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.

BACKGROUND: Emotional Stroop tasks have shown attention biases of clinical populations towards stimuli related to their condition. Asperger Syndrome (AS) is a neuropsychiatric condition with social and communication deficits, repetitive behaviours and narrow interests. Social deficits are particularly striking, including difficulties in understanding others. METHOD: We investigated colour-naming latencies of adults with and without AS to name colours of pictures containing angry facial expressions, neutral expressions or non-social objects. We tested three hypotheses: whether (1) controls show longer colour-naming latencies for angry versus neutral facial expressions with male actors, (2) people with AS show differential latencies across picture types, and (3) differential response latencies persist when photographs contain females. RESULTS: Controls had longer latencies to pictures of male faces with angry compared to neutral expressions. The AS group did not show longer latencies to angry versus neutral expressions in male faces, instead showing slower latencies to pictures containing any facial expression compared to objects. When pictures contained females, controls no longer showed longer latencies for angry versus neutral expressions. However, the AS group still showed longer latencies to all facial picture types, compared to objects, providing further evidence that faces produce interference effects for this clinical group. CONCLUSIONS: The pictorial emotional Stroop paradigm reveals normal attention biases towards threatening emotional faces. The AS group showed Stroop interference effects to all facial stimuli regardless of expression or sex, suggesting that faces cause disproportionate interference in AS.

Individuals with an autistic spectrum disorder are impaired not only in understanding others' mental states, but also in self-regulation of social-emotional behavior. Therefore, a model of the brain in autism must encompass not only those brain systems that subserve social-cognitive and emotional functioning, but also those that subserve the self-regulation of behavior in response to a changing social environment. We present evidence to support the hypothesis that developmental dysfunction of the orbitofrontal-amygdala circuit of the brain is a critical factor in the development of autism and that some of the characteristic deficits of persons with autism in socio-emotional cognition and behavioral self-regulation are related to early dysfunction of different components of this circuit. A secondary hypothesis posits that the degree of intellectual impairment present in individuals with autism is directly related to the integrity of the dorsolateral prefrontal-hippocampal circuit of the brain. Together, these hypotheses have the potential to help explain the neurodevelopmental basis of some of the primary manifestations of autism as well as the heterogeneity of outcomes.

The role of serotonin in prenatal and postnatal brain development is well documented in the animal literature. In earlier studies using positron emission tomography (PET) with the tracer alpha[(11)C]methyl-l-tryptophan (AMT), we reported global and focal abnormalities of serotonin synthesis in children with autism. In the present study, we measured brain serotonin synthesis in a large group of autistic children (n = 117) with AMT PET and related these neuroimaging data to handedness and language function. Cortical AMT uptake abnormalities were objectively derived from small homotopic cortical regions using a predefined cutoff asymmetry threshold (>2 S.D. of normal asymmetry). Autistic children demonstrated several patterns of abnormal cortical involvement, including right cortical, left cortical, and absence of abnormal asymmetry. Global brain values for serotonin synthesis capacity (unidirectional uptake rate constant, K-complex) values were plotted as a function of age. K-complex values of autistic children with asymmetry or no asymmetry in cortical AMT uptake followed different developmental patterns, compared to that of a control group of non-autistic children. The autism groups, defined by presence or absence and side of cortical asymmetry, differed on a measure of language as well as handedness. Autistic children with left cortical AMT decreases showed a higher prevalence of severe language impairment, whereas those with right cortical decreases showed a higher prevalence of left and mixed handedness. Global as well as focal abnormally asymmetric development in the serotonergic system could lead to miswiring of the neural circuits specifying hemispheric specialization.

We combined eye-tracking technology with a test of facial affect recognition and a measure of self-reported social anxiety in order to explore the aetiology of social-perceptual deficits in Asperger's syndrome (AS). Compared to controls matched for age, IQ and visual-perceptual ability, we found a group of AS adults was impaired in their recognition of fearful and sad expressions and spent significantly less time fixating the eye region of all faces. For AS subjects, but not controls, the extent of the failure to fixate the eyes predicted the degree of impairment at recognising fearful expressions. In addition, poor fear recognition and reduced fixation of the eyes were independently associated with greater levels of social anxiety in AS individuals. These findings support the hypothesis that avoidance of emotionally arousing stimuli, such as eyes, contributes to social-perceptual impairment in AS. Furthermore, our findings are consistent with theories implicating amygdala-mediated over-arousal and anxiety in the development of these social-perceptual deficits.

Diminished gaze fixation is one of the core features of autism and has been proposed to be associated with abnormalities in the neural circuitry of affect. We tested this hypothesis in two separate studies using eye tracking while measuring functional brain activity during facial discrimination tasks in individuals with autism and in typically developing individuals. Activation in the fusiform gyrus and amygdala was strongly and positively correlated with the time spent fixating the eyes in the autistic group in both studies, suggesting that diminished gaze fixation may account for the fusiform hypoactivation to faces commonly reported in autism. In addition, variation in eye fixation within autistic individuals was strongly and positively associated with amygdala activation across both studies, suggesting a heightened emotional response associated with gaze fixation in autism.

OBJECTIVE: Impaired gaze following is an important hallmark of autism spectrum disorders (ASDs) in clinical settings. Yet, ASD subjects perform normally on laboratory tasks involving gaze shifts. We investigated this contradiction, hypothesizing that impaired gaze following in ASDs is not related to basic impairments in attention orienting but to impaired emotion perception and abnormal processing of spatial frequencies (i.e., local and global information). METHOD: We tested 30 high-functioning, school-age children with ASDs and 30 age- and IQ-matched controls on a task involving gaze shifts that cue the location of targets. The cueing faces differed in emotionality and were filtered for different spatial frequencies. We recorded behavioral responses (reaction times) and brain responses (event-related potentials). RESULTS: ASD subjects performed normally when neutral faces were used. However, emotional faces elicited modified face and gaze cue processing in control subjects, but not in the ASD subjects. Furthermore, the control group was biased toward the use of low spatial frequencies (global information) to process gaze cues, whereas the ASD group was biased toward the use of high spatial frequencies (local information). CONCLUSIONS: We conclude that impaired gaze following in ASDs is related to impaired emotion processing. Moreover, ASD subjects show an abnormal reliance on local information to process gaze cues.

