Non-randomized trial of neuromodulation prehabilitation for brain tumor language networks

Patients with brain tumors involving language-critical regions face surgical limitations when balancing resection with preservation of function. Non-invasive neuromodulation-induced prehabilitation (NIP) aims to guide preoperative neuroplastic reorganization, potentially facilitating larger resections while preserving function. We investigated whether NIP selectively modulates the targeted language network compared with control networks, and whether such modulation is behaviorally safe. We enrolled 26 patients (mean age = 55.9) from the Prehabilita project (Clinical Trial: NCT05844605) with operable brain tumors affecting language or motor regions. Eleven received language-targeted NIP, combining transcranial magnetic stimulation and/or transcranial direct current stimulation with intensive language training. Fourteen patients with NIP targeting non-language networks, primarily motor networks, served controls. Assessments included task-based functional magnetic resonance imaging (tb-fMRI) and a neuropsychological battery assessing language and cognitive domains before and after prehabilitation. Results indicated a group-specific NIP effect on the language network. In the language-targeted group, tb-fMRI revealed reduced overlap between a region of interest centered on the stimulation target and fMRI-derived language activation maps, whereas no comparable changes were observed in controls. No significant modulation effects were detected in the motor network in either group. These findings indicate that NIP can selectively reorganize the language network, with modulation patterns differing in sensorimotor networks. Importantly, language network modulation occurred while preserving language and cognitive performance. These results support NIP targeting higher-order functions such as language as a safe preoperative strategy that may reduce functional constraints on surgery and enable larger and safer resections in patients with tumors involving language-critical regions.