Atypical development of subcortico-cortical effective connectivity in autism

Hypersensitivity, stereotyped behaviors and attentional problems in autism spectrum disorder (ASD) are compatible with inefficient filtering of undesired or irrelevant sensory information at early stages of neural processing. This could stem from delays in the neurotypical development of the functional segregation between cortical and subcortical brain processes, as suggested by previous findings of overconnectivity between primary sensory regions and deep brain nuclei in ASD. To test this hypothesis, we used dynamic causal modelling to quantify the effect of age on the development of (1) cortical functional segregation from subcortical activity and (2) directional influence of subcortical activity on cortical processing in 166 participants with ASD and 193 typically developing controls (TD) from the Autism Brain Imaging Data Exchange (ABIDE). We found that in TD participants age was significantly associated with increased functional segregation of cortical sensory processing from subcortical activity, paralleled by a decreased influence of subcortical activity on cortical processing. Instead these effects were highly reduced and mostly absent in ASD participants, suggesting a delayed or arrested development of the segregation between subcortical and cortical sensory processing in ASD. This atypical configuration of subcortico-cortical connectivity in ASD can result in an excessive amount of unprocessed sensory information relayed to the cortex, which is likely to impact cognitive functioning in everyday situations where it is beneficial to limit the influence of basic sensory information on cognitive processing, such as activities requiring focused attention or social interactions. ### Competing Interest Statement The authors have declared no competing interest. * ABIDE : Autism Brain Imaging Data Exchange dataset ASD : autism spectrum disorder BMA : bayesian model average BMR : bayesian model reduction DCM : dynamic causal modelling PEB : parametric empirical bayes SRS : Social responsiveness scale TD : typical development