Annual Research Review: Looking back to look forward - changes in the concept of autism and implications for future research.

The concept of autism is a significant contribution from child psychiatry that has entered wider culture and public consciousness, and has evolved significantly over the last four decades. Taking a rather personal retrospective, reflecting on our own time in autism research, this review explores changes in the concept of autism and the implications of these for future research. We focus on seven major changes in how autism is thought of, operationalised, and recognised: (1) from a narrow definition to wide diagnostic criteria; (2) from a rare to a relatively common condition, although probably still under-recognised in women; (3) from something affecting children, to a lifelong condition; (4) from something discreet and distinct, to a dimensional view; (5) from one thing to many 'autisms', and a compound or 'fractionable' condition; (6) from a focus on 'pure' autism, to recognition that complexity and comorbidity is the norm; and finally, (7) from conceptualising autism purely as a 'developmental disorder', to recognising a neurodiversity perspective, operationalised in participatory research models. We conclude with some challenges for the field and suggestions for areas currently neglected in autism research.

Selective disruption of sociocognitive structural brain networks in autism and alexithymia.

Autism spectrum conditions (ASC) are neurodevelopmental disorders characterized by abnormal social cognition. A core feature of ASC is disrupted Theory of Mind (ToM), our ability to take the mental perspective of others. ASC is also associated with alexithymia, a trait characterized by altered emotional interoception and empathy. Here, we applied structural MRI covariance analysis to assess whether ASC and alexithymia differentially affect structural brain networks associated with sociocognitive and socioaffective functions. Based on previous functional MRI findings, we expected disrupted ToM networks (centered on dorsomedial prefontal cortex [dmPFC], and temporo-parietal junction [TPJ]) in ASC, while alexithymia would affect networks centered on fronto-insular cortex (FI), regions associated with interoception of emotion and empathy. Relative to controls, ASC indeed showed reduced covariance in networks centered on dmPFC and TPJ, but not within FI networks. Irrespective of ASC, covariance was negatively modulated by alexithymia in networks extending from FI to posterior regions. Network findings were complemented by self-reports, indicating decreased perspective taking but normal empathic concern in ASC. Our results show divergent effects of ASC and alexithymia on inter-regional structural networks, suggesting that networks mediating socioaffective processes may be separable from networks mediating sociocognitive processing.

Annual research review: Towards a developmental neuroscience of atypical social cognition.

As a starting point for our review we use a developmental timeline, starting from birth and divided into major developmental epochs defined by key milestones of social cognition in typical development. For each epoch, we highlight those developmental disorders that diverge from the normal developmental pattern, what is known about these key milestones in the major disorders affecting social cognition, and any available research on the neural basis of these differences. We relate behavioural observations to four major networks of the social brain, that is, Amygdala, Mentalizing, Emotion and Mirror networks. We focus on those developmental disorders that are characterized primarily by social atypicality, such as autism spectrum disorder, social anxiety and a variety of genetically defined syndromes. The processes and aspects of social cognition we highlight are sketched in a putative network diagram, and include: agent identification, emotion processing and empathy, mental state attribution, self-processing and social hierarchy mapping involving social 'policing' and in-group/out-group categorization. Developmental disorders reveal some dissociable deficits in different components of this map of social cognition. This broad review across disorders, ages and aspects of social cognition leads us to some key questions: How can we best distinguish primary from secondary social disorders? Is social cognition especially vulnerable to developmental disorder, or surprisingly robust? Are cascading notions of social development, in which early functions are essential stepping stones or building bricks for later abilities, necessarily correct?

Mechanisms of social cognition.

