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The P300 event-related potential (ERP) varies across individuals, and exploring this variability deepens our knowledge of the event, and scope for its potential applications. Previous studies exploring the P300 have relied on either electroencephalography (EEG) or functional magnetic resonance imaging (fMRI). We applied simultaneous event-related EEG-fMRI to investigate how the network structure is updated from rest to the P300 task so as to guarantee information processing in the oddball task. We first identified 14 widely distributed regions of interest (ROIs) that were task-associated, including the inferior frontal gyrus and the middle frontal gyrus, etc. The task-activated network was found to closely relate to the concurrent P300 amplitude, and moreover, the individuals with optimized resting-state brain architectures experienced the pruning of network architecture, i.e. decreasing connectivity, when the brain switched from rest to P300 task. Our present simultaneous EEG-fMRI study explored the brain reconfigurations governing the variability in P300 across individuals, which provided the possibility to uncover new biomarkers to predict the potential for personalized control of brain-computer interfaces. • Simultaneous EEG-fMRI is used to study P300 variability during the oddball task. • Network reconfiguration helps to uncover the P300 variability. • Low P300 group shows enhanced connectivity deviating from resting state. • The smaller the network updates, the larger the P300 amplitude. [ABSTRACT FROM AUTHOR]