Auricular Transcutaneous Vagus Nerve Stimulation Specifically Enhances Working Memory Gate Closing Mechanism: A System Neurophysiological Study

Abstract

Everyday tasks and goal-directed behavior involve the maintenance and continuous updating of information in working memory (WM). WM gating reflects switches between these two core states. Neurobiological considerations suggest that the catecholaminergic and the GABAergic are likely involved in these dynamics. Both of these neurotransmitter systems likely underly the effects to auricular transcutaneous vagus nerve stimulation (atVNS). We examine the effects of atVNS on WM gating dynamics and their underlying neurophysiological and neurobiological processes in a randomized crossover study design in healthy humans of both sexes. We show that atVNS specifically modulates WM gate closing and thus specifically modulates neural mechanisms enabling the maintenance of information in WM. WM gate opening processes were not affected. AtVNS modulates WM gate closing processes through the modulation of EEG alpha band activity. This was the case for clusters of activity in the EEG signal referring to stimulus information, motor response information and fractions of information carrying stimulus-response mapping rules during WM gate closing. EEG-beamforming shows that modulations of activity in fronto-polar, orbital and inferior parietal regions are associated with these effects. The data suggest that these effects are not due to modulations of the catecholaminergic (noradrenaline) system as indicated by lack of modulatory effects in pupil diameter dynamics, in the inter-relation of EEG and pupil diameter dynamics and saliva markers of noradrenaline activity. Considering other findings, it appears that a central effect of atVNS during cognitive processing refers to the stabilization of information in neural circuits, putatively mediated via the GABAergic system.Significance statement:Goal-directed behavior depends on how well information in short-term memory can be flexibly updated but also on how well it can be shielded from distraction. These two functions were guarded by a working memory gate. We show how an increasingly popular brain stimulation techniques (atVNS) specifically enhances the ability to close the WM gate to shield information from distraction. We show what physiological and anatomical aspects underlie these effects.

Neurophysiological effective network connectivity supports a threshold-dependent management of dynamic working memory gating

“…On a behavioral level, participants committed fewer errors and showed longer RTs in gate closing than opening, replicating previous research. 7 , 8 , 9 , 10 , 11 As mentioned earlier, gate closing and opening represent switch costs from a reference to a comparison trial and vice versa. The DDM of the behavioral data provided further insights into the computational mechanisms.…”

“…For this study, data from two previous experimental studies 7 , 12 in healthy individuals of european ancestry were aggregated ( N = 63 in total; 20 males, mean age 25.1 ± 4.6 years, all right-handers). All participants had normal or corrected to normal vision, normal hearing, and no history of neurological or mental illnesses.…”

“… 2 , 3 , 4 The closed state is assumed to reflect the default WM state, which allows the maintenance of representation through shielding WM from distraction. 5 , 6 So far, several studies have showed WM gate opening and closing effects and delineated some underlying neural principles, 7 , 8 , 9 , 10 , 11 , 12 which are triggered by useful or distracting perceptual information, respectively. 13 However, it is still unclear how the decision to open or close the WM gate is implemented on a computational neural level.…”

Transcutaneous vagus nerve stimulation: a new strategy for Alzheimer’s disease intervention through the brain-gut-microbiota axis?

“…Although imaging studies elucidating tVNS effects on AD are in the preliminary stages, some hypotheses have been formulated based on existing research. A randomized crossover trial involving a healthy population found that taVNS influenced working memory by modulating the alpha band activity of the EGCs, potentially mediated by the GABA system ( Konjusha et al, 2023 ). Huang et al (2023) conducted a clinical study using fMRI and observed that repetitive taVNS could modulate functional connectivity within the CNS region of the vagal pathway and limbic system, including the bilateral hippocampus, postcentral gyrus, thalamus, and basal ganglia.…”

Cognitive Functions following Trigeminal Neuromodulation

“…However, the external ear is also innervated by trigeminal nerve fibers, partially overlapping with the vagus territory [ 100 , 101 ]; therefore, an appropriate electrode positioning easily results in the stimulation of both trigeminal and vagal afferents [ 6 , 102 ]. The study of auricular tVNS has seen great development in recent years, especially with regard to improved cognitive performance, not only in the clinical population but also in healthy subjects [ 103 , 104 , 105 , 106 , 107 ]. While the neurobiological mechanisms are still unclear, the available literature mostly seek to explain the positive effects of tVNS on cognitive performance in terms of a change in brain NE levels [ 64 , 108 ].…”