Prediction learning in adults with autism and its molecular correlates

Abstract

Abstract Background According to Bayesian hypotheses, individuals with Autism Spectrum Disorder (ASD) have difficulties making accurate predictions about their environment. In particular, the mechanisms by which they assign precision to predictions or sensory inputs would be suboptimal in ASD. These mechanisms are thought to be mostly mediated by glutamate and GABA. Here, we aimed to shed light on prediction learning in ASD and on its neurobiological correlates. Methods Twenty-six neurotypical and 26 autistic adults participated in an associative learning task where they had to learn a probabilistic association between a tone and the rotation direction of two dots, in a volatile context. They also took part in magnetic resonance spectroscopy (MRS) measurements to quantify Glx (glutamate and glutamine), GABA + and glutathione in a low-level perceptual region (occipital cortex) and in a higher-level region involved in prediction learning (inferior frontal gyrus). Results Neurotypical and autistic adults had their percepts biased by their expectations, and this bias was smaller for individuals with a more atypical sensory sensitivity. Both groups were able to learn the association and to update their beliefs after a change in contingency. Interestingly, the percentage of correct predictions was correlated with the Glx/GABA + ratio in the occipital cortex (positive correlation) and in the right inferior frontal gyrus (negative correlation). In this region, MRS results also showed an increased concentration of Glx in the ASD group compared to the neurotypical group. Limitations We used a quite restrictive approach to select the MR spectra showing a good fit, which led to the exclusion of some MRS datasets and therefore to the reduction of the sample size for certain metabolites/regions. Conclusions Autistic adults appeared to have intact abilities to make predictions in this task, in contrast with the Bayesian hypotheses of ASD. Yet, higher ratios of Glx/GABA + in a frontal region were associated with decreased predictive abilities, and ASD individuals tended to have more Glx in this region. This neurobiological difference might contribute to suboptimal predictive mechanisms in ASD in certain contexts.