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在自闭症基因敲除大鼠模型的语音辨别任务中使用预测线索。

Use of a predictor cue during a speech sound discrimination task in a knockout rat model of autism.

作者信息

Centanni Tracy M, Gunderson Logun P K, Parra Monica

机构信息

Department of Psychology, Texas Christian University, Fort Worth, TX 76129.

Department of Speech, Language, and Hearing Sciences, University of Florida, Gainesville, FL 32610.

出版信息

bioRxiv. 2024 Dec 6:2024.12.04.626861. doi: 10.1101/2024.12.04.626861.

Abstract

Autism is a common neurodevelopmental disorder that despite its complex etiology, is marked by deficits in prediction that manifest in a variety of domains including social interactions, communication, and movement. The tendency of individuals with autism to focus on predictable schedules and interests that contain patterns and rules highlights the likely involvement of the cerebellum in this disorder. One candidate-autism gene is contact in associated protein 2 (), and variants in this gene are associated with sensory deficits and anatomical differences. It is unknown, however, whether this gene directly impacts the brain's ability to make and evaluate predictions about future events. The current study was designed to answer this question by training a genetic knockout rat on a rapid speech sound discrimination task. Rats with knockout (KO) and their littermate wildtype controls (WT) were trained on a validated rapid speech sound discrimination task that contained unpredictable and predictable targets. We found that although both genotype groups learned the task in both unpredictable and predictable conditions, the KO rats responded more often to distractors during training as well as to the target sound during the predictable testing conditions compared to the WT group. There were only minor effects of sex on performance and only in the unpredictable condition. The current results provide preliminary evidence that removal of this candidate-autism gene may interfere with the learning of unpredictable scenarios and enhance reliance on predictability. Future research is needed to probe the neural anatomy and function that drives this effect.

摘要

自闭症是一种常见的神经发育障碍,尽管其病因复杂,但以预测缺陷为特征,这些缺陷表现在包括社交互动、沟通和运动在内的多个领域。自闭症患者倾向于关注包含模式和规则的可预测日程和兴趣,这凸显了小脑可能参与了这种疾病。一个候选自闭症基因是接触相关蛋白2(),该基因的变异与感觉缺陷和解剖学差异有关。然而,尚不清楚该基因是否直接影响大脑对未来事件进行预测和评估的能力。当前的研究旨在通过在快速语音辨别任务中训练基因敲除大鼠来回答这个问题。对接触相关蛋白2基因敲除(KO)大鼠及其同窝野生型对照(WT)进行了一项经过验证的快速语音辨别任务训练,该任务包含不可预测和可预测的目标。我们发现,尽管两个基因型组在不可预测和可预测条件下都学会了任务,但与WT组相比,KO大鼠在训练期间对干扰物的反应更频繁,在可预测测试条件下对目标声音的反应也更频繁。性别对表现的影响很小,且仅在不可预测条件下存在。当前结果提供了初步证据,表明去除这个候选自闭症基因可能会干扰对不可预测情景的学习,并增强对可预测性的依赖。未来需要开展研究来探究驱动这种效应的神经解剖学和功能。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9acc/11643114/6b53713ab9e9/nihpp-2024.12.04.626861v1-f0001.jpg

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