经皮迷走神经刺激在成年人执行功能中应用的Scoping综述

doi:10.3969/j.issn.1006-9771.2025.05.004

摘要/Abstract

摘要：

目的对经皮迷走神经刺激(tVNS)定向干预成年人执行功能的有效性和安全性进行Scoping综述。
方法系统检索PubMed、Web of Science、中国知网和万方数据库中tVNS干预成年人群执行功能的原始研究，检索时限为建库至2024年12月。提取数据并进行Scoping综述，采用物理治疗证据数据库(PEDro)量表评估文献质量。
结果共纳入14项研究，来自中国、德国、美国、荷兰和芬兰5个国家，涉及598例研究对象。研究对象主要为健康成年人群，同时涵盖难治性癫痫、创伤后应激障碍和睡眠剥夺等患者。干预结局包括执行功能中抑制控制(反应抑制和干扰控制)、工作记忆和认知灵活性3大核心成分。tVNS的参数设置因研究而异。刺激靶点以耳甲艇为主；刺激强度多集中于0.5~2.4 mA；刺激频率多为25 Hz；通断周期多为30 s开/30 s关；脉冲宽度为200 μs~500 ms；干预周期以30~75 min的单次急性刺激为主。行为学结果表明，tVNS对执行功能的反应抑制和工作记忆具有正向调节作用，但对干扰控制和认知灵活性的调节效应存在分歧。机制层面证据显示，tVNS通过调节额叶神经振荡及增强额叶功能连接改善反应抑制、工作记忆。安全性方面，4项研究报告短暂不良反应，无严重不良事件和受试者退出。
结论 tVNS可安全、有效地改善成年人执行功能的特定核心子成分，整体效益受执行功能子维度神经环路特异性和刺激参数的影响。

关键词: 成年人, 经皮迷走神经刺激, 执行功能, 抑制控制, 工作记忆, Scoping综述

Abstract:

Objective To review the efficacy and safety of transcutaneous vagus nerve stimulation (tVNS) in targeted interventions for executive function among adults.
Methods A systematic search of PubMed, Web of Science, CNKI and Wanfang data was conducted for original studies investigating tVNS intervention targeting executive function in adults, with publication during from inception to December, 2024. Data extraction and scoping review were performed, with literature quality assessed using the Physiotherapy Evidence Database (PEDro) scale.
Results A total of 14 researches were included, from China, Germany, United States, Netherlands and Finland, involving 598 participants. The subjects were mainly healthy adults and also covered patient groups with refractory epilepsy, post-traumatic stress disorder and sleep deprivation. The outcomes included three core components of executive function: inhibitory control (response inhibition and interference control), working memory and cognitive flexibility. The parameter settings of tVNS varied depending on the researches; the stimulation target was mainly the cymba conchae; the stimulation intensity was mostly 0.5 to 2.4 mA; the stimulation frequency was mainly 25 Hz; the on/off period was mostly 30 s on/30 s off; the pulse width was 200 μs to 500 ms; and the intervention period was mainly a single acute stimulation of 30 to 75 minutes. Behavioral results indicated that tVNS was effective on the response inhibition and working memory, but the effects on the interference control and cognitive flexibility were divergent. Mechanism-level evidence further supported that tVNS improved response inhibition and working memory by modulating frontal neural oscillations and enhancing frontal functional connectivity. In terms of safety, four researches reported transient adverse reactions, and no serious adverse events or participant withdrawals happened.
Conclusion tVNS demonstrates safe and effective improvement of some core subcomponents of executive function in adults, with overall benefits influenced by neural circuit specificity and stimulation parameters.

Key words: adult, transcutaneous vagus nerve stimulation, executive function, inhibitory control, working memory, scoping review

中图分类号:

R493

潘义, 厚双龙, 温晓妮. 经皮迷走神经刺激在成年人执行功能中应用的Scoping综述[J]. 《中国康复理论与实践》, 2025, 31(5): 520-528.

PAN Yi, HOU Shuanglong, WEN Xiaoni. Transcutaneous vagus nerve stimulation for executive function in adults: a scoping review[J]. Chinese Journal of Rehabilitation Theory and Practice, 2025, 31(5): 520-528.

