Differential activation of the amygdala and the 'social brain' during fearful face-processing in Asperger Syndrome

Impaired social cognition is a core feature of autism. There is much evidence showing people with autism use a different cognitive style than controls for face-processing. We tested if people with autism would show differential activation of social brain areas during a face-processing task. Thirteen adults with high-functioning autism or Asperger Syndrome (HFA/AS) and 13 matched controls. We used fMRI to investigate 'social brain' activity during perception of fearful faces. We employed stimuli known to reliably activate the amygdala and other social brain areas, and ROI analyses to investigate brain areas responding to facial threat as well as those showing a linear response to varying threat intensities. We predicted: (1) the HFA/AS group would show differential activation (as opposed to merely deficits) of the social brain compared to controls and (2) that social brain areas would respond to varied intensity of fear in the control group, but not the HFA/AS group. Both predictions were confirmed. The controls showed greater activation in the left amygdala and left orbito-frontal cortex, while the HFA/AS group showed greater activation in the anterior cingulate gyrus and superior temporal cortex. The control group also showed varying responses in social brain areas to varying intensities of fearful expression, including differential activations in the left and right amygdala. This response in the social brain was absent in the HFA/AS group. HFA/AS are associated with different patterns of activation of social brain areas during fearful emotion processing, and the absence in the HFA/AS brain of a response to varying emotional intensity.     

Evidence for altered amygdala activation in schizophrenia in an adaptive emotion recognition task

Deficits in social cognition seem to present an intermediate phenotype for schizophrenia, and are known to be associated with an altered amygdala response to faces. However, current results are heterogeneous with respect to whether this altered amygdala response in schizophrenia is hypoactive or hyperactive in nature. The present study used functional magnetic resonance imaging to investigate emotion-specific amygdala activation in schizophrenia using a novel adaptive emotion recognition paradigm. Participants comprised 11 schizophrenia outpatients and 16 healthy controls who viewed face stimuli expressing emotions of anger, fear, happiness, and disgust, as well as neutral expressions. The adaptive emotion recognition approach allows the assessment of group differences in both emotion recognition performance and associated neuronal activity while also ensuring a comparable number of correctly recognized emotions between groups. Schizophrenia participants were slower and had a negative bias in emotion recognition. In addition, they showed reduced differential activation during recognition of emotional compared with neutral expressions. Correlation analyses revealed an association of a negative bias with amygdala activation for neutral facial expressions that was specific to the patient group. We replicated previous findings of affected emotion recognition in schizophrenia. Furthermore, we demonstrated that altered amygdala activation in the patient group was associated with the occurrence of a negative bias. These results provide further evidence for impaired social cognition in schizophrenia and point to a central role of the amygdala in negative misperceptions of facial stimuli in schizophrenia.     

Orienting to social stimuli differentiates social cognitive impairment in autism and schizophrenia

Both autism and schizophrenia feature deficits in aspects of social cognition that may be related to amygdala dysfunction, but it is unclear whether these are similar or different patterns of impairment. We compared the visual scanning patterns and emotion judgments of individuals with autism, individuals with schizophrenia and controls on a task well characterized with respect to amygdala functioning. On this task, eye movements of participants are recorded as they assess emotional content within a series of complex social scenes where faces are either included or digitally erased. Results indicated marked abnormalities in visual scanning for both disorders. Controls increased their gaze on face regions when faces were present to a significantly greater degree than both the autism or schizophrenia groups. While the control and the schizophrenia groups oriented to face regions faster when faces were present compared to when they were absent, the autism group oriented at the same rate in both conditions. The schizophrenia group, meanwhile, exhibited a delay in orienting to face regions across both conditions, although whether anti-psychotic medication contributed to this effect is unclear. These findings suggest that while processing emotional information in social scenes, both individuals with autism and individuals with schizophrenia fixate faces less than controls, although only those with autism fail to orient to faces more rapidly based on the presence of facial information. Autism and schizophrenia may therefore share an abnormality in utilizing facial information for assessing emotional content in social scenes, but differ in the ability to seek out socially relevant cues from complex stimuli. Impairments in social orienting are discussed within the context of evidence suggesting the role of the amygdala in orienting to emotionally meaningful information.     

