A matrix method was developed to examine functional interactions between brain regions, by correlating the cerebral metabolic rate for glucose as determined by positron emission tomography in humans. The method was applied to regional metabolic data from 15 young and 15 older men. The method showed clear evidence of age differences, with older subjects having fewer significant correlations in frontal and parietal regions, indicative of reduced integrated activity in these regions with age. The correlation approach also was applied to 21 demented patients and 21 age-matched controls. The dementia group showed reduced frontal-parietal interactions, and a significant loss of correlations between left-right homologous regions. The matrix method was applied to analyze glucose metabolism in awake Fischer-344 rats, and showed patterns of correlations similar to those in humans. Reduced correlations between left and right hemispheric brain regions were found in rats that had undergone corpus callosotomies, suggesting that interhemispheric interactions are mediated in part by callosal fibers.