Recent advances in power spectral analysis of electroencephalography (EEG) signals and brain-computer interface (BCI) technology may significantly contribute to the development of psychoneurotherapies. The goal of this study was to measure the effect of a psychoneurotherapy on brain source generators of abnormal EEG activity in individuals with major depressive disorder (MDD). Thirty participants with unipolar MDD were recruited in the community. The proposed psychoneurotherapy was developed based on the relationship between the localization of abnormal EEG activity and depressive symptomatology. Brain electromagnetic abnormalities in MDD were identified with low resolution brain electromagnetic tomography (LORETA) and a normative EEG database. Localization of brain changes after treatment was assessed through the standardized version of LORETA (sLORETA). Before treatment, excessive high-beta (18-30 Hz) activity was noted in several brain regions located in the fronto-temporal regions. After treatment, only participants who successfully normalized EEG activity in cortico-limbic/paralimbic regions could be considered in clinical remission. In these regions, significant correlations were found between the percentage of change of depressive symptoms and the percentage of reduction in high-beta activity. These results suggest that the normalization of high-beta activity in cortico-limbic/paralimbic regions can be associated with a significant reduction of depressive symptoms.