图/表 5

表1

图1

表2

表3

纳入文献基本特征"

纳入文献	国家	研究类型	样本量(C/T)/n	受试对象	干预(C/T)	结局指标	评价指标	主要结局
Pan等^[2](2024)	中国	随机对照试验	9/19	难治性颞叶癫痫患者	假刺激/tVNS	工作记忆	视觉延迟与样本匹配任务，脑电图	任务反应时间缩短；额叶中线θ振荡下降
Zhao等^[12](2023)	中国	交叉研究	25	睡眠剥夺人群	假刺激/tVNS	工作记忆	N-back任务	任务准确率提高
Konjusha等^[14](2022)	德国	交叉研究	37	健康成年人	假刺激/tVNS	抑制控制	Flanker任务，脑电图	任务准确率降低；前额叶区域α波段活性降低
Camargo等^[17](2024)	美国	随机对照试验	20/21	健康成年人	假刺激/tVNS	抑制控制	Go/No-go任务，脑电图	任务表现无显著变化；N2波幅提高
Zhu等^[18](2024)	中国	随机对照试验	41/41	健康成年人	假刺激/tVNS	抑制控制	Go/No-go 任务，功能性近红外光谱	任务准确性提高；双侧颞下回-眶额叶网络连接增强
Choudhary等^[19](2023)	美国	随机对照试验	7/8	创伤后应激障碍患者	假刺激/tVNS	工作记忆	N-back任务	任务表现无显著变化
Konjusha等^[20](2023)	德国	交叉研究	37	健康成年人	假刺激/tVNS	工作记忆	N-back任务，脑电图	任务反应时间缩短，准确率提高；额叶及下顶叶区域α波活性增强
Sun等^[21](2021)	中国	交叉研究	58	健康成年人	假刺激/任务前tVNS/任务中tVNS	工作记忆	N-back任务	任务准确率提高；反应时间缩短
Pihlaja等^[22](2020)	芬兰	交叉研究	25	健康成年人	假刺激/tVNS	抑制控制	Go/No-go任务，脑电图	任务表现无显著变化；N2波幅降低
Tona等^[23](2020)	荷兰	交叉研究	72	健康成年人	不同刺激强度的tVNS	认知灵活性	可预测的线索任务转换任务	任务表现无显著变化
Borges等^[24](2020)	德国	交叉研究	64	健康成年人	假刺激/tVNS	认知灵活性	数字-字母任务，尺寸变更卡排序任务	任务反应时间缩短
Keute等^[25](2020)	德国	交叉研究	22	健康成年人	假刺激/tVNS	抑制控制	Go/No-go任务，脑电图	任务准确性提高；额中线θ活动增强
Jongkees等^[26](2018)	荷兰	随机对照试验	20/20	健康成年人	假刺激/tVNS	抑制控制	序列反应时任务	任务反应时间缩短
Beste等^[27](2016)	德国	随机对照试验	26/26	健康成年人	假刺激/tVNS	抑制控制	后抑制任务，反应抑制任务	反应抑制任务准确率提高

