Precision in Delivery, Variability in Response: A Multiscale Mechanistic Framework for Neuronavigated Transcranial Magnetic Stimulation.

BACKGROUND/OBJECTIVES: Transcranial magnetic stimulation (TMS) initiates a cascade from intracranial electric-field exposure through neural recruitment and plasticity to distributed network responses. Neuronavigation improves the geometric reproducibility of delivery but does not guarantee equivalent cortical exposure or target engagement. This narrative review integrates these levels within an operational framework for precision TMS. METHODS: Six domain-specific PubMed searches covering 1 January 1985 to 31 July 2026 were supplemented by Google Scholar and citation tracking. A documented rerun on 17 August 2026 yielded 6430 records (5617 unique after cross-query deduplication). Evidence was synthesized narratively; no quantitative synthesis or formal risk-of-bias assessment was performed. RESULTS: Neuronavigation improves geometric precision by stabilizing target definition and coil pose, whereas individualized electric-field models estimate intracranial exposure. Neither establishes biological precision, which also depends on neuronal orientation, brain state, circuit architecture, medication, and behavior. Motor-system measures are not validated as universal biomarkers for nonmotor cortex, and no single validated biomarker captures TMS-induced plasticity. Convergent, controlled multimodal evidence may strengthen inference about target engagement; adaptive and closed-loop approaches remain experimental. CONCLUSIONS: Geometric delivery, modeled exposure, biological engagement, and durable functional or clinical benefit require separate validation. Spatial accuracy alone does not establish clinical value.