Condition-and-perturb frontoparietal network disruption enhances preoperative nTMS mapping in patients with language-eloquent tumors: A proof-of-concept pilot study

The use of preoperative neuronavigated transcranial magnetic stimulation (nTMS) is becoming increasingly common in patients undergoing eloquent brain tumor surgery. Yet the optimal stimulation paradigms for language mapping still lack specificity and need to be refined. In the frontoparietal network, a protocol of dual-site TMS, termed the condition-and-perturb approach (CAP), was shown to effectively sensitize the semantic network in healthy subjects.

This study aims to evaluate the added value of the CAP to preoperative language mapping in non-aphasic patients with language-eloquent brain tumors involving the anterior inferior frontal (aIFG) or angular (AG) gyrus.

Patients underwent peritumoral online nTMS involving the affected node (AG or aIFG) with or without prior offline neuronavigated repetitive TMS (nrTMS, 1 Hz, 15 min) of the ipsilateral healthy node (aIFG or AG).

Eight patients underwent the full protocol. Offline nrTMS decreased error threshold of online language mapping in all patients in comparison to sham nrTMS in those patients. Four peritumoral language hotspots [2-5] could be isolated in each patient. Compared to direct cortical stimulation, nTMS language mapping with CAP achieved a sensitivity of 84.2%, a specificity of 98.3%, a PPV of 84.2% and an NPV of 98.3%. This means that nearly all CAP-nTMS hotspots induced language disturbances when stimulated intraoperatively with DCS.

This pilot study suggests that the CAP could be a possible solution to the specificity concerns of preoperative TMS mapping, as prior frontoparietal network disruption might enhance the precision of language mapping around semantically eloquent brain tumors.