Although global declines in structure have been documented in the aging human brain, little is known about the functional integrity of the striatum and prefrontal cortex in older adults during incentive processing. We used event-related functional magnetic resonance imaging to determine whether younger and older adults differed in both self-reported and neural responsiveness to anticipated monetary gains and losses. The present study provides evidence for intact striatal and insular activation during gain anticipation with age, but shows a relative reduction in activation during loss anticipation. These findings suggest that there is an asymmetry in the processing of gains and losses in older adults that may have implications for decision-making.Over the past several decades, scientists have made rapid progress toward determining the effects of aging on cognition. Both behavioral and neuroimaging studies show that there is a strong negative relationship between age and cognitive performance across many types of tasks 1,2 . However, a growing body of research also suggests that many affective abilities do not decline with age, and that in some cases they may improve. Accumulating behavioral evidence suggests that older adults perform relatively better on tasks that involve the processing of emotional stimuli 3 . Socioemotional selectivity theory postulates that age-related attempts to optimize emotional well-being 4 generate increased positive emotional experiences and/or decreased negative emotional experiences over the life span 5 . To date, however, very few neuroimaging studies have focused on changes in emotion with age 6,7 , with only one prior study examining changes in incentive processing over the life span 8 .Studies of brain structure and chemistry provide some evidence for age-related decline. These studies have specifically shown significant structural atrophy of the caudate, insula and prefrontal cortex, as well as global declines in dopamine receptors in the striatum and the

Individual variability in reward-based learning has been ascribed to quantitative variation in baseline levels of striatal dopamine. However, direct evidence for this pervasive hypothesis has hitherto been unavailable. We demonstrate that individual differences in reward-based reversal learning reflect variation in baseline striatal dopamine synthesis capacity, as measured with neurochemical positron emission tomography. Subjects with high baseline dopamine synthesis in the striatum showed relatively better reversal learning from unexpected rewards than from unexpected punishments, whereas subjects with low baseline dopamine synthesis in the striatum showed the reverse pattern. In addition, baseline dopamine synthesis predicted the direction of dopaminergic drug effects. The D 2 receptor agonist bromocriptine improved reward-based relative to punishment-based reversal learning in subjects with low baseline dopamine synthesis capacity, while impairing it in subjects with high baseline dopamine synthesis capacity in the striatum. Finally, this pattern of drug effects was outcome-specific, and driven primarily by drug effects on punishment-, but not reward-based reversal learning. These data demonstrate that the effects of D 2 receptor stimulation on reversal learning in humans depend on task demands and baseline striatal dopamine synthesis capacity.

Evidence from psychopharmacological research has revealed that dopamine receptor agents have opposite effects on cognitive function depending on baseline levels of working memory capacity. These contrasting effects have been interpreted to reflect differential baseline levels of dopamine. Here we demonstrate for the first time that working memory capacity as measured by listening span predicts dopamine synthesis capacity in the striatum, indicating that subjects with low working memory capacity have low DA synthesis capacity in the striatum, whereas subjects with high working memory capacity have high DA synthesis capacity in the striatum.

Dopamine release in the NAcc appears to increase local BOLD signal via agonism of postsynaptic D1 receptors. Such a physiological mechanism implies that FMRI may be used to track symptoms related to NAcc dopaminergic dysregulation in psychiatric disorders including schizophrenia and attention deficit/hyperactivity disorder.