OBJECTIVE: Converging evidence indicates that brain abnormalities in autism spectrum disorders (ASDs) involve atypical network connectivity. Given the central role of social deficits in the ASD phenotype, this investigation examined functional connectivity of the amygdala-a brain structure critically involved in processing of social information-in children and adolescents with ASDs, as well as age-dependent changes and links with clinical symptoms. METHOD: Resting-state functional magnetic resonance imaging (rs-fMRI) data from 55 participants with ASDs and 50 typically developing (TD) controls, aged 7 to 17 years, were included. Groups were matched for age, gender, IQ, and head motion. Functional connectivity MRI (fcMRI) analysis was applied to examine intrinsic functional connectivity (iFC) of the amygdala, including cross-sectional tests of age-related changes. RESULTS: Direct between-group comparisons revealed reduced functional connectivity between bilateral amygdalae and left inferior occipital cortex, accompanied by greater connectivity between right amygdala and right sensorimotor cortex in the ASD group. This atypical pattern of amygdala connectivity was associated with decreased symptom severity and better overall functioning, as specifically seen in an ASD subgroup with the most atypical amygdala iFC but the least impaired social functioning. Age-related strengthening of amygdala-prefrontal connectivity, as observed in the TD group, was not detected in children with ASDs. CONCLUSION: Findings support aberrant network sculpting in ASDs, specifically atypical integration between amygdala and primary sensorimotor circuits. Paradoxical links between atypical iFC and behavioral measures suggest that abnormal amygdala functional connections may be compensatory in some individuals with ASDs.

Cross-sectional evidence suggests that attention bias to threat is linked to anxiety disorders and anxiety vulnerability in both children and adults. However, there is a lack of developmental evidence regarding the causal mechanisms through which attention bias to threat might convey risks for socioemotional problems, such as anxiety. Gaining insights into this question demands longitudinal research to track the complex interplay between threat-related attention and socioemotional functioning. Developing and implementing reliable and valid assessments tools is essential to this line of work. This review presents theoretical accounts and empirical evidence from behavioral, eye-tracking, and neural assessments of attention to discuss our current understanding of the development of normative threat-related attention in infancy, as well as maladaptive threat-related attention patterns that may be associated with the development of anxiety. This review highlights the importance of measuring threat-related attention using multiple attention paradigms at multiple levels of analysis. In order to understand if and how threat-related attention bias in real-life, social interactive contexts can predict socioemotional development outcomes, this review proposes that future research cannot solely rely on screen-based paradigms but needs to extend the assessment of threat-related attention to naturalistic settings. Mobile eye-tracking technology provides an effective tool for capturing threat-related attention processes in vivo as children navigate fear-eliciting environments and may help us uncover more proximal bio-psycho-behavioral markers of anxiety.

The ability to assess facial expressions of others involves specialised brain systems important for emotional and social learning, a skill that emerges over childhood. We investigated the development of neural responses associated with implicit processing of facial emotions using magnetoencephalography in children (7-10 yrs), adolescents (12-15 yrs) and adults. The results demonstrated spatial-temporal activations in the ACC and amygdala emotion-processing systems that changed with age. The processing of emotions first engaged the earlier-developing amygdala responses and then involved the later-maturing ACC system. With increasing age there was a shift in lateralization of amygdala responses sensitive to the fearful faces. The findings contribute to a critical understanding of the development related to functional specialization of fear perception in the frontal-limbic emotion systems. The present study offers critical insights into the developmentally time-sensitive impact on the normal functioning of these brain regions.

Autism covers a wide spectrum of disorders for which there are many views, hypotheses and theories. Here we propose a unifying theory of autism, the Intense World Theory. The proposed neuropathology is hyper-functioning of local neural microcircuits, best characterized by hyper-reactivity and hyper-plasticity. Such hyper-functional microcircuits are speculated to become autonomous and memory trapped leading to the core cognitive consequences of hyper-perception, hyper-attention, hyper-memory and hyper-emotionality. The theory is centered on the neocortex and the amygdala, but could potentially be applied to all brain regions. The severity on each axis depends on the severity of the molecular syndrome expressed in different brain regions, which could uniquely shape the repertoire of symptoms of an autistic child. The progression of the disorder is proposed to be driven by overly strong reactions to experiences that drive the brain to a hyper-preference and overly selective state, which becomes more extreme with each new experience and may be particularly accelerated by emotionally charged experiences and trauma. This may lead to obsessively detailed information processing of fragments of the world and an involuntarily and systematic decoupling of the autist from what becomes a painfully intense world. The autistic is proposed to become trapped in a limited, but highly secure internal world with minimal extremes and surprises. We present the key studies that support this theory of autism, show how this theory can better explain past findings, and how it could resolve apparently conflicting data and interpretations. The theory also makes further predictions from the molecular to the behavioral levels, provides a treatment strategy and presents its own falsifying hypothesis.

The dot-probe task is often considered a gold standard in the field for investigating attentional bias to threat. However, serious issues with the task have been raised. Specifically, a number of studies have demonstrated that the traditional reaction time (RT) measure of attentional bias to threat in the dot-probe task has poor internal reliability and poor test-retest reliability. In addition, although threatening stimuli capture attention in other paradigms, attentional bias to threat has not usually been found in typical research participants in the dot-probe task. However, when attention is measured in the dot-probe task with the N2pc component of the event-related potential waveform, substantial attentional orienting to threat is observed, and the internal reliability is moderate. To provide a rigorous comparison of the reliability of this N2pc measure and the conventional behavioral measure, as well as to examine the relationship of these measures to anxiety, the present study examined the N2pc in conjunction with RT in the dot-probe task in a large sample of participants (N = 96). As in previous studies, RT showed no bias to threatening images across the sample and exhibited poor internal reliability. Moreover, this measure did not relate to trait anxiety. By contrast, the N2pc revealed a significant initial shift of attention to threat, and this measure was internally reliable. However, the N2pc was not correlated with trait anxiety, indicating that it does not provide a meaningful index of individual differences in anxiety in the dot-probe task. Together, these results indicate a serious need to develop new tasks and methods to more reliably investigate attentional bias to threat and its relationship to anxiety in both clinical and non-clinical populations.

AbstractDifficulty interpreting facial expressions has been reported in autism spectrum disorders (ASD) and is thought to be associated with amygdala abnormalities. To further explore the neural basis of abnormal emotional face processing in ASD, we conducted an fMRI study of emotional face matching in high-functioning adults with ASD and age, IQ, and gender matched controls. In addition, we investigated whether there was a relationship between self-reported social anxiety and fMRI activation. During fMRI scanning, study participants were instructed to match facial expressions depicting fear or anger. The control condition was a comparable shape-matching task. The control group evidenced significantly increased left prefrontal activation and decreased activation in the occipital lobes compared to the ASD group during emotional face matching. Further, within the ASD group, greater social anxiety was associated with increased activation in right amygdala and left middle temporal gyrus, and decreased activation in the fusiform face area. These results indicate that level of social anxiety mediates the neural response to emotional face perception in ASD.]]>

Atypical scan paths on emotional faces and reduced eye contact represent a prominent feature of autism symptomatology, yet the reason for these abnormalities remains a puzzle. Do individuals with autism spectrum disorders (ASDs) fail to orient toward the eyes or do they actively avoid direct eye contact? Here, we used a new task to investigate reflexive eye movements on fearful, happy, and neutral faces. Participants (ASDs: 12; controls: 11) initially fixated either on the eyes or on the mouth. By analyzing the frequency of participants' eye movements away from the eyes and toward the eyes, respectively, we explored both avoidance and orientation reactions. The ASD group showed a reduced preference for the eyes relative to the control group, primarily characterized by more frequent eye movements away from the eyes. Eye-tracking data revealed a pronounced influence of active avoidance of direct eye contact on atypical gaze in ASDs. The combination of avoidance and reduced orientation into an individual index predicted emotional recognition performance. Crucially, this result provides evidence for a direct link between individual gaze patterns and associated social symptomatology. These findings thereby give important insights into the social pathology of ASD, with implications for future research and interventions.

