Background Eye Movement Desensitization and Reprocessing (EMDR) is a recognized first-line treatment for psychological trauma. However its neurobiological bases have yet to be fully disclosed. Methods Electroencephalography (EEG) was used to fully monitor neuronal activation throughout EMDR sessions including the autobiographical script. Ten patients with major psychological trauma were investigated during their first EMDR session (T0) and during the last one performed after processing the index trauma (T1). Neuropsychological tests were administered at the same time. Comparisons were performed between EEGs of patients at T0 and T1 and between EEGs of patients and 10 controls who underwent the same EMDR procedure at T0. Connectivity analyses were carried out by lagged phase synchronization. Results During bilateral ocular stimulation (BS) of EMDR sessions EEG showed a significantly higher activity on the orbito-frontal, prefrontal and anterior cingulate cortex in patients at T0 shifting towards left temporo-occipital regions at T1. A similar trend was found for autobiographical script with a higher firing in fronto-temporal limbic regions at T0 moving to right temporo-occipital cortex at T1. The comparisons between patients and controls confirmed the maximal activation in the limbic cortex of patients occurring before trauma processing. Connectivity analysis showed decreased pair-wise interactions between prefrontal and cingulate cortex during BS in patients as compared to controls and between fusiform gyrus and visual cortex during script listening in patients at T1 as compared to T0. These changes correlated significantly with those occurring in neuropsychological tests. Conclusions The ground-breaking methodology enabled our study to image for the first time the specific activations associated with the therapeutic actions typical of EMDR protocol. The findings suggest that traumatic events are processed at cognitive level following successful EMDR therapy, thus supporting the evidence of distinct neurobiological patterns of brain activations during BS associated with a significant relief from negative emotional experiences.