Social animals including humans share a range of social mechanisms that are automatic and implicit and enable learning by observation. Learning from others includes imitation of actions and mirroring of emotions. Learning about others, such as their group membership and reputation, is crucial for social interactions that depend on trust. For accurate prediction of others' changeable dispositions, mentalizing is required, i.e., tracking of intentions, desires, and beliefs. Implicit mentalizing is present in infants less than one year old as well as in some nonhuman species. Explicit mentalizing is a meta-cognitive process and enhances the ability to learn about the world through self-monitoring and reflection, and may be uniquely human. Meta-cognitive processes can also exert control over automatic behavior, for instance, when short-term gains oppose long-term aims or when selfish and prosocial interests collide. We suggest that they also underlie the ability to explicitly share experiences with other agents, as in reflective discussion and teaching. These are key in increasing the accuracy of the models of the world that we construct.

The self and its reputation in autism.

In this issue of Neuron, a study by Chiu et al. examines the brain responses of autistic volunteers in a trust game. The findings reveal an unusual lack of brain activity in mid cingulate cortex when they make their investments. We speculate that this may arise because autistic individuals are unaware that they will also gain or lose reputation in their partner's eyes.

The mystery of the brain-culture interface.

Nature and culture work together to shape who we are. We are embedded in culture and are profoundly influenced by what those around us say and do. The interface between minds occurs at the level of explicit metacognition, which is at the top of our brain's control hierarchy. But how do our brains do this?

Empathic brain responses in insula are modulated by levels of alexithymia but not autism.

Difficulties in social cognition are well recognized in individuals with autism spectrum conditions (henceforth 'autism'). Here we focus on one crucial aspect of social cognition: the ability to empathize with the feelings of another. In contrast to theory of mind, a capacity that has often been observed to be impaired in individuals with autism, much less is known about the capacity of individuals with autism for affect sharing. Based on previous data suggesting that empathy deficits in autism are a function of interoceptive deficits related to alexithymia, we aimed to investigate empathic brain responses in autistic and control participants with high and low degrees of alexithymia. Using functional magnetic resonance imaging, we measured empathic brain responses with an 'empathy for pain' paradigm assessing empathic brain responses in a real-life social setting that does not rely on attention to, or recognition of, facial affect cues. Confirming previous findings, empathic brain responses to the suffering of others were associated with increased activation in left anterior insula and the strength of this signal was predictive of the degree of alexithymia in both autistic and control groups but did not vary as a function of group. Importantly, there was no difference in the degree of empathy between autistic and control groups after accounting for alexithymia. These findings suggest that empathy deficits observed in autism may be due to the large comorbidity between alexithymic traits and autism, rather than representing a necessary feature of the social impairments in autism.

Knowing me, knowing you: Spontaneous use of mentalistic language for self and other in autism.

LAY ABSTRACT: Autistic people can have difficulties in understanding non-autistic people's mental states such as beliefs, emotions and intentions. Although autistic adults may learn to overcome difficulties in understanding of explicit (overt) mental states, they may nevertheless struggle with implicit (indirect) understanding of mental states. This study explores how spontaneous language is used in order to specifically point to this implicit (indirect) understanding of mental states. In particular, our study compares the spontaneous statements that were used in descriptions of oneself and a familiar other person. Here, we found that autistic and non-autistic adults were comparable in the number of statements about physical traits they made. In contrast, non-autistic adults made more statements about mentalistic traits (about the mental including psychological traits, relationship traits and statements reflecting about these) both for the self and the other. Non-autistic and autistic adults showed no difference in the number of statements about relationships but in the number of statements about psychological traits and especially in the statements reflecting on these. Each group showed a similar pattern of kinds of statements for the self and for the other person. This suggests that autistic individuals show the same unique pattern of description in mentalistic terms for the self and another person. This study also indicates that investigating spontaneous use of language, especially for statements reflecting about mental states, enables us to look into difficulties with implicit (indirect) understanding of mental states.

The neural basis of mentalizing.

Mentalizing refers to our ability to read the mental states of other agents and engages many neural processes. The brain's mirror system allows us to share the emotions of others. Through perspective taking, we can infer what a person currently believes about the world given their point of view. Finally, the human brain has the unique ability to represent the mental states of the self and the other and the relationship between these mental states, making possible the communication of ideas.

