Barbetti Margherita, Ottaviani Cristina, Thayer Julian F, Sgoifo Andrea, Carnevali Luca
Stress Physiology Lab, Department of Chemistry, Life Sciences and Environmental Sustainability, University of Parma, Parma, Italy.
Department of Psychology, Sapienza University of Rome, Rome, Italy; Neuroimaging Laboratory, IRCCS, Santa Lucia Foundation, Rome, Italy.
Auton Neurosci. 2025 Feb;257:103237. doi: 10.1016/j.autneu.2024.103237. Epub 2024 Dec 13.
The identification of reliable biomarkers of transcutaneous auricular vagus nerve stimulation (taVNS) responsiveness is a key challenge both at the clinical and preclinical level. Vagally-mediated heart rate variability (vmHRV), a surrogate measure of cardiac vagal efferent activity, is an ideal candidate. Yet, the effects of taVNS on vmHRV remain inconclusive, likely due to the high degree of heterogeneity in stimulation protocols (e.g., taVNS parameters and side of the ear target), and little consideration of contributing factors such as sex differences. This study investigates sex differences in heart rate and vmHRV responses to different protocols of taVNS in adult rats. Male and female wild-type Groningen rats received sham or active stimulation (6 Hz or 20 Hz, 1 ms, 6 V) on the left or right auricular concha region. ECG signals were recorded before (10 min), during (20 min) and after (10 min) each session in a between-subject design. We found differential side-, frequency- and sex-specific chronotropic responses to taVNS, whereby heart rate decreased and vmHRV indexes increased at 6 Hz in males and at 20 Hz in females. Also, increases in vmHRV were only observed for right-side taVNS. The current findings suggest that biological sex should be considered for fine-tuning regulation of taVNS-induced cardiac responses and provide information regarding the side-specific effects of taVNS on vmHRV. These results will likely guide future rodent research to the choice of the most appropriate stimulation protocol in both sexes for generating information that can be translated into taVNS-related strategies in humans.
识别经皮耳迷走神经刺激（taVNS）反应性的可靠生物标志物是临床和临床前层面的关键挑战。迷走神经介导的心率变异性（vmHRV）是心脏迷走神经传出活动的替代指标，是一个理想的候选标志物。然而，taVNS对vmHRV的影响仍无定论，这可能是由于刺激方案（如taVNS参数和耳部靶点侧别）的高度异质性，以及对性别差异等影响因素考虑不足。本研究调查成年大鼠对不同taVNS方案的心率和vmHRV反应中的性别差异。雄性和雌性野生型格罗宁根大鼠在左耳或右耳甲区域接受假刺激或主动刺激（6Hz或20Hz，1ms，6V）。采用组间设计，在每次刺激前（10分钟）、刺激期间（20分钟）和刺激后（10分钟）记录心电图信号。我们发现taVNS存在侧别、频率和性别特异性的变时反应差异，即雄性在6Hz时心率下降，vmHRV指数增加，雌性在20Hz时心率下降，vmHRV指数增加。此外，仅在右侧taVNS时观察到vmHRV增加。目前的研究结果表明，在微调taVNS诱导的心脏反应时应考虑生物性别，并提供有关taVNS对vmHRV的侧别特异性影响的信息。这些结果可能会指导未来的啮齿动物研究，为两性选择最合适的刺激方案，以生成可转化为人类taVNS相关策略的信息。
