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To date, the structural characteristics that distinguish language-involved from non-involved cortical areas are largely unclear. Particularly in patients suffering from language-eloquent brain tumors, reliable mapping of the cortico-subcortical language network is of high clinical importance to prepare and guide safe tumor resection. To investigate differences in structural characteristics between language-positive and language-negative areas, 20 patients (mean age: 63.2 ± 12.9 years, 16 males) diagnosed with language-eloquent left-hemispheric glioblastoma multiforme (GBM) underwent preoperative language mapping by navigated transcranial magnetic stimulation (nTMS) and nTMS-based diffusion tensor imaging fiber tracking (DTI FT). The number of language-positive and language-negative points as well as the gray matter intensity (GMI), normalized volumes of U-fibers, interhemispheric fibers, and fibers projecting to the cerebellum were assessed and compared between language-positive and language-negative nTMS mappings and set in correlation with aphasia grades. We found significantly lower GMI for language-positive nTMS points (5.7 ± 1.7 versus 7.1 ± 1.6, p = 0.0121). Furthermore, language-positive nTMS points were characterized by an enhanced connectivity profile, i.e., these points showed a significantly higher ratio in volumes for U-fibers ( p ≤ 0.0056), interhemispheric fibers ( p = 0.0494), and fibers projecting to the cerebellum ( p = 0.0094). The number of language-positive nTMS points (R ≥ 0.4854, p ≤ 0.0300) as well as the ratio in volumes for U-fibers (R ≤ -0.4899, p ≤ 0.0283) were significantly associated with aphasia grades, as assessed pre- or postoperatively and during follow-up examinations. In conclusion, this study provides evidence for structural differences on cortical and subcortical levels between language-positive and language-negative areas, as detected by nTMS language mapping. The results may further increase confidence in the technique of nTMS language mapping and nTMS-based tractography in the direct clinical setting. Future studies may confirm our results in larger cohorts and may expand the findings to patients with other tumor entities than GBM.

Function-Based Tractography of the Language Network Correlates with Aphasia in Patients with Language-Eloquent Glioblastoma