Zhang Jingjing, Ma Jun, Rao Yao, Wu Jiali, Xu Hui, Ni Jiawei, Zhao Zhiwei, Wang Cong, Shan Chunlei
Rehabilitation Center, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Shanghai Key Laboratory of Flexible Medical Robotics, Tongren Hospital, Institute of Medical Robotics, Shanghai Jiao Tong University, Shanghai, China.
Front Aging Neurosci. 2025 May 30;17:1600921. doi: 10.3389/fnagi.2025.1600921. eCollection 2025.
Non-invasive brain stimulation techniques have been widely used in patients with mild cognitive impairment (MCI) to accelerate the recovery of their cognitive functions. However, the clinical efficacy of single non-invasive stimulation techniques in treating MCI still requires further improvement. The combination of two non-invasive neuromodulation techniques can enhance the synergistic effects of the treatment. Repetitive transcranial magnetic stimulation (rTMS) regulates the cortical-subcortical network in a "top-down" manner, while transcutaneous auricular vagus nerve stimulation (taVNS) modulates the brainstem-limbic system-cortical pathway in a "bottom-up" fashion. We will combine rTMS and taVNS, anticipating synergistic regulation through dual pathways to achieve multi-level neural remodeling effects and improve MCI.
This study will investigate the effectiveness of combined rTMS and taVNS therapy in improving the cognitive function of MCI patients. We will enroll 88 participants and randomly assign them to single-stimulation groups and combined-stimulation groups. The single-stimulation groups will be further randomized in a 1:1 ratio into a rTMS + sham taVNS stimulation group and a taVNS + sham rTMS stimulation group; the combined-stimulation groups will be randomized in a 1:1 ratio into an rTMS + taVNS group and an rTMS sham stimulation + taVNS sham stimulation group. All patients will receive treatment for 4 weeks. Assessments will be conducted before treatment (T0), 4-week treatment (T1), and 4-week post-treatment follow-up (T2). The primary outcome measure will be the Chinese version of the Montreal Cognitive Assessment Basic (MoCA-B), while secondary outcome measures will include the Rivermead Behaviour Memory Test (RBMT), the modified Barthel Index (MBI) for activities of daily living, and the latency and amplitude of event-related potential (ERP) P300.
This study is a clinical randomized controlled trial, which innovatively combines two non-invasive modulation techniques to improve cognitive function in patients with MCI. This study can validate the clinical efficacy of the combined TMS + taVNS stimulation, providing a theoretical basis for the application of this technology in clinical settings.
非侵入性脑刺激技术已广泛应用于轻度认知障碍（MCI）患者，以加速其认知功能的恢复。然而，单一非侵入性刺激技术治疗MCI的临床疗效仍需进一步提高。两种非侵入性神经调节技术联合使用可增强治疗的协同效应。重复经颅磁刺激（rTMS）以“自上而下”的方式调节皮质-皮质下网络，而经皮耳迷走神经刺激（taVNS）以“自下而上”的方式调节脑干-边缘系统-皮质通路。我们将联合使用rTMS和taVNS，期望通过双途径协同调节，实现多层次神经重塑效应并改善MCI。
本研究将调查rTMS与taVNS联合治疗改善MCI患者认知功能的有效性。我们将招募88名参与者，并将他们随机分配到单刺激组和联合刺激组。单刺激组将进一步按1:1比例随机分为rTMS+假taVNS刺激组和taVNS+假rTMS刺激组；联合刺激组将按1:1比例随机分为rTMS+taVNS组和rTMS假刺激+taVNS假刺激组。所有患者将接受4周的治疗。在治疗前（T0）、治疗4周时（T1）和治疗后4周随访时（T2）进行评估。主要结局指标将是中文版蒙特利尔认知评估基础版（MoCA-B），次要结局指标将包括里弗米德行为记忆测试（RBMT）、日常生活活动改良巴氏指数（MBI）以及事件相关电位（ERP）P300的潜伏期和波幅。
本研究是一项临床随机对照试验，创新性地联合两种非侵入性调节技术来改善MCI患者的认知功能。本研究可验证TMS+taVNS联合刺激的临床疗效，为该技术在临床中的应用提供理论依据。
