Model syndromes for investigating social cognitive and affective neuroscience: a comparison of Autism and Williams syndrome

Autism and Williams syndrome are genetically based neurodevelopmentaldisorders that present strikingly different social phenotypes.Autism involves fundamental impairments in social reciprocityand communication, whereas people with Williams syndrome arehighly sociable and engaging. This article reviews the behavioraland neuroimaging literature that has explored the neurocognitivemechanisms that underlie these contrasting social phenotypes,focusing on studies of face processing. The article concludeswith a discussion of how the social phenotypes of both syndromesmay be characterized by impaired connectivity between the amygdalaand other critical regions in the ‘social brain’.     

Linking social behaviour and anxiety to attention to emotional faces in Williams syndrome

The neurodevelopmental disorder Williams syndrome (WS) has been associated with a social phenotype of hypersociability, non-social anxiety and an unusual attraction to faces. The current study uses eye tracking to explore attention allocation to emotionally expressive faces. Eye gaze and behavioural measures of anxiety and social reciprocity were investigated in adolescents and adults with WS when compared to typically developing individuals of comparable verbal mental age (VMA) and chronological age (CA). Results showed significant associations between high levels of behavioural anxiety and attention allocation away from the eye regions of threatening facial expressions in WS. The results challenge early claims of a unique attraction to the eyes in WS and suggest that individual differences in anxiety may mediate the allocation of attention to faces in WS.     

Viewing it differently: social scene perception in Williams syndrome and autism

The genetic disorder Williams syndrome (WS) is associated with a propulsion towards social stimuli and interactions with people. In contrast, the neuro-developmental disorder autism is characterised by social withdrawal and lack of interest in socially relevant information. Using eye-tracking techniques we investigate how individuals with these two neuro-developmental disorders associated with distinct social characteristics view scenes containing people. The way individuals with these disorders view social stimuli may impact upon successful social interactions and communication. Whilst individuals with autism spend less time than is typical viewing people and faces in static pictures of social interactions, the opposite is apparent for those with WS whereby exaggerated fixations are prevalent towards the eyes. The results suggest more attention should be drawn towards understanding the implications of atypical social preferences in WS, in the same way that attention has been drawn to the social deficits associated with autism.     

Individual differences in social behavior predict amygdala response to fearful facial expressions in Williams syndrome

Williams syndrome (WS) is a genetic condition often paired with abnormal social functioning and behavior. In particular, those with WS are characterized as being relatively hypersocial, overly emotional/empathic, and socially uninhibited or fearless. In addition, WS is associated with abnormal amygdala structure and function. Very little is known however about the relationship between specific social behaviors and altered amygdala function in WS. This study was designed to compare three models that relate abnormal social behavior with amygdala function in WS (indiscriminate sociability, emotional and empathic sociability and social fearlessness). We used a social behavior assessment procedure (Salk Institute Sociability Questionnaire), functional magnetic resonance imaging and an implicit emotion face processing task to test these models. Our findings provide support for a model of abnormal social fearlessness by showing that in WS, abnormal amygdala response to fear is paired with an increased tendency to approach strangers. Specifically, individuals with WS that exhibited less amygdala response to fearful facial expressions (compared to neutral) also exhibited an increased tendency to approach strangers. These findings contribute to our understanding of social and emotional functioning in neurodevelopmental conditions and provide evidence that in WS, amygdala response to fear modulates social behavior.     

Affiliative behavior in Williams syndrome: Social perception and real-life social behavior

A frequently noted but largely anecdotal behavioral observation in Williams syndrome (WS) is an increased tendency to approach strangers, yet the basis for this behavior remains unknown. We examined the relationship between affect identification ability and affiliative behavior in participants with WS relative to a neurotypical comparison group. We quantified social behavior from self-judgments of approachability for faces, and from parent/other evaluations of real life. Relative to typical individuals, participants with WS were perceived as more sociable by others, exhibited perceptual deficits in affect identification, and judged faces of strangers as more approachable. In WS, high self-rated willingness to approach strangers was correlated with poor affect identification ability, suggesting that these two findings may be causally related. We suggest that the real-life hypersociability in WS may arise at least in part from abnormal perceptual processing of other people's faces, rather than from an overall bias at the level of behavior. While this did not achieve statistical significance, it provides preliminary evidence to suggest that impaired social-perceptual ability may play a role in increased approachability in WS.     

