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Noradrenergic control of human cognition

Final Report Summary - NOREPI (Noradrenergic control of human cognition)

The human brain is a network of closely connected brain areas and nuclei, which enables the flexibility in information processing that is necessary for intelligent behavior. One of these nuclei, called the locus coeruleus, a tiny structure in the brainstem, influences a greater variety of brain areas than any other single nucleus yet described. Therefore it is clear that the locus coeruleus and its connections with the rest of the brain must have pervasive influences on mental functions such as perception, memory and decision-making. However, the exact nature of these influences is still poorly understood, in part because it is exceedingly hard to study this system in human subjects. The main reason is that conventional neuroimaging methods are not capable of measuring activity of the locus coeruleus, as a result of which previous research has focused almost exclusively on animals. Using a variety of recently developed or validated methods, including functional MRI, pharmacology, pupillometry and EEG, we set out to investigate the role of the locus coeruleus in human cognition.

Our key findings are as follows. First, we found that a previously published MRI scan for visualizing the locus coeruleus has adequate test-retest reliability, and that a higher magnetic field strength did not improve the quality of the locus coeruleus image. Second, we found that the locus coeruleus plays an important role in the way that people respond when they make errors. The magnitude of error-related adjustments depends on moment-to-moment fluctuations of, and individual differences in locus coeruleus activity. Third, we found that changes in locus coeruleus activity, as indexed by pupil diameter or influenced using pharmacology, predict individuals’ lapses of attention. Fourth, we found that locus coeruleus activity influences learning rate, the degree to which new observations modify existing beliefs about statistical properties of the environment. And fifth, we found that locus coeruleus activity is determined in part by different forms of uncertainty, and plays a role in communicating this information to the entire brain. Together, these findings make a significant contribution to theories of locus coeruleus function, and to methods for examining this system in humans.