Interaction between Functional Connectivity and Neural Excitability in Autism: A Novel Framework for Computational Modeling and Application to Biological Data.

Functional connectivity (FC) and neural excitability may interact to affect symptoms of autism spectrum disorder (ASD). We tested this hypothesis with neural network simulations, and applied it with functional magnetic resonance imaging (fMRI). A hierarchical recurrent neural network embodying predictive processing theory was subjected to a facial emotion recognition task. Neural network simulations examined the effects of FC and neural excitability on changes in neural representations by developmental learning, and eventually on ASD-like performance. Next, by mapping each neural network condition to subject subgroups on the basis of fMRI parameters, the association between ASD-like performance in the simulation and ASD diagnosis in the corresponding subject subgroup was examined. In the neural network simulation, the more homogeneous the neural excitability of the lower-level network, the more ASD-like the performance (reduced generalization and emotion recognition capability). In addition, in homogeneous networks, the higher the FC, the more ASD-like performance, while in heterogeneous networks, the higher the FC, the less ASD-like performance, demonstrating that FC and neural excitability interact. As an underlying mechanism, neural excitability determines the generalization capability of top-down prediction, and FC determines whether the model's information processing will be top-down prediction-dependent or bottom-up sensory-input dependent. In fMRI datasets, ASD was actually more prevalent in subject subgroups corresponding to the network condition showing ASD-like performance. The current study suggests an interaction between FC and neural excitability, and presents a novel framework for computational modeling and biological application of a developmental learning process underlying cognitive alterations in ASD.