Effects of non-invasive prefrontal neuromodulation on acute cortisol response to stress: A systematic review and meta-analysis.

Dysregulated stress response, involving altered connectivity between the hypothalamic-pituitary-adrenal (HPA) axis and prefrontal cortex (PFC), is linked to psychiatric disorders. Non-invasive brain stimulation (NIBS) may modulate cortisol release by influencing PFC activity; however, quantitative evidence remains limited. This systematic review and meta-analysis included 16 randomized controlled trials examining NIBS effects on stress-induced cortisol release in healthy individuals. Studies were identified from five databases and analyzed following PRISMA guidelines using random-effects models. Results showed that NIBS significantly reduced acute cortisol response to stress (SMD = -0.72, 95 % CI [-1.16, -0.28], p < 0.01). Subgroup analyses indicated greater efficacy for transcranial magnetic stimulation (TMS) compared to transcranial direct current stimulation (tDCS). Stimulation applied before or after the stressor was more effective than during-task application. Female participants showed more pronounced cortisol modulation than males. Sensitivity analyses confirmed result robustness, and no publication bias was detected. When developing NIBS-based neuromodulation protocols for stress modulation, factors such as stimulation type, timing, and participant characteristics may warrant careful consideration. Overall, the evidence suggests that NIBS may modulate acute stress responses in healthy individuals.