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

海马皮质网络的多模态成像和创伤相关侵入的机制

• 批准号: 10159137
• 负责人: ISABELLE M ROSSO
• 金额: $ 67.88万
• 依托单位: MCLEAN HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-07-01 至 2024-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10159137
• 关键词: Address; Adult; Anatomy; Anisotropy; Anterior; Behavior; Binding; Biological Markers; Biology; Brain; Characteristics; Chronic; Clinical; Data; Detection; Development; Diffusion Magnetic Resonance Imaging; Dimensions; Dissociation; Distress; Ecological momentary assessment; Event; Exclusion; Fiber; Functional Magnetic Resonance Imaging; Generalized Anxiety Disorder; Glutamates; Hippocampus (Brain); Image; Individual; Investigation; Joints; Lead; Life; Magnetic Resonance Spectroscopy; Measures; Medial; Mediating; Memory; Metabolism; Modeling; Multimodal Imaging; National Institute of Mental Health; Neurobiology; Nightmare; Occipital lobe; Participant; Patients; Pattern; Phenotype; Post-Traumatic Stress Disorders; Process; Research; Research Domain Criteria; Rest; Sampling; Sensory; Severities; Structure; Symptoms; System; Testing; Training Programs; Trauma; Variant; Visual; Work; base; cognitive training; cue reactivity; experience; frontal lobe; imaging study; individualized medicine; innovation; instrument; multimodality; neural correlate; neurochemistry; neuroimaging; neuromechanism; neuroregulation; novel; post-traumatic symptoms; predictive marker; psychologic; recruit; relating to nervous system; targeted treatment; tractography; trauma exposure; trauma symptom; visual imagery; white matter

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.

概括 侵入性创伤回忆是创伤后应激障碍（PTSD）的标志性符号，表现为 闪回，噩梦和对创伤提醒的反应性。这些符号令人痛苦，残疾，并且 他们预测疾病病程较差，超过总症状严重程度。临床描述突出显示 在“现在和现在”中创伤的感官感知方面的重新体验。有人提出 这些心理机制代表了海马之间失去整合的损失 上下文结合和中线甲状腺枕皮层，这些皮质支持感觉感知阐述。 但是，尚无研究调查测试是否与海马电路的成像测量与 这些入侵的关键机械特征。大多数PTSD研究都使用仪器评估了入侵 容易受到回顾性召回偏见的影响，并且不评估入侵的心理特征 这可能对神经变异最敏感。此外，先前的研究没有解析创伤机制 与海马表型有关，例如慢性创伤（威胁）暴露，这使得 海马缺陷的严重程度。最后，大多数PTSD成像研究都认为海马是单一的 结构，而证据表明前海马和后海马（PHPC）具有可分离性 功能和连通性以及PTSD中的差异参与。拟议的研究将利用多重 证据线表明，关键的入侵的心理机制可能是通过改变 PHPC代谢和与枕皮层的连通性。我们将使用生态瞬间 评估（EMA）评估日常生活中的入侵特征（基线之后的两周期间 成像）。我们将测试假设，即对PHPC功能连通性，解剖学的成像度量 连通性和神经化学预测感官感知的生动性和侵入质量的质量 症状，随着创伤（威胁）暴露的慢性增长。最后，我们将进行多元 建模以识别最能预测EMA评估变量的神经影像学指标的组合。这 项目对Intrusions和创伤暴露的机理维度的联合检查具有创新性 根据其预测的神经生物学相关性选择。这也将是第一个应用多模式的研究 对PTSD中AHPC和PHPC网络解离的成像，并检查这些海马指标 与PTSD的现实症状有关。总体而言，我们的研究策略与NIMH的研究策略一致 研究领域标准（RDOC）关于确定与神经生物学与行为有关的维度 （侵入性记忆）及其与环境影响（创伤，威胁暴露）的相互作用。专业 隔离神经生物标志物与入侵和创伤机制有关的影响是潜在的 通过新颖的感知或认知训练计划识别有针对性治疗的神经终点， 或靶向神经调节。