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Structural brain differences in Autism Spectrum Disorder

Autism spectrum disorders (ASDs) are neurodevelopmental disorders defined by psychological and behavioural symptoms. These include restricted and repetitive behaviours (RRBs) that are abnormal in focus, impaired or underdeveloped non-verbal social communication skills and hyper/hypo-reactivity to sensory input. The term ‘autism spectrum disorder’ is an umbrella label used to refer to the three subtypes of autism defined in the Diagnostic Statistical Manual 5 (DSM-V), released in May 2013. An alternative label preferred by some is ‘autism spectrum condition’ (ASC), as to avoid the negative connotations of the term ‘disorder’. While the DSM-V classifies autism spectrum disorder into three subtypes, there is debate as to how reliable the subtypes are as a diagnostic tool when compared to previous classifications such as Asperger syndrome and pervasive developmental disorder-not otherwise specified (PDD-NOS). Reviews into the classification of ASD in the DSM-V suggest that the use of an intelligence quotient may be a valid marker to distinguish between the subtypes of ASD. Other suggestions to help improve the classification of ASD in the DSM-V include changes to symptom domains, as studies have suggested that differences in abnormal sensory processing is a distinguishing symptom of ASD. More recently, the International Criteria for Disease, Version 11 (ICD-11), released in May, 2021 classifies autism spectrum disorder into 4 subtypes defined by intellectual and functional language development.

there is no evidence that the structural and functional organisation of the brain in ASD is fundamentally different, there is evidence suggesting that the timing of critical periods and rate of neurodevelopment is different to that of the neurotypical population. astrocytes and microglia have reported to have been found in higher numbers in the cerebral cortexin ASD, this seems to be related to accelerated brain growth during neurodevelopment. Research showing how initial observations of ASD symptoms tends to be of failure to meet milestones in social communication and language development supports this, and provides insight into how ASD severity is related to key stages of development. One perspective on the neuroanatomy in ASD is that as the cerebral cortex is increased in volume and less organised, interconnectivity between regions is less efficient and therefore less integrated when compared to neurotypical organisation, however there is contrasting evidence as to the interconnectivity in ASD, for example an alternative perspective on the neuroanatomy in ASD is that cortex enlargement and reduced white matter, nerve tissue responsible for cortical interconnectivity in the brain, is the structural basis for the classical symptoms of ASD Despite contrasting views, what seems to be understood is that complex changes across the whole brain and regional areas span across the lifetime in ASD, and that these changes are dynamic and contribute to abnormal development across multiple domains. Just as autism is on a spectrum, so are the associated differences in brain connectivity and volume.

Neurodevelopment in ASD

While there is a high degree of variability in the symptomology, severity and biological differences in ASD, there is evidence that differences in neuroanatomical development are highly linked to ASD. For example one mainstream hypothesis is that autistic brains experience an early onset of brain growth, leading to enlarged brain volume in youth, then followed by a decrease in growth rate, and that this is true for temporal, parietal and especially frontal lobes of the brain. The contrasting evidence for the link between brain size and ASD in current research seems to be due to high variability in age groups across studies, as noted in a meta analysis by Redcay and Courchesne (2005). However it was also found that accelerated brain growth, leading to observed brain enlargement when compared to neurotypical development seems to be limited to the first two to four years of life in children with ASD, supporting the idea that critical periods of neurodevelopment are affected in their rates and timings.

Established differences of brain structure in ASD

Specific brain regions appear to be affected by ASD both in connectivity and volume. These findings are implicated in the symptomology of ASD, for example intellectual impairment in ASD is correlated with the depth of the intraparietal sulcus, a brain region located on the lateral surface of the parietal lobe involved in diverse social and cognitive processes such as mentalizing.

A number of structures in the brain have been found to be increased in ASD, these include the cerebral hemispheres, the cerebellum, located underneath the brain and behind the brainstem, which coordinates the precision and accuracy of movement, and caudate nucleus, a pair of brain regions located underneath the cortex with the thalamus that functions to relay sensorimotor information to the cerebral cortex. These findings may implicated the sensory processing abnormalities associated with ASD, such as hyper/hypo sensation of stimuli as well as self-stimulatory motor behaviours characteristic of ASD colloquially known as stimming, such as rocking or hand flapping.

Notably, neuroanatomical differences in the limbic system associated with a diagnosis of ASD have been documented. In an annual review by Chen et al (2015) white matter neurons in the limbic system were found to be smaller and more densely packed, suggesting abnormal interconnectivity. This finding has been linked to the symptom of underdeveloped social skills in ASD due to the limbic system’s roles in emotion regulation and memory.

One section of the limbic system, the amygdalae which are a pair of brain regions implicated in memory, decision making and emotional responses show abnormal patterns of growth during development. The amygdala is initially larger in volume than average in ASD, but growth does not follow the typical pattern associated with age. Additionally the hippocampus, another brain region that is a part of the limbic system which functions for spatial memory seems to follow an abnormal pattern of growth throughout adolescence and adulthood. Increased hippocampus volume in adults with high-functioning autism has been reliably found, which is notably theorised to be as a result of a more intense ‘experiencing’ of the world. It is relevant to consider this in tandem with the symptom of autism of hyper/hypo-reactivity to sensory input.