Use of the lesion model for examining toxicant effects on cognitive behavior

It is often beneficial to use a model to help understand unknown effects and relate those effects to an existing body of knowledge. In much of the early development of behavioral toxicology, the pharmacological model has served as a valuable theoretical guide, especially with regard to dosing and kinetic parameters. However, as with any model, it has certain limitations. The lesion model has complementary features which provide valuable insights into the behavioral effects of toxicants. This is particularly true for effects which persist long after the end of toxicant exposure. There is much literature describing effects of brain lesions on behavior. By comparing results from toxicology studies to those of lesion studies, one can take advantage of this trove of information to gain a better insight into the possible loci of toxic effects, and to identify tests which would be useful in further describing the nature of the toxic effects. In this article, we examine the theoretical and practical utility of the lesion model. Examples are given showing how it has proven useful in interpreting the cognitive effects of exposure of monkeys to lead and polychlorinated biphenyls (PCBs). These exposures produced syndromes that closely resemble the effects of lesions in the frontal cortex or limbic system.