Clinical Study: Effects Evident Within 30 Minutes! Neural Mechanism of 40Hz Auricular Electrical Stimulation in Enhancing Memory

A recent study by a team from Xuzhou Medical University in China has elucidated the key neural mechanisms underlying the improvement of working memory by a novel 40-Hertz burst-pattern transcutaneous auricular vagus nerve stimulation (taVNS). The related findings were published online on December 8, 2025, in Neuromodulation: Technology at the Neural Interface (Impact Factor 3.5).[1]

Study Highlights
This research is the first to discover that 40-Hz burst-pattern taVNS, administered in a 5-second on/5-second off cycle, can effectively enhance behavioral performance in working memory and related neuroelectrophysiological metrics by simultaneously modulating the noradrenergic and GABAergic systems.

 

Introduction
Working memory (WM) is crucial, yet conventional enhancement methods have limited efficacy. Although transcutaneous auricular vagus nerve stimulation (taVNS) shows potential, its effects vary significantly depending on the stimulation parameters.

Traditional long-duration stimulation paradigms (e.g., 30-second on/30-second off) may lead to neural adaptation, whereas brief burst stimulation could more effectively activate the locus coeruleus–norepinephrine (LC-NE) system.

This study aimed to evaluate whether a novel 40-Hz burst (40-Hz-B, 5-second on/5-second off) taVNS protocol could enhance WM and to investigate its neural mechanisms using electroencephalography (EEG), focusing on components such as P3b, Theta event-related synchronization (ERS), and Alpha event-related desynchronization (ERD).

 

Methods

Design: Prospective, randomized, double-blind, controlled trial.

Participants: Eighty healthy, right-handed students were randomly assigned to one of four groups (20 participants per group).

Table 1: Demographic Characteristics of Participants.

 

Intervention:

• All groups received 30 minutes of left-ear taVNS.
• Sham Group: Electrodes were placed identically, but the output current was set to 0 milliamperes.
• 5 Hz Group: Conventional frequency stimulation, delivered in a 30-second on/30-second off cycle.
• 25 Hz Group: Conventional frequency stimulation, delivered in a 30-second on/30-second off cycle.
• 40-Hz-B Group: 40 Hz frequency stimulation, delivered in a burst-pattern of 5-second on/5-second off cycles.

Stimulation Device: A commercial taVNS device (RISHENA; tVNS501) was used, with stimulation intensity individualized to each participant's maximum tolerable level.

Efficacy Assessment Metrics:

Primary Behavioral Metrics: Accuracy (ACC) and reaction time (RT) on a visual Three-back task administered post-stimulation.

Neurophysiological Metrics (recorded via 64-channel EEG):

• Event-Related Potential (ERP): Amplitude of the P3b component over parietal regions (reflecting attentional resource allocation).
• Event-Related Synchronization/Desynchronization (ERS/ERD): Frontal Theta-band ERS (reflecting cognitive control) and parietal Alpha-band ERD (reflecting interference suppression).

 

Results

The results demonstrated that a single 30-minute session of 40-Hz burst-pattern taVNS significantly improved working memory performance.

Figure 1: Experimental Design and Working Memory Task Performance.

a. Schematic of the three-back task; a "+" indicates the fixation cross presented before task initiation. b. Experimental setup for EEG recording. A participant wearing a 64-channel EEG cap performs the task in a sound-attenuated booth. c. Temporal patterns of the four taVNS stimulation protocols. d, e. Statistical results for accuracy and reaction time, respectively.

 

Participants in this group not only responded more accurately (significantly higher accuracy rates) but also more quickly (significantly shorter reaction times) during the high-cognitive-load Three-back task.

Figure 2: Event-Related Potential (ERP) Features During the Three-Back Task.
a. Scalp topography maps reflecting the distribution of the P3b component between 300 and 500 milliseconds post-stimulus (during the P3b peak).
b. Grand-average P3b waveforms at parietal electrode sites (highlighted in gray).
c. Comparison of the mean P3b amplitude at parietal sites across the four groups during the three-back task.

 

Neurophysiological Basis:

EEG data indicated that participants in the 40-Hz-B group exhibited enhanced allocation of attentional resources (increased P3b amplitude), stronger cognitive control (enhanced frontal Theta synchronization), and more effective suppression of interfering information (enhanced parietal Alpha desynchronization) during the task.

Significant correlations were found between the degree of improvement in these neural metrics and the extent of behavioral enhancement. This confirms that 40-Hz-B taVNS improves working memory by optimizing the brain's internal resource utilization and inhibitory control.

The study further revealed statistically significant correlations within the 40-Hz-B group between the improvement in the aforementioned neural indicators and the behavioral gains in working memory (i.e., increased accuracy and shortened reaction time). This provides strong evidence that the behavioral improvements were directly driven by these specific neural activity changes. 

Figure 3: Characteristic Theta and Alpha Oscillation Patterns During the Three-Back Task.
a. Topographic maps of Theta event-related synchronization (ERS) and Alpha event-related desynchronization (ERD).
b. Statistical results for Theta ERS in the frontal region.
c. Statistical results for Alpha ERD in the parietal region.

 

Conclusion
A single session of 40-Hz-B taVNS can enhance working memory in healthy young adults by optimizing its fundamental gating mechanisms.

This improvement is supported by distinct neurophysiological signatures: increased P3b amplitude and enhanced frontal Theta ERS, reflecting improved attention allocation and cognitive control mediated via the LC-NE system; and enhanced parietal Alpha ERD, likely mediated by GABAergic pathways, reflecting superior interference suppression.

The efficacy of this specific stimulation paradigm underscores the critical importance of temporal precision in taVNS for cognitive enhancement.

 

 

 

[1] Yuning Sun, Yan Zhang, Meiyan Zhou, Liwei Wang, et al. Temporal Precision of 40-Hz Burst Transcutaneous Auricular Vagus Nerve Stimulation Improves Working Memory in Healthy Volunteers. Neuromodulation, January 03, 2026

https://www.neuromodulationjournal.org/article/S1094-7159(25)01187-0/fulltext