Dottorato in PLASTICITÀ NEUROSENSORIALE

Titolo della tesi: Neuroimaging of Language Reorganization in the Preoperative Setting of Brain Tumors

Neuroplasticity is extremely relevant in the preoperative setting of brain tumors, due to the potential dramatic consequences of iatrogenic damage to eloquent cortices. The surgical resection of left-hemispheric brain tumors is often complicated by ipsilateral lateralization of language, which is usually localized in the left perisylvian region. Functional MRI (fMRI) is the most widely employed non-invasive method to evaluate language function in the preoperative planning of brain tumors, thanks to its versatility and proven clinical benefits. The implementation of functional connectivity analyses in clinical fMRI can provide new insights about the mechanisms of compensation that the brain develops in response to focal lesions. Language plasticity or reorganization may be associated with tumor growth in the dominant hemisphere for speech preservation against the detrimental effects of neoplastic invasion. Such phenomenon has important effects on patients’ outcome and life quality, including the reduction of post-surgical language deficits. In this work we explored language reorganization in the setting of brain tumors, focusing on three specific aims: 1) To demonstrate the existence of language reorganization on fMRI and to identify tumor- and patient-related determinants of language plasticity; 2) To investigate anatomical changes of the cortex in patients with language reorganization by means of structural MRI techniques; 3) To characterize different patterns of language reorganization in brain tumors by means of fMRI, graph theory and intra-operative stimulation. Our results confirmed that tumor growth in the left hemisphere is associated with inter-hemispheric language reorganization, as well as structural modifications of cortical volume in the newly activated areas. Language reorganization appears to be influenced by age, sex, frontal location, Broca’s and Wernicke’s area invasion, tumor pathology, EGFR amplification, IDH mutation, MGMT methylation, FGFR mutation. Low-grade gliomas show more favorable connectivity changes than high-grade gliomas, in terms of network efficiency and information transfer. Language reorganization develops over time in response to tumor growth or treatments, including surgery, showing progressive recruitment of the right hemisphere. Patients with surgically-proven reorganization display a shift of core language areas to the right side, and demonstrate better language performance compared to the patients who remain left-dominant.