LEAD EFFECTS ON THE AUDITORY SYSTEM IN MONKEYS

前一批款期内的工作显示了重大和持久的 非人灵长类动物模型(恒河猴)对听觉功能的影响 (猴子)儿童时期的铅暴露。听性脑干诱发反应 在先前接触铅的猴子中，(ABERs)延迟，并且有 耳蜗病理和更显著的ABERs干扰的证据 铅暴露最严重的两只恒河猴。此外，措施 在听觉检测反应时测试中的注意力不同于铅 控制猴子。这些影响代表着持久的、可能的 从猴子11岁起对神经系统功能的不可逆转影响- 测试时年仅13岁。铅暴露是在早期 年，铅的发育和身体负担一直处于无法检测的水平。 在进行这些评估的时候已经有很多年了。来自这一领域的其他研究 实验室和其他人已经证明了早期接触铅的影响 儿童铅中毒动物模型的听觉注意过程研究 暴露和在儿童中。在这些研究中评估的注意力过程 研究是许多更具全球性的认知异常的基础 与儿童时期的铅接触有关。除了关注之外 缺陷障碍和其他注意力问题，包括智商 (尤其是言语智商)、言语感知、语言产生、阅读、 还有学业上的问题。铅对听觉系统处理的影响如下 尤其重要的是，口语是主要的途径 这种学习发生在年幼的孩子身上。更好地理解 早期铅暴露对听觉注意的不良影响 进程将促进治疗干预措施的设计，并 为已知有以下情况的儿童和成人提供特殊教育计划 经历过早期的铅暴露。 本申请的目的是表征可能存在的缺陷 以前未评估过的听觉功能，并进一步描绘 在之前的授权期内观察到的基于听觉的注意缺陷。 频率特定阈值、频率调谐和非线性过程 将进行电生理学评估。广泛的关注范围 将从行为上对流程进行评估。其中包括简单的 在上一次拨款中产生铅影响的注意措施 句号。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 定向注意力也将按照行为方式进行评估 易分心和跟踪。长期计划包括审查 程序改变和药物干预的疗效 减轻铅对儿童行为和运动能力的影响 生理学研究。 这项拟议研究的对象是17只15岁的猴子。 铅暴露是在发育的早期，猴子现在是成年的， 因此，对持久的和可能不可逆转的影响进行评估是最终的 进球。铅摄入量的水平不会产生明显的铅迹象 毒性。自那以后，这些猴子基本上受到了同等对待。 出生，并在听觉功能的行为测试中有经验。铅 曝光参数和实验历史已经被广泛地 所有猴子一生中都有的特征。

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.