Large-scale neuroimaging study finds no evidence of atypical amygdala connectivity in autism

A neuroimaging study of over 200 individuals with autism found no evidence of atypical functional connectivity in the amygdala, a brain region critical for processing emotions, particularly fear, and for threat detection. The paper was published in the American Journal of Psychiatry.

Autism, or autism spectrum disorder, is a neurodevelopmental condition characterized by challenges in social interaction, communication, and repetitive behaviors. The symptoms and severity of autism vary widely, which is why it is considered a spectrum disorder. Individuals with autism often have difficulty understanding social cues, forming relationships, and adapting to changes in routine.

Despite extensive research, the causes and neural basis of autism remain poorly understood. One long-standing and popular hypothesis suggests that individuals with autism exhibit reduced functional connectivity between various brain regions. Another hypothesis posits that autistic individuals have an atypical amygdala structure. Some researchers also suggest that structural brain atypicalities may depend on the autism subtype and vary between individuals. However, tests of these hypotheses have produced inconsistent findings so far.

Study author Dorit Kliemann and her colleagues sought to test these hypotheses comprehensively using a large sample of individuals with autism. They conducted a neuroimaging study examining functional connectivity between multiple pairs of brain regions using functional magnetic resonance imaging (fMRI). Functional connectivity refers to the temporal correlation of neural activity across different brain areas, indicating how they communicate and work together during various cognitive and behavioral processes.

The researchers analyzed data from the Autism Brain Imaging Data Exchange (ABIDE) datasets, publicly available collections of neuroimaging data from individuals with and without autism. ABIDE aims to advance research on the neural basis of autism through large-scale, multi-site collaborations. The study included data from 488 individuals between 16 and 50 years of age, of whom 212 had autism.

The results showed no evidence of reduced functional connectivity in individuals with autism. Although certain analytic approaches pointed to some regions with slightly lower functional connectivity, these findings varied depending on the analytic method used and were not consistent.

Similarly, analyses did not reveal any atypical connectivity patterns in the amygdala of individuals with autism. The individual differences in functional connectivity of the amygdala among participants with autism were no greater than those found in neurotypical participants.

Overall, the study did not find any consistent differences in amygdala functional connectivity between individuals with autism and neurotypical participants.

“A preregistered set of analyses found no reliable evidence for atypical functional connectivity of the amygdala in autism, contrary to leading hypotheses. Future studies should test an expanded set of hypotheses across multiple processing pipelines, collect deeper data per individual, and include a greater diversity of participants to ensure robust generalizability of findings on amygdala FC [functional connectivity] in ASD [autism spectrum disorder],” the study authors concluded.

The study contributes to the scientific understanding of the neural basis of autism. However, the analysis was based on resting-state functional connectivity data, meaning it examined brain activity while participants were at rest—that is, not engaged in any specific tasks. It is possible that the brains of individuals with and without autism function similarly in a resting state but exhibit differences when engaged in specific activities, particularly those that highlight the distinctions between autistic and neurotypical individuals.

The paper, “Resting-State Functional Connectivity of the Amygdala in Autism: A Preregistered Large-Scale Study,” was authored by Dorit Kliemann, Paola Galdi, Avery L. Van De Water, Brandon Egger, Dorota Jarecka, Ralph Adolphs, and Satrajit S. Ghosh.