Consequential works in cognitive neuroscience have led to the formulation of an interactive dual-stream model of language processing: the dorsal stream may process the phonological aspects of language, whereas the ventral stream may process the semantic aspects of language. While it is well-accepted that the dorsal route is subserved by the arcuate fasciculus, the structural connectivity of the semantic ventral stream is a matter of dispute. Here we designed a longitudinal study to gain new insights into this central but controversial question. Thirty-one patients harboring a left diffuse low-grade glioma—a rare neurological condition that infiltrates preferentially white matter associative pathways—were assessed with a prototypical task of language (i.e. verbal fluency) before and after surgery. All were operated under local anesthesia with a cortical and subcortical brain mapping—enabling to identify and preserve eloquent structures for language. We performed voxel-based lesion-symptom (VLSM) analyses on pre- and postoperative behavioral data. Preoperatively, we found a significant relationship between semantic fluency scores and the white matter fibers shaping the ventro-lateral connectivity (P < 0.05 corrected). The statistical map was found to substantially overlap with the spatial position of the inferior fronto-occipital fasciculus (IFOF) (37.7%). Furthermore, a negative correlation was observed between semantic fluency scores and the infiltration volumes in this fasciculus (r = -0.4, P = 0.029). Postoperatively, VLSM analyses were inconclusive. Taken as a whole and when combined with the literature data, our findings strengthen the view that the IFOF plays an essential role in semantic processing and may subserve the direct ventral pathway of language.

Glioblastoma multiforme (GBM) is the most common form of primary brain tumor in adults, often characterized by poor survival. Glioma-initiating cells (GiCs) are defined by their extensive self-renewal, differentiation, and tumor initiation properties. GiCs are known to be involved in tumor growth and recurrence, and in resistance to conventional treatments. One strategy to efficiently target GiCs in GBM consists in suppressing their stemness and consequently their tumorigenic properties. In this study, we show that the miR-302-367 cluster is strongly induced during serum-mediated stemness suppression. Stable miR-302-367 cluster expression is sufficient to suppress the stemness signature, self-renewal, and cell infiltration within a host brain tissue, through inhibition of the CXCR4 pathway. Furthermore, inhibition of CXCR4 leads to the disruption of the sonic hedgehog (SHH)-GLI-NANOG network, which is involved in self-renewal and expression of the embryonic stem cell-like signature. In conclusion, we demonstrated that the miR-302-367 cluster is able to efficiently trigger a cascade of inhibitory events leading to the disruption of GiCs stem-like and tumorigenic properties.

ObjectiveTo assess the homotopic structural plasticity in case of unilateral damage of the insula.MethodsTo detect changes in gray matter volumes of the contralesional insula from structural MRIs, we used voxel-based morphometry (VBM) in a sample of 84 patients with a diffuse low-grade glioma invading the left insula (insL group; n = 47) or the right insula (insR group; n = 37).ResultsThe region of interest–based VBM analysis highlighted a large cluster of voxels with gray matter volume increase in the contralesional insula in both patient groups (k = 2,214 voxels for insL and k = 879 voxels for insR, p < 0.05, family-wise error corrected) compared with 24 age-matched healthy controls. Gray matter volume was increased for the entire insula (t69 = 3.63, p = 0.0016 for insL; t59 = 3.54, p = 0.0024 for insR, Bonferroni corrected), whereas no significant changes were found in 2 control regions for both patient groups. Furthermore, an increase of 24.6% and 31.6% in the gray matter volume was observed in the insula-related VBM cluster for insL and insR patients, respectively, compared with healthy controls (t69 = 7.39, p = 2.59 × 10−10 and t59 = 7.51, p = 3.61 × 10−10).ConclusionsThe reported results demonstrate that slow-growing but massive lesion infiltration of the insula induces marked increase of gray matter volume in the contralateral one. Our findings give support for a homotopic reorganization that might be a physiologic basis for the high level of functional compensation observed in patients with glioma.