To investigate the brain networks involved in epileptogenesis/encephalopathy associated with hypothalamic hamartoma (HH) by EEG with functional MRI (EEG-fMRI), and evaluate its efficacy inlocating the HH interface in comparison with subtraction ictal SPECT coregistered to MRI (SISCOM).Methods: Eight HH patients underwent EEG-fMRI. All had gelastic seizures (GS) and 7 developed other seizure types. Using a general linear model, spike-related activation/deactivation was analyzed indi-vidually by applying a hemodynamic response function before, at, and after spike onset (time-shift model = −8–+4 s). Group analysis was also performed. The sensitivity of EEG-fMRI in identifying the hypothalamic hamartoma interface was compared with SISCOM in HH patients having unilateral hypothalamic attachment.