A functional and structural study of emotion and face processing in children with autism

Children with autism exhibit impairment in the processing of socioemotional information. The amygdala, a core structure centrally involved in socioemotional functioning, has been implicated in the neuropathology of autism. We collected structural and functional magnetic resonance images (MRI) in children 8 to 12 years of age with high-functioning autism (n = 12) and typical development (n = 15). The functional MRI experiment involved matching facial expressions and people. Volumetric analysis of the amygdala was also performed. The results showed that children with autism exhibited intact emotion matching, while showing diminished activation of the fusiform gyrus (FG) and the amygdala. Conversely, the autism group showed deficits in person matching amidst some FG and variable amygdala activation. No significant between-group differences in the volume of the left or right amygdala were found. There were associations between age, social anxiety and amygdala volume in the children with autism such that smaller volumes were generally associated with more anxiety and younger age. In summary, the data are consistent with abnormalities in circuits involved in emotion and face processing reported in studies of older subjects with autism showing reductions in amygdala activation related to emotion processing and reduced fusiform activation involved in face processing.     

Emotion Recognition and Visual-Scan Paths in Fragile X Syndrome

This study investigated emotion recognition abilities and visual scanning of emotional faces in 16 Fragile X syndrome (FXS) individuals compared to 16 chronological-age and 16 mental-age matched controls. The relationships between emotion recognition, visual scan-paths and symptoms of social anxiety, schizotypy and autism were also explored. Results indicated that, compared to both control groups, the FXS group displayed specific emotion recognition deficits for angry and neutral (but not happy or fearful) facial expressions. Despite these evident emotion recognition deficits, the visual scanning of emotional faces was found to be at developmentally appropriate levels in the FXS group. Significant relationships were also observed between visual scan-paths, emotion recognition performance and symptomology in the FXS group.     

Intact emotion facilitation for nonsocial stimuli in autism: is amygdala impairment in autism specific for social information?

Atypical amygdala development may play a key role in the emergence of social disability and other symptoms of autism (Baron-Cohen et al., 2000; Schultz, 2005). The mechanisms by which this may occur have received little attention, however, and most support from behavioral and imaging studies has been concerned with socially relevant stimuli such as faces. Given the complexity of amygdala function and its known role in many other emotional tasks, we examined whether individuals with autism would demonstrate impaired performance on several tasks that have been shown to require activation of the amygdala but that do not have any explicit social meaning. Relative to a typical comparison group matched for age and IQ, our sample of 37 adolescents and adults with autism (mean age=19.7 years) demonstrated equivalent facilitation for perception and learning of emotionally relevant stimuli. On each of four tasks, there were significant main effects of emotion condition on performance for both groups. Future research regarding atypical amygdala function and emotion processing in autism should consider whether the response to nonsocial emotion factors (including negative valence or high arousal) may be intact, despite difficulties in responding to socially relevant stimuli.     

MRI amygdala volume in Williams Syndrome

One of the most intriguing characteristics of Williams Syndrome individuals is their hypersociability. The amygdala has been consistently implicated in the etiology of this social profile, particularly given its role in emotional and social behavior. This study examined amygdala volume and symmetry in WS individuals and in age and sex matched controls. Magnetic resonance imaging scans were obtained on a GE 1.5-T magnet with 1.5-mm contiguous slices and were used to measure whole gray matter, white matter and cerebrospinal fluid volumes, as well as amygdala volume (right and left). Results revealed significantly reduced intracranial volume in individuals with WS, compared with controls. There were no differences between groups in absolute amygdalae volume, although there was a relative increase in amygdalae volumes, when adjusted for total intracranial content. There were no inter-hemispheric differences in amygdalae volumes in both groups. These results suggest a relative increase in amygdala volume in WS compared with healthy controls that likely reflects abnormal neurodevelopmental processes of midline brain structures.     

Impaired recognition of social emotions following amygdala damage

Lesion, functional imaging, and single-unit studies in human and nonhuman animals have demonstrated a role for the amygdala in processing stimuli with emotional and social significance. We investigated the recognition of a wide variety of facial expressions, including basic emotions (e.g., happiness, anger) and social emotions (e.g., guilt, admiration, flirtatiousness). Prior findings with a standardized set of stimuli indicated that recognition of social emotions can be signaled by the eye region of the face and is disproportionately impaired in autism (Baron-Cohen, Wheelwright, & Jolliffe, 1997). To test the hypothesis that the recognition of social emotions depends on the amygdala, we administered the same stimuli to 30 subjects with unilateral amygdala damage (16 left, 14 right), 2 with bilateral amygdala damage, 47 brain-damaged controls, and 19 normal controls. Compared with controls, subjects with unilateral or bilateral amygdala damage were impaired when recognizing social emotions; moreover, they were more impaired in recognition of social emotions than in recognition of basic emotions, and, like previously described patients with autism, they were impaired also when asked to recognize social emotions from the eye region of the face alone. The findings suggest that the human amygdala is relatively specialized to process stimuli with complex social significance. The results also provide further support for the idea that some of the impairments in social cognition seen in patients with autism may result from dysfunction of the amygdala.     

