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.

Public Health Relevance

This project aims to investigate whether adults with autism spectrum disorder (ASD) have difficulties predicting what happens next during movement, language and social interaction tasks, and whether we can improve their performance by stimulating the brain with low-level electrical current. We will apply the current to a part of the brain called the cerebellum, which is involved in prediction and has been shown to differ both structurally and functionally in ASD, and we will monitor brain activation changes using neuroimaging. This study will provide important information that will help us to determine whether cerebellar stimulation is a potential treatment for adults with ASD.

National Institute of Health (NIH)
National Institute of Mental Health (NIMH)
Academic Research Enhancement Awards (AREA) (R15)
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Special Emphasis Panel (ZRG1-BBBP-X (81))
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Gilotty, Lisa
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American University
Schools of Arts and Sciences
United States
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Stoodley, Catherine J; D'Mello, Anila M; Ellegood, Jacob et al. (2017) Altered cerebellar connectivity in autism and cerebellar-mediated rescue of autism-related behaviors in mice. Nat Neurosci 20:1744-1751
D'Mello, Anila M; Turkeltaub, Peter E; Stoodley, Catherine J (2017) Cerebellar tDCS Modulates Neural Circuits during Semantic Prediction: A Combined tDCS-fMRI Study. J Neurosci 37:1604-1613
Schutter, Dennis J L G (2016) A Cerebellar Framework for Predictive Coding and Homeostatic Regulation in Depressive Disorder. Cerebellum 15:30-3
Stoodley, Catherine J (2016) The Cerebellum and Neurodevelopmental Disorders. Cerebellum 15:34-7
Turkeltaub, Peter E; Swears, Mary K; D'Mello, Anila M et al. (2016) Cerebellar tDCS as a novel treatment for aphasia? Evidence from behavioral and resting-state functional connectivity data in healthy adults. Restor Neurol Neurosci 34:491-505
Stoodley, Catherine J; Limperopoulos, Catherine (2016) Structure-function relationships in the developing cerebellum: Evidence from early-life cerebellar injury and neurodevelopmental disorders. Semin Fetal Neonatal Med 21:356-64
D'Mello, Anila M; Stoodley, Catherine J (2015) Cerebro-cerebellar circuits in autism spectrum disorder. Front Neurosci 9:408