Looking at movies and cartoons: eye-tracking evidence from Williams syndrome and autism

Background   Autism and Williams syndrome (WS) are neuro-developmental disorders associated with distinct social phenotypes. While individuals with autism show a lack of interest in socially important cues, individuals with WS often show increased interest in socially relevant information.
Methods   The current eye-tracking study explores how individuals with WS and autism preferentially attend to social scenes and movie extracts containing human actors and cartoon characters. The proportion of gaze time spent fixating on faces, bodies and the scene background was investigated.
Results   While individuals with autism preferentially attended to characters' faces for less time than was typical, individuals with WS attended to the same regions for longer than typical. For individuals with autism atypical gaze behaviours extended across human actor and cartoon images or movies but for WS atypicalities were restricted to human actors.
Conclusions   The reported gaze behaviours provide experimental evidence of the divergent social interests associated with autism and WS.     

The changing face of emotion: age-related patterns of amygdala activation to salient faces

The present study investigated age-related differences in the amygdala and other nodes of face-processing networks in response to facial expression and familiarity. fMRI data were analyzed from 31 children (3.5–8.5 years) and 14 young adults (18–33 years) who viewed pictures of familiar (mothers) and unfamiliar emotional faces. Results showed that amygdala activation for faces over a scrambled image baseline increased with age. Children, but not adults, showed greater amygdala activation to happy than angry faces; in addition, amygdala activation for angry faces increased with age. In keeping with growing evidence of a positivity bias in young children, our data suggest that children find happy faces to be more salient or meaningful than angry faces. Both children and adults showed preferential activation to mothers’ over strangers’ faces in a region of rostral anterior cingulate cortex associated with self-evaluation, suggesting that some nodes in frontal evaluative networks are active early in development. This study presents novel data on neural correlates of face processing in childhood and indicates that preferential amygdala activation for emotional expressions changes with age.     

Frontostriatal dysfunction during response inhibition in Williams syndrome.

BACKGROUND: Williams syndrome (WS) has provided researchers with an exciting opportunity to understand the complex interplay among genes, neurobiological and cognitive functions. However, despite a well-characterized cognitive and behavioral phenotype, little attention has been paid to the marked deficits in social and behavioral inhibition. Here we explore the neural systems that mediate response inhibition in WS. METHODS: We used functional MRI (fMRI) to obtain blood oxygenation level dependence (BOLD) signal maps during the performance of a Go/NoGo response inhibition task from 11 clinically and genetically diagnosed WS patients and 11 age- and gender-matched typically developing (TD) control subjects. Correlations between behavioral, neuropsychological measures, and BOLD signal were also conducted. RESULTS: Although TD control subjects showed significantly faster response times, no group differences in behavioral accuracy were observed. Compared with control subjects, WS participants demonstrated significantly reduced activity in the striatum, dorsolateral prefrontal, and dorsal anterior cingulate cortices. These findings support the hypothesis that persons with WS fail to activate critical cortical and subcortical structures involved in behavioral inhibition. CONCLUSIONS: Our results provide important evidence for reduced engagement of the frontostriatal circuits in WS and provide putative biological markers for the deficits in response inhibition and the unusual social phenotype.     

Face repetition detection and social interest: An ERP study in adults with and without Williams syndrome

The present study examined possible neural mechanisms underlying increased social interest in persons with Williams syndrome (WS). Visual event-related potentials (ERPs) during passive viewing were used to compare incidental memory traces for repeated vs. single presentations of previously unfamiliar social (faces) and nonsocial (houses) images in 26 adults with WS and 26 typical adults. Results indicated that participants with WS developed familiarity with the repeated faces and houses (frontal N400 response), but only typical adults evidenced the parietal old/new effect (previously associated with stimulus recollection) for the repeated faces. There was also no evidence of exceptional salience of social information in WS, as ERP markers of memory for repeated faces vs. houses were not significantly different. Thus, while persons with WS exhibit behavioral evidence of increased social interest, their processing of social information in the absence of specific instructions may be relatively superficial. The ERP evidence of face repetition detection in WS was independent of IQ and the earlier perceptual differentiation of social vs. nonsocial stimuli. Large individual differences in ERPs of participants with WS may provide valuable information for understanding the WS phenotype and have relevance for educational and treatment purposes.     

