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

Abstract

<jats:p>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.</jats:p>

Middle Frontal Gyrus and Area 55b: Perioperative Mapping and Language Outcomes

“…Therefore, two hypotheses can be formulated to support the interaction of posterior MFG and area 55b with both streams of language: a direct connectivity via relay of some subcomponents of both AF and IFOF and an indirect connectivity via the stimulation of U-fibers to the adjacent gyri (IFG and SMA). In addition to previous imaging and dissection data, recent nTMS data support a strong connectivity of language positive sites via the U-fiber system, supporting the indirect connectivity theory ( 52 ). The strong connectivity to the primary motor cortex further supports the potential role for hand movement integration in language ( 43 ) and the involvement of this area in the articulation and praxis of speech ( 9 ).…”

Modern Developments in Transcranial Magnetic Stimulation: The Editorial

“…This Special Issue entitled "Modern Developments in Transcranial Magnetic Stimulation (TMS)-Applications and Perspectives in Clinical Neuroscience" in Brain Sciences received studies covering various applications of TMS, with focuses on neuronavigated TMS (nTMS) for mapping of cortical functions [10][11][12][13][14], treatment and modulatory effects [15][16][17][18][19], and basic neuromechanisms [20][21][22], all clinically relevant and supporting the aims set for the Special Issue.…”

“…Their results provided additional and new evidence in patients with glioblastoma multiforme regarding the connection of speech and language function and brain anatomy, with nTMS demonstrating that responsiveness to stimulation is critically related to cortical and subcortical interplay and the rate of speech impairment [14]. They considered that the results further increase confidence in nTMS language mapping and nTMS-based tractography in the clinical setting [14]. In their study, Baro et al reported a case of nTMS-based tractography application in neurosurgery in a bilingual patient affected by a brain tumor in the left temporal lobe, who underwent nTMS mapping for both languages (Romanian and Italian) [10].…”

“…By mapping language-related areas, Zhang et al provided evidence for structural differences on cortical and subcortical levels between language-positive (i.e., locations where upon stimulation, a modulatory effect on language performance was detected) and language-negative areas (i.e., locations where no effect of nTMS was detected) during nTMS language mapping among patients with language-eloquent brain tumors [14]. Their results provided additional and new evidence in patients with glioblastoma multiforme regarding the connection of speech and language function and brain anatomy, with nTMS demonstrating that responsiveness to stimulation is critically related to cortical and subcortical interplay and the rate of speech impairment [14]. They considered that the results further increase confidence in nTMS language mapping and nTMS-based tractography in the clinical setting [14].…”

Assessment of a Reliable Fractional Anisotropy Cutoff in Tractography of the Corticospinal Tract for Neurosurgical Patients

“…The FA is a measure for the directedness of diffusion, with values between 0 and 1, and is low in fluids and high in fiber bundles [ 11 ]. In iPlan Cranial 3.0 (Brain Lab AG, Munich, Germany), a prevalent software tool for neurosurgical planning, the standard cutoff is set to 0.3 [ 12 , 13 , 14 ]. In recent studies, this cutoff has been individually determined by a structured process of trial and error, with the lowest value at 0.1 [ 6 , 15 ].…”