New research using brain imaging technology has shed light on why children with autism spectrum disorder (ASD) can differ so dramatically in their abilities and daily functioning, with scientists identifying distinct patterns of brain activity that set high-functioning and low-functioning autism apart.
The study, published in BMC Psychiatry, examined 72 children aged two to four years, comparing those with high-functioning ASD (HF-ASD), low-functioning ASD (LF-ASD), and typically developing children. Researchers used resting-state functional magnetic resonance imaging (fMRI) to analyse spontaneous brain activity without requiring participants to perform any tasks, making it particularly suited to very young children.
Scientists measured two complementary indicators of brain function: regional homogeneity (ReHo), which reflects how synchronised neighbouring brain regions are, and fractional amplitude of low-frequency fluctuations (fALFF), which captures the intensity of spontaneous neural activity. Using both measures together gave a richer and more detailed picture of how the autistic brain differs depending on a child’s level of functioning.
Children with low-functioning autism showed significantly reduced activity in the temporal regions of the brain and in an area called the fusiform gyrus, which plays a key role in face recognition and social perception. This widespread reduction in activity in regions critical to social cognition may help explain the more severe communication difficulties and adaptive impairments seen in children with LF-ASD. The absence of any compensatory brain activity elsewhere suggests a broader disruption to the neural networks that typically support social and cognitive development.
By contrast, children with high-functioning autism displayed increased activity in the prefrontal cortex, particularly in the dorsolateral superior frontal gyrus and the orbital part of the inferior frontal gyrus. Researchers interpret this as evidence of a compensatory mechanism, whereby the brain recruits additional resources in the prefrontal region to support cognitive control and social processing despite underlying disruptions elsewhere. This pattern of prefrontal overactivation was not seen in the low-functioning group, pointing to a qualitatively different neural profile rather than simply a milder version of the same condition.
The diagnostic potential of these findings is notable. When the two brain measures were combined, the resulting model distinguished low-functioning autism from typically developing children with 99% accuracy, and was also able to differentiate high-functioning from low-functioning autism with a high degree of reliability.
The study also found that activity in the temporal lobes correlated with adaptive behaviour scores, meaning children whose brain activity in these regions was closer to typical levels tended to show better day-to-day functioning. This link between brain biology and real-world ability is clinically significant, as it suggests these imaging markers could one day inform personalised treatment and rehabilitation approaches for different subtypes of autism.
The researchers acknowledge limitations including a small sample size, a predominantly male cohort, and the narrow age range studied. Larger, more diverse studies will be needed to confirm and extend these findings.

