Jiangxi Puzhuo Medical Equipment Co., Ltd

Stepping on the brakes when seeing a red light while driving, striking keys when seeing characters while typing, executing movement instructions prompted by visual cues during rehabilitation training for stroke patients... The most common behaviors in these daily and rehabilitation scenarios all rely on a core basic brain ability — Visuomotor Association Learning (VMA).

As the core cornerstone of adaptive behavior, the efficiency of visuomotor association learning directly determines how fast healthy people acquire skills, and is closely related to clinical issues such as motor-cognitive rehabilitation after stroke, associative learning deficits following brain injury, and age-related cognitive decline. Once this ability is impaired, patients develop obvious visual-motor coordination deficits, seriously affecting the rehabilitation process and activities of daily living.

Recently, the team led by Professor Ming Dong and Researcher Wang Zhongpeng from Tianjin University published their latest research findings in NeuroImage (2026), a top international journal in neuroimaging. Through rigorous dual evidence from behavioral and electroencephalographic measurements, the study systematically demonstrated that transcutaneous auricular vagus nerve stimulation can significantly promote visuomotor association learning, and for the first time fully revealed the underlying neuromodulatory mechanism, laying a solid evidence-based medical foundation for the clinical application of taVNS in cognitive enhancement and neurorehabilitation.

I. Why focus on Visuomotor Association Learning and taVNS?

01 Visuomotor Association Learning (VMA)

Visuomotor Association Learning (VMA) is essentially the core neurocognitive ability of the brain to rapidly and flexibly establish stable associations between visual cues and corresponding motor responses. It is the basic skill for humans to adapt to the environment and survive, and also a core target for motor-cognitive function assessment and rehabilitation intervention.

Previous neurophysiological studies have confirmed that the acquisition of VMA is not a simple activation of a single neural pathway, but is accompanied by dynamic remodeling of multidimensional neural activity across the whole brain, covering the full chain of cognitive processes from early visual perceptual input, visual-motor signal transformation, to online behavioral monitoring, error feedback processing, and synchronous integration of neural circuits. The strength of this ability directly determines an individual's response efficiency to complex environments, and its functional deficit is also a core manifestation of motor-cognitive impairment after stroke, brain injury and other neurological disorders. Therefore, mechanism decoding and targeted modulation of VMA represent an important direction in basic neuroscience research and clinical rehabilitation.

02 Transcutaneous Auricular Vagus Nerve Stimulation (taVNS)

Transcutaneous Auricular Vagus Nerve Stimulation (taVNS) is a mature non-invasive neuromodulation technique. By applying low-frequency electrical pulses to the auricular branch of the vagus nerve distributed in the ear, it can achieve precise and non-invasive modulation of the central nervous system through vagal conduction pathways, with the advantages of convenient operation, high safety and wide adaptability.

A large body of existing evidence-based studies has confirmed that taVNS has definite efficacy in depression intervention, post-stroke neurological function rehabilitation, and cognitive and memory function improvement. It also shows the potential to enhance motor control and higher-order cognitive functions in healthy populations. The mainstream mechanistic hypothesis in academia holds that the pro-learning effect of taVNS may be achieved by activating subcortical nuclei such as the locus coeruleus and nucleus tractus solitarius, enhancing central noradrenergic signaling, and thereby modulating key cognitive states such as arousal and attention to promote learning-related neuroplasticity.

However, to date, whether taVNS can effectively modulate VMA — a core motor-cognitive ability — and the deep neural mechanism underlying its action remain systematically unclear; and answering this key scientific question is precisely the core prerequisite for determining whether taVNS can truly translate from basic research findings to clinical motor-cognitive rehabilitation settings.

