Resting motor threshold in navigated transcranial magnetic stimulation: relationship between inter-individual variance and distinct clinical and anatomical factors

Background Navigated transcranial magnetic stimulation (nTMS) is increasingly used in neurosurgical practice for preoperative motor mapping. The resting motor threshold (RMT), a measure of cortical excitability, has been linked to postoperative motor outcomes. However, RMT is influenced by many inter-individual factors, potentially limiting its interpretability. This study aimed to assess the influence of clinical and anatomical variables on RMT variability in neurosurgical patients. Methods A total of 642 patients with motor-eloquent brain lesions underwent preoperative nTMS, yielding 1,193 bilateral RMT observations. Variables included age, sex, tumor volume, peritumoral edema, tumor side, skull-to-cortex distance (SCD), recurrence, motor deficits, tumor dominance, handedness, histology, anatomical location, and use of anticonvulsants, benzodiazepines, corticosteroids, or antidepressants. Linear mixed models were applied. Results RMT showed substantial inter-individual variability (mean 34 ± 8%, range 15–86%). Higher RMT included smaller peritumoral edema (estimate: -0.01; 95% CI: - 0.03, -0.001; p = 0.032), greater SCD (estimate: 0.85; 95% CI: 0.63, 1.09; p < 0.001) and presence of motor deficits (estimate: 2.26; 95% CI: 0.89, 3.64; p = 0.001). Tumors outside the central region were associated with lower RMT (estimate: -1.87; 95% CI: -3.26, -0.47; p = 0.010). Medication analysis revealed that carbamazepine (estimate: 3.82; 95% CI: 0.81, 6.87; p = 0.014), benzodiazepines (estimate: 3.45; 95% CI: 1.11, 5.78; p = 0.004), and corticosteroids increased RMT (estimate: 1.56; 95% CI: 0.03, 3.09; p = 0.049), whereas antidepressants decreased it (estimate: -3.24; 95% CI: -5.90, -0.58; p = 0.019). Other factors showed no statistically significant effect. Conclusion This study modeled the influence of clinical and anatomical factors on corticospinal excitability. This highlights the need for consideration of these variables when interpreting intervention-related changes in RMT or for risk stratification. Notably, the detailed analysis of common neurosurgical medications on RMT is unprecedented, emphasizing the importance of considering these factors.