Intraoperative temporal interference (TI)-noninvasive brain stimulation prevents postoperative delirium in mice

Postoperative delirium (POD), a common neurocognitive complication in the early postoperative period associated with high morbidity in elderly and high-risk surgical patients, faces fundamental research constraints due to the lack of quantitative rodent behavioral assessment tools, hindering therapeutic innovation. Herein, we employed a 3D-AI animal behavior analysis system to evaluate spontaneous behaviors in mice post laparotomy surgery with isoflurane anesthesia. Mice exhibited apathy, bradykinesia, inflexible motion, and abnormal behavioral transitions at the 3-day after surgery. Based on unsupervised clustering and manifold analysis, we then quantized the dynamic alteration of comprehensive behavioral phenotypes in fear conditioning test. The cued memory, cognitive flexibility, and cognitive robustness were also impaired after surgery. Furthermore, we developed a novel intraoperative temporal interference-noninvasive brain stimulation (TI-NIBS), inducing a stereo-focusing electric field targeting the dentate gyrus of dorsal hippocampus, which significantly mitigated POD symptoms by restoring hippocampal neural activity and neurotransmitter homeostasis. This study elucidates a comprehensive behavioral profile of POD symptoms and provides a therapeutic non-invasive neuro-modulatory strategy to prevent POD by restoring hippocampal function.