03 Electroencephalogram (EEG): The core decoding tool for VMA neural processes and taVNS modulatory effects

Electroencephalogram (EEG), with its ultra-high millisecond-level temporal resolution and non-invasive detection characteristics, can precisely capture dynamic changes in brain neural activity, and is the core technical means for dynamically decoding the full chain of VMA learning processes and quantifying the neuromodulatory effects of taVNS. Based on the cognitive processing stages of VMA and the modulatory mechanism of taVNS, the core EEG indicator system set in this study is divided into the following four categories, which can systematically verify the modulatory effect of taVNS on VMA learning:

◼Early visual perception and discrimination processing indicators: centered on Event-related Potentials (ERPs) in the occipital-parietal regions, including key indicators N170, P200 and P300, used to reflect the perceptual, discrimination and attention allocation processing of early visual input in VMA tasks, and to quantify the modulatory effect of taVNS on the early-stage visual perception processing.

◼Behavioral monitoring and error processing indicators: centered on Error-related Negativity (ERN), an indicator specifically elicited after erroneous responses, which can precisely capture the online behavioral performance monitoring, error detection and feedback processing in VMA tasks, and is used to evaluate the effect of taVNS on behavioral regulation and feedback learning.

◼Cross-frequency functional integration indicator between brain regions: centered on Phase-Amplitude Coupling (PAC). Traditional neural connectivity indicators can only reflect same-frequency neural synchronization between brain regions, whereas PAC can capture the modulation effect of low-frequency phase on high-frequency amplitude, precisely quantifying the cross-frequency dynamics between brain regions that support visual-motor signal transformation. It can further quantify phase-amplitude synchronization between brain regions through phase locking value, serving as a key indicator for evaluating the modulatory effect of taVNS on the core transformation stage of VMA.

◼Neural processing stability indicator: centered on Inter-Trial Phase Coherence (ITPC), used to evaluate the inter-trial consistency of neural processing at key task nodes, and can objectively reflect the modulatory effect of taVNS on the stability and reliability of VMA-related neural processing.

Study Design and Core Objectives

Based on the theoretical foundations of the above three modules, this study proposes the core hypothesis: transcutaneous auricular vagus nerve stimulation (taVNS) can promote visuomotor association learning by enhancing multidimensional neurocognitive processing during VMA acquisition. To verify this hypothesis, the Tianjin University team conducted a single-blind, sham-controlled, between-subject clinical trial, aiming to comprehensively verify the facilitating effect of taVNS on VMA learning and systematically reveal the underlying neurophysiological mechanism, so as to provide evidence-based basis for the clinical translation of taVNS in the field of motor-cognitive rehabilitation.

II. Rigorous study design makes research conclusions more convincing

A total of 38 healthy right-handed participants were recruited and randomly divided into a real stimulation group and a sham stimulation group, with 19 in each group. There were no significant differences in baseline levels between the two groups, and a single-blind design was adopted throughout to minimize the interference of subjective factors on the results. It is worth noting that the non-dominant hand (left hand) was used to complete the tasks throughout the experiment, which maximally avoided the "ceiling effect" brought by the proficiency of the dominant hand, allowing the intervention effect of taVNS to be captured more accurately and sensitively.

The entire experimental procedure consists of four core stages, fully covering the whole process from pre-intervention baseline acquisition, intervention implementation, to post-intervention effect verification:

Figure 1: Experimental procedure.

A: Single-trial procedure: participants needed to make visuomotor judgments within 1500 ms; correct responses received immediate feedback, while trials exceeding this time window triggered a speed reminder and were counted as errors.

B: Complete experimental procedure: after landscape/button association training, participants completed a pre-stimulation task of 320 trials. This was followed by a 20-minute active-sham taVNS treatment and a post-stimulation task of 320 trials.