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参考文献 40

[1]	DIAMOND A. Executive functions[J]. Annu Rev Psychol, 2013, 64: 135-168. doi: 10.1146/annurev-psych-113011-143750 pmid: 23020641
[2]	PAN L, WANG J, WU W, et al. Transcutaneous auricular vagus nerve stimulation improves working memory in temporal lobe epilepsy: a randomized double-blind study[J]. CNS Neurosci Ther, 2024, 30(2): e14395.
[3]	LEVINE D A, GALECKI A T, LANGA K M, et al. Trajectory of cognitive decline after incident stroke[J]. JAMA, 2015, 314(1): 41-51. doi: 10.1001/jama.2015.6968 pmid: 26151265
[4]	ROCK P L, ROISER J P, RIEDEL W J, et al. Cognitive impairment in depression: a systematic review and meta-analysis[J]. Psychol Med, 2014, 44(10): 2029-2040. doi: 10.1017/S0033291713002535 pmid: 24168753
[5]	THAI M L, ANDREASSEN A K, BLIKSTED V. A meta-analysis of executive dysfunction in patients with schizophrenia: different degree of impairment in the ecological subdomains of the behavioural assessment of the dysexecutive syndrome[J]. Psychiatry Res, 2019, 272: 230-236.
[6]	KIROVA A M, BAYS R B, LAGALWAR S. Working memory and executive function decline across normal aging, mild cognitive impairment, and Alzheimer's disease[J]. Biomed Res Int, 2015, 2015: 748212.
[7]	RATTANAVICHIT Y, CHAIKEEREE N, BOONSINSUKH R, et al. The age differences and effect of mild cognitive impairment on perceptual-motor and executive functions[J]. Front Psychol, 2022, 13: 906898.
[8]	FERGUSON H J, BRUNSDON V E A, BRADFORD E E F, et al. The developmental trajectories of executive function from adolescence to old age[J]. Sci Rep, 2021, 11(1): 1382. doi: 10.1038/s41598-020-80866-1 pmid: 33446798
[9]	WANG Y, LI SY, WANG D, et al. Transcutaneous auricular vagus nerve stimulation: from concept to application[J]. Neurosci Bull, 2021, 37(6): 853-862. doi: 10.1007/s12264-020-00619-y pmid: 33355897
[10]	SHARON O, FAHOUM F, NIR Y. Transcutaneous vagus nerve stimulation in humans induces pupil dilation and attenuates alpha oscillations[J]. J Neurosci, 2021, 41(2): 320-330. doi: 10.1523/JNEUROSCI.1361-20.2020 pmid: 33214317
[11]	YAN L, ZHANG J, SUN Y, et al. Transcutaneous vagus nerve stimulation: a bibliometric study on current research hotspots and status[J]. Front Neurosci, 2024, 18: 1406135.
[12]	ZHAO R, CHANG M Y, CHENG C, et al. Transcutaneous auricular vagus nerve stimulation (taVNS) improves human working memory performance under sleep deprivation stress[J]. Behav Brain Res, 2023, 439: 114247.
[13]	TAN G, ADAMS J, DONOVAN K, et al. Does vibrotactile stimulation of the auricular vagus nerve enhance working memory? A behavioral and physiological investigation[J]. Brain Stimul, 2024, 17(2): 460-468. doi: 10.1016/j.brs.2024.04.002 pmid: 38593972
[14]	KONJUSHA A, COLZATO L, MÜCKSCHEL M, et al. Auricular transcutaneous vagus nerve stimulation diminishes alpha-band-related inhibitory gating processes during conflict monitoring in frontal cortices[J]. Int J Neuropsychopharmacol, 2022, 25(6): 457-467.
[15]	TRICCO AC, LILLIE E, ZARIN W, et al. PRISMA Extension for Scoping Reviews (PRISMA-ScR): checklist and explanation[J]. Ann Intern Med, 2018, 169(7): 467-473. doi: 10.7326/M18-0850 pmid: 30178033
[16]	CASHIN A G, MCAULEY J H. Clinimetrics: Physiotherapy Evidence Database (PEDro) scale[J]. J Physiother, 2020, 66(1): 59. doi: S1836-9553(19)30092-X pmid: 31521549
[17]	CAMARGO L, PACHECO-BARRIOS K, GIANLORENÇO A C, et al. Evidence of bottom-up homeostatic modulation induced taVNS during emotional and Go/No-Go tasks[J]. Exp Brain Res, 2024, 242(9): 2069-2081. doi: 10.1007/s00221-024-06876-x pmid: 38963558
[18]	ZHU S, LIU Q, ZHANG X, et al. Transcutaneous auricular vagus nerve stimulation enhanced emotional inhibitory control via increasing intrinsic prefrontal couplings[J]. Int J Clin Health Psychol, 2024, 24(2): 100462.
[19]	CHOUDHARY T, ELLIOTT M, EULIANO N R, et al. Effect of transcutaneous cervical vagus nerve stimulation on declarative and working memory in patients with posttraumatic stress disorder (PTSD): a pilot study[J]. J Affect Disord, 2023, 339: 418-425.
[20]	KONJUSHA A, YU S, MÜCKSCHEL M, et al. Auricular transcutaneous vagus nerve stimulation specifically enhances working memory gate closing mechanism: a system neurophysiological study[J]. J Neurosci, 2023, 43(25): 4709-4724. doi: 10.1523/JNEUROSCI.2004-22.2023 pmid: 37221097
