We investigate cognitive and neural origins of the intellectual changes that accompany the adult aging process. Different research perspectives are pursued including behavioral studies, functional and molecular neuroimaging, and neurocomputational modeling. We share a specific interest in exploring the influence of age-related changes in various dopamine (DA) functions on age-related cognitive changes. Specifically, we seek to delineate the cross-level links that relate neuromodulation to patterns of brain activation and cognitive performance

Research in neurochemistry and cognitive neuroscience permits the following empirical generalizations: (a) extrastriatal and nigrostriatal dopamine (DA) systems decline across the adult life span; (b) many cognitive functions deteriorate during normal aging; (c) DA is critically implicated in several cognitive functions and DA losses are linked to both lower overall performance and increased within-person variability; and (d) older adults often exhibit both under- and additional recruitment of different brain regions during cognitive processing compared to young adults.

Current work on the correlative triad among age, DA, and cognition indicates remarkably strong associations between age-dependent DA losses and deficits in tasks assessing executive functions, episodic memory, and perceptual and motor speed. These patterns have been accounted for in neurocomputational models. Here, a key assumption is that non-optimal DA modulation hampers the neural signal relative to background noise, resulting in less distinctive representations and lower cognitive performance.

Supplementary biogenetic research shows that Catechol-O-Methyltransferase (COMT) genotypes differ in level of DA signaling: met/met > val/met > val/val, and that the met genotype is associated with more efficient cognitive and brain responses. In addition, administration of DA agonists may enhance performance in a variety of cognitive tasks. However, more DA is not always better; rather, the relationship of DA signaling to cognitive and brain function may be characterized as an inverted U-shaped function. Consistent with this claim, young individuals with less DA signaling (val/val) show enhanced neural efficiency under the influence of a DA agonist, whereas those with more DA signaling (met/met) exhibit performance decrements following drug administration.

Although few would disagree with the notion that DA is implicated in age-related cognitive changes, its specific role is debated. An outstanding issue in the cognitive neuroscience of aging concerns how to interpret age-differential brain activation patterns during cognitive activity. One possibility is that deficient DA neurotransmission in old age leads to decreased levels of task-related brain activity (as reflected by regional blood flow). To be sure, findings of a strong relationship between DA receptor binding and frontal and cingulate glucose metabolism indicate a transmitter-activation relationship. However, in some task situations older adults may exhibit greater activity than younger adults in specific brain regions. Such findings have been interpreted by some to reflect functional (compensatory) recruitment in the aging brain, with increased activity in older adults being associated with better cognitive performance. By contrast, others have proposed that greater regional activity of older adults may reflect lack of specificity in neural processing due to age-related neuromodulatory deficits. By merging behavioral and neuroimaging expertise in cognitive aging, we intend to examine these theoretical possibilities, along with how the recently discovered relations among COMT genotype, DA agonists, and neurocognitive function are influenced by aging.