Repetition Suppression and Memory for Faces is Reduced in Adults with Autism Spectrum Conditions.

Autism spectrum conditions (ASC) are associated with a number of atypicalities in face processing, including difficulties in face memory. However, the neural mechanisms underlying this difficulty are unclear. In neurotypical individuals, repeated presentation of the same face is associated with a reduction in activity, known as repetition suppression (RS), in the fusiform face area (FFA). However, to date, no studies have investigated RS to faces in individuals with ASC, or the relationship between RS and face memory. Here, we measured RS to faces and geometric shapes in individuals with a clinical diagnosis of an ASC and in age and IQ matched controls. Relative to controls, the ASC group showed reduced RS to faces in bilateral FFA and reduced performance on a standardized test of face memory. By contrast, RS to shapes in object-selective regions and object memory did not differ between groups. Individual variation in face-memory performance was positively correlated with RS in regions of left parietal and prefrontal cortex. These findings suggest difficulties in face memory in ASC may be a consequence of differences in the way faces are stored and/or maintained across a network of regions involved in both visual perception and short-term/working memory.

Mapping the structural organization of the brain in conduct disorder: replication of findings in two independent samples.

BACKGROUND: Neuroimaging methods that allow researchers to investigate structural covariance between brain regions are increasingly being used to study psychiatric disorders. Structural covariance analyses are particularly well suited for studying disorders with putative neurodevelopmental origins as they appear sensitive to changes in the synchronized maturation of different brain regions. We assessed interregional correlations in cortical thickness as a measure of structural covariance, and applied this method to investigate the coordinated development of different brain regions in conduct disorder (CD). We also assessed whether structural covariance measures could differentiate between the childhood-onset (CO-CD) and adolescence-onset (AO-CD) subtypes of CD, which may differ in terms of etiology and adult outcomes. METHODS: We examined interregional correlations in cortical thickness in male youths with CO-CD or AO-CD relative to healthy controls (HCs) in two independent datasets. The age range in the Cambridge sample was 16-21 years (mean: 18.0), whereas the age range of the Southampton sample was 13-18 years (mean: 16.7). We used FreeSurfer to perform segmentations and applied structural covariance methods to the resulting parcellations. RESULTS: In both samples, CO-CD participants displayed a strikingly higher number of significant cross-cortical correlations compared to HC or AO-CD participants, whereas AO-CD participants presented fewer significant correlations than HCs. Group differences in the strength of the interregional correlations were observed in both samples, and each set of results remained significant when controlling for IQ and comorbid attention-deficit/hyperactivity disorder symptoms. CONCLUSIONS: This study provides new evidence for quantitative differences in structural brain organization between the CO-CD and AO-CD subtypes, and supports the hypothesis that both subtypes of CD have neurodevelopmental origins.

Network Interactions Explain Sensitivity to Dynamic Faces in the Superior Temporal Sulcus.

The superior temporal sulcus (STS) in the human and monkey is sensitive to the motion of complex forms such as facial and bodily actions. We used functional magnetic resonance imaging (fMRI) to explore network-level explanations for how the form and motion information in dynamic facial expressions might be combined in the human STS. Ventral occipitotemporal areas selective for facial form were localized in occipital and fusiform face areas (OFA and FFA), and motion sensitivity was localized in the more dorsal temporal area V5. We then tested various connectivity models that modeled communication between the ventral form and dorsal motion pathways. We show that facial form information modulated transmission of motion information from V5 to the STS, and that this face-selective modulation likely originated in OFA. This finding shows that form-selective motion sensitivity in the STS can be explained in terms of modulation of gain control on information flow in the motion pathway, and provides a substantial constraint for theories of the perception of faces and biological motion.

Repetition Suppression in Ventral Visual Cortex Is Diminished as a Function of Increasing Autistic Traits.