Theoretical models of attention for affective information have assigned a special status to the cognitive processing of emotional facial expressions. One specific claim in this regard is that emotional faces automatically attract visual attention. In three experiments, the authors investigated attentional cueing by angry, happy, and neutral facial expressions that were presented under conditions of limited awareness. In these experiments, facial expressions were presented in a masked (14 ms or 34 ms, masked by a neutral face) and unmasked fashion (34 ms or 100 ms). Compared with trials containing neutral cues, delayed responding was found on trials with emotional cues in the unmasked, 100-ms condition, suggesting stronger allocation of cognitive resources to emotional faces. However, in both masked and unmasked conditions, the hypothesized cueing of visual attention to the location of emotional facial expression was not found. In contrary, attentional cueing by emotional faces was less strong compared with neutral faces in the unmasked, 100-ms condition. These data suggest that briefly presented emotional faces influence cognitive processing but do not automatically capture visual attention.

Asperger syndrome (AS) and autistic disorder are two subtypes of pervasive developmental disorders (PDD), but there has been considerable debate over whether AS and autistic disorder without mental retardation (IQ > or = 70), called high-functioning autism (HFA), are distinct conditions or not. The aim of the present paper was to clarify this issue through a comparison of cognitive function and autistic symptom profiles. Based on the DSM-IV and ICD-10 definitions of language acquisition, 36 age- and IQ-balanced subjects with AS (mean age, 12.8 years; mean full-scale IQ, 98.3) were compared with 37 subjects with HFA (mean age, 12.6 years; mean full-scale IQ, 94.6) on the Japanese version of the Wechsler Intelligence Scales and the Childhood Autism Rating Scale-Tokyo Version (CARS-TV). Compared with the HFA subjects, the AS subjects scored significantly higher on Verbal IQ, Vocabulary, and Comprehension, but scored significantly lower on Coding. Although the total CARS-TV score did not differ significantly between the two groups, AS subjects scored significantly lower (i.e. less abnormal) on Verbal communication and Non-verbal communication than did the HFA subjects. A history of normal language acquisition in early childhood could predict his/her better verbal ability in mid-childhood or later. Autistic cognitive characteristics shared by both AS and HFA subjects appear to support the validity of the current diagnostic classification of PDD.

Neuropeptides such as oxytocin (OXT) are known facilitators of social behavior across species. Variants of the OXT receptor gene (OXTR) have been tested for association with autism spectrum disorder (ASD) across manifold ethnicities, yielding both positive and negative findings. A recent meta-analysis, comprising 16 single nucleotide polymorphisms (SNPs), has corroborated the implication of OXTR in the etiology of ASD. Here, we genotyped and tested two additional variants (rs237889 and rs237897) for association with ASD in two German predominantly high-functioning ASD samples. We found nominal over-transmission (OR = 1.48, CI95 = 1.06-2.08, P = 0.022) for the minor A allele of variant rs237889G>A in sample 1 (N = 135 complete parent-offspring trios, 29 parent child duos), but not in sample 2 (362 trios, 69 duos). Still, in a meta-analysis comprising four different studies including the two unreported German data sets (N = 542 families), this finding was confirmed (OR = 1.12; CI95 = 1.01-1.24, random effects P = 0.012). In addition, carriers of the minor risk allele rs237889-A showed significantly increased severity scores, as assessed through the autism diagnostic interview - revised (ADI-R), with highly significant increases in social interaction deficits. Our results corroborate the implication of common OXTR variants in the etiology of ASD. There is a need for functional studies to delineate the neurobiological implications of this and other association findings. (172/250). Autism Res 2016, 9: 1036-1045. (c) 2016 International Society for Autism Research, Wiley Periodicals, Inc.

AbstractIdentifying threatening expressions is a significant social perceptual skill. Individuals with autism spectrum disorders (ASD) are impaired in social interaction, show deficits in face and emotion processing, show amygdala abnormalities and display a disadvantage in the perception of social threat. According to the anger superiority hypothesis, angry faces capture attention faster than happy faces in individuals with a history of typical development [Hansen, C. H., & Hansen, R. D. (1988). Finding the face in the crowd: An anger superiority effect. Journal of Personality and Social Psychology, 54(6), 917–924]. We tested threat detection abilities in ASD using a facial visual search paradigm. Participants were asked to detect an angry or happy face image in an array of distracter faces. A threat-detection advantage was apparent in both groups: participants showed faster and more accurate detection of threatening over friendly faces. Participants with ASD showed similar reaction time, but decreased overall accuracy compared to controls. This provides evidence for less robust, but intact or learned implicit processing of basic emotions in ASD.]]>

The investigation of emotion recognition in autism spectrum disorder (ASD) has both theoretical and practical implications. However, although many studies have examined facial emotion recognition in ASD, some points remain unclear. We therefore studied facial emotion recognition in young children with ASD across a small age range, in order to determine (1) their ability to recognize emotion and (2) the developmental trajectory of this ability. Twenty-two children with ASD aged 4-8 years were compared with typically developing children matched on either chronological age or verbal mental age. We administered three facial emotion tasks: matching, identification, and labeling. Results showed that children with ASD and typically developing children had difficulty with labeling emotions, but not with matching or identifying them. Happiness was the easiest to recognize, and surprise the hardest. The children with ASD did not exhibit delayed onset in the development of facial emotion recognition. To conclude, emotion recognition difficulties in children with ASD primarily concern the recognition of negative emotions and the identification of surprise, as they do in TD groups. This should be taken into account in future research, as well as in the design of future intervention programs. (C) 2014 Elsevier Ltd.

BACKGROUND: Whole blood serotonin (5-HT) and C-terminally directed beta-endorphin protein immunoreactivity (C-ter-beta-EP-ir) are known to be elevated in autistic subjects and might be possible markers of genetic liability to autism. This study thus investigates the familial aggregation of 5-HT and of C-ter-beta-EP-ir levels in first degree relatives of autistic probands. METHODS: In a sample of 62 autistic subjects and 122 of their first-degree relatives, compared to age and sex-matched controls, we measured 5-HT by radioenzymology and C-ter-beta-EP-ir by radioimmunoassay. RESULTS: We confirm the previously reported familiality of hyperserotoninemia in autism as mothers (51%), fathers (45%) and siblings (87%) have elevated levels of 5-HT, and we reveal presence of elevated levels of C-ter-beta-EP-ir in mothers (53%) of autistic subjects. CONCLUSIONS: Familial aggregation of quantitative variables, such as concentration of neurotransmitters, within unaffected relative could serve as an intermediate phenotype and might thus help the search of genetic susceptibility factors in autism.

