Around 70% of patients with epilepsy respond to antiepileptic drugs.1 For patients who do not respond, surgery is an accepted treatment option.2 Seizure recurrence after resection is seen in 30-70% of patients and follows predictable slopes based on multiple factors, including the duration of epilepsy, history of generalised tonic seizures, frequency of preoperative seizures, and the presumptive pathological cause of epilepsy on MRI.3 Half of treatment failures after surgery lead to early recurrence of seizures, generally because of mislocalisation of seizure onset or incomplete resection of the epileptogenic substrate.4 Reccurrence of seizures later than 6 months after surgery is probably due to proepileptic cortical pathology that was unidentified in the presurgical assessment.4,5 In The Lancet Neurology, Dennis Spencer and colleagues6 discuss in a Personal View the possible roles of overlapping brain networks in focal epilepsy and its psychiatric comorbidities (eg, depression and anxiety). Visual analysis of recorded ictal patterns does not clearly identify the epileptogenic substrate, but it can be delineated by mathematical signal processing methods.7 Once validated as reliable predictors of the epileptogenic substrate, these signal processing methods will enable not only localisation of epileptogenic substrate but also testing of the hypothesis that epileptogenicity is distributed across an epileptic network. A study using single-cell gene mapping in malformations of cortical development showed somatic mutations in the mammalian target of rapamycin (mTOR) pathway in, for example, focal cortical dysplasia.8 These mutations result in the activation of the mTOR pathway that leads to synaptogenesis and play an important part in epileptogenesis.8 Similar findings for other mutations might lead to the design of highly efficacious disease-modifying drugs.