Anatomical Substrates of Behavioral Impairment Induced by Developmental Lead Exposure in Monkeys: Inferences from Brain Lesions

Abstract

There is a substantial literature exploring the behavioral consequences of developmental lead exposure in the monkey; deficits have been observed on a number of tasks assessing learning and memory including spatial delayed alternation, discrimination reversal, matching to sample, and concurrent discrimination. Differences in performance between control and lead-exposed monkeys have also been observed on intermittent schedules of reinforcement. Comparison of the effects of lead with the extensive literature on the consequences of lesions in discrete areas of brain on the same tasks may provide insight into the possible sites of brain damage responsible for lead-induced behavioral impairment. Available data strongly suggest that prefrontal cortical areas are damaged by lead, based on the pattern of performance deficits across specific tasks. In addition, a constellation of global deficits including perseveration, increased distractibility, inability to change response strategy, and inability to inhibit inappropriate responding are hallmarks of both prefrontal damage and developmental lead exposure. Evidence also implicates basal forebrain structures in behavior impairment produced by lead based on the pattern of deficits across numerous tasks, although the evidence is much weaker than for prefrontal cortex. In contrast, the pattern of behavioral impairment produced by limbic system lesions is different in many respects from that produced by lead; in addition, the scant neuropathological data available suggest that limbic structures are not a target of lead even at high blood lead levels in the monkey. Comparison of the pattern of damage following lead exposure with the effects of lesions, presented here, provides direction for further morphological or neurochemical exploration of lead-induced brain damage in the monkey.