Impaired social interaction is one of the hallmarks of Autism Spectrum Disorder (ASD). Emotional faces are arguably the most critical visual social stimuli and the ability to perceive, recognize, and interpret emotions is central to social interaction and communication, and subsequently healthy social development. However, our understanding of the neural and cognitive mechanisms underlying emotional face processing in adolescents with ASD is limited. We recruited 48 adolescents, 24 with high functioning ASD and 24 typically developing controls. Participants completed an implicit emotional face processing task in the MEG. We examined spatiotemporal differences in neural activation between the groups during implicit angry and happy face processing. While there were no differences in response latencies between groups across emotions, adolescents with ASD had lower accuracy on the implicit emotional face processing task when the trials included angry faces. MEG data showed atypical neural activity in adolescents with ASD during angry and happy face processing, which included atypical activity in the insula, anterior and posterior cingulate and temporal and orbitofrontal regions. Our findings demonstrate differences in neural activity during happy and angry face processing between adolescents with and without ASD. These differences in activation in social cognitive regions may index the difficulties in face processing and in comprehension of social reward and punishment in the ASD group. Thus, our results suggest that atypical neural activation contributes to impaired affect processing, and thus social cognition, in adolescents with ASD.

The current investigation compares the results of two commonly used visual detection paradigms-the standard adult button-press detection paradigm used in Ohman, Flykt, and Esteves (2001), and the new child-friendly touch-screen detection paradigm used in LoBue and DeLoache (2008)-within the same samples of adult participants. Results suggest that both paradigms produce the same pattern of findings with regard to detection latency for threat-relevant versus threat-irrelevant stimuli: Adults detected threat-relevant targets more quickly than threat-irrelevant targets across the varying procedures. However, results with respect to automaticity of detection as suggested by Ohman et al. (2001) were only replicated with the classic button-press paradigm. The findings validate the touch-screen visual search procedure and have important implications for choosing an appropriate methodology for studying threat detection.

This study evaluated the effectiveness of a school-based Cognitive Behavioural Therapy (CBT) on symptoms of anxiety, social worry and social responsiveness, and indices of attentional control and attentional biases to threat in adolescents diagnosed with Autism Spectrum Disorder. Thirty-five young people (11-14 years; IQ > 70) with ASD and elevated teacher or parent reported anxiety were randomly assigned to 6 sessions of the Exploring Feelings CBT intervention (Attwood in Exploring feelings (anxiety). Future Horizons, Arlington, 2004) (n = 18) or a wait-list control group (n = 17). The intervention (compared to the wait-list control) group showed positive change for parent, teacher and self-reported anxiety symptoms, and more marginal effects of increased teacher-reported social responsiveness. The discussion highlights the potential value and limitations of school-based CBT for young people with ASD.

BACKGROUND: The ongoing controversy over the distinction between autistic disorder and Asperger's disorder is important to resolve because of the implications regarding an understanding of the aetiology and prognosis, and the diagnostic and clinical practices relating to these conditions. This paper provides a critical evaluation of current published research evidence. METHOD: Databases, such as PsychINFO and Medline, as well as book chapters, reference lists from relevant articles, and recent editions of key journals were searched for all relevant studies (until 2002) which incorporated participants diagnosed with high-functioning autism and Asperger's disorder using either cluster analysis or comparative approaches to examine similarities and differences between these groups. Keywords used in the searches included autistic disorder, Asperger's disorder, autism, high-functioning autism, and pervasive developmental disorder. RESULTS: On the basis of the available evidence, there seem to be few qualitative differences between autistic disorder and Asperger's disorder. CONCLUSION: There is currently insufficient evidence to establish the validity of Asperger's disorder as a syndrome distinct from high-functioning autism. The findings are consistent with the view that these disorders belong on an autism spectrum.

Autism is a devastating neurodevelopmental disorder with a polygenetic predisposition that seems to be triggered by multiple environmental factors during embryonic and/or early postnatal life. While significant advances have been made in identifying the neuronal structures and cells affected, a unifying theory that could explain the manifold autistic symptoms has still not emerged. Based on recent synaptic, cellular, molecular, microcircuit, and behavioral results obtained with the valproic acid (VPA) rat model of autism, we propose here a unifying hypothesis where the core pathology of the autistic brain is hyper-reactivity and hyper-plasticity of local neuronal circuits. Such excessive neuronal processing in circumscribed circuits is suggested to lead to hyper-perception, hyper-attention, and hyper-memory, which may lie at the heart of most autistic symptoms. In this view, the autistic spectrum are disorders of hyper-functionality, which turns debilitating, as opposed to disorders of hypo-functionality, as is often assumed. We discuss how excessive neuronal processing may render the world painfully intense when the neocortex is affected and even aversive when the amygdala is affected, leading to social and environmental withdrawal. Excessive neuronal learning is also hypothesized to rapidly lock down the individual into a small repertoire of secure behavioral routines that are obsessively repeated. We further discuss the key autistic neuropathologies and several of the main theories of autism and re-interpret them in the light of the hypothesized Intense World Syndrome.

The type, frequency and inter-relationships of emotional and behavioural problems in 863 children with autism spectrum disorder (ASD) were investigated using the population-based Database of children with ASD living in the North East of England (Dasl(n)e). A high rate of problems was reported, with 53 % of children having 4 or more types of problems frequently. Sleep, toileting and eating problems, hyperactivity, self injury and sensory difficulties were greater in children with lower language level and in special schooling. However, anxiety, tantrums and aggression towards others were frequent regardless of age, ability or schooling. The frequency of co-existing conditions, including such emotional and behavioural problems, in children with ASD has implications for designing appropriate support services for children and families.

Children with autism spectrum disorder (ASD) have high levels of anxiety. It is unclear whether they exhibit threat-related attentional biases commensurate with anxiety disorders as manifest in non-ASD populations, such as facilitated attention toward, and difficulties disengaging engaging from, threatening stimuli. Ninety children, 45 cognitively able with ASD and 45 age, perceptual-IQ, and gender matched typically developing children, aged 7-12 years, were administered a visual dot probe task using threatening facial pictures. Parent-reported anxiety symptoms were also collected. Children with ASD showed similarly high levels of anxiety compared with normative data from an anxiety disordered sample. Children with ASD had higher levels of parent-reported anxiety but did not show differences in disengaging from, or facilitated attention toward, threatening facial stimuli compared with typically developing children. In contrast to previously published studies of anxious children, in this study there were no differences in attentional biases in children with ASD meeting clinical cutoff for anxiety and those who did not. There were no correlations between attentional biases and anxiety symptoms and no gender differences. These findings indicate the cognitive mechanisms underlying anxiety in cognitively able children with ASD could differ from those commonly found in anxious children which may have implications for both understanding the aetiology of anxiety in ASD and for anxiety interventions.

