High-Intensity, Low-Frequency Periodic rTMS Over the Right Dorsolateral Prefrontal Cortex on Cardiac Autonomic Regulation in Women With Recurrent Pregnancy Loss and Anxiety

Recurrent pregnancy loss (RPL) is frequently associated with persistent anxiety and cardiac autonomic dysregulation, forming a vicious cycle that impacts emotional and reproductive outcomes. Neuroimaging studies suggest that lateralised dysfunction of the dorsolateral prefrontal cortex (DLPFC) contributes to both emotional dysregulation and sympathetic overactivation. Building upon the proposed Brain-Heart-Emotion interaction model, we hypothesise that excessive right DLPFC activity amplifies emotional arousal and cardiac sympathetic drive, while insufficient left DLPFC regulation fails to provide cognitive control over anxiety. This imbalance may underlie the comorbidity of anxiety and autonomic dysfunction in women with RPL. This proof-of-concept clinical trial applies high-intensity, low-frequency repetitive transcranial magnetic stimulation (rTMS) to the right DLPFC, aiming to assess its acute neurocardiac effects, specifically rTMS-induced changes in heart rate and heart rate variability (HRV)-two key indicators of autonomic modulation. By using a sequential stimulation paradigm combined with real-time ECG acquisition, this trial will identify the optimal intensity threshold for autonomic modulation and determine whether right DLPFC-targeted rTMS can transiently reduce cardiac sympathetic tone. Findings from this study will inform future trials evaluating rTMS as a precision treatment for anxiety and autonomic dysfunction in RPL, potentially improving psychophysiological health and pregnancy outcomes without relying on pharmacotherapy.