Repeated viewing of a stimulus causes a change in perceptual sensitivity, known as a visual aftereffect. Similarly, in neuroimaging, repetitions of the same stimulus result in a reduction in the neural response, known as repetition suppression (RS). Previous research shows that aftereffects for faces are reduced in both children with autism and in first-degree relatives. With functional magnetic resonance imaging, we found that the magnitude of RS to faces in neurotypical participants was negatively correlated with individual differences in autistic traits. We replicated this finding in a second experiment, while additional experiments showed that autistic traits also negatively predicted RS to images of scenes and simple geometric shapes. These findings suggest that a core aspect of neural function--the brain's response to repetition--is modulated by autistic traits.

Direct gaze elicits atypical activation of the theory-of-mind network in autism spectrum conditions.

Eye contact plays a key role in social interaction and is frequently reported to be atypical in individuals with autism spectrum conditions (ASCs). Despite the importance of direct gaze, previous functional magnetic resonance imaging in ASC has generally focused on paradigms using averted gaze. The current study sought to determine the neural processing of faces displaying direct and averted gaze in 18 males with ASC and 23 matched controls. Controls showed an increased response to direct gaze in brain areas implicated in theory-of-mind and gaze perception, including medial prefrontal cortex, temporoparietal junction, posterior superior temporal sulcus region, and amygdala. In contrast, the same regions showed an increased response to averted gaze in individuals with an ASC. This difference was confirmed by a significant gaze direction × group interaction. Relative to controls, participants with ASC also showed reduced functional connectivity between these regions. We suggest that, in the typical brain, perceiving another person gazing directly at you triggers spontaneous attributions of mental states (e.g. he is "interested" in me), and that such mental state attributions to direct gaze may be reduced or absent in the autistic brain.

How is facial expression coded?

Facial expression is theorized to be visually represented in a multidimensional expression space, relative to a norm. This norm-based coding is typically argued to be implemented by a two-pool opponent coding system. However, the evidence supporting the opponent coding of expression cannot rule out the presence of a third channel tuned to the center of each coded dimension. Here we used a paradigm not previously applied to facial expression to determine whether a central-channel model is necessary to explain expression coding. Participants identified expressions taken from a fear/antifear trajectory, first at baseline and then in two adaptation conditions. In one condition, participants adapted to the expression at the center of the trajectory. In the other condition, participants adapted to alternating images from the two ends of the trajectory. The range of expressions that participants perceived as lying at the center of the trajectory narrowed in both conditions, a pattern that is not predicted by the central-channel model but can be explained by the opponent-coding model. Adaptation to the center of the trajectory also increased identification of both fear and antifear, which may indicate a functional benefit for adaptive coding of facial expression.

Top-down control of visual responses to fear by the amygdala.

The visual cortex is sensitive to emotional stimuli. This sensitivity is typically assumed to arise when amygdala modulates visual cortex via backwards connections. Using human fMRI, we compared dynamic causal connectivity models of sensitivity with fearful faces. This model comparison tested whether amygdala modulates distinct cortical areas, depending on dynamic or static face presentation. The ventral temporal fusiform face area showed sensitivity to fearful expressions in static faces. However, for dynamic faces, we found fear sensitivity in dorsal motion-sensitive areas within hMT+/V5 and superior temporal sulcus. The model with the greatest evidence included connections modulated by dynamic and static fear from amygdala to dorsal and ventral temporal areas, respectively. According to this functional architecture, amygdala could enhance encoding of fearful expression movements from video and the form of fearful expressions from static images. The amygdala may therefore optimize visual encoding of socially charged and salient information.

Overlapping and distinct representations of advantageous and disadvantageous inequality.

Advantageous inequality (AI) aversion, or paying at a personal cost to achieve equal reward distribution, represents a unique feature of human behavior. Here, we show that individuals have strong preferences for fairness in both disadvantageous (DI) and advantageous inequality (AI) situations, such that they alter others' payoff at a personal financial cost. At the neural level, we found that both types of inequality activated the putamen, orbitofrontal cortex, and insula, regions implicated in motivation. Individual difference analyses found that those who spent more money to increase others' payoff had stronger activity in putamen when they encountered AI and less functional connectivity between putamen and both orbitofrontal cortex and anterior insula. Conversely, those who spent more money to reduce others' payoff had stronger activity in amygdala in response to DI and less functional connectivity between amygdala and ventral anterior cingulate cortex. These dissociations suggest that both types of inequality are processed by similar brain areas, yet modulated by different neural pathways.