Despite face and emotion recognition deficits, individuals with Autism Spectrum Disorder (ASD) appear to experience the anger superiority effect, where an angry face in a crowd is detected faster than a neutral face. This study extended past research to examine the impacts of ecologically valid photographic stimuli, gender and anxiety symptoms on the anger superiority effect in children with and without ASD. Participants were 81, 7-12year old children, 42 with ASD matched on age, gender and perceptual IQ to 39 typically developing (TYP) children. The photographic stimuli did not impact on task performance in ASD with both groups exhibiting the anger superiority effect. There were no gender differences and no associations with anxiety. Age was associated with the effect in the TYP but not ASD group. These findings confirm a robust effect of speeded detection of threat in ASD which does not appear to be confounded by gender or anxiety, but may have different underlying age-associated mechanisms.

Evidence of preattentive and attentional biases in anxiety is evaluated from a cognitive-motivational perspective. According to this analysis, vulnerability to anxiety stems mainly from a lower threshold for appraising threat, rather than a bias in the direction of attention deployment. Thus, relatively innocuous stimuli are evaluated as having higher subjective threat value by high than low trait anxious individuals, and it is further assumed that everyone orients to stimuli that are judged to be significantly threatening. This account is contrasted with other recent cognitive models of anxiety, and implications for the etiology, maintenance and treatment of anxiety disorders are discussed.

BACKGROUND: Autism spectrum disorders (ASD) are associated with severe impairments in social functioning. Because faces provide nonverbal cues that support social interactions, many studies of ASD have examined neural structures that process faces, including the amygdala, ventromedial prefrontal cortex and superior and middle temporal gyri. However, increases or decreases in activation are often contingent on the cognitive task. Specifically, the cognitive domain of attention influences group differences in brain activation. We investigated brain function abnormalities in participants with ASD using a task that monitored attention bias to emotional faces. METHODS: Twenty-four participants (12 with ASD, 12 controls) completed a functional magnetic resonance imaging study while performing an attention cuing task with emotional (happy, sad, angry) and neutral faces. RESULTS: In response to emotional faces, those in the ASD group showed greater right amygdala activation than those in the control group. A preliminary psychophysiological connectivity analysis showed that ASD participants had stronger positive right amygdala and ventromedial prefrontal cortex coupling and weaker positive right amygdala and temporal lobe coupling than controls. There were no group differences in the behavioural measure of attention bias to the emotional faces. LIMITATIONS: The small sample size may have affected our ability to detect additional group differences. CONCLUSION: When attention bias to emotional faces was equivalent between ASD and control groups, ASD was associated with greater amygdala activation. Preliminary analyses showed that ASD participants had stronger connectivity between the amygdala ventromedial prefrontal cortex (a network implicated in emotional modulation) and weaker connectivity between the amygdala and temporal lobe (a pathway involved in the identification of facial expressions, although areas of group differences were generally in a more anterior region of the temporal lobe than what is typically reported for emotional face processing). These alterations in connectivity are consistent with emotion and face processing disturbances in ASD.

There is growing interest regarding the impact of affect-biased attention on psychopathology. However, most of the research to date lacks a developmental approach. In the present review, we examine the role affect-biased attention plays in shaping socioemotional trajectories within a developmental neuroscience framework. We propose that affect-biased attention, particularly if stable and entrenched, acts as a developmental tether that helps sustain early socioemotional and behavioral profiles over time, placing some individuals on maladaptive developmental trajectories. Although most of the evidence is found in the anxiety literature, we suggest that these relations may operate across multiple domains of interest, including positive affect, externalizing behaviors, drug use, and eating behaviors. We also review the general mechanisms and neural correlates of affect-biased attention, as well as the current evidence for the co-development of attention and affect. Based on the reviewed literature, we propose a model that may help us better understand the nuances of affect-biased attention across development. The model may serve as a strong foundation for ongoing attempts to identify neurocognitive mechanisms and intervene with individuals at risk. Finally, we discuss open issues for future research that may help bridge existing gaps in the literature.

Fearful temperament, mostly studied as behavioral inhibition (BI), has been extensively associated with social withdrawal in childhood and the later emergence of anxiety disorders, especially social anxiety disorder (SAD). Recent studies have characterized a distinct type of fearful temperament marked by high levels of fear in low threat situations - labeled dysregulated fear. Dysregulated fear has been related to SAD over and above risks associated with BI. However, the mechanism by which dysregulated fear is related to SAD has not been studied. Cognitive mechanisms, such as attentional bias towards threat, may be a possible conduit. We examined differences in attentional bias towards threat in six-year-olds who displayed a pattern of dysregulated fear at age two (N = 23) compared with children who did not display dysregulated fear (N = 33). Moreover, we examined the concurrent relation between attentional bias and social withdrawal. Results indicated that children characterized by dysregulated fear showed a significant bias away from threat, and that this bias was significantly different from the children without dysregulated fear, who showed no significant bias. Moreover, attentional bias towards threat was positively related to social withdrawal only for the dysregulated fear group. These results are discussed in consideration of the existing knowledge of attentional bias to threat in the developmental and pediatric anxiety literatures, as well as recent studies that find important heterogeneity in attentional bias.

Recent findings suggest the processing of emotional stimuli is prioritized compared to neutral stimuli; however, it is not necessarily automatic and depends on several modulating factors. The current paper highlights three major factors that affect the reactions to emotional stimuli: (i) stimulus properties, (ii) task demands and attention, and (iii) individual characteristics. The evidence reviewed here suggests that individual characteristics shape the structure, function and connectivity within a neural network that is involved in the reactions to emotional stimuli. This neural network includes regions related to emotion and attention, in line with evidence for reciprocal connections between these two processes. Activation in this network further depends on the emotional value of a certain item, as well as physical features of the stimulus. This integrative view can lead to better understanding of the underlying mechanisms of emotional reactions, as well as better therapeutic approaches. (c) 2012 Elsevier B.V.

Anxiety is a pervasive, impairing, and early appearing form of psychopathology. Even when anxiety remits, children remain at a two- to threefold increased risk for the later emergence of a mood disorder. Therefore, it is imperative to identify and examine underlying mechanisms that may shape early emerging patterns of behavior that are associated with anxiety. One of the strongest and first visible risk factors is childhood temperament. In particular, children who are behaviorally inhibited or temperamentally shy are more likely to exhibit signs of anxiety by adolescence. However, not all shy children do so, despite the early risk. We know that attention mechanisms, particularly the presence of attention biases toward or away from threat, can play a critical role in the emergence of anxiety. The current chapter will bring together these separate lines of research to examine the ways in which attention can modulate the documented link between early temperament and later anxiety. In doing so, the chapter will highlight multiple levels of analysis that focus on the behavioral, cognitive, and neural mechanisms in the temperament-attention-anxiety network. The chapter will help identify both markers and mechanisms of risk, supporting future work aimed at improving theory and intervention by focusing on attention biases to environmental threat.

