In Search of the Trauma Memory: A Meta-Analysis of Functional Neuroimaging Studies of Symptom Provocation in Posttraumatic Stress Disorder (PTSD)

Gudrun Sartory, Jan Cwik, Helge Knuppertz, Benjamin Schürholt, Morena Lebens, Rüdiger J. Seitz, Ralf Schulze

Notwithstanding some discrepancy between results from neuroimaging studies of symptom provocation in posttraumatic stress disorder (PTSD), there is broad agreement as to the neural circuit underlying this disorder. It is thought to be characterized by an exaggerated amygdalar and decreased medial prefrontal activation to which the elevated anxiety state and concomitant inadequate emotional regulation are attributed. However, the proposed circuit falls short of accounting for the main symptom, unique among anxiety disorders to PTSD, namely, reexperiencing the precipitating event in the form of recurrent, distressing images and recollections. Owing to the technical demands, neuroimaging studies are usually carried out with small sample sizes. A meta-analysis of their findings is more likely to cast light on the involved cortical areas. Coordinate-based meta-analyses employing ES-SDM (Effect Size Signed Differential Mapping) were carried out on 19 studies with 274 PTSD patients. Thirteen of the studies included 145 trauma-exposed control participants. Comparisons between reactions to trauma-related stimuli and a control condition and group comparison of reactions to the trauma-related stimuli were submitted to meta-analysis. Compared to controls and the neutral condition, PTSD patients showed significant activation of the mid-line retrosplenial cortex and precuneus in response to trauma-related stimuli. These midline areas have been implicated in self-referential processing and salient autobiographical memory. PTSD patients also evidenced hyperactivation of the pregenual/anterior cingulate gyrus and bilateral amygdala to trauma-relevant, compared to neutral, stimuli. Patients showed significantly less activation than controls in sensory association areas such as the bilateral temporal gyri and extrastriate area which may indicate that the patients' attention was diverted from the presented stimuli by being focused on the elicited trauma memory. Being involved in associative learning and priming, the retrosplenial cortex may have an important function in relation to trauma memory, in particular, the intrusive reexperiencing of the traumatic event.