The prefrontal cortex, and especially the Dorsolateral Prefrontal Cortex (DLPFC), plays an inhibitory role in the regulation of the Hypothalamic-Pituitary-Adrenal (HPA) axis under stressful situations. Moreover, recent evidence suggests that a sustained DLPFC activation is associated with adaptive stress regulation in anticipation of a stressful event, leading to a reduced stress-induced amygdala response, and facilitating the confrontation with the stressor. However, studies using experimental manipulation of the activity of the DLPFC before a stressor are scarce, and more research is needed to understand the specific role of this brain area in the stress-induced physiological response. This pre-registered study investigated the effect on stress regulation of a single excitatory high frequency (versus sham) repetitive transcranial magnetic stimulation (HF-rTMS) session over the left DLPFC applied before the Trier Social Stress Test in 75 healthy young women (M = 21.05, SD = 2.60). Heart rate variability (HRV) and salivary cortisol were assessed throughout the experimental protocol. The active HF-rTMS and the sham group showed a similar cognitive appraisal of the stress task. No differences in HRV were observed during both the anticipation and the actual confrontation with the stress task and therefore, our results did not reflect DLPFC-related adaptive anticipatory adjustments. Importantly, participants in the active HF-rTMS group showed a lower cortisol response to stress. The effect of left prefrontal HF-rTMS on the stress system provides further critical experimental evidence for the inhibitory role played by the DLPFC in the regulation of the HPA axis.

前额叶皮层，尤其是背外侧前额叶皮层（DLPFC），在压力下对下丘脑-垂体-肾上腺（HPA）轴的调节起抑制作用。此外，最近的证据表明，持续的DLPFC激活与预期应激事件时的适应性应激调节相关，从而导致应激诱导的杏仁核反应减少，并促进与应激源的对抗。然而，在应激前使用DLPFC活性实验性操作的研究很少，需要更多的研究来了解该脑区在应激诱导的生理反应中的特定作用。这项预先注册的研究调查了在75名健康的年轻女性中，在Trier社会压力测试之前，在左DLPFC上进行的单一兴奋性高频（相对于假手术）重复经颅磁刺激（HF-rTMS）会话对压力调节的影响（M = 21.05，SD = 2.60）。在整个实验方案中评估了心率变异性（HRV）和唾液皮质醇。活跃的HF-rTMS和假手术组对压力任务表现出相似的认知评价。在预期和实际对抗压力任务的过程中，HRV均未观察到差异，因此，我们的结果未反映与DLPFC相关的自适应预期调整。重要的是，活跃的HF-rTMS组的参与者表现出较低的皮质醇对压力的反应。