Autism spectrum disorder (ASD) is a common neurodevelopmental condition characterized by marked genetic heterogeneity. Recent studies of rare structural and sequence variants have identified hundreds of loci involved in ASD, but our knowledge of the overall genetic architecture and the underlying pathophysiological mechanisms remains incomplete. Glycine receptors (GlyRs) are ligand-gated chloride channels that mediate inhibitory neurotransmission in the adult nervous system but exert an excitatory action in immature neurons. GlyRs containing the alpha2 subunit are highly expressed in the embryonic brain, where they promote cortical interneuron migration and the generation of excitatory projection neurons. We previously identified a rare microdeletion of the X-linked gene GLRA2, encoding the GlyR alpha2 subunit, in a boy with autism. The microdeletion removes the terminal exons of the gene (GLRA2(Deltaex8-9)). Here, we sequenced 400 males with ASD and identified one de novo missense mutation, p.R153Q, absent from controls. In vitro functional analysis demonstrated that the GLRA2(Deltaex8)(-)(9) protein failed to localize to the cell membrane, while the R153Q mutation impaired surface expression and markedly reduced sensitivity to glycine. Very recently, an additional de novo missense mutation (p.N136S) was reported in a boy with ASD, and we show that this mutation also reduced cell-surface expression and glycine sensitivity. Targeted glra2 knockdown in zebrafish induced severe axon-branching defects, rescued by injection of wild type but not GLRA2(Deltaex8-9) or R153Q transcripts, providing further evidence for their loss-of-function effect. Glra2 knockout mice exhibited deficits in object recognition memory and impaired long-term potentiation in the prefrontal cortex. Taken together, these results implicate GLRA2 in non-syndromic ASD, unveil a novel role for GLRA2 in synaptic plasticity and learning and memory, and link altered glycinergic signaling to social and cognitive impairments.

The purpose of this study was to investigate sex differences in behavioral and emotional problems in high-functioning girls and boys with autism spectrum disorder. The results obtained by adolescents with autism spectrum disorder were compared with those of typically developing girls and boys. Correlations between parents' and adolescents' ratings were also analyzed. Participants were 35 girls and 35 boys with autism spectrum disorder, aged 11-18 years, matched for chronological age and full-scale IQ. The control group consisted of 24 typically developing girls and 24 boys of the same age and IQ. The parents of adolescent participants were also included in the study. The measures used were the Child Behavior Checklist (4-18) completed by parents and Youth Self-Report (11-18) completed by adolescents. The adolescents with autism spectrum disorder presented higher levels of behavioral and emotional problems than the control group, according to both the parents' reports and the adolescents' self-reports. No sex differences were found in that respect. More differences between the assessments of adolescents and their parents occurred in the control group, and the effect size was larger.

The neuropeptide oxytocin has shown promise as a treatment for symptoms of autism spectrum disorders (ASD). However, clinical research progress has been hampered by a poor understanding of oxytocin's dose-response and sub-optimal intranasal delivery methods. We examined two doses of oxytocin delivered using a novel Breath Powered intranasal delivery device designed to improve direct nose-to-brain activity in a double-blind, crossover, randomized, placebo-controlled trial. In a randomized sequence of single-dose sessions, 17 male adults with ASD received 8 international units (IU) oxytocin, 24IU oxytocin or placebo followed by four social-cognitive tasks. We observed an omnibus main effect of treatment on the primary outcome measure of overt emotion salience as measured by emotional ratings of faces (eta(2)=0.18). Compared to placebo, 8IU treatment increased overt emotion salience (P=0.02, d=0.63). There was no statistically significant increase after 24IU treatment (P=0.12, d=0.4). The effects after 8IU oxytocin were observed despite no significant increase in peripheral blood plasma oxytocin concentrations. We found no significant effects for reading the mind in the eyes task performance or secondary outcome social-cognitive tasks (emotional dot probe and face-morphing). To our knowledge, this is the first trial to assess the dose-dependent effects of a single oxytocin administration in autism, with results indicating that a low dose of oxytocin can significantly modulate overt emotion salience despite minimal systemic exposure.

In 3 facial expression identification studies, college students matched a variety of disgust faces to verbally described eliciting situations. The faces depicted specific muscle action movements in accordance with P. Ekman and W. V. Friesen's (1978) Facial Action Coding System. The nose wrinkle is associated with either irritating or offensive smells and, to some extent, bad tastes. Gape and tongue extrusion are associated primarily with what we call core or food-offense disgust and also oral irritation. The broader range of disgust elicitors, including stimuli that remind humans of their animal origins (e.g., body boundary violations, inappropriate sex, poor hygiene, and death), a variety of aversive interpersonal contacts, and certain moral offenses are associated primarily with the raised upper lip. The results support a theory of disgust that posits its origin as a response to bad tastes and maps its evolution onto a moral emotion.

We performed a comprehensive assessment of rare inherited variation in autism spectrum disorder (ASD) by analyzing whole-genome sequences of 2,308 individuals from families with multiple affected children. We implicate 69 genes in ASD risk, including 24 passing genome-wide Bonferroni correction and 16 new ASD risk genes, most supported by rare inherited variants, a substantial extension of previous findings. Biological pathways enriched for genes harboring inherited variants represent cytoskeletal organization and ion transport, which are distinct from pathways implicated in previous studies. Nevertheless, the de novo and inherited genes contribute to a common protein-protein interaction network. We also identified structural variants (SVs) affecting non-coding regions, implicating recurrent deletions in the promoters of DLG2 and NR3C2. Loss of nr3c2 function in zebrafish disrupts sleep and social function, overlapping with human ASD-related phenotypes. These data support the utility of studying multiplex families in ASD and are available through the Hartwell Autism Research and Technology portal.

Impairments in visual disengagement are a current focus of research in autism spectrum disorders (ASD) and may play a key role in the early expression of social-emotional deficits associated with the disorder. This review summarizes current knowledge of visual disengagement and orienting in ASD. Convergent reports from infancy to adulthood indicate that (1) impairments to visual disengagement are apparent on Gap-Overlap tasks, spatial orienting tasks, and tasks involving social stimuli; and (2) these impairments emerge in the first year of life and continue into adulthood. The relationships between visual disengagement, orienting, joint attention, emotional regulation, and IQ are discussed in relation to ASD.

The detection of emotional facial expressions plays an indispensable role in social interaction. Psychological studies have shown that typically developing (TD) individuals more rapidly detect emotional expressions than neutral expressions. However, it remains unclear whether individuals with autistic phenotypes, such as autism spectrum disorder (ASD) and high levels of autistic traits (ATs), are impaired in this ability. We examined this by comparing TD and ASD individuals in Experiment 1 and individuals with low and high ATs in Experiment 2 using the visual search paradigm. Participants detected normal facial expressions of anger and happiness and their anti-expressions within crowds of neutral expressions. In Experiment 1, reaction times were shorter for normal angry expressions than for anti-expressions in both TD and ASD groups. This was also the case for normal happy expressions vs. anti-expressions in the TD group but not in the ASD group. Similarly, in Experiment 2, the detection of normal vs. anti-expressions was faster for angry expressions in both groups and for happy expressions in the low, but not high, ATs group. These results suggest that the detection of happy facial expressions is impaired in individuals with ASD and high ATs, which may contribute to their difficulty in creating and maintaining affiliative social relationships.

