Vibrotactile transcutaneous auricular vagus nerve stimulation (taVNS) during working memory: convergent...

Working memory, the cognitive ability to maintain and manipulate a finite amount of information, is fundamental in reasoning, learning, and decision-making. Working memory erodes in conditions from Alzheimer's disease to stroke to healthy aging. Transcutaneous auricular vagus nerve stimulation (taVNS) is a promising neuromodulation method for improving working memory. By stimulating the auricular branch of the vagus nerve, taVNS is thought to engage ascending arousal systems such as the locus coeruleus-norepinephrine (LC-NE) system. However, the physiological link between LC-NE system modulation via taVNS and improved working memory remains largely unknown. This mechanistic gap limits the rational optimization of the stimulation protocol and the identification of the cognitive functions and patient populations that are likely to benefit.

We test two competing hypotheses for how taVNS may improve working memory: sensory amplification or enhancement of cortical efficiency. The sensory-amplification hypothesis predicts increased cortical responses to stimuli, whereas the cortical-efficiency hypothesis predicts reduced cortical responses.

Twenty healthy adults completed N-back working memory tasks during three counterbalanced sessions: baseline, active vibrotactile taVNS (vtaVNS), and sham stimulation, while we simultaneously recorded electroencephalography, electrocardiography, eye-tracking, and behavioral responses. To study the effect of vtaVNS on neuronal activity, we also recruited 20 patients with epilepsy undergoing invasive monitoring. Of these, 19 fully completed the spatial working-memory task. We quantified cortical responses to visual stimuli using event-related potentials (ERPs) in scalp EEG and high-gamma activity in intracranial local field potentials. To examine prediction of the cortical-efficiency hypothesis, we further explored the effect of vtaVNS on distance to criticality and heartbeat-evoked potentials.

Active vtaVNS reduced both scalp-recorded visual ERP and high-gamma response in temporal cortices, relative to sham stimulation. Moreover, smaller visual event-related potentials were associated with successful encoding during the most demanding working-memory condition (i.e., 4-back task). Exploratory analyses showed that vtaVNS shifted cortical dynamics closer to criticality.

Our results converge on the conclusion that vtaVNS does not uniformly amplify cortical responses to external stimuli. Instead, vtaVNS enhances cortical efficiency, supporting more effective allocation of cognitive resources between exteroceptive and mnemonic processes. These findings provide a framework for predicting when taVNS will be most beneficial and for optimizing stimulation protocols across cognitive and clinical applications.

Consistent visual event-related potential in human subjects during an N-back working memory taskVibrotactile taVNS reduced stimulus-evoked cortical responses in both scalp EEG and intracranial high-gamma activity (70-150 Hz).Reduced visual event-related potentials are associated with successful encoding in the 4-back task.Vibrotactile taVNS shifted cortical dynamics toward a near-critical regime.