Fetal Irradiation Interferes with Adult Cognition in the Nonhuman Primate

BackgroundExposure to x-irradiation in early gestation has been shown to disrupt normal thalamocortical development in the monkey and thereby model one key feature of the neuropathology of schizophrenia. However, the effect of fetal irradiation on cognitive functions that are vulnerable in schizophrenia (e.g., working memory) has not been examined.MethodsFour fetally irradiated macaque monkeys (FIMs) and four age-matched controls (CONs) were tested as juveniles (12-30 months) and again as adults (∼5 years) on delayed spatial response (DR), a working memory task that is dependent on intact prefrontal cortical circuitry.ResultsAs juveniles, seven of eight monkeys learned DR; one FIM refused to test. Performance in the two groups was not different. As adults, only one FIM achieved criterion on DR. Three of four FIMs did not reach criterion at the 0-sec delay interval of the DR task, whereas all four CONs mastered DR at the maximum tested delay of 10 sec. FIMs completed fewer DR test sessions compared with CONs. In contrast, all FIMs and three of four CONs learned an associative memory task, visual pattern discrimination.ConclusionsFetal exposure to irradiation resulted in an adult-onset cognitive impairment in the working memory domain that is relevant to understanding the developmental etiology of schizophrenia.