Abstract
The decline in noradrenergic (NE) locus coeruleus (LC) function in aging is thought to be implicated in episodic memory decline. Transcutaneous auricular vagus nerve stimulation (taVNS), which supports LC function, might serve to preserve or improve memory function in aging. However, taVNS effects are generally very heterogeneous, and it is currently unclear whether taVNS has an effect on memory. In this study, an emotional memory task with negative events involving the LC-NE system was combined with the short burst of event-related taVNS (3 s) in younger adults (N = 24). The aim was to investigate taVNS-induced changes in pupil dilation during encoding and possible taVNS-induced improvements in (emotional) memory performance for early and delayed (24 h) recognition. Negative events were associated with increased pupil dilation and better memory performance. Additionally, real as compared to sham or no stimulation selectively increased memory for negative events. Short bursts of stimulation, whether real or sham, led to an increase in pupil dilation and an improvement in memory performance over time, likely due to the attention-inducing sensory modulation of electrical stimulation.

Abstract
The efcacy of transcutaneous auricular vagus nerve stimulation (taVNS) as a non-invasive method to modulate physiological markers of noradrenergic activity of the Locus Coeruleus (LC), such as pupil dilation, is increasingly more discussed. However, taVNS studies show high heterogeneity of stimulation efects. Therefore, a taVNS setup was established here to test diferent frequencies (10 Hz and 25 Hz) and intensities (3 mA and 5 mA) during phasic stimulation (3 s) with time-synchronous recording of pupil dilation in younger adults. Specifcally, phasic real taVNS and higher intensity led to increased pupil dilation, which is consistent with phasic invasive VNS studies in animals. The results also suggest that the infuence of intensity on pupil dilation may be stronger than that of frequency. However, there was an attenuation of taVNS-induced pupil dilation when diferences in perception of sensations were considered. Specifcally, pupil dilation during phasic stimulation increased with perceived stimulation intensity. The extent to which the efect of taVNS induces pupil dilation and the involvement of sensory perception in the stimulation process are discussed here and require more extensive research. Additionally, it is crucial to strive for comparable stimulation sensations during systematic parameter testing in order to investigate possible efects of phasic taVNS on pupil dilation in more detail. 

Abstract
The locus coeruleus (LC), our main source of norepinephrine (NE) in the brain, declines with age and is a potential epicentre of protein pathologies in neurodegenerative diseases (ND). In vivo measurements of LC integrity and function are potentially important biomarkers for healthy ageing and early ND onset. In the present study, high-resolution functional MRI (fMRI), a reversal reinforcement learning task, and dedicated post-processing approaches were used to visualise age differences in LC function (N = 50). Increased LC responses were observed during emotionally and task-related salient events, with subsequent accelerations and decelerations in reaction times, respectively, indicating context-specific adaptive engagement of the LC. Moreover, older adults exhibited increased LC activation compared to younger adults, indicating possible compensatory overactivation of a structurally declining LC in ageing. Our study shows that assessment of LC function is a promising biomarker of cognitive aging. 

Abstract

Transcutaneous auricular vagus nerve stimulation (taVNS), as a non-invasive brain stimulation technique may influence the locus coeruleus-norepinephrine system (LC-NE system) via modulation of the Vagus Nerve (VN) which projects to the LC. Few human studies exist examining the effects of taVNS on the LC-NE system and studies to date assessing the ability of taVNS to target the LC yield heterogeneous results. The aim of this review is to present an overview of the current challenges in assessing effects of taVNS on LC function and how translational approaches spanning animal and human research can help in this regard. A particular emphasis of the review discusses how the effects of taVNS may be influenced by changes in structure and function of the LC-NE system across the human lifespan and in disease.