# Lesion topography shapes motor thresholds in brain tumor patients

## TL;DR

This study shows that the location of brain tumors affects motor cortex excitability, with different areas causing either increased or decreased excitability.

## Contribution

The first study to combine nTMS and VLSM to map excitability changes in brain tumor patients based on lesion location.

## Key findings

- Postcentral tumors are linked to lower RMT, indicating increased cortical excitability.
- Precentral and premotor lesions are associated with higher RMT, suggesting disfacilitation.
- Tumor location and age are significant predictors of resting motor threshold.

## Abstract

•Tumor location significantly modulates resting motor threshold in brain tumor patients.•VLSM reveals opposing excitability effects from precentral vs. postcentral lesions.•Postcentral tumors are linked to lower RMT, indicating increased cortical excitability.•Precentral and premotor lesions are associated with higher RMT, suggesting disfacilitation.•This is the first study combining nTMS and VLSM to map excitability in tumor patients.

Tumor location significantly modulates resting motor threshold in brain tumor patients.

VLSM reveals opposing excitability effects from precentral vs. postcentral lesions.

Postcentral tumors are linked to lower RMT, indicating increased cortical excitability.

Precentral and premotor lesions are associated with higher RMT, suggesting disfacilitation.

This is the first study combining nTMS and VLSM to map excitability in tumor patients.

Navigated transcranial magnetic stimulation (nTMS) has become a cornerstone in preoperative functional mapping for brain tumor patients. The resting motor threshold (RMT) derived from nTMS reflects motor cortex excitability and may be influenced by tumor-related and patient-specific factors. However, the specific contribution of tumor location within cortical motor networks to RMT remains insufficiently understood.

In this prospective study, 223 patients with motor-eloquent brain tumors underwent nTMS-based motor mapping. Individual RMTs were determined using the Rossini-Rothwell method. Preoperative MRIs were normalized to MNI space, and tumor lesions were manually segmented. Voxel-based lesion-symptom mapping (VLSM) was performed to assess voxel-wise associations between tumor location and RMT. Multivariate regression identified clinical and anatomical predictors of RMT.

Lesions were predominantly located in the perirolandic region, involving the primary motor cortex (MC) as well as precentral (preMC) and postcentral (postMC) areas. Multivariate analysis revealed that postMC tumor location and age were significant negative predictors of RMT, while meningioma histology was a positive predictor. VLSM revealed that lesions in the postcentral gyrus, superior parietal lobule, and precuneus were associated with lower RMT (i.e., increased excitability), whereas lesions in the precentral gyrus, supplementary motor area (SMA), and dorsal premotor cortex (PMd) were associated with higher RMT (i.e., decreased excitability).

Motor cortex excitability in brain tumor patients is shaped by the functional integrity of interconnected cortical hubs. Disruption of inhibitory (e.g., sensory cortex) or facilitatory (e.g., premotor cortex) inputs to MC can modulate excitability in opposing directions. The combined use of nTMS and VLSM enables a network-level understanding of tumor-induced excitability changes and supports individualized surgical planning based on lesion topography.