The Cambridge Centre for Ageing and Neuroscience (Cam-CAN) study protocol: a cross-sectional, lifespan, multidisciplinary examination of healthy cognitive ageing.

BACKGROUND: As greater numbers of us are living longer, it is increasingly important to understand how we can age healthily. Although old age is often stereotyped as a time of declining mental abilities and inflexibility, cognitive neuroscience reveals that older adults use neural and cognitive resources flexibly, recruiting novel neural regions and cognitive processes when necessary. Our aim in this project is to understand how age-related changes to neural structure and function interact to support cognitive abilities across the lifespan. METHODS/DESIGN: We are recruiting a population-based cohort of 3000 adults aged 18 and over into Stage 1 of the project, where they complete an interview including health and lifestyle questions, a core cognitive assessment, and a self-completed questionnaire of lifetime experiences and physical activity. Of those interviewed, 700 participants aged 18-87 (100 per age decile) continue to Stage 2 where they undergo cognitive testing and provide measures of brain structure and function. Cognition is assessed across multiple domains including attention and executive control, language, memory, emotion, action control and learning. A subset of 280 adults return for in-depth neurocognitive assessment in Stage 3, using functional neuroimaging experiments across our key cognitive domains.Formal statistical models will be used to examine the changes that occur with healthy ageing, and to evaluate age-related reorganisation in terms of cognitive and neural functions invoked to compensate for overall age-related brain structural decline. Taken together the three stages provide deep phenotyping that will allow us to measure neural activity and flexibility during performance across a number of core cognitive functions. This approach offers hypothesis-driven insights into the relationship between brain and behaviour in healthy ageing that are relevant to the general population. DISCUSSION: Our study is a unique resource of neuroimaging and cognitive measures relevant to change across the adult lifespan. Because we focus on normal age-related changes, our results may contribute to changing views about the ageing process, lead to targeted interventions, and reveal how normal ageing relates to frail ageing in clinicopathological conditions such as Alzheimer's disease.

Different neural mechanisms within occipitotemporal cortex underlie repetition suppression across same and different-size faces.

Repetition suppression (RS) (or functional magnetic resonance imaging adaptation) refers to the reduction in blood oxygen level-dependent signal following repeated presentation of a stimulus. RS is frequently used to investigate the role of face-selective regions in human visual cortex and is commonly thought to be a "localized" effect, reflecting fatigue of a neuronal population representing a given stimulus. In contrast, predictive coding theories characterize RS as a consequence of "top-down" changes in between-region modulation. Differentiating between these accounts is crucial for the correct interpretation of RS effects in the face-processing network. Here, dynamic causal modeling revealed that different mechanisms underlie different forms of RS to faces in occipitotemporal cortex. For both familiar and unfamiliar faces, repetition of identical face images (same size) was associated with changes in "forward" connectivity between the occipital face area (OFA) and the fusiform face area (FFA) (OFA-to-FFA). In contrast, RS across image size was characterized by altered "backward" connectivity (FFA-to-OFA). In addition, evidence was higher for models in which information projected directly into both OFA and FFA, challenging the role of OFA as the input stage of the face-processing network. These findings suggest "size-invariant" RS to faces is a consequence of interactions between regions rather than being a localized effect.

Eye gaze is not coded by cardinal mechanisms alone.

Gaze is an important social cue in regulating human and non-human interactions. In this study, we employed an adaptation paradigm to examine the mechanisms underlying the perception of another's gaze. Previous research has shown that the interleaved presentation of leftwards and rightwards gazing adaptor stimuli results in observers judging a wider range of gaze deviations as being direct. We applied a similar paradigm to examine how human observers encode oblique (e.g. upwards and to the left) directions of gaze. We presented observers with interleaved gaze adaptors and examined whether adaptation differed between congruent (adaptor and test along same axis) and incongruent conditions. We find greater adaptation in congruent conditions along cardinal (horizontal and vertical) and non-cardinal (oblique) directions suggesting gaze is not coded alone by cardinal mechanisms. Our results suggest that the functional aspects of gaze processing might parallel that of basic visual features such as orientation.

