The ascending arousal system and its impact on cognition

Lloyd, B. (2025)

Doctoral Thesis

Arousal plays a crucial role in how our brain functions, influencing thoughts, emotions, and behaviour. It fluctuates throughout the day and is driven by four major neurotransmitter systems: the noradrenergic, cholinergic, serotonergic and dopaminergic systems. These systems together form the ascending arousal system. This thesis explored arousal from three angles: tracking natural fluctuations, modulating arousal with brain stimulation, and examining its impact on memory. The first part of this thesis examined natural fluctuations in arousal at rest. By simultaneously measuring pupil size and brain activity, we found that pupil changes reflect activity across the broader arousal system—not just the noradrenergic locus coeruleus, but also dopamine-, serotonin-, and acetylcholine-related regions. The second part tested whether transcutaneous vagus nerve stimulation (tVNS), a non-invasive technique delivering mild electrical stimulation to the ear, can modulate arousal. While tVNS increased pupil size, suggesting elevated arousal, it did not reliably alter brain activity or motivation, indicating that more research is needed to understand its effects. The final section explored how arousal impacts memory. We tested whether anticipating a reward during learning boosts memory performance. Reward anticipation increased arousal, as shown by pupil size and brain activity, and was associated with improved memory for reward-related items.

• Arousal
• Pupillometry
• fMRI
• brainstem
• memory
• reward anticipation

• All authors: Lloyd, B.
• Supervisor: Nieuwenhuis, S.T.
• Co-supervisor: Wurm, F.
• Committee: Hulst, H.E; Rombouts, S.A.R.B.; Schomaker, J.; Forstmann, B.U.; Jacobs, H.
• Qualification: Doctor (dr.)
• Awarding Institution: Institute of Psychology, Faculty of Social and Behavioural Sciences, Leiden University
• Date: 2025-06-06