized closely to an area sensitive to word form in the human brain (‘Visual Word Form Area’ – VWFA), the enhanced left lateralization of the FFA in left-handers may be due to a decreased competition with the representation of words. The implications for the neural basis of face perception, aetiology of brain lateralization in general, and prosopagnosia are also discussed.     

Perceived social support moderates the link between threat-related amygdala reactivity and trait anxiety

Several lines of research have illustrated that negative environments can precipitate psychopathology, particularly in the context of relatively increased biological risk, while social resources can buffer the effects of these environments. However, little research has examined how social resources might buffer proximal biological risk for psychopathology or the neurobiological pathways through which such buffering may be mediated. Here we report that the expression of trait anxiety as a function of threat-related amygdala reactivity is moderated by perceived social support, a resource for coping with adversity. A significant positive correlation between amygdala reactivity and trait anxiety was evident in individuals reporting below average levels of support but not in those reporting average or above average levels. These results were consistent across multiple measures of trait anxiety and were specific to anxiety in that they did not extend to measures of broad negative or positive affect. Our findings illuminate a biological pathway, namely moderation of amygdala-related anxiety, through which social support may confer resilience to psychopathology. Moreover, our results indicate that links between neural reactivity and behavior are not static but rather may be contingent on social resources.