Research review: evaluating and reformulating the developmental taxonomic theory of antisocial behaviour.

BACKGROUND: The developmental taxonomic theory proposes that there are two subtypes of antisocial behaviour. The first is a neurodevelopmental disorder which emerges in early childhood and follows a life-course persistent course, whereas the second emerges in adolescence, remits in early adulthood and reflects peer processes such as mimicry of antisocial peers. The aim of this review was to evaluate the developmental taxonomic theory in the light of recent empirical research. METHODS: We conducted a comprehensive literature review comparing these subtypes of antisocial behaviour based on searches on PubMed and other scientific databases covering the period from 1993 to 2013. We focused on research encompassing psychiatric epidemiology, personality assessment, neuropsychology, neuroendocrinology, genetics, and structural and functional neuroimaging. Sixty one empirical studies were identified that investigated one of these forms of antisocial behaviour separately or explicitly compared childhood-onset and adolescence-onset forms of antisocial behaviour. RESULTS: Empirical research provides support for the hypothesis that life-course persistent antisocial behaviour is a neurodevelopmental disorder which emerges in the transactions between individual vulnerabilities and environmental adversity. In contrast to the developmental taxonomic theory, however, empirical findings suggest that severe antisocial behaviour that emerges in adolescence frequently has a negative prognosis and is rarely limited to the adolescent period. In addition, both forms of antisocial behaviour are associated with emotion processing deficits, changes in brain structure and function, alterations in cortisol secretion, and atypical personality traits (such as increased callous-unemotional traits). CONCLUSIONS: We conclude that the developmental taxonomic theory is in need of revision, as differences between life-course persistent and adolescence-onset forms of antisocial behaviour appear to be quantitative, rather than qualitative, in nature. In addition, evidence is accumulating that adolescence-onset antisocial behaviour may also be a neurodevelopmental disorder. To account for the similarities between these groups, despite the differences in their age-of-onset, we propose that the quality of the child's early environment moderates the relationship between individual vulnerabilities and the age-of-onset of antisocial behaviour.

Brain structure abnormalities in adolescent girls with conduct disorder.

BACKGROUND: Conduct disorder (CD) in female adolescents is associated with a range of negative outcomes, including teenage pregnancy and antisocial personality disorder. Although recent studies have documented changes in brain structure and function in male adolescents with CD, there have been no neuroimaging studies of female adolescents with CD. Our primary objective was to investigate whether female adolescents with CD show changes in grey matter volume. Our secondary aim was to assess for sex differences in the relationship between CD and brain structure. METHODS: Female adolescents with CD (n = 22) and healthy control participants matched in age, performance IQ and handedness (n = 20) underwent structural magnetic resonance imaging. Group comparisons of grey matter volume were performed using voxel-based morphometry. We also tested for sex differences using archive data obtained from male CD and control participants. RESULTS: Female adolescents with CD showed reduced bilateral anterior insula and right striatal grey matter volumes compared with healthy controls. Aggressive CD symptoms were negatively correlated with right dorsolateral prefrontal cortex volume, whereas callous-unemotional traits were positively correlated with bilateral orbitofrontal cortex volume. The sex differences analyses revealed a main effect of diagnosis on right amygdala volume (reflecting reduced amygdala volume in the combined CD group relative to controls) and sex-by-diagnosis interactions in bilateral anterior insula. CONCLUSIONS: We observed structural abnormalities in brain regions involved in emotion processing, reward and empathy in female adolescents with CD, which broadly overlap with those reported in previous studies of CD in male adolescents.

Atypical activation during the Embedded Figures Task as a functional magnetic resonance imaging endophenotype of autism.