Social cognition in humans.

We review a diversity of studies of human social interaction and highlight the importance of social signals. We also discuss recent findings from social cognitive neuroscience that explore the brain basis of the capacity for processing social signals. These signals enable us to learn about the world from others, to learn about other people, and to create a shared social world. Social signals can be processed automatically by the receiver and may be unconsciously emitted by the sender. These signals are non-verbal and are responsible for social learning in the first year of life. Social signals can also be processed consciously and this allows automatic processing to be modulated and overruled. Evidence for this higher-level social processing is abundant from about 18 months of age in humans, while evidence is sparse for non-human animals. We suggest that deliberate social signalling requires reflective awareness of ourselves and awareness of the effect of the signals on others. Similarly, the appropriate reception of such signals depends on the ability to take another person's point of view. This ability is critical to reputation management, as this depends on monitoring how our own actions are perceived by others. We speculate that the development of these high level social signalling systems goes hand in hand with the development of consciousness.

Fast Lane to Slow Science.

Fast Science is bad for scientists and bad for science. Slow Science may actually help us to make faster progress, but how can we slow down? Here, I offer preliminary suggestions for how we can transition to a healthier and more sustainable research culture.

Vagaries of visual perception in autism.

Three classes of perceptual phenomena have repeatedly been associated with autism spectrum disorder (ASD): superior processing of fine detail (local structure), either inferior processing of overall/global structure or an ability to ignore disruptive global/contextual information, and impaired motion perception. This review evaluates the quality of the evidence bearing on these three phenomena. We argue that while superior local processing has been robustly demonstrated, conclusions about global processing cannot be definitively drawn from the experiments to date, which have generally not precluded observers using more local cues. Perception of moving stimuli is impaired in ASD, but explanations in terms of magnocellular/dorsal deficits do not appear to be sufficient. We suggest that abnormalities in the superior temporal sulcus (STS) may provide a neural basis for the range of motion-processing deficits observed in ASD, including biological motion perception. Such an explanation may also provide a link between perceptual abnormalities and specific deficits in social cognition associated with autism.

Big heads, small details and autism.

Autism is thought to be associated with a bias towards detail-focussed processing. While the cognitive basis remains controversial, one strong hypothesis is that there are high processing costs associated with changing from local into global processing. A possible neural mechanism underlying this processing style is abnormal neural connectivity; specifically reduced structural or functional connectivity between brain regions might lead to good exemplar-based processing but poor generalisation. Abnormal neural connectivity has also been suggested to account for the increased incidence of macrocephaly in autism (increased head/brain size). The present study therefore investigated the effect of head size on the ability to switch between global and local processing in autism. 49 high-functioning 7-12 year olds with autism (12 with macrocephaly) were compared to 25 normally developing children in their performance on a Local-Global Switching task. Those children with autism who also had macrocephaly showed a greater processing cost when switching into global processing, or 'zooming out', than both the remaining children with autism and the control children. A second experiment revealed that macrocephaly in the context of normal development is not associated with difficulty switching into global processing but rather occurs in children who are physically large. Macrocephaly in the context of autism may therefore be a biological marker of abnormal neural connectivity, and of a local processing bias.

Revisiting the strange stories: revealing mentalizing impairments in autism.

A test of advanced theory of mind (ToM), first introduced by F. Happé (1994), was adapted for children (mental, human, animal, and nature stories plus unlinked sentences). These materials were closely matched for difficulty and were presented to forty-five 7- to 12-year-olds with autism and 27 control children. Children with autism who showed ToM impairment on independent tests performed significantly more poorly than controls solely on the mental, human, and animal stories with greatest impairment on the former and least on the latter. Thus, a mentalizing deficit may affect understanding of biologic agents even when this does not explicitly require understanding others' mental states.

Flux of life.

