Taken together the results of the latter two studies indicate that the decrease in regional blood flow following successful EMDR therapy was associated with the remission of symptoms such as flashbacks, intrusive and stressful memories, hallucinations, and persistent trauma reliving at somatic level. On the other hand, EMDR normalized the capability to retrieve important aspects of the trauma and improved attention levels and sense of self. Furthermore, the activation of the prefrontal cortex, which has been shown to inhibit the limbic system in response to pathological stimuli that resemble the traumatic event, recovered its inhibitory role, reducing amygdala hyperactivation and the corresponding cortical hyperarousal.

The latest SPECT EMDR study to date related to two patients suffering from a psychological traffic trauma (Oh and Choi 2007). After EMDR, the authors found an increase in cerebral perfusion in the bilateral dorsolateral prefrontal cortex and a decrease in the temporal association cortex. In addition, the SPECT scans were compared to those of a non-traumatized control group, and the findings were in line with the above indicating a tracer uptake normalization following EMDR therapy. As Levin’s first study showed, also in this case, the significance of the results is reduced by the extremely low number of patients included in the sample, as well as by relatively poor statistics (p < 0.01). However, this study also confirmed the general neurobiological effect of EMDR, with a tendency to restore cortical control over the hyperaroused subcortical limbic structures.

In 2007 a SPECT study of 16 PTSD patients, before and after exposure to cognitive restructuring therapy and following successful psychotherapy, reported a higher activation in cortical (temporal, parietal, and prefrontal lobes) and subcortical (thalamus) regions in the left hemisphere during a script-driven provocation paradigm (Peres et al. 2007). This investigation was also performed using a low statistical threshold (p < 0.001 uncorrected for multiple comparisons) and the results should be viewed with caution.

In the following year, Lindauer et al. (2008), using brief eclectic psychotherapy (BET), investigated the cerebral blood flow in ten traumatized police officers using SPECT and reported that, after psychotherapy with a positive clinical outcome, the activation found during the script listening at baseline was significantly lowered in the middle frontal gyrus. Furthermore, treatment efficacy, as measured by PTSD scores, correlated positively with CBF in temporal and frontal cortex. However, this study was performed with a low-resolution SPECT camera and statistical differences thresholded at the liberal level of p < 0.01 uncorrected for multiple comparisons at voxel level. The same group published a MRI study in 2005 in which the same subjects showed a lack of volumetric changes following BET (Lindauer et al. 2005). However, the hippocampi were found to be smaller in patients than in traumatized controls, a finding often reproduced in PTSD research. The question of whether this anatomical condition is a trait (present before the index traumas) or state (following the index trauma) characteristic has not yet been clarified. In addition, due to a lack of follow-up, the study did not conclusively shed light on the effects of therapy on the subcortical structures. In fact, the relatively short duration of therapy (4 months) and the minimal time elapsed between the end of psychotherapy and the MRI (about a week) may not have been long enough to produce detectable anatomical changes, as such changes may occur only after a longer interval following successful treatment.

In summary, during the past 13 years a body of research has been carried out on humans to evaluate psychotherapies’ effectiveness, and a number of studies are focused on revealing their functional substrates despite difficulties arising from both time and spatial resolution of the selected techniques. The neurobiological grounds for psychotherapies’ effectiveness in the treatment of PTSD have been supported by SPECT studies showing that, after comparing the brain activity before and after therapy, significant changes in blood flow occur mainly in limbic areas and the prefrontal cortex. Overall, the results of these studies indicate a posttreatment reversal of the prefrontal and limbic abnormalities, which were clearly recognized at pretreatment and are a frequent neuroimaging finding in patients with PTSD. In fact, despite the relatively low spatial resolution of SPECT, the increased blood flow found at posttreatment mainly in the right middle inferior temporal gyrus may reflect a higher control over the amygdala and an increased stabilization of the pathological brain hyperactivation, resulting in a reduction in somatosensory symptoms of anxiety. These findings are consistent with clinical improvements, including depression and general affective disorders, demonstrating that psychotherapies have a significant impact on brain function and that the emergent normalized pattern of brain activity is consistent with changes that may be mitigating posttraumatic and anxiety conditions.

In the last 2 years, a new and groundbreaking investigation has been carried out, based on online EEG monitoring of the functional response during psychotherapy (Pagani et al. 2011, 2012). A preliminary methodological validation report describing the methodology and feasibility of this approach (Pagani et al. 2011) was recently published. To allow the experiment to be as patient friendly as possible, the EEGs in a group of ten subjects with major psychic trauma were recorded in a private practitioner’s quiet room. The activation of the human cortex in “live mode” throughout the EMDR session was compared between traumatized individuals both in the acute phase and after clinical recovery. The comparison between the patients’ EEGs recorded during the first and the last EMDR sessions showed a significantly greater activation during the latter in the temporo-occipital cortex mainly on the left side (Pagani et al. 2012). In patients after therapy, a significant decrease in the fast alpha and gamma components of the activation present in the frontoparietal cortex at the first EMDR session was also observed.

In our opinion, the importance of this latter study lies not only in the validation, through a different neuroimaging technique, of the results obtained with SPECT and PET but also in the critical importance of PTSD-related psychotherapy research. Being able to perform EEG studies in a quiet and cozy environment helps to avoid biases caused by patient discomfort and possible psychological constraints (i.e., claustrophobia, anxiety, panic) which can occur in PET or SPECT (Mazard et al. 2002).