Atypical activation during the Embedded Figures Task has been demonstrated in autism, but has not been investigated in siblings or related to measures of clinical severity. We identified atypical activation during the Embedded Figures Task in participants with autism and unaffected siblings compared with control subjects in a number of temporal and frontal brain regions. Autism and sibling groups, however, did not differ in terms of activation during this task. This suggests that the pattern of atypical activation identified may represent a functional endophenotype of autism, related to familial risk for the condition shared between individuals with autism and their siblings. We also found that reduced activation in autism relative to control subjects in regions including associative visual and face processing areas was strongly correlated with the clinical severity of impairments in reciprocal social interaction. Behavioural performance was intact in autism and sibling groups. Results are discussed in terms of atypical information processing styles or of increased activation in temporal and frontal regions in autism and the broader phenotype. By separating the aspects of atypical activation as markers of familial risk for the condition from those that are autism-specific, our findings offer new insight into the factors that might cause the expression of autism in families, affecting some children but not others.

Social cognitive deficits and their neural correlates in progressive supranuclear palsy.

Although progressive supranuclear palsy is defined by its akinetic rigidity, vertical supranuclear gaze palsy and falls, cognitive impairments are an important determinant of patients' and carers' quality of life. Here, we investigate whether there is a broad deficit of modality-independent social cognition in progressive supranuclear palsy and explore the neural correlates for these. We recruited 23 patients with progressive supranuclear palsy (using clinical diagnostic criteria, nine with subsequent pathological confirmation) and 22 age- and education-matched controls. Participants performed an auditory (voice) emotion recognition test, and a visual and auditory theory of mind test. Twenty-two patients and 20 controls underwent structural magnetic resonance imaging to analyse neural correlates of social cognition deficits using voxel-based morphometry. Patients were impaired on the voice emotion recognition and theory of mind tests but not auditory and visual control conditions. Grey matter atrophy in patients correlated with both voice emotion recognition and theory of mind deficits in the right inferior frontal gyrus, a region associated with prosodic auditory emotion recognition. Theory of mind deficits also correlated with atrophy of the anterior rostral medial frontal cortex, a region associated with theory of mind in health. We conclude that patients with progressive supranuclear palsy have a multimodal deficit in social cognition. This deficit is due, in part, to progressive atrophy in a network of frontal cortical regions linked to the integration of socially relevant stimuli and interpretation of their social meaning. This impairment of social cognition is important to consider for those managing and caring for patients with progressive supranuclear palsy.

Direction-sensitive codes for observed head turns in human superior temporal sulcus.

Humans and other primates are adept at using the direction of another's gaze or head turn to infer where that individual is attending. Research in macaque neurophysiology suggests that anterior superior temporal sulcus (STS) contains a direction-sensitive code for such social attention cues. By contrast, most human functional Magnetic resonance imaging (fMRI) studies report that posterior STS is responsive to social attention cues. It is unclear whether this functional discrepancy is caused by a species difference or by experimental design differences. Furthermore, social attention cues are dynamic in naturalistic social interaction, but most studies to date have been restricted to static displays. In order to address these issues, we used multivariate pattern analysis of fMRI data to test whether response patterns in human right STS distinguish between leftward and rightward dynamic head turns. Such head turn discrimination was observed in right anterior STS/superior temporal gyrus (STG). Response patterns in this region were also significantly more discriminable for head turn direction than for rotation direction in physically matched ellipsoid control stimuli. Our findings suggest a role for right anterior STS/STG in coding the direction of motion in dynamic social attention cues.

Gaze categorization under uncertainty: psychophysics and modeling.

The accurate perception of another person's gaze direction underlies most social interactions and provides important information about his or her future intentions. As a first step to measuring gaze perception, most experiments determine the range of gaze directions that observers judge as being direct: the cone of direct gaze. This measurement has revealed the flexibility of observers' perception of gaze and provides a useful benchmark against which to test clinical populations with abnormal gaze behavior. Here, we manipulated effective signal strength by adding noise to the eyes of synthetic face stimuli or removing face information. We sought to move beyond a descriptive account of gaze categorization by fitting a model to the data that relies on changing the uncertainty associated with an estimate of gaze direction as a function of the signal strength. This model accounts for all the data and provides useful insight into the visual processes underlying normal gaze perception.

Changes in "top-down" connectivity underlie repetition suppression in the ventral visual pathway.

