ObjectiveSeizure-related respiratory or cardiac dysfunction was once thought to be the direct cause of sudden unexpected death in epilepsy (SUDEP), but both may be secondary to postictal cerebral inhibition. An important issue that has not been explored to date is the neural network basis of cerebral inhibition. Our aim was to investigate the features of neural networks in patients at high risk for SUDEP using a blood oxygen level-dependent (BOLD) resting-state functional MRI (Rs-fMRI) technique. MethodsRs-fMRI data were recorded from 13 patients at high risk for SUDEP and 12 patients at low risk for SUDEP. The amplitude of low-frequency fluctuations (ALFF) values were compared between the two groups to decipt the regional brain activities. ResultsCompared with patients at low risk for SUDEP, patients at high risk exhibited significant ALFF reductions in the right superior frontal gyrus, the left superior orbital frontal gyrus, the left insula and the left thalamus; and ALFF increase in the right middle cigulum gyrus, the right supplementary motor area and the left thalamus. ConclusionsThese findings highlight the need to understand the fundamental neural network dysfunction in SUDEP, which may fill the missing link between seizure-related cardiorespiratory dysfunction and SUDEP, and provide a promising neuroimaging biomarker for risk prediction of SUDEP.