Divergent Patterns of Social Cognition Performance in Autism and 22q11.2 Deletion Syndrome (22q11DS)

Individuals with developmental disorders frequently report a range of social cognition deficits including difficulties identifying facial displays of emotion. This study examined the specificity of face emotion processing deficits in adolescents with either autism or 22q11DS compared to typically developing (TD) controls. Two tasks (face emotion recognition and weather scene recognition) were used to explore group differences in visual scanpath strategy and concurrent recognition accuracy. For faces, the autism and 22q11DS groups demonstrated lower emotion recognition accuracy and fewer fixations compared to the TD group. Individuals with autism demonstrated fewer fixations to some weather scene stimuli compared to 22q11DS and TD groups, yet achieved a level of recognition accuracy comparable to the TD group. These findings provide evidence for a divergent pattern of social cognition dysfunction in autism and 22q11DS.     

Recognition of emotional and nonemotional facial expressions: A comparison between Williams syndrome and autism

The aim of our study was to compare two neurodevelopmental disorders (Williams syndrome and autism) in terms of the ability to recognize emotional and nonemotional facial expressions. The comparison of these two disorders is particularly relevant to the investigation of face processing and should contribute to a better understanding of social behaviour and social cognition. Twelve participants with WS (from 6;1 to 15 years) and twelve participants with autism (from 4;9 to 8 years) were matched on verbal mental age. Their performances were compared with those of twelve typically developing controls matched on verbal mental age (from 3;1 to 9;2). A set of five tasks assessing different dimensions of emotional and nonemotional facial recognition were administered. Results indicated that recognition of emotional facial expressions is more impaired in Williams syndrome than in autism. Our study comparing Williams syndrome and autism over a small age range highlighted two distinct profiles which call into question the relationships between social behaviour/cognition and emotion perception.     

Selective impairment of cognitive empathy for moral judgment in adults with high functioning autism

Faced with a moral dilemma, conflict arises between a cognitive controlled response aimed at maximizing welfare, i.e. the utilitarian judgment, and an emotional aversion to harm, i.e. the deontological judgment. In the present study, we investigated moral judgment in adult individuals with high functioning autism/Asperger syndrome (HFA/AS), a clinical population characterized by impairments in prosocial emotions and social cognition. In Experiment 1, we compared the response patterns of HFA/AS participants and neurotypical controls to moral dilemmas with low and high emotional saliency. We found that HFA/AS participants more frequently delivered the utilitarian judgment. Their perception of appropriateness of moral transgression was similar to that of controls, but HFA/AS participants reported decreased levels of emotional reaction to the dilemma. In Experiment 2, we explored the way in which demographic, clinical and social cognition variables including emotional and cognitive aspects of empathy and theory of mind influenced moral judgment. We found that utilitarian HFA/AS participants showed a decreased ability to infer other people’s thoughts and to understand their intentions, as measured both by performance on neuropsychological tests and through dispositional measures. We conclude that greater prevalence of utilitarianism in HFA/AS is associated with difficulties in specific aspects of social cognition.     

Abnormal processing of social information from faces in autism

Autism has been thought to be characterized, in part, by dysfunction in emotional and social cognition, but the pathology of the underlying processes and their neural substrates remain poorly understood. Several studies have hypothesized that abnormal amygdala function may account for some of the impairments seen in autism, specifically, impaired recognition of socially relevant information from faces. We explored this issue in eight high-functioning subjects with autism in four experiments that assessed recognition of emotional and social information, primarily from faces. All tasks used were identical to those previously used in studies of subjects with bilateral amygdala damage, permitting direct comparisons. All subjects with autism made abnormal social judgments regarding the trustworthiness of faces; however, all were able to make normal social judgments from lexical stimuli, and all had a normal ability to perceptually discriminate the stimuli. Overall, these data from subjects with autism show some parallels to those from neurological subjects with focal amygdala damage. We suggest that amygdala dysfunction in autism might contribute to an impaired ability to link visual perception of socially relevant stimuli with retrieval of social knowledge and with elicitation of social behavior.     

