Unveiling neurophysiological alterations in brain tumor patients: insights from resting-EEG and TMS-EEG data

This thesis aims to explore the neurophysiological alterations in patients with brain tumors, specifically gliomas and meningiomas, using an integrative approach that combines resting-state electroencephalography (EEG) and transcranial magnetic stimulation coupled with EEG (TMS-EEG). The rationale for this research lies in the need to bridge the gap between structural neuroimaging techniques, such as MRI, and functional assessments that can capture the dynamic changes in cortical reactivity and neural connectivity induced by brain tumors. While MRI excels in visualizing tumor boundaries, it falls short in providing insights into the functional disruptions that occur in both local and distant brain regions. This thesis leverages the strengths of EEG, with its high temporal resolution, and TMS, with its ability to directly stimulate cortical areas, to provide a more nuanced understanding of tumor-induced changes in brain function. Chapter 1 provides a thorough review of the literature, discussing the classification, etiology, epidemiology, and clinical manifestations of brain tumors, particularly gliomas and meningiomas. This chapter highlights the limitations of existing neurophysiological techniques and introduces TMS-EEG as a novel approach to address these gaps, enabling a more comprehensive assessment of how tumors alter brain function. The chapter also outlines the key hypotheses driving this research: that brain tumors will induce specific changes in spontaneous EEG activity, with distinct differences between gliomas and meningiomas, and that these tumors will modulate cortical reactivity differently, potentially creating multiple reactivity states within a single patient. Chapters 2, 3, and 4 focus on the central experiment, involving both brain tumor patients and a control group of healthy volunteers. The research is divided into two key components: the first examines baseline brain activity using resting-state EEG, while the second evaluates cortical reactivity using TMS-EEG. Chapter 2 details the methodology, including participant recruitment, experimental design, and data analysis techniques. Chapter 3 presents the experimental findings, divided into preoperative and postoperative data. Resting-state EEG results reveal altered spectral properties in brain tumor patients, particularly increased power in the beta and gamma bands. TMS-EEG findings show that tumoral regions exhibit reduced amplitude and complexity in TMS-evoked potentials (TEPs), reflecting diminished cortical reactivity and neural synchrony, with these effects being more pronounced in gliomas compared to meningiomas. Postoperative data indicate a partial recovery of cortical function, especially in peritumoral regions, suggesting that surgical resection promotes neural recovery by alleviating some of the disruptions caused by the tumor. Chapter 4 addresses the limitations identified in the experimental study and proposes a new protocol to improve the robustness and reproducibility of future research. This chapter emphasizes the potential of TMS-EEG not only to enhance our understanding of tumor-related brain dysfunction but also to serve as a longitudinal tool for tracking cortical recovery post-surgery. The chapter suggests improvements to data acquisition and analysis techniques, aiming to better capture the complexity of cortical responses in both preoperative and postoperative phases. Chapter 5 discusses the broader clinical and research implications of the findings, emphasizing the potential of TMS-EEG as a non-invasive tool for assessing brain function in tumor patients and monitoring post-surgical recovery. The integration of resting-state EEG with TMS-EEG provides a comprehensive view of both spontaneous brain activity and cortical reactivity, offering valuable insights for personalized clinical management and targeted therapeutic interventions.