Cortico-Cerebellar Hyper-Connections and Reduced Purkinje Cells Behind Abnormal Eyeblink Conditioning in a Computational Model of Autism Spectrum Disorder.

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Front Syst Neurosci. 2021 Dec 17;15:666649. doi: 10.3389/fnsys.2021.666649. eCollection 2021.

Cortico-Cerebellar Hyper-Connections and Reduced Purkinje Cells Behind Abnormal Eyeblink Conditioning in a Computational Model of Autism Spectrum Disorder.

Frontiers in systems neuroscience

Emiliano Trimarco, Pierandrea Mirino, Daniele Caligiore

Affiliations

Computational and Translational Neuroscience Laboratory, Institute of Cognitive Sciences and Technologies, National Research Council, Rome, Italy.
Laboratory of Neuropsychology of Visuo-Spatial and Navigational Disorders, Department of Psychology, "Sapienza" University, Rome, Italy.
AI2Life s.r.l., Innovative Start-Up, ISTC-CNR Spin-Off, Rome, Italy.

PMID: 34975423 PMCID: PMC8719301 DOI: 10.3389/fnsys.2021.666649

Abstract

Empirical evidence suggests that children with autism spectrum disorder (ASD) show abnormal behavior during delay eyeblink conditioning. They show a higher conditioned response learning rate and earlier peak latency of the conditioned response signal. The neuronal mechanisms underlying this autistic behavioral phenotype are still unclear. Here, we use a physiologically constrained spiking neuron model of the cerebellar-cortical system to investigate which features are critical to explaining atypical learning in ASD. Significantly, the computer simulations run with the model suggest that the higher conditioned responses learning rate mainly depends on the reduced number of Purkinje cells. In contrast, the earlier peak latency mainly depends on the hyper-connections of the cerebellum with sensory and motor cortex. Notably, the model has been validated by reproducing the behavioral data collected from studies with real children. Overall, this article is a starting point to understanding the link between the behavioral and neurobiological basis in ASD learning. At the end of the paper, we discuss how this knowledge could be critical for devising new treatments.

Keywords: associative learning; autism; cerebellar-cortical circuit; hyper-connectivity; prefrontal cortex; sensory-motor cortex; spiking neuron models; system-level neuroscience

Conflict of interest statement

PM and DC were employed by the company AI2Life s.r.l. The remaining author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed

Publication Types

Journal Article