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Low-frequency stimulation (LFS) is emerging as a new option for the treatment of epilepsy. The present study was designed to determine whether there is a crucial period for the treatment of epileptogenesis with LFS. LFS was delivered at different time-points to evaluate its anti-epileptogenic effect on amygdala-kindling rats. ¹⁸F-fluorodeoxyglucose small-animal positron-emission tomography (microPET) and multi-channel EEG recording (MER) were used to investigate the dynamics of brain networks during epileptogenesis and LFS treatment. Interestingly, LFS delivered in the first 7 days significantly retarded the progression of behavioral seizure stages and shortened the afterdischarge duration (ADD), LFS delivered throughout the whole process resulted in similar effects. However, if LFS was delivered at the beginning of seizure stage 2 or 3 (5 ± 0.3 days during kindling acquisition), it had no anti …