LEAD EFFECTS ON THE AUDITORY SYSTEM IN MONKEYS

在上一个资助期间的工作显示出显著和持续

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.