Gurtubay Iñaki G, Perez-Rodriguez Diego R, Fernandez Enrique, Librero-Lopez Julian, Calvo David, Bermejo Pedro, Pinin-Osorio Carolina, Lopez Miguel
Department of Neurophysiology, University Hospital of Navarre, Pamplona, Spain.
Navarrabiomed Biomedical Research Centre, Pamplona, Spain.
Front Neurosci. 2023 Mar 27;17:1096865. doi: 10.3389/fnins.2023.1096865. eCollection 2023.
Transcutaneous auricular vagus nerve stimulation (taVNS) is a neuromodulatory technique that stimulates the auricular branch of the vagus nerve. The modulation of the locus coeruleus-norepinephrine (LC-NE) network is one of the potential working mechanisms of this method. Our aims were 1-to investigate if short and single applications of taVNS can modulate the P300 cognitive event-related potential (ERP) as an indirect marker that reflects NE brain activation under control of the LC, and 2-to evaluate the duration of these changes.
20 healthy volunteers executed an auditory oddball paradigm to obtain P300 and reaction time (RT) values. Then a 7 min active or sham taVNS period was initiated and simultaneously a new P300 paradigm was performed. We successively repeated the paradigm on 4 occasions with different time intervals up to 56 min after the stimulation onset.
During active taVNS an immediate and significant effect of increasing the amplitude and reducing the latency of P300, as well as a shortening in the RT was observed. This effect was prolonged in time up to 28 min. The values then returned to pre-stimulation levels. Sham stimulation did not generate changes.
Our results, demonstrate differential facilitating effects in a concrete time window after taVNS. Literature about the modulatory effect of taVNS over P300 ERP shows a wide spread of results. There is not a standardized system for taVNS and currently the great heterogeneity of stimulation approaches concerning targets and parameters, make it difficult to obtain conclusions about this relationship. Our study was designed optimizing several stimulation settings, such as a customized earbud stimulator, enlarged stimulating surface, simultaneous stimulation over the cymba and cavum conchae, a Delayed Biphasic Pulse Burst and current controlled stimulation that adjusted the output voltage and guaranteed the administration of a preset electrical dose. Under our stimulation conditions, targeting vagal nerve fibers via taVNS modulates the P300 in healthy participants. The optimal settings of modulatory function of taVNS on P300, and their interdependency is insufficiently studied in the literature, but our data provides several easily optimizable parameters, that will produce more robust results in future.
经皮耳迷走神经刺激(taVNS)是一种刺激迷走神经耳支的神经调节技术。蓝斑 - 去甲肾上腺素(LC - NE)网络的调节是该方法潜在的作用机制之一。我们的目的是:1. 研究taVNS的短期单次应用是否能调节P300认知事件相关电位(ERP),作为反映在LC控制下NE脑激活的间接指标;2. 评估这些变化的持续时间。
20名健康志愿者执行听觉oddball范式以获得P300和反应时间(RT)值。然后开始7分钟的主动或假taVNS刺激期,同时进行新的P300范式。在刺激开始后长达56分钟的不同时间间隔内,我们连续4次重复该范式。
在主动taVNS期间,观察到P300波幅增加、潜伏期缩短以及RT缩短的即时且显著效果。这种效果持续延长至28分钟。然后这些值恢复到刺激前水平。假刺激未产生变化。
我们的结果表明,taVNS后在特定时间窗口内具有不同的促进作用。关于taVNS对P300 ERP调节作用的文献结果差异很大。目前taVNS没有标准化系统,且刺激靶点和参数的方法存在很大异质性,难以得出关于这种关系的结论。我们的研究在设计上优化了多个刺激设置,如定制耳塞式刺激器、扩大刺激表面、同时刺激鼓室和耳甲腔、延迟双相脉冲串以及电流控制刺激,可调节输出电压并确保给予预设电剂量。在我们的刺激条件下,通过taVNS靶向迷走神经纤维可调节健康参与者的P300。taVNS对P300调节功能的最佳设置及其相互依赖性在文献中研究不足,但我们的数据提供了几个易于优化的参数,未来将产生更可靠的结果。