Deciphering the role of noradrenergic ascending neuromodulation in large-scale system communication

Abstract

The current thesis investigates the intricate role played by the locus coeruleus noradrenergic system (LC-NA) in shaping adaptive cognitive and neurobiological processes. The LC is the central hub of the ascending noradrenergic system, adaptatively regulating its state in response to environmental and internal states and demands. The LC system has been associated with the adaptive modification of functional network architecture and cortical states by modulating the excitability of brain regions. Furthermore, the LC alters overall vigilance states as well as moment-to-moment fluctuations in brain state. In this thesis, we delve deeper into the dynamics and role of the arousal system in the modulation of large-scale system dynamics across various cognitive domains. First, we demonstrate its involvement in perceptual reset under ambiguity using pupillometry, fMRI, and computational models. Next, we shed light on the role of the LC arousal system and its adaptive changes in large-scale topological signatures towards integration during a visuospatial attention-demanding task. Finally, we show the impact of catecholamines on executive function processes and the influence of genetic variability and pharmacological manipulation on its dynamics. This research demonstrates the importance of the LC in modulating large-scale dynamics across different cognitive conditions. Furthermore, it highlights its central role in neurobiological and cognitive processes across scales and context, with implications for understanding the basics mechanism of neuromodulation and brain function.