# Cerebellar Dysfunction in Autism

> **NIH NIH R21** · TRUSTEES OF INDIANA UNIVERSITY · 2020 · $196,875

## Abstract

ABSTRACT
 Converging findings from diverse levels of analysis provide compelling evidence of cerebellar (CB)
abnormalities in autism spectrum disorder (ASD), including decreased Purkinje cell numbers, neurochemical
abnormalities, and increased glial cell activation. However, little is known about in vivo CB structure and
function, nor the behavioral consequences of CB abnormalities. The proposed research tests a novel theoretical
model using cutting-edge brain connectivity approaches to explore pathophysiological mechanisms associated
with ASD and explicitly targets the CB, a brain area known to be abnormal in ASD. We will recruit 40 high
functioning individuals with ASD and 40 neurotypical controls. Specific Aim 1 will determine how CB
functional and structural abnormalities contribute to documented CB-dependent task-related deficits in the
disorder. Specifically, we will determine if CB fMRI activation and CB gray matter volumes predict CB-
dependent delay eyeblink conditioning (dEBC) behavioral abnormalities in ASD. Regression analyses will
quantify the CB's specific contribution over and above other contributing regions (e.g., middle frontal,
temporal & parietal cortices, basal ganglia). Specific Aim 2 will determine CB task-related (dEBC) effective
connectivity and resting state functional connectivity to brain regions with which it has strong neuroanatomical
connections, and the extent to which connectivity is disrupted in ASD. Path analysis will be used to determine
CB effective connectivity and directionality. Resting state functional connectivity will be quantified using seed-
based and ROI-based approaches. These functional analyses will explore CB connectivity and directional
influence in the context of a network and rule out models where the deficit is systemic or due to extra-CB areas.
Specific Aim 3 will determine whether core ASD symptom domains correlate with functional connectivity
within specific closed-loop CB-cortical circuits. We hypothesize the following with respect to ASD functional
connectivity: 1) CB anterior lobe and lobules VII-VIII to somatosensory/motor cortex will be inversely
correlated with dEBC timing impairment and with Repetitive Behaviors Scale Revised (RBS-R) scores; 2)
Posterior CB (including Crus I/II) to temporal and prefrontal cortex will be positively correlated with the social
cognition scale of the Social Responsiveness Scale (SRS); 3) Crus I & II with cortical language regions will be
inversely correlated with receptive language processing. The proposed research could identify critical
mechanisms underlying ASD by re-shaping ideas about the role of the CB in the disorder's fundamental motor,
social, and cognitive deficits. Moreover, these aims are consistent with NIMH priorities including developing
an integrative understanding of basic brain-behavior processes that provide the foundation for understanding
mental disorders and probing the connectivity of brain networks.

## Key facts

- **NIH application ID:** 9952421
- **Project number:** 5R21MH118617-02
- **Recipient organization:** TRUSTEES OF INDIANA UNIVERSITY
- **Principal Investigator:** WILLIAM P HETRICK
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $196,875
- **Award type:** 5
- **Project period:** 2019-07-01 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9952421

## Citation

> US National Institutes of Health, RePORTER application 9952421, Cerebellar Dysfunction in Autism (5R21MH118617-02). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/9952421. Licensed CC0.

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