Social Competence Intervention for Youth with Asperger Syndrome and High-functioning Autism: An Initial Investigation

Individuals with high functioning autism (HFA) or Asperger Syndrome (AS) exhibit difficulties in the knowledge or correct performance of social skills. This subgroup’s social difficulties appear to be associated with deficits in three social cognition processes: theory of mind, emotion recognition and executive functioning. The current study outlines the development and initial administration of the group-based Social Competence Intervention (SCI), which targeted these deficits using cognitive behavioral principles. Across 27 students age 11–14 with a HFA/AS diagnosis, results indicated significant improvement on parent reports of social skills and executive functioning. Participants evidenced significant growth on direct assessments measuring facial expression recognition, theory of mind and problem solving. SCI appears promising, however, larger samples and application in naturalistic settings are warranted.     

Disrupted neural processing of emotional faces in psychopathy

Psychopaths show a reduced ability to recognize emotion facial expressions, which may disturb the interpersonal relationship development and successful social adaptation. Behavioral hypotheses point toward an association between emotion recognition deficits in psychopathy and amygdala dysfunction. Our prediction was that amygdala dysfunction would combine deficient activation with disturbances in functional connectivity with cortical regions of the face-processing network. Twenty-two psychopaths and 22 control subjects were assessed and functional magnetic resonance maps were generated to identify both brain activation and task-induced functional connectivity using psychophysiological interaction analysis during an emotional face-matching task. Results showed significant amygdala activation in control subjects only, but differences between study groups did not reach statistical significance. In contrast, psychopaths showed significantly increased activation in visual and prefrontal areas, with this latest activation being associated with psychopaths’ affective–interpersonal disturbances. Psychophysiological interaction analyses revealed a reciprocal reduction in functional connectivity between the left amygdala and visual and prefrontal cortices. Our results suggest that emotional stimulation may evoke a relevant cortical response in psychopaths, but a disruption in the processing of emotional faces exists involving the reciprocal functional interaction between the amygdala and neocortex, consistent with the notion of a failure to integrate emotion into cognition in psychopathic individuals.     

Impaired recognition of negative basic emotions in autism: a test of the amygdala theory

Autism and Asperger Syndrome are autism spectrum conditions (ASC) characterized by deficits in understanding others' minds, an aspect of which involves recognizing emotional expressions. This is thought to be related to atypical function and structure of the amygdala, and performance by people with ASC on emotion recognition tasks resembles that seen in people with acquired amygdala damage. In general, emotion recognition findings in ASC have been inconsistent, which may reflect low numbers of participants, low numbers of stimuli and trials, heterogeneity of symptom severity within ASC groups, and ceiling effects on some tasks. The present study tested 39 male adults with ASC and 39 typical male controls on a task of basic emotion recognition from photographs, in two separate experiments. On a control face discrimination task the group with ASC were not impaired. People with ASC were less accurate on the emotion recognition task compared to controls, but only for the negative basic emotions. This is discussed in the light of similar findings from people with damage to the amygdala.     

Temporal Lobe Structures and Facial Emotion Recognition in Schizophrenia Patients and Nonpsychotic Relatives

Temporal lobe abnormalities and emotion recognition deficits are prominent features of schizophrenia and appear related to the diathesis of the disorder. This study investigated whether temporal lobe structural abnormalities were associated with facial emotion recognition deficits in schizophrenia and related to genetic liability for the disorder. Twenty-seven schizophrenia patients, 23 biological family members, and 36 controls participated. Several temporal lobe regions (fusiform, superior temporal, middle temporal, amygdala, and hippocampus) previously associated with face recognition in normative samples and found to be abnormal in schizophrenia were evaluated using volumetric analyses. Participants completed a facial emotion recognition task and an age recognition control task under time-limited and self-paced conditions. Temporal lobe volumes were tested for associations with task performance. Group status explained 23% of the variance in temporal lobe volume. Left fusiform gray matter volume was decreased by 11% in patients and 7% in relatives compared with controls. Schizophrenia patients additionally exhibited smaller hippocampal and middle temporal volumes. Patients were unable to improve facial emotion recognition performance with unlimited time to make a judgment but were able to improve age recognition performance. Patients additionally showed a relationship between reduced temporal lobe gray matter and poor facial emotion recognition. For the middle temporal lobe region, the relationship between greater volume and better task performance was specific to facial emotion recognition and not age recognition. Because schizophrenia patients exhibited a specific deficit in emotion recognition not attributable to a generalized impairment in face perception, impaired emotion recognition may serve as a target for interventions.     

