Role of the locus coeruleus arousal system in cognitive control

Cognitive control lies at the core of human adaptive behaviour. Humans vary substantially in their ability to execute cognitive control with respect to optimally facing environmental challenges, although the neural origins of this heterogeneity are currently not well understood. Recent theoretical frameworks implicate the locus coeruleus noradrenergic arousal system (LC-NE) in that process. Invasive neurophysiological work in rodents has shown that the LC-NE is an important homeostatic control centre of the body. LC-NE innervates the entire neocortex and has particularly strong connections with the cingulate gyrus. In the present study, using a response conflict task, functional magnetic resonance imaging and concurrent pupil dilation measures (a proxy for LC-NE firing), we provide empirical evidence for a decisive role of the LC-NE in cognitive control in humans. We show that the level of individual behavioural adjustment in cognitive control relates to the level of functional coupling between LC-NE and the dorsomedial prefrontal cortex, as well as dorsolateral prefrontal cortex. Moreover, we show that the pupil is substantially more dilated during conflict trials requiring behavioural adjustment than during no conflict trials. In addition, we explore a potential relationship between pupil dilation and neural activity during choice conflict adjustments. Our data provide novel insight into arousal-related influences on cognitive control and suggest pupil dilation as a potential external marker for endogenous neural processes involved in optimising behavioural control. Our results may also be clinically relevant for a variety of pathologies where cognitive control is compromised, such as anxiety, depression, addiction and post-traumatic stress disorder.