OBJECTIVE: The aim is to gain insight into the pathophysiological mechanisms underlying interictal epileptiform discharges observed in electroencephalographic (EEG) and stereo-EEG (SEEG, depth electrodes) recordings performed during pre-surgical evaluation of patients with drug-resistant epilepsy. METHODS: We developed novel neuro-inspired computational models of the human cerebral cortex at three different levels of description: i) microscale (detailed neuron models), ii) mesoscale (neuronal mass models) and iii) macroscale (whole brain models). Although conceptually different, micro- and mesoscale models share some similar features, such as the typology of neurons (pyramidal cells and three types of interneurons), their spatial arrangement in cortical layers, and their synaptic connectivity (excitatory and inhibitory). The whole brain model consists of a large-scale network of interconnected neuronal masses, with connectivity based on the human connectome. RESULTS: For these three levels of description, the fine-tuning of free parameters and the quantitative comparison with real data allowed us to reproduce interictal epileptiform discharges with a high degree of fidelity and to formulate hypotheses about the cell- and network-related mechanisms underlying the generation of fast ripples and SEEG-recorded epileptic spikes and spike-waves. CONCLUSIONS: The proposed models provide valuable insights into the pathophysiological mechanisms underlying the generation of epileptic events. The knowledge gained from these models effectively complements the clinical analysis of SEEG data collected during the evaluation of patients with epilepsy. SIGNIFICANCE: These models are likely to play a key role in the mechanistic interpretation of epileptiform activity.