Training stage

Participants completed 30 trial-and-error training sessions to familiarize themselves with the oracle-bone-script image to keyboard key mapping task and establish basic task cognition; no formal data were collected in this stage;

Pre-stimulation baseline test

Participants completed 320 VMA trials, with simultaneous collection of behavioral data (reaction time, accuracy) and 64-channel EEG data to obtain the pre-intervention baseline level;

taVNS intervention stage

The real stimulation group received 20 minutes of taVNS intervention over the left ear concha (a region densely innervated by the auricular branch of the vagus nerve), while the sham stimulation group received stimulation with the same parameters only over the left earlobe (where no effective vagal innervation exists, serving as a clinically recognized sham control). Stimulation parameters adopted the commonly used clinical protocol: 25 Hz frequency, 200-300 μs pulse width, with intensity set to the individual perception threshold, balancing intervention effectiveness and comfort;

Post-stimulation effect verification

Participants completed 320 brand-new VMA trials, with simultaneous collection of behavioral and EEG data; through between-group comparison, the intervention effect of taVNS was clarified.

Electroencephalogram (EEG) data were collected before and after stimulation using a 64-channel SysAmps2 system with standard Ag/AgCl electrodes (10-20 system). The reference electrode was placed on the nose and the ground electrode on the forehead. Before the experiment and at the beginning of each experimental phase (pre- and post-stimulation), the impedance of all electrodes was monitored using the supporting SCAN4.5 software — ensuring that the impedance of all electrodes was adjusted and maintained below 20 kΩ to guarantee signal quality. The sampling rate was set at 1000 Hz.

III. Core findings: taVNS comprehensively empowers visuomotor association learning from behavioral to neural levels

Through behavioral data analysis and in-depth mining of EEG signals, the research team, from "visible effects" to "invisible neural mechanisms", fully confirmed the facilitating effect of taVNS on VMA learning.

01 Definitive behavioral evidence: taVNS achieves "fast and accurate" improvement in learning efficiency

After correcting for baseline levels, the between-group comparison clearly demonstrated the intervention value of taVNS:

◼Significantly faster response speed: the mean task reaction time of the real stimulation group was 761.7 ms, significantly shorter than 825.7 ms in the sham group (p=0.026);

◼Significantly higher response accuracy: the mean task accuracy of the real stimulation group was 83.0%, significantly higher than 77.0% in the sham group (p=0.009);

◼Significantly faster learning process: the learning curve constructed by the Bayesian state-space model showed that the learning curve integral of the real stimulation group was significantly higher, meaning that participants could complete the learning process from unfamiliarity to proficiency faster, greatly shortening the skill acquisition cycle.

More clinically meaningful is that reaction time and accuracy in the real stimulation group showed a significant negative correlation, breaking the traditional "speed-accuracy trade-off" effect — after taVNS intervention, participants did not need to sacrifice accuracy to improve speed, nor slow down to ensure accuracy, achieving a "fast and accurate" learning outcome. This is precisely the core sign of the brain's visuomotor processing shifting from "controlled processing" to "automatic processing", directly confirming that taVNS provides a substantial promotion of VMA learning rather than merely an attention improvement.

Figure 3: Behavioral results.

A. Bar chart of reaction time in the post-stimulation phase. B. Bar chart of reaction accuracy in the post-stimulation phase. C. Scatter plot of mean probabilities under four conditions (active-pre, sham-pre, active-post and sham-post periods). D. Bar chart of integral values in the post-stimulation phase.

Note: Post-stimulation data shown are uncorrected. The statistical method is based on analysis of covariance (ANCOVA) taking baseline covariates into account.

02 Neural mechanism revealed: four dimensions reshape brain learning-related neural activity

Behavioral results confirmed that taVNS "works", while in-depth analysis of EEG data answered the core question of "why it works". The research team fully revealed the neurophysiological mechanism by which taVNS promotes VMA learning from four dimensions.

Optimizing early visual information processing, allowing the brain to "see more accurately and process faster"

Efficient recognition and processing of visual information is the first step of VMA learning. The study found that taVNS significantly modulated key visual event-related potential (ERP) components in the occipital-parietal regions:

◼Enhanced N170 negative amplitude: N170 is a core indicator of visual stimulus discrimination processing, and its amplitude is sensitive to the recognition of human faces and words. The enhancement of its negative amplitude means that the brain's recognition and discrimination ability for visual characters is significantly improved, achieving cognitive gain consistent with repeated memory reinforcement. Current data indicate that taVNS enhances the N170 negativity, suggesting that neural efficiency in VMA learning is improved. This pattern is similar to the cognitive benefits under frequent memory conditions, suggesting that taVNS may optimize visual stimulus processing through a mechanism akin to memory reinforcement.

