Fluid intelligence and the locus coeruleus–norepinephrine system

The last decade has seen significant progress identifying genetic and brain differences related to intelligence. However, there remain considerable gaps in our understanding of how cognitive mechanisms that underpin intelligence map onto various brain functions. In this article, we argue that the locus coeruleus–norepinephrine system is essential for understanding the biological basis of intelligence. We review evidence suggesting that the locus coeruleus–norepinephrine system plays a central role at all levels of brain function, from metabolic processes to the organization of large-scale brain networks. We connect this evidence with our executive attention view of working-memory capacity and fluid intelligence and present analyses on baseline pupil size, an indicator of locus coeruleus activity. Using a latent variable approach, our analyses showed that a common executive attention factor predicted baseline pupil size. Additionally, the executive attention function of disengagement––not maintenance––uniquely predicted baseline pupil size. These findings suggest that the ability to control attention may be important for understanding how cognitive mechanisms of fluid intelligence map onto the locus coeruleus–norepinephrine system. We discuss how further research is needed to better understand the relationships between fluid intelligence, the locus coeruleus–norepinephrine system, and functionally organized brain networks.

Pupillometry Reveals the Role of Arousal in a Postexercise Benefit to Executive Function

A single bout of aerobic exercise improves executive function; however, the mechanism(s) underlying this improvement remains unclear. Here, we employed a 20-min bout of aerobic exercise, and at pre- and immediate post-exercise sessions examined executive function via pro- (i.e., saccade to veridical target location) and anti-saccade (i.e., saccade mirror symmetrical to a target) performance and pupillometry metrics. Notably, tonic and phasic pupillometry responses in oculomotor control provided a framework to determine the degree that arousal and/or executive resource recruitment influence behavior. Results demonstrated a pre- to post-exercise decrease in pro- and anti-saccade reaction times (p = 0.01) concurrent with a decrease and increase in tonic baseline pupil size and task-evoked pupil dilations, respectively (ps < 0.03). Such results demonstrate that an exercise-induced improvement in saccade performance is related to an executive-mediated “shift” in physiological and/or psychological arousal, supported by the locus coeruleus norepinephrine system to optimize task engagement.

Pupil dilation predicts individual self-regulation success across domains

Multiple theories have proposed that increasing central arousal through the brain’s locus coeruleus—norepinephrine system may facilitate cognitive control and memory. However, the role of the arousal system in emotion regulation is less well understood. Pupil diameter is a proxy to infer upon the central arousal state. We employed an emotion regulation paradigm with a combination of design features that allowed us to dissociate regulation from emotional arousal in the pupil diameter time course of 34 healthy adults. Pupil diameter increase during regulation predicted individual differences in emotion regulation success beyond task difficulty. Moreover, the extent of this individual regulatory arousal boost predicted performance in another self-control task, dietary health challenges. Participants who harnessed more regulation-associated arousal during emotion regulation were also more successful in choosing healthier foods. These results suggest that a common arousal-based facilitation mechanism may support an individual’s self-control across domains.

The Neuroscience of the Flow State: Involvement of the Locus Coeruleus Norepinephrine System

Flow is a state of full task engagement that is accompanied with low-levels of self-referential thinking. Flow is considered highly relevant for human performance and well-being and has, therefore, been studied extensively. Yet, the neurocognitive processes of flow remain largely unclear. In the present mini-review we focus on how the brain's locus coeruleus-norepinephrine (LC-NE) system may be involved in a range of behavioral and subjective manifestations of flow. The LC-NE system regulates decisions regarding task engagement vs. disengagement. This is done via different modes of baseline and stimulus-evoked norepinephrine release. We emphasize the theoretical and empirical overlap between the LC-NE system and flow. For both, a match between a person's skill and task challenge is important in order to induce high levels task-related attention. Moreover, psychophysiological indicators of LC-NE system activity, such as eye pupil diameter and arousal are also sensitive to flow states. Flow is related to arousal in an inverted U-shape. Similarly, in theories on the LC-NE system, task engagement is highest with intermediate levels of arousal. We argue that knowledge about the role of the LC-NE system in establishing the flow experience may help to gain fundamental knowledge of flow and can contribute to unifying various empirical findings on this topic.

