Transient blood pressure elevation during temporal interference stimulation of the right centromedian nucleus in a pDoC patient

Background Temporal interference (TI) stimulation is an emerging non-invasive technology for deep brain neuromodulation. While generally considered safe, the potential risks of off-target autonomic activation in patients with severe structural brain lesions remain poorly understood. Case presentation We report a 42-year-old female with unresponsive wakefulness syndrome (UWS) secondary to bilateral basal ganglia hemorrhage with intraventricular extension. During a sequential multi-target TI intervention, stimulation of the bilateral dorsolateral prefrontal cortex (DLPFC), anterior cingulate cortex (ACC), nucleus accumbens (NAc), and left centromedian (CM) nucleus elicited no hemodynamic changes. Strikingly, targeted stimulation of the right CM induced a transient, significant blood pressure surge (up to 190/120 mmHg). This target-specific hypertension was precisely reproduced during a next-day independent re-challenge. Individualized finite element method (FEM) modeling revealed that the abnormal accumulation of highly conductive cerebrospinal fluid (CSF) in the enlarged ventricles triggered a robust current shunting effect. This caused severe spatial defocusing of the electric field, leading to an unexpected spill-over into adjacent autonomic regulatory centers, including the hypothalamus. Conclusions This unprecedented hemodynamic fluctuation unveils a “physiological-physical synergistic effect”: physical electric field distortion driven by pathological anatomy, amplified by the physiological right-hemispheric dominance of the central autonomic network (CAN). This case strongly advocates that individualized high-precision FEM modeling and continuous cardiovascular monitoring are absolute prerequisites for safe deep neuromodulation in patients with severe structural brain variations.