Mills-Nithi algorithm for navigated transcranial magnetic stimulation motor mapping in healthy subjects and brain tumor patients.

OBJECTIVE: Navigated TMS (nTMS) motor mapping is typically performed at a fixed percentage of the resting motor threshold (rMT), most commonly 110%. The Mills-Nithi algorithm's upper threshold (UT), the minimal stimulation intensity evoking MEPs with 100% probability, has been proposed as an alternative. This study compared motor mapping at 110% rMT with the Mills-Nithi method in healthy subjects and patients with brain tumors. METHODS: 11 healthy controls and 14 patients with supratentorial tumors underwent FDI motor mapping using both UT of the Mills-Nithi algorithm, and 110% rMT estimated with an adaptive threshold-hunting algorithm. Outcomes included the number of pulses, hotspot localization, map area, volume, centers of gravity, and DTI parameters (i.e., fiber count, FA, ADC, fiber length). Personalized sigmoid curves were fitted to estimate response probabilities. An independent control group of 12 healthy subjects underwent two nTMS mapping sessions at 110% rMT to establish baseline Earth Movers Distance (EMD) values. RESULTS: Motor map characteristics and DTI metrics did not differ significantly between methods in either group. In healthy subjects, UT-based motor mapping required fewer stimuli than 110% rMT (110%: 256 ± 95 stimuli; UT: 227 ± 97; p = 0.03) and was more likely to elicit responses (p = 0.0375), with markedly reduced inter-individual variability (p < 0.0001). CONCLUSIONS: Motor mapping based on UT produces results comparable to 110% rMT, while improving procedural efficiency and response consistency in healthy subjects. SIGNIFICANCE: Our findings support the Mills-Nithi algorithm as a practical alternative for clinical nTMS motor mapping.