Repetition of the same stimulus leads to a reduction in neural activity known as repetition suppression (RS). In functional magnetic resonance imaging (fMRI), RS is found for multiple object categories. One proposal is that RS reflects locally based "within-region" changes, such as neural fatigue. Thus, if a given region shows RS across changes in stimulus size or view, then it is inferred to hold size- or view-invariant representations. An alternative hypothesis characterizes RS as a consequence of "top-down" between-region modulation. Differentiating between these accounts is central to the correct interpretation of fMRI RS data. It is also unknown whether the same mechanisms underlie RS to identical stimuli and RS across changes in stimulus size or view. Using fMRI, we investigated RS within a body-sensitive network in human visual cortex comprising the extrastriate body area (EBA) and the fusiform body area (FBA). Both regions showed RS to identical images of the same body that was unaffected by changes in body size or view. Dynamic causal modeling demonstrated that changes in backward, top-down (FBA-to-EBA) effective connectivity play a critical role in RS. Furthermore, only repetition of the identical image showed additional changes in forward connectivity (EBA-to-FBA). These results suggest that RS is driven by changes in top-down modulation, whereas the contribution of "feedforward" changes in connectivity is dependent on the precise nature of the repetition. Our results challenge previous interpretations regarding the underlying nature of neural representations made using fMRI RS paradigms.

Autism spectrum traits predict the neural response to eye gaze in typical individuals.

Autism Spectrum Disorders (ASD) are neurodevelopmental disorders characterised by impaired social interaction and communication, restricted interests and repetitive behaviours. The severity of these characteristics are posited to lie on a continuum extending into the typical population, and typical adults' performance on behavioural tasks that are impaired in ASD is correlated with the extent to which they display autistic traits (as measured by Autism Spectrum Quotient, AQ). Individuals with ASD also show structural and functional differences in brain regions involved in social perception. Here we show that variation in AQ in typically developing individuals is associated with altered brain activity in the neural circuit for social attention perception while viewing others' eye gaze. In an fMRI experiment, participants viewed faces looking at variable or constant directions. In control conditions, only the eye region was presented or the heads were shown with eyes closed but oriented at variable or constant directions. The response to faces with variable vs. constant eye gaze direction was associated with AQ scores in a number of regions (posterior superior temporal sulcus, intraparietal sulcus, temporoparietal junction, amygdala, and MT/V5) of the brain network for social attention perception. No such effect was observed for heads with eyes closed or when only the eyes were presented. The results demonstrate a relationship between neurophysiology and autism spectrum traits in the typical (non-ASD) population and suggest that changes in the functioning of the neural circuit for social attention perception is associated with an extended autism spectrum in the typical population.

5-HTTLPR-environment interplay and its effects on neural reactivity in adolescents.

It is not known how 5-HTTLPR genotype x childhood adversity (CA) interactions that are associated with an increased risk for affective disorders in population studies operate at the neural systems level. We hypothesized that healthy adolescents at increased genetic and environmental risk for developing mood disorders (depression and anxiety) would demonstrate increased amygdala reactivity to emotional stimuli compared to those with only one such risk factor or those with none. Participants (n=67) were classified into one of 4 groups dependent on being homozygous for the long or short alleles within the serotonin-transporter-linked polymorphic region (5-HTTLPR) of the SLC6A4 gene and exposure to CA in the first 11 years of life (present or absent). A functional magnetic resonance imaging investigation was undertaken which involved viewing emotionally-salient face stimuli. In addition, we assessed the role of other variables hypothesized to influence amygdala reactivity, namely recent negative life-events (RNLE) assessed at ages 14 and 17, current anxiety symptoms and psychiatric history. We replicated prior findings demonstrating moderation by gene variants in 5-HTTLPR, but found no support for an effect of CA on amygdala reactivity. We also found a significant effect of RNLE aged 17 with amygdala reactivity demonstrating additive, but not interactive effects with 5-HTTLPR. A whole-brain analysis found a 5-HTTLPR×CA interaction in the lingual gyrus whereby CA appears to differentially modify neural reactivity depending on genotype. These results demonstrate that two different forms of environmental adversities interplay with 5-HTTLPR and thereby differentially impact amygdala and cortical reactivity.