Orienting and Reorienting: The Locus Coeruleus Mediates Cognition through Arousal

Sara, Susan J.; Bouret, Sébastien

doi:10.1016/j.neuron.2012.09.011

Cited by 851 publications

(799 citation statements)

References 136 publications

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“…A great deal of research has investigated the role of norepinephrine within the LC-NE system in supporting sustained attention (for review, see [18,19]) or attentional lapses [20]. The dynamics of the LC-NE system are commonly 4 separated into slow, tonic fluctuations and fast, phasic responses to stimuli that are connected via an inverse U-shape relationship: When tonic LC activity is low or high, performancerelevant phasic responses are attenuated.…”

Section: Mind Wandering and The Brainmentioning

confidence: 99%

A Neural Model of Mind Wandering

Mittner

Hawkins²,

Boekel³

et al. 2016

Trends in Cognitive Sciences

173

114

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Section: Mind Wandering and The Brainmentioning

confidence: 99%

A Neural Model of Mind Wandering

Mittner

Hawkins²,

Boekel³

et al. 2016

Trends in Cognitive Sciences

173

114

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“…The P3 component is thought to originate from neuronal inhibitory signals that inhibit unrelated neural activity to promote processing efficiency of task-relevant stimuli, thereby yielding large P3 amplitudes [13]. Correspondingly, activation of the LC-NE system in response to an important stimulus sends a "network reset" signal to the brain that interrupts the activity of the ongoing functional networks and facilitates their reorganization to promote rapid behavioral adaptation [18,55]. It is probable that only in the group of responders, because of differences in network connectivity and interactions with other neuromodulators, the VNS-induced activation of the LC-NE system results in a stronger inhibition and network reorganization that causes the antiepileptic effect.…”

Section: Discussionmentioning

confidence: 99%

The P3 Event-Related Potential is a Biomarker for the Efficacy of Vagus Nerve Stimulation in Patients with Epilepsy

et al. 2014

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Currently, the mechanism of action of vagus nerve stimulation (VNS) is not fully understood, and it is unclear which factors determine a patient's response to treatment. Recent preclinical experiments indicate that activation of the locus coeruleus noradrenergic system is critical for the antiepileptic effect of VNS. This study aims to evaluate the effect of VNS on noradrenergic signaling in the human brain through a noninvasive marker of locus coeruleus noradrenergic activity: the P3 component of the event-related potential. We investigated whether VNS differentially modulates the P3 component in VNS responders versus VNS nonresponders. For this purpose, we recruited 20 patients with refractory epilepsy who had been treated with VNS for at least 18 months. Patients were divided into 2 groups with regard to their reduction in mean monthly seizure frequency: 10 responders (>50 %) and 10 nonresponders (≤50 %). Two stimulation conditions were compared: VNS OFF and VNS ON. In each condition, the P3 component was measured during an auditory oddball paradigm. VNS induced a significant increase of the P3 amplitude at the parietal midline electrode, in VNS responders only. In addition, logistic regression analysis showed that the increase of P3 amplitude can be used as a noninvasive indicator for VNS responders. These results support the hypothesis that activation of the locus coeruleus noradrenergic system is associated with the antiepileptic effect of VNS. Modulation of the P3 amplitude should be further investigated as a noninvasive biomarker for the therapeutic efficacy of VNS in patients with refractory epilepsy.

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“…We finally used our model to study how phasic activation of LC may shape the cortical information representation of sensory stimuli. Phasic activation of LC refers to brief transient bursts of firing of LC neurons, which may happen spontaneously or be brought about by electrical stimulation of LC or by a salient external event (5).…”

Section: Modeling the Effect Of Lc Phasic Activation On Cortical Respmentioning

confidence: 99%

“…The locus coeruleus (LC) is a brainstem neuromodulatory nucleus that likely plays a prominent role in shaping cortical states via a highly distributed noradrenaline release in the forebrain (5). In particular, the LC contributes to regulation of arousal and sleep; it is involved in cognitive functions such as vigilance, attention, and selective sensory processing (5-7); and it modulates cortical sensory responses and cortical excitability (8).…”

mentioning

confidence: 99%

Modeling the effect of locus coeruleus firing on cortical state dynamics and single-trial sensory processing

Safaai

Neves

Eschenko

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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Neuronal responses to sensory stimuli are not only driven by feedforward sensory pathways but also depend upon intrinsic factors (collectively known as the network state) that include ongoing spontaneous activity and neuromodulation. To understand how these factors together regulate cortical dynamics, we recorded simultaneously spontaneous and somatosensory-evoked multiunit activity from primary somatosensory cortex and from the locus coeruleus (LC) (the neuromodulatory nucleus releasing norepinephrine) in urethane-anesthetized rats. We found that bursts of ipsilateral-LC firing preceded by few tens of milliseconds increases of cortical excitability, and that the 1-to 10-Hz rhythmicity of LC discharge appeared to increase the power of deltaband (1-4 Hz) cortical synchronization. To investigate quantitatively how LC firing might causally influence spontaneous and stimulus-driven cortical dynamics, we then constructed and fitted to these data a model describing the dynamical interaction of stimulus drive, ongoing synchronized cortical activity, and noradrenergic neuromodulation. The model proposes a coupling between LC and cortex that can amplify delta-range cortical fluctuations, and shows how suitably timed phasic LC bursts can lead to enhanced cortical responses to weaker stimuli and increased temporal precision of cortical stimulus-evoked responses. Thus, the temporal structure of noradrenergic modulation may selectively and dynamically enhance or attenuate cortical responses to stimuli. Finally, using the model prediction of single-trial cortical stimulus-evoked responses to discount single-trial state-dependent variability increased by ∼70% the sensory information extracted from cortical responses. This suggests that downstream circuits may extract information more effectively after estimating the state of the circuit transmitting the sensory message.oscillations | state dependence | dynamical systems | information coding | somatosensation R esponsiveness of cortical sensory neurons is state dependent. In other words, the neural responses to a sensory stimulus do not only depend on the features of extrinsic sensory inputs but also on intrinsic network variables that can be collectively defined as the "network state" (1). Cortical sensory neurons receive information about the external world from peripheral receptors via feedforward sensory pathways. However, the abundance of recurrent and feedback connectivity (2) may generate ongoing activity that shapes the background on which the afferent information is processed (3). In addition, neuromodulatory inputs from neurochemically specialized brain nuclei that are not part of the direct spino-thalamo-cortical pathway can modulate the dynamics of cortical networks (4), as well as control the animal's behavioral state. The concurrent integration of information about the external world and about internal states is likely to be central for computational operations of cortical circuits and for the production of complex behavior, yet its mechanisms and implications for...

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Orienting and Reorienting: The Locus Coeruleus Mediates Cognition through Arousal

Cited by 851 publications

References 136 publications

A Neural Model of Mind Wandering

A Neural Model of Mind Wandering

The P3 Event-Related Potential is a Biomarker for the Efficacy of Vagus Nerve Stimulation in Patients with Epilepsy

Modeling the effect of locus coeruleus firing on cortical state dynamics and single-trial sensory processing

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