Autistic Symptomatology,Face Processing Abilities,and Eye Fixation Patterns

Deviant gaze behavior is a defining characteristic of autism. Its relevance as a pathophysiological mechanism, however, remains unknown. In the present study, we compared eye fixations of 20 adults with autism and 21 controls while they were engaged in taking the Multifaceted Empathy Test (MET). Additional measures of face emotion and identity recognition were also obtained. While both groups fixated more on the face and mouth in the emotion recognition than in the face identity condition of the MET, individuals with autism fixated less on the face across MET conditions. Correlation analysis revealed associations between fixation time on the eyes and face processing abilities. Our results suggest that eye fixation patterns are an important characteristic of the social phenotype of autism.     

Facial emotion recognition impairment predicts social and emotional problems in children with (subthreshold) ADHD

Children with attention-deficit/hyperactivity disorder (ADHD) symptoms often experience social and emotional problems. Impaired facial emotion recognition has been suggested as a possible underlying mechanism, although impairments may depend on the type and intensity of emotions. We investigated facial emotion recognition in children with (subthreshold) ADHD and controls using a novel task with children’s faces of emotional expressions varying in type and intensity. We further investigated associations between emotion recognition accuracy and social and emotional problems in the ADHD group. 83 children displaying ADHD symptoms and 30 controls (6–12 years) completed the Morphed Facial Emotion Recognition Task (MFERT). The MFERT assesses emotion recognition accuracy on four emotions using five expression intensity levels. Teachers and parents rated social and emotional problems on the Strengths and Difficulties Questionnaire. Repeated measures analysis of variance revealed that the ADHD group showed poorer emotion recognition accuracy compared to controls across emotions (small effect). The significant group by expression intensity interaction (small effect) showed that the increase in accuracy with increasing expression intensity was smaller in the ADHD group compared to controls. Multiple regression analyses within the ADHD group showed that emotion recognition accuracy was inversely related to social and emotional problems, but not prosocial behavior. Not only children with an ADHD diagnosis, but also children with subthreshold ADHD experience impairments in facial emotion recognition. This impairment is predictive for social and emotional problems, which may suggest that emotion recognition may contribute to the development of social and emotional problems in these children.

     

Explicit identification and implicit recognition of facial emotions: II. Core domains and relationships with general cognition

Both general and social cognition are important in providing endophenotypic markers and predicting real-world functional outcomes of clinical psychiatric disorders. However, to date, focus has been on general cognition, rather than on core domains of social/emotional cognition. This study sought to determine core domains of emotion processing for both explicit identification and implicit recognition and their relationships with core domains of general cognition. Age effects and sex differences were also investigated. A sample of 1,000 healthy individuals (6 to 91 years, 53.5% female) undertook the WebNeuro tests of emotion identification and recognition and tests of general cognitive function. Factor analysis revealed seven core domains of emotion processing: speed of explicit emotion identification, speed of implicit emotion recognition, implicit emotion recognition accuracy, "threat" processing, sadness-disgust identification, "positive emotion" processing, and general "face perception." Seven corresponding core domains of general cognition were identified: information-processing speed, executive function, sustained attention/vigilance, verbal memory, working-memory capacity, inhibition/impulsivity, and sensorimotor function. Factors of emotion processing generally showed positive associations with those of general cognitive function, suggesting commonality in processing speed in particular. Moreover, age had a consistent nonlinear impact on both emotion processing and general cognitive factors, while sex differences were more specific. These findings contribute to a normative and standardized structure for assessment of emotional and general cognition in clinical groups.     

Childhood trauma,brain structure and emotion recognition in patients with schizophrenia and healthy participants

Childhood trauma, and in particular physical neglect, has been repeatedly associated with lower performance on measures of social cognition (e.g. emotion recognition tasks) in both psychiatric and non-clinical populations. The neural mechanisms underpinning this association have remained unclear. Here, we investigated whether volumetric changes in three stress-sensitive regions—the amygdala, hippocampus and anterior cingulate cortex (ACC)—mediate the association between childhood trauma and emotion recognition in a healthy participant sample (N = 112) and a clinical sample of patients with schizophrenia (N = 46). Direct effects of childhood trauma, specifically physical neglect, on Emotion Recognition Task were observed in the whole sample. In healthy participants, reduced total and left ACC volumes were observed to fully mediate the association between both physical neglect and total childhood trauma score, and emotion recognition. No mediating effects of the hippocampus and amygdala volumes were observed for either group. These results suggest that reduced ACC volume may represent part of the mechanism by which early life adversity results in poorer social cognitive function. Confirmation of the causal basis of this association would highlight the importance of resilience-building interventions to mitigate the detrimental effects of childhood trauma on brain structure and function.