Focal epilepsy is a network pathology, where the brain connectivity of the epileptic focus (EF) influences seizure frequency and cortical dysfunction. Growing evidence supports a clinical efficacy of cathodal transcranial direct current stimulation (ctDCS) in drug-resistant epilepsy (DRE). ctDCS effects can be merely attributed to the inhibition of cortical excitability, which is abnormally increased in epilepsy, but its effect on brain network of DRE patients has never been reported. We aimed at exploring the hypothesis that functional connectivity (FC) changes may explain part of ctDCS clinical effects in DRE patients. We assessed the ctDCS-induced changes of electroencephalography-derived brain FC of a group of six temporal lobe DRE patients receiving a seizure reduction after ctDCS. By a single-subject eLORETA analysis, we compared the FC among the EF region and other nine bilateral macro-regions, before and after Real and Sham ctDCS in a double-blind Sham-controlled crossover design. FC changed after Real ctDCS in all patients despite no appreciable changes occurred after Sham. Most of FC changes (73%) involved the EF region. The epileptic seizure reduction correlated with the increase of the EF FC, in the whole frequency band and in the theta band. This small-sample analysis clearly revealed that ctDCS induced FC changes in the brain network of temporal lobe DRE patients. Our data support the hypothesis that FC changes may contribute to explain the effects of ctDCS in epilepsy, offering a new scenario in the personalization of neuromodulation interventions in epileptic people.