Cognitive theories of anxiety disorders and depression posit that attentional biases play a role in the development, maintenance, and recurrence of these disorders. Several paradigms have been used to examine attentional biases in anxiety and depression, but information on the reliability of different attentional bias indices is limited. In this study we examined the internal consistency and 6-month test-retest reliability of attentional bias indices derived from a free-viewing eye-tracking paradigm. Participants completed two versions of an eye-tracking task-one that used naturalistic images as stimuli, and one that used face images. In both tasks, participants viewed displays of four images, each display consisting of one threat image, one sad image, one positive/happy image, and one neutral image. The internal consistency of the fixation indices (dwell time and number of fixations) for threat, sad, and positive images over the full 8-s display was moderate to excellent. When the 8-s display was divided into 2-s intervals, the dwell times for the 0- to 2-s and 2- to 4-s intervals showed lower reliability, particularly for the face images. The attentional bias indices for the naturalistic images showed adequate to good stability over the test-retest period, whereas the test-retest reliability estimates for the face images were in the low to moderate range. The implications of these results for attentional bias research are discussed.

Current models of conditioned fear expression and extinction involve the basolateral amygdala (BLA), ventral medial prefrontal cortex (vmPFC), and the hippocampus (HPC). There is some disagreement with respect to the specific roles of these structures, perhaps due to subregional differences within each area. For example, growing evidence suggests that infralimbic (IL) and prelimbic (PL) subregions of vmPFC have opposite influences on fear expression. Moreover, it is the ventral HPC (vHPC), rather than the dorsal HPC, that projects to vmPFC and BLA. To help determine regional specificity, we used small doses of the GABA(A) agonist muscimol to selectively inactivate IL, PL, BLA, or vHPC in an auditory fear conditioning and extinction paradigm. Infusions were performed prior to extinction training, allowing us to assess the effects on both fear expression and subsequent extinction memory. Inactivation of IL had no effect on fear expression, but impaired the within-session acquisition of extinction as well as extinction memory. In contrast, inactivation of PL impaired fear expression, but had no effect on extinction memory. Inactivation of the BLA or vHPC impaired both fear expression and extinction memory. Post-extinction inactivations had no effect in any structure. We suggest a model in which amygdala-dependent fear expression is modulated by inputs from PL and vHPC, whereas extinction memory requires extinction-induced plasticity in IL, BLA, and/or vHPC.

Anxiety is characterized by the anticipation of aversive future events. The importance of prestimulus anticipatory factors, such as goals and expectations, is well-established in both visual perception and attention. Nevertheless, the prioritized perception of threatening stimuli in anxiety has been attributed to the automatic processing of these stimuli and the role of prestimulus factors has been neglected. The present review will focus on the role of top-down processes that occur before stimulus onset in the perceptual and attentional prioritization of threatening stimuli in anxiety. We will review both the cognitive and neuroscience literature, showing how top-down factors, and interactions between top-down and bottom-up factors may contribute to biased perception of threatening stimuli in normal function and anxiety. The shift in focus from stimulus-driven to endogenous factors and interactions between top-down and bottom-up factors in the prioritization of threat-related stimuli represents an important conceptual advance. In addition, it may yield important clues into the development and maintenance of anxiety, as well as inform novel treatments for anxiety.

Many emotional stimuli are processed without being consciously perceived. Recent evidence indicates that subcortical structures have a substantial role in this processing. These structures are part of a phylogenetically ancient pathway that has specific functional properties and that interacts with cortical processes. There is now increasing evidence that non-consciously perceived emotional stimuli induce distinct neurophysiological changes and influence behaviour towards the consciously perceived world. Understanding the neural bases of the non-conscious perception of emotional signals will clarify the phylogenetic continuity of emotion systems across species and the integration of cortical and subcortical activity in the human brain.

The dot-probe task is a common task to assess attentional bias toward different stimuli and how groups differ (e.g., attentional bias in anxiety disorders). However, measuring reaction time has been suggested to be unreliable. Neuroimaging methods such as fMRI were shown to be more reliable in assessing attentional bias, but fMRI has poor temporal resolution and therefore cannot assess timing of attention. ERPs have been used to examine the time course of attentional bias. Although ERP research may be more reliable than reaction time, there have been inconsistencies in the literature. This review systematically searched for articles that used the dot-probe task with facial expressions and measured neural correlates with ERP. We found that some of the inconsistencies might be the cause of methodological differences (e.g., timing of stimuli), differences in emotional expression, and/or sample differences (e.g., sex, age, etc.). Suggestions on how future research could address the issues presented in this review were discussed.

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.

Although impaired joint attention is one of the core clinical features of pervasive developmental disorder including autistic disorder and Asperger's disorder, experimental studies failed to report its impairment. This discrepancy might be the result of differences between real-life and experimental situations. The present study examined joint attention in 11 individuals with Asperger's disorder and 11 age-matched controls under naturalistic conditions using a target detection paradigm with dynamic emotional gaze cues. Although both groups showed gaze-triggered attention orienting as assessed by the differences in reaction time for invalid minus valid cues, enhancement of joint attention by fearful (vs. neutral) gaze was observed in the control, but not in the Asperger group. This suggests that the integration of emotion and gaze direction that elicits strong joint attention is impaired in individuals with Asperger's disorder.

BACKGROUND: The fear-reducing properties of testosterone have been firmly established in animals but not in humans. However, human data on the relation between testosterone, fear, and anxiety have predominantly involved questionnaires that index cortically executed conscious appraisal of anxious mood. Animal studies, on the other hand, indicate that the effects of testosterone on motivation and emotion are of subcortical origin and of unconscious nature. Presently, it was hypothesized that a single testosterone administration to humans would reduce unconscious fear but not consciously experienced anxiety. METHODS: In a placebo-controlled, double-blind crossover design, a single dose of testosterone (.5 mg) or placebo was administered to 16 healthy female volunteers. Afterward, a masked emotional Stroop task measured unconscious emotional responses to fearful faces, while multiple self-reports of mood indexed consciously experienced anxiety. RESULTS: As hypothesized, the habitual vigilant emotional response to the masked fearful face observed in the placebo condition was significantly reduced after testosterone was administered, while the self-reported measures of anxiety remained unaffected. CONCLUSIONS: These data provide the first direct evidence for fear-reducing properties of testosterone in humans. Furthermore, by dissociating specific aspects of fear and anxiety in humans, this outcome highlights that testosterone's effects on motivation and emotion concern the subcortical affective pathways of the brain.

