Comparable Measures of Cognitive Function in Human Infants and Laboratory Animals to Identify Environmental Health Risks to Children

Article excerpt

The importance of including neurodevelopmental end points in environmental studies is clear. A validated measure of cognitive function in human infants that also has a homologous or parallel test in laboratory animal studies will provide a valuable approach for large-scale studies. Such a comparable test will allow researchers to observe the effect of environmental neurotoxicants in animals and relate those findings to humans. In this article, we present the results of a review of post-1990, peer-reviewed literature and current research examining measures of cognitive function that can be applied to both human infants (0-12 months old) and laboratory animals. We begin with a discussion of the definition of cognitive function and important considerations in cross-species research. We then describe identified comparable measures, providing a description of the test in human infants and animal subjects. Available information on test reliability, validity, and population norms, as well as test limitations and constraints, is also presented. Key words: attention, behavioral testing methodology, cognitive function, developmental neurotoxicology, environmental health, infant, intelligence, learning, memory, neurobehavior. Environ Health Perspect 111:1630-1639 (2003). doi: 10.1289/ehp.6205 available via http://dx.doi.org/[Online 2 July 2003]

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Impairment of cognitive function is a recognized primary outcome of exposure to developmental neurotoxicants, such as lead, methyl mercury, polychlorinated biphenyls (PCBs), and other chemicals. Efficient inclusion of this end point in environmental studies will rely on a validated measure of cognitive function in human infants that has a parallel test in laboratory animal studies. The identification of a comparable measure of cognitive function in human infant and animal studies will facilitate toxicology studies designed to evaluate mechanistic and dose-response aspects of effects observed in human infants.

In this article, we present the results of a review of post-1990, peer-reviewed literature examining measures of cognitive function that can be applied to both human infants (0-12 months old) and laboratory animals.

What Is Cognitive Function?

"Cognition" is vaguely defined as "the act or process of knowing, including both awareness and judgement" (Merriam-Webster On-Line: The Language Center 2003). Hence, it is important to define cognitive function in the context in which it is used. For this article, we define "cognitive function" as encompassing learning, memory, and attention processes (Cory-Slechta et al. 2001). "Learning" is classically defined as a relatively permanent behavior change as a result of practice or experience. When an infant or young animal responds in an adaptive way to a stimulus, learning (or information processing) has occurred (Fagen and Ohr 2001). "Memory" is then defined as the persistence of a learned behavior over time (U.S. EPA 1998). "Attention" refers to a global behavioral construct that includes numerous response classes such as impulsivity, sensitivity to delay, activity level, sustained attention, and ability to manage delay of reward (Bushnell 1998; Bushnell and Rice 1999; Cory-Slechta et al. 2001). In infants, attention research has focused on four areas of visual attention: alertness, spatial orienting, attention to object features, and endogenous or internally directed, attentional functions (e.g., attention span, perseverance, and distractibility; Colombo 2001).

Cross-Species Developmental Neurotoxicity

The adverse effects of developmental exposure to neurotoxicants on various cognitive functions can be assessed in both humans and animals. However, the degree to which specific assessment techniques are comparable across species can vary dramatically. The 1990 Workshop on Qualitative and Quantitative Comparability of Human and Animal Developmental Neurotoxicity (Stanton and Spear 1990), sponsored by the U. …