? DESCRIPTION (provided by applicant): The goal of this project is to use neuroimaging and neuromodulation to test the hypothesis that cerebellar dysfunction contributes to predictive processing deficits in autism spectrum disorder (ASD). ASD is a neurodevelopmental disorder characterized by social and communication deficits, repetitive behaviors, and restricted interests. The rapidly rising incidence of ASD represents a considerable public health issue, and a better understanding of the neurobiological bases of ASD is necessary to improve diagnosis and treatments. Structural and functional differences in the cerebellum are amongst the most commonly-reported brain findings in ASD populations. However, despite extensive evidence of cerebellar dysfunction in ASD, the exact contribution of the cerebellum to ASD remains unclear. Our previous work has helped to establish a role for the human cerebellum in cognitive and affective processing and has elucidated functional subregions within the cerebellum, providing a new framework for understanding the role of the cerebellum in ASD. Our investigations of the relationship between cerebellar subregions and core ASD symptoms have shown convergence between structural differences and functional deficits in the right posterolateral cerebellum (lobule VII). It is thought that the cerebellum can modulate cortical function to optimize performance, specifically during tasks requiring prediction based on context; therefore, we propose that cerebellar dysfunction may underlie the proposed deficits in Bayesian prediction in ASD. We will use cerebellar transcranial direct current stimulation (tDCS) and neuroimaging in typically-developing (TD) and ASD adults to test the hypothesis that cerebellar dysfunction leads to predictive processing deficits in ASD. TD individuals and adults with ASD will complete motor, social, and language prediction tasks after anodal, cathodal and sham tDCS is applied to right lobule VII, the most consistent cerebellar candidate region. We will use a within-subjects design to determine the effects of tDCS polarity on task performance and combine tDCS and neuroimaging to investigate resting-state and task-based functional MRI activation patterns after cerebellar tDCS. We predict that: ASD participants will show specific deficits on predictive trials that are modulated by cerebellar tDCS; cerebellar tDCS will specifically affect performance during predictive vs. non-predictive trials in TD and ASD groups; and there will be activation changes in the cerebellum and broader cerebro-cerebellar circuits following tDCS. To better understand individual differences, we will examine the behavioral profiles and the neural signatures of those that respond vs. those that do not respond to tDCS. This project will advance our understanding of the neurobiological bases of ASD and lay the groundwork for future translational research. Our use of neuroimaging will allow us to determine the neural effects of cerebellar tDCS, and we hope to gain a better understanding of which individuals might benefit from cerebellar tDCS. Cerebellar neuromodulation offers an inexpensive and novel potential therapeutic option for adults with ASD that targets the neurobiological basis of the disorder.

R15MH106957

2015-04-01

2019-03-31