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

基本信息

批准号：
10393641
负责人：
ISABELLE M ROSSO
金额：
$ 66.66万
依托单位：
MCLEAN HOSPITAL
依托单位国家：
美国
项目类别：
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/10393641
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 Persons 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

项目摘要

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) 的标志性症状，表现为闪回、噩梦和对创伤提醒的反应这些症状令人痛苦、丧失能力。他们预测病情会恶化，临床描述会突出显示症状的严重程度。有人提出，在“此时此地”重新体验创伤的感官知觉方面。这些心理机制代表海马体之间整合的丧失，海马体介导上下文结合和中线顶枕皮质，支持感觉-知觉的阐述。然而，没有研究调查测试海马回路的成像测量是否与大多数 PTSD 研究都使用仪器评估了入侵的这些关键机制特征。容易受到回顾性回忆偏差的影响，并且不评估入侵的心理特征此外，先前的研究尚未解析创伤机制。与海马体表型相关，例如长期遭受创伤（威胁），这会调节最后，大多数 PTSD 成像研究认为海马体是一个整体。结构，而证据表明前海马 (aHPC) 和后海马 (pHPC) 具有可分离的功能和连接性，以及 PTSD 的不同参与度拟议的研究将利用多种方法。有证据表明，入侵的关键心理机制可能是通过改变 pHPC 代谢和与顶枕皮质的连接我们将使用生态瞬时。评估（EMA），以评估日常生活中的入侵特征（基线后两周内）我们将测试 pHPC 功能连接、解剖学成像测量的假设。连接性和神经化学可预测入侵的感官知觉生动性和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，我们将进行多变量分析。建模以确定最能预测 EMA 评估变量的神经影像指标组合。该项目的创新之处在于它联合检查了入侵和创伤暴露的机械维度，两者根据他们预测的神经生物学相关性进行选择，这也将是第一个应用多模式的研究。 PTSD 中 aHPC 和 pHPC 网络解离的成像，并检查这些海马体指标总体而言，我们的研究策略与 NIMH 的研究策略是一致的。关于识别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（创伤、威胁暴露）的相互作用。分离与入侵和创伤机制相关的神经生物标志物的含义是潜在的通过新颖的感知或认知训练计划确定有利于针对性治疗的神经终点，或有针对性的神经调节。