Elevated amygdala response to faces and gaze aversion in autism spectrum disorder

Autism spectrum disorders (ASD) are often associated with impairments in judgment of facial expressions. This impairment is often accompanied by diminished eye contact and atypical amygdala responses to face stimuli. The current study used a within-subjects design to examine the effects of natural viewing and an experimental eye-gaze manipulation on amygdala responses to faces. Individuals with ASD showed less gaze toward the eye region of faces relative to a control group. Among individuals with ASD, reduced eye gaze was associated with higher threat ratings of neutral faces. Amygdala signal was elevated in the ASD group relative to controls. This elevated response was further potentiated by experimentally manipulating gaze to the eye region. Potentiation by the gaze manipulation was largest for those individuals who exhibited the least amount of naturally occurring gaze toward the eye region and was associated with their subjective threat ratings. Effects were largest for neutral faces, highlighting the importance of examining neutral faces in the pathophysiology of autism and questioning their use as control stimuli with this population. Overall, our findings provide support for the notion that gaze direction modulates affective response to faces in ASD.     

Time-varying amygdala response to emotional faces in generalized social phobia.

BACKGROUND: Individuals with social phobia (SP) have altered behavioral and neural responses to emotional faces and are hypothesized to have deficits in inhibiting emotion-related amygdala responses. We tested for such amygdala deficits to emotional faces in a sample of individuals with SP. METHOD: We used functional magnetic resonance imaging (fMRI) to examine the neural substrates of emotional face processing in 14 generalized SP (gSP) and 14 healthy comparison (HC) participants. Analyses focused on the temporal dynamics of the amygdala, prefrontal cortex (PFC), and fusiform face area (FFA) across blocks of neutral, fear, contempt, anger, and happy faces in gSP versus HC participants. RESULTS: Amygdala responses in participants with gSP occurred later than the HC participants to fear, angry, and happy faces. Parallel PFC responses were found for happy and fear faces. There were no group differences in temporal response patterns in the FFA. CONCLUSIONS: This finding might reflect a neural correlate of atypical orienting responses among individuals with gSP. Commonly reported SP deficits in habituation might reflect neural regions associated with emotional self-evaluations rather than the amygdala. This study highlights the importance of considering time-varying modulation when examining emotion-related processing in individuals with gSP.     

Regionally specific increased volume of the amygdala in Williams syndrome: Evidence from surface‐based modeling

Williams syndrome (WS) is a condition caused by a contiguous deletion of approximately 26–28 genes from chromosome 7, and is characterized by abnormal social and emotional processing and abnormal structure and function of the amygdala. Prior studies show that the amygdala is relatively enlarged in WS, but very little is known regarding the regional specificity of increased amygdalar volume in this condition. Here we investigated the regional specificity of structural alterations of the amygdala in WS, compared to a typically developing (TD) control group. We acquired high resolution brain MRI data from 79 participants (39 WS, 40 TD) and used a surface‐based analytical modeling approach. The WS group exhibited several areas of increased radial expansion of the amygdalar surface and no areas of decreased radial expansion of the amygdalar surface compared to TD controls. The areas found to exhibit particularly increased radial expansion in WS included the bilateral posterior cortical nucleus, lateral nucleus, and the central nucleus. This greater regional and anatomical specificity of altered amygdala structure in WS contributes to a model relating genetic risk in WS to the development of key brain regions for social and emotional functioning. Hum Brain Mapp 35:866–874, 2014. © 2012 Wiley Periodicals, Inc.     