[21]	SUN J B, CHENG C, TIAN Q Q, et al. Transcutaneous auricular vagus nerve stimulation improves spatial working memory in healthy young adults[J]. Front Neurosci, 2021, 15: 790793.
[22]	PIHLAJA M, FAILLA L, PERÄKYLÄ J, et al. Reduced frontal No-go-N2 with uncompromised response inhibition during transcutaneous vagus nerve stimulation-more efficient cognitive control[J]. Front Hum Neurosci, 2020, 14: 561780.
[23]	TONA K D, REVERS H, VERKUIL B, et al. Noradrenergic regulation of cognitive flexibility: no effects of stress, transcutaneous vagus nerve stimulation, and atomoxetine on task-switching in humans[J]. J Cogn Neurosci, 2020, 32(10): 1881-1895.
[24]	BORGES U, KNOPS L, LABORDE S, et al. Transcutaneous vagus nerve stimulation may enhance only specific aspects of the core executive functions. A randomized crossover trial[J]. Front Neurosci, 2020, 14: 523.
[25]	KEUTE M, BARTH D, LIEBRAND M, et al. Effects of transcutaneous vagus nerve stimulation (tVNS) on conflict-related behavioral performance and frontal midline theta activity[J]. J Cogn Enhanc, 2020, 4(4): 121-130.
[26]	JONGKEES B J, IMMINK M A, FINISGUERRA A, et al. Transcutaneous vagus nerve stimulation (tVNS) enhances response selection during sequential action[J]. Front Psychol, 2018, 9: 1159. doi: 10.3389/fpsyg.2018.01159 pmid: 30034357
[27]	BESTE C, STEENBERGEN L, SELLARO R, et al. Effects of concomitant stimulation of the GABAergic and norepinephrine system on inhibitory control: a study using transcutaneous vagus nerve stimulation[J]. Brain Stimul, 2016, 9(6): 811-818.
[28]	BUTT M F, ALBUSODA A, FARMER A D, et al. The anatomical basis for transcutaneous auricular vagus nerve stimulation[J]. J Anat, 2020, 236(4): 588-611. doi: 10.1111/joa.13122 pmid: 31742681
[29]	BONAZ B, BAZIN T, PELLISSIER S. The vagus nerve at the interface of the microbiota-gut-brain axis[J]. Front Neurosci, 2018, 12: 49.
[30]	WANG C, CAO X, GAO Z, et al. Training and transfer effects of combining inhibitory control training with transcutaneous vagus nerve stimulation in healthy adults[J]. Front Psychol, 2022, 13: 858938.
[31]	ARON A R. From reactive to proactive and selective control: developing a richer model for stopping inappropriate responses[J]. Biol Psychiatry, 2011, 69(12): e55-68.
[32]	FAN J, FLOMBAUM J I, MCCANDLISS B D, et al. Cognitive and brain consequences of conflict[J]. NeuroImage, 2003, 18(1): 42-57. doi: 10.1006/nimg.2002.1319 pmid: 12507442
[33]	OWEN A M, MCMILLAN K M, LAIRD A R, et al. N-back working memory paradigm: a meta-analysis of normative functional neuroimaging studies[J]. Hum Brain Mapp, 2005, 25(1): 46-59. doi: 10.1002/hbm.20131 pmid: 15846822
[34]	ZHAO R, HE Z Y, CHENG C, et al. Assessing the effect of simultaneous combining of transcranial direct current stimulation and transcutaneous auricular vagus nerve stimulation on the improvement of working memory performance in healthy individuals[J]. Front Neurosci, 2022, 16: 947236.
[35]	HULSEY D R, RILEY J R, et al. Parametric characterization of neural activity in the locus coeruleus in response to vagus nerve stimulation[J]. Exp Neurol, 2017, 289: 21-30. doi: S0014-4886(16)30405-8 pmid: 27988257
[36]	FARMER A D, STRZELCZYK A, FINISGUERRA A, et al. International consensus based review and recommendations for minimum reporting standards in research on transcutaneous vagus nerve stimulation (version 2020)[J]. Front Hum Neurosci, 2021, 14: 568051.
[37]	SUN L, PERÄKYLÄ J, HOLM K, et al. Vagus nerve stimulation improves working memory performance[J]. J Clin Exp Neuropsychol, 2017, 39(10): 954-964. doi: 10.1080/13803395.2017.1285869 pmid: 28492363
[38]	OEHRN C R, MOLITOR L, KRAUSE K, et al. Non-invasive vagus nerve stimulation in epilepsy patients enhances cooperative behavior in the prisoner's dilemma task[J]. Sci Rep, 2022, 12(1): 10255. doi: 10.1038/s41598-022-14237-3 pmid: 35715460
[39]	REDGRAVE J, DAY D, LEUNG H, et al. Safety and tolerability of transcutaneous vagus nerve stimulation in humans; a systematic review[J]. Brain Stimul, 2018, 11(6): 1225-1238. doi: S1935-861X(18)30293-6 pmid: 30217648
[40]	DUFF I T, LIKAR R, PERRUCHOUD C, et al. Clinical efficacy of auricular vagus nerve stimulation in the treatment of chronic and acute pain: a systematic review and meta-analysis[J]. Pain Ther, 2024, 13(6): 1407-1427. doi: 10.1007/s40122-024-00657-8 pmid: 39382792

