loading . . . Mixed reality assisted target localization for transcranial magnetic stimulation navigation: a feasibility study - Journal of NeuroEngineering and Rehabilitation Background Transcranial magnetic stimulation (TMS), as a non-invasive neurostimulation technique, modulates neural activity by applying electromagnetic fields to specific areas of the brain. It is clinically used for several approved indications, including major depressive disorder, obsessive‑compulsive disorder, and migraine with aura, and is under active investigation for other neurological and psychiatric conditions. Accurate stimulation targeting is crucial for the effectiveness of TMS. Existing targeting methods, such as generic brain localization caps and the international 10–20 electroencephalogram (EEG) system, generally provide only rough localization, leading to significant targeting errors. In recent years, significant progress has been made in the application of mixed reality (MR) technology in medicine, particularly in surgical navigation, offering new ideas and possibilities for developing a simple, low-cost, and efficient TMS navigation system. Objective This study proposes, for the first time, a portable MR navigation system for non-invasive neural modulation target localization. The aim is to evaluate its localization accuracy and operational efficiency in TMS through preclinical validation. This system seeks to provide a simple and high-precision localization solution for other non-invasive technologies, with the goal of improving localization accuracy and simplifying the operational workflow in clinical applications. Methods The system is based on Microsoft HoloLens 2 and features three specifically designed interaction tools. Five different types of simulation head models were selected, and ten target points were set on each head model. CT scanning was used to obtain imaging data for each head model. Three researchers used the system to perform target localization and repeated the verification process by adjusting the head model posture (from standing to lying) to assess localization accuracy and efficiency. Results The validation conducted by the three researchers showed the following results: In the standing position of the simulated head model, the measurement errors were 2.4 (IQR: 1.4–2.7) mm, 2.3 (IQR: 1.7–2.7) mm, and 2.6 (IQR: 1.9–3.0) mm, respectively. In the lying position of the simulated head model, the measurement errors were 1.9 (IQR: 1.6–2.4) mm, 2.0 (IQR: 1.4–3.0) mm, and 2.5 (IQR: 1.9–2.9) mm, respectively. There was a significant difference between researchers (p < 0.05), but no significant difference within the same researcher (p > 0.05). Conclusion The TMS-Guide, based on mixed reality technology, is a portable and simple navigation solution that provides higher localization accuracy than traditional manual targeting. It shows promising potential for broader applications in non-invasive neural modulation and brain-computer interface fields. https://doi.org/10.1186/s12984-026-02045-z