An integrative theory of locus coeruleus-norepinephrine function: adaptive gain and optimal performance.

@article{AstonJones2005AnIT,
  title={An integrative theory of locus coeruleus-norepinephrine function: adaptive gain and optimal performance.},
  author={Gary Aston-Jones and Jonathan D. Cohen},
  journal={Annual review of neuroscience},
  year={2005},
  volume={28},
  pages={
          403-50
        }
}
Historically, the locus coeruleus-norepinephrine (LC-NE) system has been implicated in arousal, but recent findings suggest that this system plays a more complex and specific role in the control of behavior than investigators previously thought. We review neurophysiological and modeling studies in monkey that support a new theory of LC-NE function. LC neurons exhibit two modes of activity, phasic and tonic. Phasic LC activation is driven by the outcome of task-related decision processes and is… Expand
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Adaptive gain and the role of the locus coeruleus–norepinephrine system in optimal performance
TLDR
It is proposed that prefrontal areas of the locus coeruleus–norepinephrine system produce the above patterns of LC activity to optimize the utility of performance on both short and long time scales. Expand
DREADD-mediated modulation of locus coeruleus inputs to mPFC improves strategy set-shifting
TLDR
The experiments sought to exogenously induce an elevated pattern of activity in LC neurons and their medial prefrontal cortical (mPFC) targets to test the tenets of the Adaptive Gain Theory (AGT) of LC function, and extend the understanding of the role of LC in PFC and flexible behavior. Expand
Locus Coeruleus Norepinephrine in Learned Behavior: Anatomical Modularity and Spatiotemporal Integration in Targets
TLDR
New evidence suggests that the modular input-output organization of the LC could enable transient, task-specific modulation of distinct brain regions, and future work must further assess whether this spatial modularity coincides with functional differences in LC-NE subpopulations acting at specific times, and how such spatiotemporal specificity might influence learned behaviors. Expand
Modafinil Shifts Human Locus Coeruleus to Low-Tonic, High-Phasic Activity During Functional MRI
TLDR
The pharmacological agent modafinil was used to promote low-tonic/high-phasic LC-NE activity in healthy humans performing a cognitive control task during event-related functional magnetic resonance imaging (fMRI). Expand
Functional specificity of the locus coeruleus-norepinephrine system in the attentional networks
TLDR
The reported results seem to suggest that Pa characterizes both alerting and orienting processes, since the temporally informative (alerting) double-cue evoked larger Pa amplitude compared to the no-cue condition, whereas the temporalally-and-spatially informative cue additionally accelerated Pa activation compared toThe alerting cue. Expand
The Neuroscience of the Flow State: Involvement of the Locus Coeruleus Norepinephrine System
TLDR
It is argued 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. Expand
Role of the locus coeruleus arousal system in cognitive control
TLDR
Empirical evidence is provided for a decisive role of the locus coeruleus noradrenergic arousal system in cognitive control in humans and novel insight into arousal‐related influences on cognitive control is provided. Expand
Locus Coeruleus Engagement Drives Network Connectivity Dynamics In Humans And Rats
TLDR
Examining how LC engagement impacted BOLD and functional connectivity variability and dynamics in resting state and attentional networks in humans and rats provides preliminary cross-species evidence suggesting that LC’s computational role in regulating performance may rest largely on its role in regulation. Expand
Context-Dependent Relationships between Locus Coeruleus Firing Patterns and Coordinated Neural Activity in the Anterior Cingulate Cortex
TLDR
The results suggest that modulations of information processing that reflect changes in coordinated activity patterns in cortical networks can result partly from ongoing, context-dependent, arousal-related changes in activation of the LC-NE system. Expand
Locus Coeruleus Phasic, But Not Tonic, Activation Initiates Global Remapping in a Familiar Environment
TLDR
The results support a role for phasic LC responses in generating novel hippocampal sequences during memory encoding and, potentially, memory updating and strengthen the view that internal states are major determinants of the brain's construction of environmental representations. Expand
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References

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TLDR
A computational model of the LC explains the relationship between patterns of LC firing and task performance by changes in electrotonic coupling among LC neurons and demonstrates that an increase in coupling results in greater phasic responses to target but not nontarget cues and also produces lower spontaneous activity. Expand
Role of locus coeruleus in attention and behavioral flexibility
TLDR
Recent work examining activity of LC neurons in monkeys performing a visual discrimination task that requires focused attention indicates that LC cells exhibit phasic or tonic modes of activity, that closely correspond to good or poor performance on this task, respectively. Expand
Role of the locus coeruleus in emotional activation.
TLDR
Although the LC is not typically considered in the context of emotion, the analysis suggests that the LC system could play an important role in the process of emotional activation. Expand
The locus coeruleus–noradrenergic system: modulation of behavioral state and state-dependent cognitive processes
TLDR
It is suggested that dysregulation of locus coeruleus-noradrenergic neurotransmission may contribute to cognitive and/or arousal dysfunction associated with a variety of psychiatric disorders, including attention-deficit hyperactivity disorder, sleep and arousal disorders, as well as certain affective Disorders, including post-traumatic stress disorder. Expand
Reward expectation, orientation of attention and locus coeruleus‐medial frontal cortex interplay during learning
TLDR
Recordings from LC and prelimbic cortex during an odour‐reward association task in the rat suggest that the activity of both these structures is related to reward anticipation and LC neurons exhibited rapid plasticity when the reward‐contingency was modified. Expand
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TLDR
Noradrenergic locus coeruleus neurons were recorded in monkeys performing a visual discrimination task, and a computational model was developed addressing the role of the LC brain system in cognitive performance, suggesting electrotonic coupling in LC may play an important role in attentional modulation and the regulation of goal-directed versus exploratory behaviors. Expand
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TLDR
The theoretical framework emerging from this research synthesis suggests that the P3 reflects the response of the LC-NE system to the outcome of internal decision-making processes and the consequent effects of noradrenergic potentiation of information processing. Expand
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TLDR
The goal of the proposed studies is to characterize the effects of noradrenergic (NA) afferents on cortical information processing and examine the relationship between the intensity of LC neuronal activity and rates of norepinephrine release in neocortex and hippocampus during manipulation of LC activity. Expand
Phasic Activation of Monkey Locus Ceruleus Neurons by Simple Decisions in a Forced-Choice Task
TLDR
It is hypothesized that the noradrenergic locus ceruleus responds to the outcome of task-related decision processes, facilitating their influence on overt behavior and this role of the LC in regulating the behavioral outcome of decisional processes contrasts with more traditional views of LC responses as primarily related to sensory processes. Expand
Discharge of noradrenergic locus coeruleus neurons in behaving rats and monkeys suggests a role in vigilance.
TLDR
The above results, in view of previous findings for postsynaptic effects of norepinephrine, are interpreted to reveal a role for the LC system in regulating attentional state or vigilance. Expand
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