2 Research Highlights• We present a new hypothesis of the underlying cause of autistic spectrum disorders (ASD) that explains the lack of some observed differences from typical development in early infancy and heterogeneity in the timing of manifestation of the disorder• The over--pruning hypothesis proposes that ASD results from over--pruning of brain connectivity early in development, particularly impacting long--range connections; we review evidence relating to the hypothesis from behavioural, brain, genetic, and intervention studies• We present a neurocomputational model instantiating the over--pruning hypothesis, extending the work of Thomas, Knowland & Karmiloff--Smith (2011) to demonstrate: (1) that the three main sub--types of ASD (early onset, late onset, regressive) can be produced by a single pathological mechanism interacting with population--wide individual differences in neurocomputational properties; and (2) unaffected siblings of individuals with ASD may differ from controls either by inheriting a milder version of the pathological mechanism or by inheriting the risk factors without the pathological mechanism.• The over--pruning hypothesis generates several novel predictions, including that the first few months of development in ASD will be indistinguishable from typical, and that the earliest atypicalities will be sensory and motor rather than social; both predictions gain cautious support from emerging longitudinal studies of infants at risk of ASD 3 AbstractThis article outlines the over-pruning hypothesis of autism. The hypothesis originates in a neurocomputational model of the regressive sub--type (Thomas, Knowland & Karmiloff--Smith, 2011a,b). Here we develop a more general version of the over--pruning hypothesis to address heterogeneity in the timing of manifestation of ASD, including new computer simulations which can reconcile the different observed developmental trajectories (early onset, late onset, regression) via a single underlying atypical mechanism; and which show how unaffected siblings of individuals with ASD may differ from controls either by inheriting a milder version of the pathological mechanism or by co--inheriting the risk factors without the pathological mechanism. The proposed atypical mechanism involves overly aggressive synaptic pruning in infancy and early childhood, an exaggeration of a normal phase of brain development. We show how the hypothesis generates novel predictions that differ from existing theories, including that (1) the first few months of development in ASD will be indistinguishable from typical, and (2) the earliest atypicalities in ASD will be sensory and motor rather than social. Both predictions gain cautious support from emerging longitudinal studies of infants at risk of ASD. We review evidence consistent with the over--pruning hypothesis, its relation to other current theories (including C. Frith's under--pruning proposal; C. Frith, 2003Frith, , 2004, as well as inconsistent data and current limitations. The hypothesis situates causal accou...

Deficit-based accounts of social and communication abilities continue to dominate autism research. However, emerging findings suggest that this view may be overly simplistic and discount the two-way nature of interaction. Here we discuss the reconceptualization of social cognition to consider such difficulties as examples of bidirectional, multifaceted misattunement between autistic and nonautistic individuals. Aligned with progressive theoretical frameworks, emerging empirical research indicates that mismatches in communication styles can contribute to autistic social difficulties and the important role that nonautistic difficulties play. We highlight two areas of future research with the aim of providing empirical support for the views that the autistic community has proposed over the past 2 decades. We discuss the impact of such a paradigm shift on a number of levels, including how bridging the gap between different interaction styles can reduce stigma and increase understanding. Adopting such a framework will provide radical opportunities for transformative societal changes and education around inclusion.

A robust left side cradling bias (LCB) in humans is argued to reflect an evolutionarily old left visual field bias and right hemisphere dominance for processing social stimuli. A left visual field bias for face processing, invoked via the LCB, is known to reflect a human population-level right cerebral hemisphere specialization for processing social stimuli. We explored the relationship between cradling side biases, hand dominance and socio-communicative abilities. Four and five year old typically-developing children (N = 98) participated in a battery of manual motor tasks interspersed by cradling trials comprising a(n): infant human doll, infant primate doll, proto-face pillow and no-face pillow. Mean social and communication ability scores were obtained via a survey completed by each child's key teacher. We found a population-level LCB for holding an infant human doll that was not influenced by hand dominance, sex, age or experience of having a younger sibling. Children demonstrating a LCB, did however, obtain a significantly higher mean social ability score compared with their right side cradling counterparts. Like the infant human doll, the proto-face pillow's schematic face symbol was sufficient to elicit a population-level LCB. By contrast, the infant primate doll elicited a population-level right side cradling bias, influenced by both hand dominance and sex. The findings suggest that the LCB is present and visible early in development and is likely therefore, to represent evolutionarily old domain-specific organization and function of the right cerebral hemisphere. Additionally, results suggest that a LCB requires minimal triggering but can be reversed in some situations, possibly in response to species-type or levels of novelty or stress as perceived by the viewer. Patterns of behavioral biases within the context of social stimuli and their associations with cognitive ability are important for understanding how socio-communication abilities emerge in developing children.

Cerebral lateralisation of function is a common characteristic across vertebrate species and is positively associated with fitness of the organism, in humans we hypothesise that it is associated with cognitive fitness. This investigation evaluated the early development of lateralised gaze behaviour for face stimuli in infants at high and low risk for autism from the British Autism Sibling Infant Study (BASIS). The BASIS cohort includes a low risk group and three high-risk groups who at age 3 were developing (i) typically, (ii) atypically or (iii) had received a diagnosis for ASD. Using eye-tracking data derived from a face pop-out task at 6 and 14 months of age, all non-ASD groups showed a bias for stimuli on the left at both timepoints. At 6 months the ASD group demonstrated a preference for stimuli on the right and were slower than their neurotypical counterparts to look at faces on the left. However, by 14 months these differences disappear. Longitudinal associations between lateral looking behaviour at 6 months and language and motor ability at 14 months were also found. Results suggest that infants who go on to be diagnosed with autism exhibit early differences in gaze behaviour that may be associated with subsequent cognitive outcomes.

Evolution has endowed vertebrates with a divided brain that allows for processing of critical survival behaviours in parallel. Most humans possess a standard functional brain organisation for these ancient sensory-motor behaviours, favouring the right hemisphere for fight-or-flight processes and the left hemisphere for performing structured motor sequences. However, a significant minority of the population possess an organisational phenotype that represents crowding of function in one hemisphere, or a reversal of the standard functional organisation. Using behavioural biases as a proxy for brain organisation, results indicate that reversed brain organisation phenotype increases in populations with autism and is associated with weaker cognitive abilities. Moreover, this study revealed that left-handedness, alone, is not associated with decreased cognitive ability or autism. Rather, left-handedness acts as a marker for decreased cognitive performance when paired with the reversed brain phenotype. The results contribute to comparative research suggesting that modern human abilities are supported by evolutionarily old, lateralised sensory-motor processes. Systematic, longitudinal investigations, capturing genetic measures and brain correlates, are essential to reveal how cognition emerges from these foundational processes. Importantly, strength and direction of biases can act as early markers of brain organisation and cognitive development, leading to promising, novel practices for diagnoses and interventions.