For social animals, attending to and recognizing the emotional expressions of other individuals is of crucial importance for their survival and likely has a deep evolutionary origin. Gaining insight into how emotional expressions evolved as adaptations over the course of evolution can be achieved by making direct cross-species comparisons. To that extent, experimental paradigms that are suitable for investigating emotional processing across species need to be developed and evaluated. The emotional dot-probe task, which measures attention allocation toward emotional stimuli, has this potential. The task is implicit, and subjects need minimal training to perform the task successfully. Findings in nonhuman primates, although scarce, show that they, like humans, have an attentional bias toward emotional stimuli. However, the wide literature on human studies has shown that different factors can have important moderating effects on the results. Due to the large heterogeneity of this literature, these moderating effects often remain unnoticed. We here review this literature and show that subject characteristics and differences in experimental designs affect the results of the dot-probe task. We conclude with specific recommendations regarding these issues that are particularly relevant to take into consideration when applying this paradigm to study animals.

Previous research has found that a common polymorphism in the serotonin transporter gene (5-HTTLPR) is an important mediator of individual differences in brain responses associated with emotional behaviour. In particular, relative to individuals homozygous for the l-allele, carriers of the s-allele display heightened amygdala activation to emotional compared to non-emotional stimuli. However, there is some debate as to whether this difference is driven by increased activation to emotional stimuli, resting baseline differences between the groups, or decreased activation to neutral stimuli. We performed functional imaging during an implicit facial expression processing task in which participants viewed angry, sad and neutral faces. In addition to neutral faces, we included two further baseline conditions, houses and fixation. We found increased amygdala activation in s-allele carriers relative to l-homozygotes in response to angry faces compared to neutral faces, houses and fixation. When comparing neutral faces to houses or fixation, we found no significant difference in amygdala response between the two groups. In addition, there was no significant difference between the groups in response to fixation when compared with a houses baseline. Overall, these results suggest that the increased amygdala response observed in s-allele carriers to emotional faces is primarily driven by an increased response to emotional faces rather than a decreased response to neutral faces or an increased resting baseline. The results are discussed in relation to the tonic and phasic hypotheses of 5-HTTLPR-mediated modulation of amygdala activity.

Individuals with autism spectrum disorder (ASD) often have difficulty with social-emotional cues. This study examined the neural, behavioral, and autonomic correlates of emotional face processing in adolescents with ASD and typical development (TD) using eye-tracking and event-related potentials (ERPs) across two different paradigms. Scanning of faces was similar across groups in the first task, but the second task found that face-sensitive ERPs varied with emotional expressions only in TD. Further, ASD showed enhanced neural responding to non-social stimuli. In TD only, attention to eyes during eye-tracking related to faster face-sensitive ERPs in a separate task; in ASD, a significant positive association was found between autonomic activity and attention to mouths. Overall, ASD showed an atypical pattern of emotional face processing, with reduced neural differentiation between emotions and a reduced relationship between gaze behavior and neural processing of faces.

Social anxiety is common among adolescents with Autism Spectrum Disorder (ASD). In this modest-sized pilot study, we examined the relationship between social worries and gaze patterns to static social stimuli in adolescents with ASD (n = 15) and gender-matched adolescents without ASD (control; n = 18). Among cognitively unimpaired adolescents with ASD, self-reported fear of negative evaluation predicted greater gaze duration to social threat cues (i.e., faces depicting disgust and anger). By comparison, there was no relationship between self-reported social fears and gaze duration in the controls. These findings call attention to the potential import of the impact of co-occurring psychopathology such as social anxiety, and particularly fear of negative evaluation, on social attention and cognition with adolescents who have ASD.

The ability to disengage attention and reengage elsewhere has been proposed as a fundamental deficit in the autism spectrum, potentially disrupting development of higher cognitive domains. Eye-movements were recorded while 16 autism spectrum children of mixed ability, and 18 typically developing age-matched controls, completed the Gap-Overlap paradigm. A significant difference in latency to fixate target was found between Gap and Overlap conditions. A significant interaction with group was due to autism spectrum participants' shorter latencies to fixate target in the Gap condition, but similar group responses in the Overlap condition. Considerable within-group variability emerged. We predicted that attentional disengaging would be related to specific features of the phenotype; however, there was no evidence of an association with receptive language, non-verbal IQ, sensory behaviors, or autistic severity in autism spectrum or typically developing groups. In conclusion, while atypical visual attention mechanisms may be a feature of autism spectrum, this is not explained by impaired visual disengaging but is more likely due to increased susceptibility of visual fixation offset cueing. Despite best efforts, nine additional autism spectrum children could not complete testing, and data from a further six were unusable; more work is needed to develop research methods that enable individuals across the spectrum to participate.

There is considerable interest in the potential therapeutic role of the neuropeptide oxytocin in altering attentional bias towards emotional social stimuli in psychiatric disorders. However, it is still unclear whether oxytocin primarily influences attention towards positive or negative valence social stimuli. Here in a double-blind, placebo controlled, between subject design experiment in 60 healthy male subjects we have used the highly sensitive dual-target rapid serial visual presentation (RSVP) paradigm to investigate whether intranasal oxytocin (40IU) treatment alters attentional bias for emotional faces. Results show that oxytocin improved recognition accuracy of neutral and happy expression faces presented in the second target position (T2) during the period of reduced attentional capacity following prior presentation of a first neutral face target (T1), but had no effect on recognition of negative expression faces (angry, fearful, sad). Oxytocin also had no effect on recognition of non-social stimuli (digits) in this task. Recognition accuracy for neutral faces at T2 was negatively associated with autism spectrum quotient (ASQ) scores in the placebo group, and oxytocin's facilitatory effects were restricted to a sub-group of subjects with higher ASQ scores. Our results therefore indicate that oxytocin primarily enhances the allocation of attentional resources towards faces expressing neutral or positive emotion and does not influence that towards negative emotion ones or non-social stimuli. This effect of oxytocin is strongest in healthy individuals with higher autistic trait scores, thereby providing further support for its potential therapeutic use in autism spectrum disorder.

In the last few decades there has been increasing interest in the role of the amygdala in psychiatric disorders and, in particular, in its contribution to the socio-emotional impairments in autism spectrum disorders (ASDs). Given that the amygdala is a component structure of the

Previous studies on attentional bias towards emotional faces in individuals with autism spectrum disorders (ASD) provided mixed results. This might be due to differences in the examined attentional bias components and emotional expressions. This study assessed three bias components, hypervigilance, disengagement, and avoidance, using faces with a disgust, happy, or neutral expression in a dot-probe and external cuing task in 18 children with ASD and 21 typically developing (TD) children. The children with ASD initially displayed hypervigilance towards the disgust faces, followed by a general tendency to avoid looking back at the spatial location at which any face, irrespective of its emotional expression, had been presented. These results highlight the importance of differentiating between attentional bias components in research on ASD.