LEAD EFFECTS ON THE AUDITORY SYSTEM IN MONKEYS

上一个赠款期的工作表明， 对非人灵长类动物模型（恒河猴）听觉功能的影响 儿童期铅暴露。 听觉脑干诱发电位 （ABER）在先前暴露于铅的猴子中延迟， 耳蜗病理学的证据和更显着的破坏ABER在 这两只恒河猴铅暴露量最大。 此外，措施 听觉检测反应时间测试中的注意力在铅 和对照组猴子。 这些影响是持久的， 从猴子11岁开始， 13岁时参加考试。 铅暴露是在早期 铅的发展和身体负担一直处于无法检测的水平， 在这些评估的时候很多年了。 其他相关研究 实验室和其他人已经证明了早期接触铅的影响 儿童期铅中毒动物模型的注意加工 暴露和儿童。 在这些评估的注意过程 研究揭示了许多全球性的认知异常， 与儿童期铅暴露有关。 除了注意 缺陷障碍和其他注意力问题，包括智商 （特别是语言智商），言语感知，语言产生，阅读， 还有学校的问题 铅对听觉系统加工的影响 特别重要的是，口语是主要的途径， which哪一个learning学习occurs发生in young小children儿童. 更好地理解 早期铅暴露对认知注意力的不良影响 这些过程将有助于设计治疗干预措施， 为儿童和成人提供特殊教育计划， 早期铅暴露。 本申请的目的是表征以下方面的可能缺陷： 听觉功能以前没有评估，并进一步描绘 在上一个资助期观察到的基于认知的注意力缺陷。 频率特定阈值、频率调谐和非线性过程 将进行电生理学评价。 广泛的注意力 将从行为上对进程进行评估。 其中包括简单的 注意力的措施，产生的影响，铅在以前的赠款 期 他们将在不同的任务条件下进行评估 复杂性和注意力需求。 提示注意，时间处理和 定向注意力也将在行为上进行评估， 注意力分散和追踪 长期计划包括审查 程序变更和药物干预的有效性， 减弱铅对行为和行为表现的影响， 生理学研究 所提议的研究的受试者是17只15岁的猴子。 铅暴露是在早期发展和猴子现在是成年人， 因此，评估持久的和可能不可逆转的影响是最终的， 目标. 铅摄入量处于不会产生明显铅迹象的水平 毒性 从那以后， 出生，并在听觉功能的行为测试中有经验。 铅 暴露参数和实验历史已经被广泛地 所有猴子在整个生命周期内的特征。

Work during the previous grant period revealed significant and persistent effects on auditory function in a nonhuman primate model (the rhesus monkey) of childhood lead exposure. Auditory brain stem evoked responses (ABERs) were delayed in monkeys previously exposed to lead and there was evidence for cochlear pathology and more remarkable disruptions of ABERs in the two rhesus monkeys with greatest lead exposure. In addition, measures of attention in an auditory detection reaction time test differed in lead and control monkeys. These effects represent enduring and probably irreversible effects on nervous system function since the monkeys were 11- 13 years old at the time of testing. Lead exposure was during early development and body burdens of lead had been at undetectable levels for many years at the times of these evaluations. Other research from this laboratory and by others has demonstrated effects of early exposure to lead on auditory-based attentional processes in animal models of childhood lead exposure and in children. The attentional processes evaluated in these studies underlie many of the more global cognitive abnormalities that have been associated with childhood lead exposure. In addition to attention deficit disorder and other attentional problems, these include IQ (especially verbal IQ), speech perception, language production, reading, and school problems. Effects of lead on auditory system processing are of particular importance given that spoken language is the primary route by which learning occurs in young children. A better understanding of the adverse consequences of early lead exposure on auditory-based attentional processes would facilitate the design of therapeutic interventions and special education programs for children and adults who are known to have experienced early lead exposure. The aim of the present application is to characterize possible deficits in auditory function not previously assessed and to further delineate the auditory-based attentional deficits observed in the previous grant period. Frequency specific thresholds, frequency tuning, and nonlinear processes will be evaluated electrophysiologically. A broad range of attentional processes will be evaluated behaviorally. These include the simple measures of attention which yielded effects of lead in the previous grant period. they will be evaluated under different conditions of task complexity and attentional demand. Cued attention, temporal processing and directed attention also will be evaluated behaviorally as will distractibility and tracking. Long-range plans include examination of the efficacy of procedural changes and pharmacological interventions to attenuate effects of lead on performance in the behavioral and physiological studies. Subjects for the proposed studies are seventeen 15 - year old monkeys. Lead exposure was during early development and the monkeys are now adult, so evaluation of enduring and possibly irreversible effects is the ultimate goal. Lead intake was at levels that did not produce overt signs of lead toxicity. The monkeys have been treated essentially identically since birth and are experienced in behavioral tests of auditory function. Lead exposure parameters and experimental histories have been extensively characterized for all monkeys over th life span.