The investigator of antipsychotic drug effects on neuropsychological functions faces a range of conceptual, methodological, and technical obstacles. Some of these hurdles are pointed out in a brief review of existing literature, and a more detailed consideration of instrumentation issues is presented. The need for hypothesis-driven assessment strategies is highlighted. Interpretive difficulties are posed by the polyfactorial nature of the most widely used neuropsychological tests, and emphasis is placed on the use and development of methods that enable isolation of specific neuropsychological constructs. Examples of this strategy are drawn from ongoing work in the Neuropsychology Unit of the Clinical Research Center for the Study of Schizophrenia at Hillside Hospital, where hypotheses about the behavioral site of action of dopamine agonists and antagonists are used to guide the construction of novel computerized tests.

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