◼Reduced P200 and P300 amplitudes: P200 is closely related to visual information integration, while P300 directly reflects stimulus familiarity and working memory load. The reduction in both amplitudes indicates that taVNS reduces the neural resources required by the brain to complete visual information integration, lowers working memory load, and makes visual processing more efficient and automatic.

Figure 4: ERP results.

A: Topographic maps of mean amplitudes in key time windows. B: Statistical analysis results of ERP (N170, P200 and P300) amplitudes.

Weakening error-related cognitive conflict, allowing the brain to "learn more stably and allocate resources more optimally"

ERN is a response-locked potential elicited by unexpected errors. During learning, erroneous responses trigger conflict monitoring in the brain and occupy a large amount of attentional resources, which in turn interfere with subsequent learning.

In the sham group, the ERN showed a more pronounced (i.e., more negative) pattern from pre- to post-stimulation; whereas the active stimulation group showed the opposite trend, with the ERN attenuated (i.e., less negative) after transcutaneous vagus nerve stimulation (taVNS).

ANCOVA confirmed that the post-stimulation ERN component was significantly larger (more negative) in the sham group than in the active group. A larger ERN component reflects increased attention allocation and cognitive investment during error monitoring. The current results suggest that taVNS may reduce perceived error conflict by enhancing cognitive and memory abilities, which potentially allows participants to allocate resources more effectively during visuomotor association learning (VMA learning).

Figure 5: ERN results.

A: ERN and CRN curves under four conditions. B: Box plots of ERN and ΔERN amplitudes.

Enhancing cross-brain-region, cross-frequency synchronization, allowing the brain to have "better visual-motor-cognitive coordination"

Visuomotor association learning is not the work of a single brain region, but requires high coordination among visual, motor, and prefrontal cognitive brain regions.

Theta-band neural activity in the occipital region is related to visual recognition processes. Parietal alpha-band activity is related to sensory information processing and integration.

While alpha-band activity in the frontoparietal-parietal region usually represents motor preparatory responses.

Low-gamma activity in the frontal region is closely related to cognitive decision-making.

In addition, frontoparietal synchronization can predict the accuracy of value-based decision-making.

Based on these findings, the research team calculated PLVPAC signals across brain regions and frequency bands to evaluate inter-regional oscillatory synchronization. Current results indicate that transcutaneous auricular vagus nerve stimulation (taVNS) enhanced (low-frequency) phase-(high-frequency) amplitude coupling, including between occipital and premotor regions, and between parietal and prefrontal regions.

Enhanced phase-amplitude coherence may promote visuomotor coordination and cognitive integration, thereby improving the efficiency of visuomotor association learning.

Figure 6: Box plots of PLVPAC.

A: Box plot of OT-CA PLVPAC during the post-stimulation period. B: Box plot of PA-FG PLVPAC during the post-stimulation period. The topoplots in the upper right corner represent channel selection (gray-purple: low frequency; rose-pink: high frequency).

Improving neural response stability, allowing the brain to process information "more consistently and reliably"

Improving learning efficiency requires not only efficient coordination between brain regions, but also stable and consistent neural responses of the brain to each task. Through Inter-Trial Phase Coherence (ITPC) analysis, the study found that taVNS significantly increased the ITPC values of participants' parieto-occipital regions in three core frequency bands: theta, alpha and beta.

ITPC reflects the phase consistency of the brain's neural responses across different task trials; the higher the value, the more stable and precise the brain's neural processing of visual stimuli, and the stronger the reliability of information transmission. Meanwhile, correlation analysis also confirmed that the ITPC value in the alpha band was significantly negatively correlated with reaction time — the more stable the neural response, the faster the participant's reaction speed, directly establishing a strong association between neural indicators and behavioral performance.

