# Neural Mechanisms of Predictive Impairments in Autism

> **NIH NIH R01** · PURDUE UNIVERSITY · 2020 · $373,253

## Abstract

Project Summary
Autism Spectrum Disorders (ASDs) are characterized by a range of reported deficits and impairments.
However, detailed knowledge about their underlying mechanisms and explanatory models is currently lacking.
A novel concept, supported by growing evidence, is that autism may well be primarily a disorder of prediction.
Impairments of structural and functional connectivity reported in children with ASD are entirely consistent with
this concept. The brain processes information by constantly making predictions about future developments in
the surrounding environment, based on information from previous experience. Violations of expectations are
used by the brain to adjust and make future more accurate predictions as part of the learning process.
Impairments in this function may be among the key underlying core deficits in ASD. Of direct relevance to this
concept, we have recently discovered a new mechanism for predictive learning in the visual cortex, which acts
through modulation of persistent activity (neuronal activity, which lasts beyond the time of initial sensory
stimulus). Persistent activity functions to encode information about the timing of prospective salient events, and
is hypothesized to be the underlying cellular basis of working memory. Since Fragile X Syndrome, like other
forms of ASDs, is characterized by impairment of structural and functional circuit connectivity, there is a critical
need to establish how these aberrations of circuit connectivity lead to impaired neural activity and predictive
learning in ASDs. To address this need, we will first identify impaired synaptic connections within the cortical
microcircuit of Fragile X mice. Second, we will test the hypothesis that predictive coding is impaired in Fragile X
mice. Finally, we will establish a causal link between impaired persistent activity and aberrant visual perception
and learning in Fragile X mice. The results of these studies are expected to help establish a strong evidence-
based framework for systematic characterization of additional single gene mutations associated with ASD,
which may ultimately lead to potential development of targeted circuit-specific therapies for successful
treatment of autism.

## Key facts

- **NIH application ID:** 9955321
- **Project number:** 5R01MH116500-04
- **Recipient organization:** PURDUE UNIVERSITY
- **Principal Investigator:** Alexander Chubykin
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $373,253
- **Award type:** 5
- **Project period:** 2017-09-20 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9955321

## Citation

> US National Institutes of Health, RePORTER application 9955321, Neural Mechanisms of Predictive Impairments in Autism (5R01MH116500-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9955321. Licensed CC0.

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