Chronic deficits in auditory communication following early life seizures

早期癫痫发作后听觉交流的慢性缺陷

• 批准号: 9790991
• 负责人: Paul Bernard
• 金额: $ 13.81万
• 依托单位: UNIVERSITY OF PRINCE EDWARD ISLAND
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-09-30 至 2023-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9790991
• 关键词: Address; Adult; Affect; Animal Model; Auditory; Auditory area; Behavioral; Behavioral Paradigm; Brain Stem; Chronic; Clinical; Communication; Cues; Data; Desire for food; Development; Disease; Distress; Early treatment; Effectiveness; Ensure; Epilepsy; Etiology; Future; Goals; Hippocampus (Brain); Individual; Infant; Intellectual functioning disability; Intervention; Knowledge; Life; Link; Measures; Modality; Modeling; Motivation; Mus; Nature; Neurodevelopmental Disorder; Neurological outcome; Odors; Outcome; Pharmacology; Phenotype; Process; Production; Radial; Rattus; Recording of previous events; Research; Rodent Model; Running; Seizures; Severities; Social Behavior; Social Environment; Socialization; Synaptic plasticity; Ultrasonics; Work; approach behavior; arm; auditory processing; base; behavior test; behavioral response; clinically relevant; developmental disease; experimental study; interest; kainate; maternal separation; normal hearing; novel; prevent; response; social; social deficits; synaptic function; tool; vocalization

Abstract: Chronic deficits in auditory communication following early life seizures Early life seizures (ELS) are prevalent and affect approximately 3/1000 infants. Many individuals with social and communicative deficits, have a history of ELS. ELS and epilepsy correlate with deficits in auditory communication. Initial experimental evidence suggests that ELS cause chronic abnormalities in social behavior and result in vocalization deficits. This leads to the question, if present, what is the nature of auditory communicative deficits triggered by ELS? This must first be addressed in order to understand how these deficits may or may not contribute to the manifestation of chronic social abnormalities following ELS. Clinically the influence of ELS on causation and severity of social deficits remains correlative. An animal model is required to clarify causation and identify underlying mechanisms. Gaps in knowledge: 1. Communication has not been thoroughly explored in any ELS model and the need to complete this assessment has been highlighted. 2. Auditory communicative deficits associated with developmental disorders are not well understood. It is unknown if abnormal auditory function contributes to social deficits seen following ELS. The proposed studies are a first step towards answering this question. 3. A behavioral testing paradigm to thoroughly assess auditory communicative deficits associated with neurodevelopmental disorders is lacking. Goals: We will develop a behavioral test battery to assess auditory communication in rodent models of neurodevelopmental disorders. We will explore deficits in communication following ELS and determine if these deficits impact receptive and/or expressive auditory communication. Supported by preliminary data, we hypothesize that ELS results in chronic socially relevant auditory communicative deficits. These communicative abnormalities may contribute to social deficits in this model and these findings may be applicable to neurodevelopmental disorders that manifest social/communicative abnormalities. Our research will allow future work to explore the underlying mechanistic changes with the aim of rescuing the chronic phenotype. We will assess the ability to respond to and express socially relevant auditory cues in a rat model of ELS with the following specific aims: Expected outcomes: We will determine if socially relevant auditory processing deficits exist in a clinically relevant ELS model. By comparing these results with olfactory communicative function, we will determine if communicative deficits are restricted to auditory communication, suggesting that auditory communicative deficits that occur following ELS contribute to social abnormalities. Alternatively, communicative deficits may extend to the olfactory modality, suggesting that deficits may be the result of reduced social motivation. Our studies may suggest that targeting auditory processing deficits is a viable strategy to rescue deficits associated with ELS, including social deficits. Results may also indicate that aggressive treatment of ELS may prevent the development of chronic communicative deficits.

翻译后摘要：在听觉沟通的早期生活癫痫发作后的慢性缺陷 生命早期癫痫发作（ELS）很普遍，大约每1000名婴儿中就有3名受到影响。许多人与 社交和沟通障碍，有ELS病史。ELS和癫痫与以下缺陷相关： 听觉交流最初的实验证据表明，ELS导致慢性异常， 社会行为，并导致发声缺陷。这就引出了一个问题，如果存在， ELS引发的听觉交流障碍吗首先必须解决这个问题，以便了解 这些缺陷如何可能或可能不会导致慢性社会异常的表现， ELS。在临床上，ELS对社会缺陷的病因和严重程度的影响仍然是相关的。一个 需要动物模型来阐明因果关系并确定潜在机制。 知识差距：1。在任何ELS模型中，都没有对沟通进行彻底的探讨， 需要完成这一评估已得到强调。2.听觉交流障碍相关 与发育障碍的关系还不太清楚。目前尚不清楚异常的听觉功能是否 导致ELS后出现的社会赤字。拟议的研究是回答以下问题的第一步： 这个问题3.一种全面评估听觉交流障碍的行为测试范式 与神经发育障碍相关的疾病目标：我们将开发一套行为测试组合 评估神经发育障碍啮齿动物模型中的听觉交流。我们将探讨 ELS后的沟通缺陷，并确定这些缺陷是否影响接受和/或表达 听觉交流在初步数据的支持下，我们假设ELS导致慢性 社会相关的听觉交流障碍这些交流异常可能会导致 在这个模型中的社会缺陷，这些发现可能适用于神经发育障碍， 明显的社交/交流异常。我们的研究将使未来的工作，探索 潜在的机制变化，目的是挽救慢性表型。我们将评估 在ELS大鼠模型中，用以下特定的 目的： 预期结果：我们将确定儿童中是否存在与社会相关的听觉处理缺陷 临床相关ELS模型。通过将这些结果与嗅觉交际功能进行比较， 确定沟通障碍是否仅限于听觉沟通，这表明听觉 ELS后出现的沟通缺陷会导致社交异常。可选择地， 沟通缺陷可能会延伸到嗅觉模态，这表明缺陷可能是由于 减少社会动机。我们的研究可能表明，针对听觉处理缺陷是一个可行的 拯救与ELS相关的赤字（包括社会赤字）的战略。结果还可能表明， 积极治疗ELS可以防止慢性沟通缺陷的发展。