Developmental cognitive neuroscience is flourishing but there are new challenges and new questions to be asked. I argue that we need a bigger picture and an evolutionary framework. This brings some challenges, such as the need to rewrite the old story of nature and nurture, and the need to systematically investigate innate predispositions. While brain imaging has provided some splendid insights and new puzzles to solve, its limitations must not be ignored. Can they help us to find out more about the extent to which the infant brain already configures the adult brain? Can we find out why neurodevelopmental disorders often have severe consequences on cognition and behaviour, despite the mitigating force of brain plasticity? I wish to encourage researchers of the future to take risks by letting their imagination inspire theories to pursue hard questions. I end with a wish list of topics, from start-up kits to abstract reasoning, that I hope can be tackled afresh. However, collecting physiological and behavioural data is not enough. We need a deeper understanding of the mechanisms of cognitive development.

Your own action influences how you perceive another person's action.

A growing body of neuroimaging and neurophysiology studies has demonstrated the motor system's involvement in the observation of actions, but the functional significance of this is still unclear. One hypothesis suggests that the motor system decodes observed actions. This hypothesis predicts that performing a concurrent action should influence the perception of an observed action. We tested this prediction by asking subjects to judge the weight of a box lifted by an actor while the subject either lifted or passively held a light or heavy box. We found that actively lifting a box altered the perceptual judgment; an observed box was judged to be heavier when subjects were lifting the light box, and it was judged to be lighter when they were lifting the heavy box. This result is surprising because previous studies have found facilitating effects of movement on perceptual judgments and facilitating effects of observed actions on movements, but here we found the opposite. We hypothesize that this effect can be understood in terms of overlapping neural systems for motor control and action-understanding if multiple models of possible observed and performed actions are processed.

Imitation and action understanding in autistic spectrum disorders: how valid is the hypothesis of a deficit in the mirror neuron system?

The motor mirror neuron system supports imitation and goal understanding in typical adults. Recently, it has been proposed that a deficit in this mirror neuron system might contribute to poor imitation performance in children with autistic spectrum disorders (ASD) and might be a cause of poor social abilities in these children. We aimed to test this hypothesis by examining the performance of 25 children with ASD and 31 typical children of the same verbal mental age on four action representation tasks and a theory of mind battery. Both typical and autistic children had the same tendency to imitate an adult's goals, to imitate in a mirror fashion and to imitate grasps in a motor planning task. Children with ASD showed superior performance on a gesture recognition task. These imitation and gesture recognition tasks all rely on the mirror neuron system in typical adults, but performance was not impaired in children with ASD. In contrast, the ASD group were impaired on the theory of mind tasks. These results provide clear evidence against a general imitation impairment and a global mirror neuron system deficit in children with autism. We suggest this data can best be understood in terms of multiple brain systems for different types of imitation and action understanding, and that the ability to understand and imitate the goals of hand actions is intact in children with ASD.

How we predict what other people are going to do.

We present a framework for discussing two major aspects of social cognition: the ability to predict what another person is like and what another person is likely to do next. In the first part of this review, we discuss studies that concern knowledge of others as members of a group and as individuals with habitual dispositions. These include studies of group stereotypes and of individual reputation, derived either from experience in reciprocal social interactions such as economic games or from indirect observation and cultural information. In the second part of the review, we focus on processes that underlie our knowledge about actions, intentions, feelings and beliefs. We discuss studies on the ability to predict the course of motor actions and of the intentions behind actions. We also consider studies of contagion and sharing of feelings. Lastly, we discuss studies of spatial and mental perspective taking and the importance of the perception of communicative intent. In the final section of this review, we suggest that the distinction between top-down and bottom-up processes, originally applied to non-social cognitive functions, is highly relevant to social processes. While social stimuli automatically elicit responses via bottom-up processes, responses to the same stimuli can be modulated by explicit instructions via top-down processes. In this way, they provide an escape from the tyranny of strong emotions that are readily aroused in social interactions.