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.