纳入文献	1	2	3	4	5	6	7	8	9	10	11	总分
Pan等^[2](2024)	√	√		√	√		√	√		√	√	7
Zhao等^[12](2023)	√	√		√				√		√	√	5
Konjusha等^[14](2022)	√	√		√	√			√		√	√	6
Camargo等^[17](2024)	√	√	√	√	√	√	√	√	√	√	√	10
Zhu等^[18](2024)	√	√		√	√			√		√	√	6
Choudhary等^[19](2023)	√	√		√	√		√	√	√	√	√	8
Konjusha等^[20](2023)	√	√		√	√			√		√	√	6
Sun等^[21](2021)	√	√		√				√		√	√	5
Pihlaja等^[22](2020)	√			√	√			√	√	√	√	6
Tona等^[23](2020)	√	√		√	√		√	√	√			6
Borges等^[24](2020)	√	√		√	√			√		√	√	6
Keute等^[25](2020)	√	√		√	√			√	√	√	√	7
Jongkees等^[26](2018)	√	√		√				√	√	√	√	6
Beste等^[27](2016)	√	√		√	√			√		√	√	6

纳入文献	刺激靶点	刺激强度	脉冲宽度	频率	通断周期	持续时间
Pan等^[2](2024)	耳甲艇	30~50 V	250 μs	25 Hz	未报告	每次30 min，每天3~5次，共20周
Zhao等^[12](2023)	左侧耳甲艇	患者主观感受中等强度	500 ms	25 Hz	30 s开/30 s关	每次30 min，共1次
Konjusha等^[14](2022)	左侧耳甲艇	0.5 mA	200~300 ms	25 Hz	30 s开/30 s关	任务前20 min+任务全过程，共1次
Camargo等^[17](2024)	双侧耳甲	患者主观耐受阈值	200~250 μs	30 Hz	连续刺激	每次60 min，共1次
Zhu等^[18](2024)	左侧耳甲	平均0.8 mA	200~250 μs	30 Hz	30 s开/30 s关	每次30 min，共1次
Choudhary等^[19](2023)	左侧颈部靠近甲状软骨区域	30 V	200 μs	25 Hz	未报告	每次5 min，每天2次，共12周
Konjusha等^[20](2023)	耳甲艇	患者主观耐受阈值	200~300 ms	25 Hz	连续刺激	任务前20 min+任务全过程，共1次
Sun等^[21](2021)	左侧耳甲艇	患者主观感受中等强度	500 ms	25 Hz	30 s开/30 s关	每次40 min，共1次
Pihlaja等^[22](2020)	耳屏	患者主观耐受阈值	250 ms	25 Hz	未报告	每次52 min，共1次
Tona等^[23](2020)	左侧耳甲	0.5 mA	200~300 μs	25 Hz	30 s开/30 s关	每次75 min，共1次
Borges等^[24](2020)	左侧耳甲艇	平均2.2 mA	200~300 μs	25 Hz	连续刺激	任务前16 min+任务全过程，共1次
Keute等^[25](2020)	左侧耳甲艇	平均2.4 mA	200 μs	25 Hz	30 s开/30 s关	每次46 min，共1次
Jongkees等^[26](2018)	左侧耳屏	0.5 mA	200~300 μs	25 Hz	30 s开/30 s关	每次45 min，共1次
Beste等^[27](2016)	左侧耳甲	0.5 mA	200~300 μs	25 Hz	30 s开/30 s关	每次30 min，共1次