The role of the amygdala in implicit evaluation of emotionally neutral faces

The amygdala is involved in the evaluation of novel stimuli, including faces. We examined whether the amygdala is engaged during the evaluation of emotionally neutral faces along trait-specific dimensions such as trustworthiness and attractiveness or along a general valence dimension. Using behavioral data from evaluation of faces on 14 trait dimensions and fMRI data from an implicit evaluation paradigm, we show that the extent to which the amygdala responds to variations of faces on specific dimensions is a function of the valence content of these dimensions. Variations on dimensions with clear valence connotations (e.g. trustworthiness) engaged the amygdala more strongly than variations on dimensions with less clear valence connotations (e.g. dominance). In addition to the amygdala, several other regions—right superior occipital gyrus, right middle temporal/occipital gyrus and bilateral fusiform gyri—were involved in valence evaluation of faces. However, the relation between these regions and face valence was accounted for by the amygdala''s response to faces. The findings suggest that the amygdala (i) automatically evaluates novel faces along a general valence dimension; and (ii) modulates a face responsive network of regions in occipital and temporal cortices.     

Audiovisual speech perception in Williams syndrome

People with the genetic disorder of Williams syndrome (WS) show an anomalous cognitive profile, wherein some purely verbal and social communicative abilities are relatively proficient, while visuo-spatial skills can be extremely impaired. Face processing, while apparently relatively spared among visuo-spatial skills, can show deficits suggesting developmental immaturity. In this context, the exploration of visual and audiovisual speech perception in WS is of interest. A new test based on tokens from a single natural English speaker of the form /(inverted v)ba:/, /(inverted v) va:/, /(inverted v)(theta)a:/, /(inverted v)da:/ and /(inverted v)ga:/, digitally manipulated and presented in unimodal (vision alone, audition alone) and audiovisual conditions, was presented for participants to identify each token.Compared with age-matched controls, WS participants were impaired at visual but not auditory identification, and in audiovisual testing showed correspondingly reduced effects of vision on report of auditory token identity. Audiovisual integration was nevertheless demonstrable in WS. Speech-reading may require skills which do not reach age-appropriate levels in WS, despite their age-appropriate (auditory) phonological abilities.     

Association between amygdala hyperactivity to harsh faces and severity of social anxiety in generalized social phobia.

BACKGROUND: Previous functional brain imaging studies of social anxiety have implicated amygdala hyperactivity in response to social threat, though its relationship to quantitative measures of clinical symptomatology remains unknown. The primary aim of this study was to examine the association between response to emotionally harsh faces in the amygdala, a region implicated in social and threat-related processing, and severity of social anxiety symptoms in patients with generalized social phobia (GSP). METHODS: Ten subjects with GSP naive to psychotropic medications and without psychiatric comorbidity and ten healthy comparison subjects matched on age, gender, ethnicity, and education completed the Liebowitz Social Anxiety Scale and underwent high-field (4Tesla) functional magnetic resonance imaging while viewing blocks of emotionally salient faces. RESULTS: Relative to happy faces, activation of the amygdala in response to harsh (angry, disgusted, fearful) faces was greater in GSP patients than in controls, and the extent of amygdala activation was positively correlated with severity of social anxiety symptoms, but not general state or trait anxiety levels. CONCLUSIONS: Our findings suggest that amygdala activation to interpersonal threat can be specifically linked to the severity of social anxiety symptoms of individual GSP patients, and thus, may serve as a useful functional marker of disease severity.     

The social evaluation of faces: a meta-analysis of functional neuroimaging studies

Neuroscience research on the social evaluation of faces has accumulated over the last decade, yielding divergent results. We used a meta-analytic technique, multi-level kernel density analysis (MKDA), to analyze 29 neuroimaging studies on face evaluation. Across negative face evaluations, we observed the most consistent activations in bilateral amygdala. Across positive face evaluations, we observed the most consistent activations in medial prefrontal cortex, pregenual anterior cingulate cortex (pgACC), medial orbitofrontal cortex (mOFC), left caudate and nucleus accumbens (NAcc). Based on additional analyses comparing linear and non-linear responses, we propose a ventral/dorsal dissociation within the amygdala, wherein separate populations of neurons code for face valence and intensity, respectively. Finally, we argue that some of the differences between studies are attributable to differences in the typicality of face stimuli. Specifically, extremely attractive faces are more likely to elicit responses in NAcc/caudate and mOFC.