Intrusive trauma recollections are hallmark symptoms of posttraumatic stress disorder (PTSD), manifesting as flashbacks, nightmares, and reactivity to trauma reminders. These symptoms are distressing, disabling, and they predict worse illness course, above-and-beyond total symptom severity. Clinical descriptions highlight the re-experiencing of sensory-perceptual aspects of the trauma in the ?here-and-now?. It has been proposed that these psychological mechanisms represent a loss of integration between the hippocampus, which mediates contextual binding, and midline parieto-occipital cortices, which support sensory-perceptual elaboration. However, no research investigations have tested whether imaging measures of hippocampus circuitry relate to these key mechanistic features of intrusions. Most PTSD studies have assessed intrusions using instruments that are vulnerable to retrospective recall bias and that do not assess psychological characteristics of intrusions that may be most sensitive to neural variation. In addition, prior studies have not parsed trauma mechanisms relevant to hippocampus phenotypes, such as chronicity of trauma (threat) exposure, which moderates the severity of hippocampus deficits. Finally, most PTSD imaging studies considered the hippocampus as a unitary structure, whereas evidence shows that anterior (aHPC) and posterior hippocampus (pHPC) have dissociable functions and connectivity, as well as differential involvement in PTSD. The proposed study will leverage multiple lines of evidence suggesting that key psychological mechanisms of intrusions may be mediated by alterations in pHPC metabolism and connectivity with parieto-occipital cortices. We will use ecological momentary assessment (EMA) to assess intrusion characteristics in daily life (over a two-week period following the baseline imaging). We will test hypotheses that imaging measures of pHPC functional connectivity, anatomical connectivity, and neurochemistry predict sensory-perceptual vividness and out-of-context quality of intrusion symptoms, more so with increasing chronicity of trauma (threat) exposure. Finally, we will conduct multivariate modeling to identify combinations of neuroimaging metrics that best predict EMA-assessed variables. This project is innovative for its joint examination of mechanistic dimensions of intrusions and trauma exposure, both selected based on their predicted neurobiological relevance. This also will be the first study to apply multimodal imaging for the dissociation of aHPC and pHPC networks in PTSD, and to examine these hippocampus metrics in relation to real-world symptoms of PTSD. Overall our research strategy is consistent with that of the NIMH Research Domain Criteria (RDOC) with regards to identifying neurobiologically-relevant dimensions of behavior (intrusive memory) and their interactions with environmental influences (trauma, threat exposure). A major implication of segregating neural biomarkers in relation to intrusion and trauma mechanisms is the potential for identifying neural endpoints conducive to targeted treatment with novel perceptual or cognitive training programs, or targeted neuromodulation.
The clinical presentation of intrusive trauma symptoms, such as flashbacks and nightmares, is well described as being dominated by vivid sensory-perceptual experiences (predominantly visual images) and a sense that the trauma is re-occurring in the here-and-now. In the short term, this study will identify brain processes that are associated with these distinctive characteristics of trauma memories, and that may be different than the brain processes previously identified in PTSD. In the longer-term, these findings may lead to developing novel and individualized treatments that specifically target those brain processes in people who are impacted by the reliving of a past trauma.