The Locus Coeruleus- Norepinephrine System in Stress and Arousal: Unraveling Historical, Current, and Future Perspectives

Arousal may be understood on a spectrum, with excessive sleepiness, cognitive dysfunction, and inattention on one side, a wakeful state in the middle, and hypervigilance, panic, and psychosis on the other side. However, historically, the concepts of arousal and stress have been challenging to define as measurable experimental variables. Divergent efforts to study these subjects have given rise to several disciplines, including neurobiology, neuroendocrinology, and cognitive neuroscience. We discuss technological advancements that chronologically led to our current understanding of the arousal system, focusing on the multifaceted nucleus locus coeruleus. We share our contemporary perspective and the hypotheses of others in the context of our current technological capabilities and future developments that will be required to move forward in this area of research.

Comparisons of neuroinflammation, microglial activation, and degeneration of the locus coeruleus-norepinephrine system in APP/PS1 and aging mice

Background The role of microglia in Alzheimer’s disease (AD) pathogenesis is becoming increasingly important, as activation of these cell types likely contributes to both pathological and protective processes associated with all phases of the disease. During early AD pathogenesis, one of the first areas of degeneration is the locus coeruleus (LC), which provides broad innervation of the central nervous system and facilitates norepinephrine (NE) transmission. Though the LC-NE is likely to influence microglial dynamics, it is unclear how these systems change with AD compared to otherwise healthy aging. Methods In this study, we evaluated the dynamic changes of neuroinflammation and neurodegeneration in the LC-NE system in the brain and spinal cord of APP/PS1 mice and aged WT mice using immunofluorescence and ELISA. Results Our results demonstrated increased expression of inflammatory cytokines and microglial activation observed in the cortex, hippocampus, and spinal cord of APP/PS1 compared to WT mice. LC-NE neuron and fiber loss as well as reduced norepinephrine transporter (NET) expression was more evident in APP/PS1 mice, although NE levels were similar between 12-month-old APP/PS1 and WT mice. Notably, the degree of microglial activation, LC-NE nerve fiber loss, and NET reduction in the brain and spinal cord were more severe in 12-month-old APP/PS1 compared to 12- and 24-month-old WT mice. Conclusion These results suggest that elevated neuroinflammation and microglial activation in the brain and spinal cord of APP/PS1 mice correlate with significant degeneration of the LC-NE system.

Pupil dilation predicts individual success in emotion regulation and dietary self-control

Multiple theories have proposed that increasing central arousal through the brain’s locus coeruleus – norepinephrine system may facilitate cognitive control and memory. However, for emotion research this hypothesis poses a puzzle, because conventionally, successful emotion regulation is associated with a decrease in arousal.Pupil diameter is a proxy to infer upon the central arousal state. We employed an emotion regulation paradigm with a combination of design features that allowed us to dissociate regulation- from stimulus-associated arousal in the pupil diameter time course of healthy adults. A pupil diameter increase during regulation predicted individual differences in emotion regulation success beyond task difficulty. Moreover, the extent of this individual arousal boost predicted performance in another self-control task, dietary health challenges. Participants who harnessed more regulation-associated arousal during emotion regulation were also more successful in choosing healthier foods. These results suggest that a common arousal-based facilitation mechanism may support an individual’s self-control across domains.

Pupil-linked arousal is sensitive to subconscious processing of auditory novelty

The ability to detect novelty in sensory stimuli is at the base of autonomic and goal-directed behavior. Pupil size, a proxy of the Locus Coeruleus-Norepinephrine system, is sensitive to auditory novelty. However, whether this response reliably reflects conscious processing of novelty remains contentious. Here, we characterized pupil and electrophysiological responses during conscious and subconscious processing of auditory novelty by presenting participants deviant stimuli that were below and above their discriminatory thresholds. We found higher pupil responses to subthreshold targets that were not consciously perceived as deviant stimuli. Larger pupil size and dilation rates were associated to more negative Event-Related Potential values extracted from temporal, prefrontal and anterior cingulate regions. We suggest that increased phasic responses to deviant targets that escape conscious perception reflect Norepinephrine-mediated adaptation of arousal levels in order to meet the perceptual and behavioral demands imposed by the task at hand.