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Transcutaneous auricular vagus nerve stimulation (taVNS) has garnered increasing attention as a safe and effective peripheral neuromodulation technique in various clinical and cognitive neuroscience fields. However, there is ongoing debate about whether the commonly used earlobe control interferes with the objective assessment of taVNS regulatory effects. This study aims to further explore the regulatory effects of taVNS and earlobe stimulation (ES) on alertness levels and physiological indicators following 24 h of sleep deprivation (SD), based on previous findings that both taVNS and ES showed significant positive effects. The goal is to evaluate whether ES can serve as a neutral sham condition. Using a within-subject randomized experimental design involving 56 participants, we assessed alertness, heart rate variability (HRV), and salivary alpha-amylase (sAA) levels in the morning of the first day. After 24 h of SD and 30 min of either taVNS or ES intervention, these indicators were re-evaluated, and the changes in both groups were analyzed. The results indicated that both taVNS and ES improved alertness levels following SD. However, taVNS significantly increased sAA levels, indicating activation of the LC-NE system, whereas ES significantly increased HR and reduced HRV, promoting sympathetic nervous activity. Additionally, the regulatory effect of taVNS on the alertness showed a higher correlation with SD impairment. Although taVNS and ES may involve different and separable neuromodulation mechanisms, both can enhance alertness following SD. Future studies should carefully consider the potential regulatory effects of ES when using it as a sham condition in taVNS research., (© 2024 Society for Psychophysiological Research.)

Transcranial magnetic stimulation (TMS) is pivotal in the field of major depressive disorder treatment. Due to its unsatisfied response rate, an increasing number of researchers have turned their attention towards optimizing TMS site localization. Since the influence of TMS in reducing heart rate (HR) offers insights into its regulatory impact on the autonomic nervous system, a novel approach, called neurocardiac-guided TMS (NCG-TMS), has been proposed to pinpoint the brain region eliciting the maximal individual reduction in HR as a personalized optimal stimulation target. The present study intends to systematically explore the effects of stimulation frequency, left and right hemispheres, stimulation positions, and individual differences on HR modulation using the NCG-TMS method. In experiment 1, low-frequency TMS was administered to 30 subjects, and it was found that low-frequency NCG-TMS significantly downregulated HR, with more significant effects in the right hemisphere than in the left hemisphere and the prefrontal cortex than in other brain areas. In experiment 2, high-frequency NCG-TMS stimulation was administered to 30 subjects, showing that high-frequency NCG-TMS also downregulated HR and had the greatest modulatory effect in the right prefrontal region. Simultaneously, both experiments revealed sizeable individual variability in the optimal stimulation site, which in turn validated the feasibility of the NCG-TMS method. In conclusion, the present experiments independently replicated the effect of NCG-TMS, provided an effect of high-/low-frequency TMS stimulation to downregulate HR, and identified a right lateralization of the HR modulation effect., (© 2024 Society for Psychophysiological Research.)