This thesis explores the integration of non-invasive high-density electroencephalography (hd-EEG) with invasive stereoelectroencephalography (SEEG) to enhance understanding of brain electrophysiology in pathological, physiological and paraphysiological contexts. The combination of these two methods, known as "co-registration," leverages the high temporal resolution and full-brain coverage of hd-EEG with the spatial precision of SEEG, allowing for a more comprehensive view of brain activity. The thesis is divided into three primary areas of investigation. First, it examines pathological brain activity, specifically focusing on interictal epileptiform discharges (IEDs). These discharges, often difficult to detect with scalp EEG alone, were successfully localized using co-registration. By guiding hd-EEG analysis with SEEG data, hidden epileptic activity was revealed, contributing to more accurate non-invasive identification of epileptic foci, which is critical for surgical planning in drug-resistant epilepsy cases. Second, the study investigates physiological brain responses to sensory stimuli using median nerve stimulation. Co-registration enabled the analysis of how brain signals propagate from primary sensory regions to higher-order areas involved in perception. While hd-EEG captured fast, large-scale activity, SEEG provided detailed recordings from deep cortical structures. This integration revealed both phasic and tonic gamma band brain responses, offering new insights into sensory processing and conscious perception. Third, the thesis evaluates brain responses to artificial stimulation via single-pulse electrical stimulation (SPES), which evoked cortico-cortical evoked potentials (CCEPs). Co-registration allowed for a detailed analysis of how artificial stimulation propagates through brain circuits. While SEEG detected localized responses, hd-EEG captured broader patterns of brain activation, enhancing the understanding of brain connectivity and reactivity to external stimuli. Overall, the combination of hd-EEG and SEEG offers unique advantages, providing a more accurate and detailed picture of brain dynamics. This method not only refines neuroimaging techniques but also holds promise for improving clinical diagnostics and treatments, particularly in epilepsy. In essence, this thesis demonstrates that co-registration can bridge the gap between non-invasive and invasive brain recordings, offering significant benefits for both neuroscience research and clinical applications.

EXPLORING PHYSIOLOGICAL, PATHOLOGICAL AND PARAPHYSIOLOGICAL BRAIN ACTIVITY ACROSS SCALES WITH SIMULTANEOUS INVASIVE AND NON-INVASIVE EEG / F.m. Zauli ; tutor: M. Massimini ; supervisori: A. Pigorini, E. Mikulan ; PhD coordinator: F. Guala. - DIPARTIMENTO DI SCIENZE BIOMEDICHE E CLINICHE "LUIGI SACCO" (MILANO). Dipartimento di Scienze Biomediche e Cliniche, 2025. 37. ciclo, Anno Accademico 2023/2024.

EXPLORING PHYSIOLOGICAL, PATHOLOGICAL AND PARAPHYSIOLOGICAL BRAIN ACTIVITY ACROSS SCALES WITH SIMULTANEOUS INVASIVE AND NON-INVASIVE EEG

F.M. Zauli
2025

Abstract

This thesis explores the integration of non-invasive high-density electroencephalography (hd-EEG) with invasive stereoelectroencephalography (SEEG) to enhance understanding of brain electrophysiology in pathological, physiological and paraphysiological contexts. The combination of these two methods, known as "co-registration," leverages the high temporal resolution and full-brain coverage of hd-EEG with the spatial precision of SEEG, allowing for a more comprehensive view of brain activity. The thesis is divided into three primary areas of investigation. First, it examines pathological brain activity, specifically focusing on interictal epileptiform discharges (IEDs). These discharges, often difficult to detect with scalp EEG alone, were successfully localized using co-registration. By guiding hd-EEG analysis with SEEG data, hidden epileptic activity was revealed, contributing to more accurate non-invasive identification of epileptic foci, which is critical for surgical planning in drug-resistant epilepsy cases. Second, the study investigates physiological brain responses to sensory stimuli using median nerve stimulation. Co-registration enabled the analysis of how brain signals propagate from primary sensory regions to higher-order areas involved in perception. While hd-EEG captured fast, large-scale activity, SEEG provided detailed recordings from deep cortical structures. This integration revealed both phasic and tonic gamma band brain responses, offering new insights into sensory processing and conscious perception. Third, the thesis evaluates brain responses to artificial stimulation via single-pulse electrical stimulation (SPES), which evoked cortico-cortical evoked potentials (CCEPs). Co-registration allowed for a detailed analysis of how artificial stimulation propagates through brain circuits. While SEEG detected localized responses, hd-EEG captured broader patterns of brain activation, enhancing the understanding of brain connectivity and reactivity to external stimuli. Overall, the combination of hd-EEG and SEEG offers unique advantages, providing a more accurate and detailed picture of brain dynamics. This method not only refines neuroimaging techniques but also holds promise for improving clinical diagnostics and treatments, particularly in epilepsy. In essence, this thesis demonstrates that co-registration can bridge the gap between non-invasive and invasive brain recordings, offering significant benefits for both neuroscience research and clinical applications.
16-gen-2025
Settore BIOS-06/A - Fisiologia
High-density EEG; Stereo-EEG; simultaneous recordings
MASSIMINI, MARCELLO
PIGORINI, ANDREA
MIKULAN, EZEQUIEL PABLO
GUALA, FRANCESCO
Doctoral Thesis
EXPLORING PHYSIOLOGICAL, PATHOLOGICAL AND PARAPHYSIOLOGICAL BRAIN ACTIVITY ACROSS SCALES WITH SIMULTANEOUS INVASIVE AND NON-INVASIVE EEG / F.m. Zauli ; tutor: M. Massimini ; supervisori: A. Pigorini, E. Mikulan ; PhD coordinator: F. Guala. - DIPARTIMENTO DI SCIENZE BIOMEDICHE E CLINICHE "LUIGI SACCO" (MILANO). Dipartimento di Scienze Biomediche e Cliniche, 2025. 37. ciclo, Anno Accademico 2023/2024.
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