A Closed-Loop ta-VNS System Synchronized with BCI-Based Motor Training for Post-Stroke Upper Limb Rehabilitation

Summary

This study demonstrates a standardized protocol for a closed-loop ta-VNS system synchronized with BCI-based motor training. Furthermore, it compares the efficacy of the closed-loop ta-VNS system synchronized with BCI-based motor training with that of sham ta-VNS, providing significant evidence for its clinical application in stroke rehabilitation.

Abstract

Transcutaneous auricular vagus nerve stimulation (ta-VNS) involves applying electrical stimulation via electrodes to the auricular concha. This activates vagal afferent fibers, initiating an ascending pathway from the periphery to the brainstem, which ultimately stimulates central vagal projections and promotes neural plasticity. Previous studies have demonstrated that combining ta-VNS with motor training offers synergistic benefits for motor recovery after stroke. However, these combined approaches typically employ open-loop stimulation with fixed parameters, lacking real-time closed-loop responsiveness to dynamic neural activity. To address this limitation, we developed a novel closed-loop ta-VNS system synchronized with electroencephalography (EEG)-triggered brain-computer interface (BCI) motor training. This system was designed to enhance corticospinal coupling and promote synaptic plasticity. We established a standardized protocol for applying this closed-loop ta-VNS system synchronized with BCI-based motor training in stroke patients. Using EEG-based functional assessment, we compared the effects of the closed-loop ta-VNS system synchronized with BCI-based motor training to those of sham ta-VNS synchronized with BCI-based motor training. This work provides the methodological and theoretical groundwork for the clinical application of this approach in stroke rehabilitation.

Introduction

Transcutaneous auricular vagus nerve stimulation (ta-VNS) is a non-invasive neuromodulation technique used to ameliorate post-stroke motor impairments¹. This method entails stimulating the auricular concha with electrodes to activate the auricular branch of the vagus nerve. Such stimulation initiates the nucleus tractus solitarius (NTS)-locus coeruleus (LC) pathway², which ascends to central vagal projections in the motor cortex, frontal lobe, thalamus, and cerebellum. This process enhances neural plasticity and network reorganization³. Compared with traditional invasive vagus nerve stimulation, t....

Protocol

The study was approved by the Medical Ethics Association of the Seventh Affiliated Hospital of Sun Yat-sen University (Shenzhen, China) (approval number: KY-2025-318-01) on April 30, 2025. The trial was registered in the Chinese Clinical Trials Registry (registration number: ChiCTR2500104317) on June 16, 2025. The subject signed the informed consent form.

1. Recruitment

1. Inclusion criteria
   1. Recruit subjects with stroke diagnosis that meets the criteria (encompassing cerebral hemorrhage and infarction) established by the Fourth National Cerebral Vascular Disease Academic Conference.
   2. Recr....

Results

A 37-year-old male stroke patient successively underwent two interventions: a closed-loop ta-VNS system synchronized with BCI-based motor training, and a sham ta-VNS system synchronized with BCI-based motor training. Baseline characteristics are presented in Table 1. System Intervention Parameters are presented in Table 2.

For the stroke patient, the number of successful motor imagery trials was recorded for both intervention protocols. During the 20 min close.......

Discussion

Prior research confirms that synchronizing ta-VNS with traditional motor training optimizes therapeutic efficacy for post-stroke motor recovery, likely through precise neuromodulation that enhances neural reorganization^8,14. Building on this evidence, we established a standardized experimental protocol and employed EEG biomarkers to monitor sensorimotor cortical activation patterns, particularly reflected in alpha and beta band topographic distributions during th.......

Materials

List of materials used in this article

Name	Company	Catalog Number	Comments
Alcohol pads	Steady Medical Group Co., Ltd.		Skin disinfection
Electrolyte bottle	Xi'an Zhentai Intelligent Technology Co., Ltd.		Capacity: 150 mL, used for storing electrolyte solution
Fugl-Meyer Assessment of Upper Extremity Motor Function	The standardized assessment developed by Swedish scholar Fugl-Meyer	FMA-UE	It is mainly used for clinical assessment of the reflex activities, motor control and muscle strength of the upper limbs of stroke patients.
Hand function rehabilitation training and evaluation system	Xi'an Zhentai Intelligent Technology Co., Ltd.	ZhenTec-H1	The training system controlled the rehabilitation training gloves in a pneumatic way, and helped the patients gradually realize the rehabilitation training through multi-mode training Rehabilitation training for hand muscles. The training is highly interesting, highly immersive, and has an evaluation function, which can evaluate the hand function of patients Recovery status.
Heart rate monitors	Shenzhen Huiying Electronic Technology Co., Ltd.	HY-HRV-001	Monitor heart rate
Lingke cotton	Xi'an Zhentai Intelligent Technology Co., Ltd.		Used to absorb salt water and transmit signals
Mini-Mental State Examination	The standardized assessment developed by Marshal F. Folstein et al.	MMSE	Rapid screening of adult cognitive impairment
Pure water	China Resources Tianbo Beverage (China) Co., Ltd.	Yibao Purified Water	150 mL is used for preparing the electrolyte solution
Saline electrode wireless multi-channel EEG acquisition and analysis system	Xi'an Zhentai Intelligent Technology Co., Ltd.	ZhenTec-NT1-G	The EEG acquisition equipment was a 32-lead saline electrode wireless multi-channel EEG acquisition and analysis system. According to the international 10-10 system, there were 30 acquisition electrodes and 2 ophthalmic electrodes. The input impedance of the device was 1 GΩ, the input noise was less than 0.4 μV, and the common mode rejection ratio was -120 dB. The electrode wear impedance was below 5 kΩ, and the EEG sampling rate was 500Hz.
Sodium chloride	Xi'an Zhentai Intelligent Technology Co., Ltd.		4.5 g, used for preparing the electrolyte solution
Transcutaneous auricular vagus nerve stimulator	Shenzhen Huiying Electronic Technology Co., Ltd.	HY-TVNS-001	The product is mainly composed of non-invasive vagus nerve stimulator host, non-invasive vagus nerve stimulator surface electrode, charging cable. The electrodes of the stimulator can be controlled by software, and the stimulation parameters include frequency, pulse width, time, mode, etc.
Wetting bottle	Xi'an Zhentai Intelligent Technology Co., Ltd.		Capacity: 250 mL, used for soaking lint cotton