A revisit of the amygdala theory of autism: Twenty years after

The human amygdala has long been implicated to play a key role in autism spectrum disorder (ASD). Yet it remains unclear to what extent the amygdala accounts for the social dysfunctions in ASD. Here, we review studies that investigate the relationship between amygdala function and ASD. We focus on studies that employ the same task and stimuli to directly compare people with ASD and patients with focal amygdala lesions, and we also discuss functional data associated with these studies. We show that the amygdala can only account for a limited number of deficits in ASD (primarily face perception tasks but not social attention tasks), a network view is, therefore, more appropriate. We next discuss atypical brain connectivity in ASD, factors that can explain such atypical brain connectivity, and novel tools to analyze brain connectivity. Lastly, we discuss new opportunities from multimodal neuroimaging with data fusion and human single-neuron recordings that can enable us to better understand the neural underpinnings of social dysfunctions in ASD. Together, the influential amygdala theory of autism should be extended with emerging data-driven scientific discoveries such as machine learning-based surrogate models to a broader framework that considers brain connectivity at the global scale.