Figure 7: ITPC results for three frequency bands.

A: ITPC curves for three frequency bands. Shaded areas indicate selected time points. B: Bar chart of ITPC peaks.

Summary of the effects and mechanism of taVNS modulation on VMA learning

Through a single-blind, between-subject visuomotor association learning (VMA) experiment, this study systematically explored the modulatory effect of transcutaneous auricular vagus nerve stimulation (taVNS) on left-hand VMA learning, with simultaneous collection and analysis of behavioral and EEG data. It finally confirmed that taVNS can significantly promote VMA learning, and its effects are highly consistent with the presupposed neurophysiological mechanism.

From the perspective of mechanism of action

The modulatory effect of taVNS is mainly achieved through two core pathways:

taVNS modulates the GABAergic system and the LC-NTS (locus coeruleus-nucleus tractus solitarius) system.

①As an inhibitory neurotransmitter, GABA is crucial for learning and memory encoding; it can enhance inhibitory control over competing responses and suppress erroneous choices to promote accurate decision-making.

taVNS can exert its effect by modulating the GABAergic system, a conclusion supported by research findings related to "enhanced short-interval intracortical inhibition after stimulation";

②Norepinephrine released by the NTS-LC system affects cognitive tasks, and previous studies have demonstrated its role in modulating various memory processes, such as emotional memory and selective memory. taVNS can activate the locus coeruleus-norepinephrine (LC-NE) pathway through the nucleus tractus solitarius, and multiple pupillometry studies further support the activation of this pathway — compared with sham stimulation, both phasic and tonic taVNS protocols can induce rapid pupil dilation, a peripheral indicator of LC-NE activity.

Behavioral results showed that

The active taVNS group showed significantly better task performance after intervention than the sham group, with shorter reaction times, higher accuracy and steeper learning curves, providing direct behavioral evidence that taVNS promotes VMA learning.

At the electrophysiological level

taVNS comprehensively modulated a series of task-related neural indicators: the intervention significantly altered the amplitudes of visual event-related potentials (N170, P200, P300) and the response-locked error-related negativity (ERN), enhanced cross-brain-region cross-frequency phase-amplitude coupling (PAC), and simultaneously improved inter-trial phase coherence (ITPC) in the theta, alpha and beta bands.

Significant correlations exist among the above indicators, further confirming their synergistic role during VMA learning.

Study limitations and future research directions

01. Limitations in mechanism elucidation

Direct neurochemical indicators such as norepinephrine and GABA at taVNS modulation targets were not obtained, making it impossible to deeply elucidate the underlying mechanism by which taVNS modulates VMA learning. Future studies need to supplement detection of relevant neurochemical indicators to improve the pathway analysis of taVNS modulation of visuomotor learning.

02. Limitations in stimulation parameters

Parameters such as taVNS intensity and duration were not systematically optimized in this study, and the optimal stimulation protocol for visuomotor learning has not yet been determined. Future studies need to conduct parameter gradient experiments to determine the optimal stimulation paradigm that maximizes learning gains.

03. Limitations in statistical power

The sample size was limited, and post-hoc sensitivity analysis showed that this design could only reliably detect large effect sizes (f=0.467, Cohen's d=0.934), easily missing small but potentially meaningful effects. Future studies need to expand the sample size (35-50 per group) to verify existing findings and explore the fine-grained effects of medium-sized effects.

04. Limitations in neural localization

EEG was only analyzed at the sensor level, unable to precisely localize the neural sources of phase coherence effects. Future studies need to combine high-density EEG source localization or multimodal imaging techniques to clarify the neural origin of the effects and the regulatory networks.

05. Limitations in result generalization

Only right-handed participants were included and a non-dominant-hand VMA task was used, resulting in insufficient generalizability of the results. Future studies need to extend to the dominant limb and left-handed populations to verify the generalizability of the effects and potential lateralization characteristics.