Multimodal imaging of hippocampal-cortical networks and mechanisms of trauma-related intrusions

摘要 侵入性创伤回忆是创伤后应激障碍(PTSD)的显著症状，表现为 闪回，噩梦，以及对创伤提醒的反应。这些症状令人痛苦，使人无力，而且 他们预测更糟糕的病程，超过总的症状严重程度。临床描述强调了 在“此时此刻”中重新体验感官--创伤的感官方面。有人提议， 这些心理机制代表着海马体之间整合的丧失，海马体是 上下文绑定，以及支持感觉-知觉阐述的中线顶枕叶皮质。 然而，没有研究调查测试海马体回路的成像测量是否与 入侵的这些关键机械特征。大多数创伤后应激障碍的研究都使用工具评估了入侵 容易受到追溯性回忆偏见的影响，并且不评估入侵的心理特征 这可能是对神经变异最敏感的。此外，以前的研究还没有分析创伤的机制 与海马体表型有关，例如慢性创伤(威胁)暴露，它缓和了 海马体缺陷的严重程度。最后，大多数创伤后应激障碍成像研究认为海马体是一个整体 结构，而证据表明，前(AHPC)和后(PHPC)有分离 功能和连接，以及在创伤后应激障碍中的不同参与。拟议的研究将利用多个 一系列证据表明，入侵的关键心理机制可能是由 PHPC的代谢和与顶枕叶皮质的连接。我们将用生态瞬间 评估(EMA)以评估日常生活中的入侵特征(在基线之后的两周内 成像)。我们将检验以下假设：PHPC功能连通性的成像测量，解剖学上 连接性和神经化学预测感觉-知觉的生动程度和入侵的脱离上下文的质量 症状，随着创伤(威胁)暴露的长期性增加，情况更是如此。最后，我们将进行多变量 建模以确定最佳预测EMA评估变量的神经成像指标组合。这 该项目对侵入和创伤暴露的机械维度进行了联合检查，两者都具有创新性 根据他们预测的神经生物学相关性进行选择。这也将是第一次应用多式联运的研究 创伤后应激障碍患者aHPC和PHPC网络分离的成像，并检查这些海马区指标 与创伤后应激障碍的真实症状有关。总体而言，我们的研究策略与NIMH的一致 关于确定神经生物学相关行为维度的研究领域标准(RDoC) (侵入性记忆)及其与环境影响的相互作用(创伤、威胁暴露)。一位少校 分离神经生物标志物与入侵和创伤机制有关的含义是潜在的 通过新的感知或认知训练计划识别有利于靶向治疗的神经端点， 或有针对性的神经调节。

SUMMARY 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.