NEURAL SUBSTRATES OF EMOTION IN BORDERLINE PATIENTS

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目及 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 边缘型人格障碍（BPD）是一种持续性的严重精神障碍，具有高死亡率、高发病率和高痛苦水平。情绪失调或对环境事件的反应，特别是分离，挫折或损失等事件被认为是这种疾病的定义特征。这种障碍很少受到调查审查，异常情绪处理的神经相关性也不清楚。惊吓眨眼修正（SEM）方法为情绪加工的研究提供了一种非语言的定量工具。当在不愉快的刺激期间呈现短暂的惊吓刺激时，惊吓反应的幅度增强;愉快的刺激引起惊吓反应的相对抑制;并且中性刺激是中间的。本研究使用扫描电镜和功能性神经成像（事件相关的功能磁共振成像和FDG-PET），以探索强度，时间过程，习惯化和功能神经解剖学的情绪反应在三个严格筛选的群体：26例BPD患者（无共病轴I障碍或群集A或C人格障碍），26名非BPD患者（诊断为典型人格障碍，没有共病的B或C群人格障碍或轴I障碍）和26名健康对照。在fMRI扫描和PET的FDG摄取过程中，参与者将看到一系列混杂的不愉快（例如，讨厌），愉快（例如，快乐）和中性（例如，查看）的话。SEM幅度差分数（例如，不愉快-愉快）将提供对不愉快刺激的情绪处理的强度、时间过程和习惯化的测量，并与局部葡萄糖代谢相关。关键脑区的fMRI BOLD反应差异分数将提供脑激活的强度和时间过程的测量。我们关注三个被认为与情绪处理有关的大脑区域：杏仁核、前扣带回和前额叶皮层（眶额和背外侧）。这些区域是大脑回路的一部分，被认为介导情绪体验，并在BPD症状的表达中发挥重要作用。这种心理生理学和功能神经解剖学方法的结合，有可能提供急需的信息规范方面的情绪处理和洞察神经解剖学的基础上观察到的BPD的情绪失调。 假设： 假设（1a）：BPD患者在听到不愉快的言语时的惊吓反应强度高于正常对照组，但对愉快或中性刺激无组间差异。试验项目：将对SEM百分比变化评分进行MANOVA，其中组作为组间因素，单词和探针条件作为重复测量：组（BPD患者与对照组）+单词条件（不愉快、愉快、中性）+探针位置（3000 ms、4000 ms、5000 ms）。我们预测一个显着的组+字条件的相互作用。接下来，Fisher LSD检验将被事后使用以确定是否观察到我们的假设，即在不愉快的词语期间BPD> N SEM，但不是愉快的或中性的。 假设（1b）：BPD患者在较后的探测位置的不愉快的话期间将表现出更大的惊吓情感潜能，并且（1c）BPD患者的这种潜能将表现出缓慢的习惯化。测试1b：1a中的MANOVA将测试这一假设，我们预测一个显着的组+词条件+探针位置的相互作用。事后检验显示在不愉快的话期间在5000 ms探针位置处的BPD> N SEM，但不是愉快或中性的，这将证实我们的假设。1c的检验：我们将在1a中的MANOVA中添加时间因素（早期试验，晚期试验）来检验这一假设。假设存在显著的组+词条件+探针位置+时间交互作用。事后检验显示，在不愉快的词的后期试验期间，在5000 ms处的BPD> N SEM，但不是愉快或中性的，这将证实我们的假设。 假设（2a）： 正常人的前额叶区域比杏仁核区域表现出更大的差异激活（不愉快-愉快的词条件）。测试2a，前额：对于健康对照组，将对Brodmann程序的BOLD反应进行重复测量MANOVA。这种分析将允许检查前额叶皮层对不愉快与愉快的词语条件的反应。设计将是：词条件（不愉快，愉快）+额区（背外侧，眶额）+布罗德曼区（背外侧：BA 44，45，46;眶额：BA 11，12，47）+半球（右，

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Borderline personality disorder (BPD) is a persistent and severe mental disorder with high mortality, morbidity and levels of distress. Emotional dysregulation or reactivity to environmental events, particularly events such as separations, frustrations, or losses is considered a defining feature of this disorder. This disorder has received little investigative scrutiny and the neural correlates of abnormal emotional processing are not understood. Startle eyeblink modification (SEM) methodology provides a non-verbal, quantitative tool for the study of emotional processing. When a brief startle stimulus is presented during an unpleasant stimulus, the amplitude of the startle response is potentiated; a pleasant stimulus occasions a relative inhibition of the startle response; and a neutral stimulus is intermediate. This study uses SEM and functional neuroimaging (event-related fMRI and FDG-PET) to explore the intensity, time course, habituation and functional neuroanatomy of emotional responses in three rigorously screened groups: 26 BPD patients (with no comorbid Axis I disorder or Cluster A or C personality disorders), 26 non-BPD patients (with a diagnosis of schizotypal personality disorder and no comorbid Cluster B or C personality disorders or Axis I disorder) and 26 healthy controls. During both the fMRI scan and FDG-uptake for PET, participants will view an intermixed series of unpleasant (e.g., hate), pleasant (e.g., happy) and neutral (e.g., view) words. SEM amplitude difference scores (e.g., unpleasant-pleasant) measured during simultaneous FDG uptake will provide a measure of the intensity, time course, and habituation of emotional processing of unpleasant stimuli and be correlated with regional glucose metabolism. fMRI BOLD response difference scores in key brain regions will provide measurement of the intensity and time course of brain activation. We focus on three brain regions thought to be involved in emotional processing: amygdala, anterior cingulate, and prefrontal cortex (orbitofrontal and dorsolateral). These regions are part of a brain circuit thought to mediate emotional experience and play a significant role in the expression of BPD symptoms. This proposed combination of a psychophysiological and functional neuroanatomy approach holds the potential to provide much-needed information on normative aspects of emotional processing and insights into the neuroanatomy underlying the emotional dysregulation observed in BPD. Hypothesis: Hypothesis (1a): Greater intensity of the startle response magnitude during the unpleasant words in BPD patients than normal controls, but there will be no between-group differences for the pleasant or neutral stimuli. Test: MANOVA on SEM percent change scores will be conducted with Group as the between-group factor and Word and Probe condition as repeated measures: Group (BPD patients vs. Controls)+Word condition (unpleasant, pleasant, neutral)+Probe position (3000ms, 4000ms, 5000ms). We predict a significant Group+Word condition interaction. Next, Fisher LSD tests will be used post-hoc to determine whether our hypothesis of BPD>N SEM during unpleasant words, but not pleasant or neutral is observed. Hypothesis (1b): BPD patients will exhibit greater affective potentation of startle during unpleasant words at the later probe position and (1c) this potentiation in BPD patients will show slow habituation. Test for 1b: The MANOVA in 1a will test this hypothesis and we predict a significant Group+Word condition+Probe position interaction. Post-hoc tests showing BPD>N SEM at 5000 ms probe position during unpleasant words, but not pleasant or neutral will confirm our hypothesis. Test for 1c: We will add the factor of Time (early trials, late trials) to the MANOVA in 1a to test this hypothesis. A significant Group+Word condition+Probe position+Time interaction is hypothesized. Post-hoc tests showing BPD>N SEM at 5000 ms during late trials of unpleasant words, but not pleasant or neutral will confirm our hypothesis. Hypothesis (2a): Normals will show greater differential activation (unpleasant-pleasant word condition) in prefrontal regions than in amygdala. Test 2a, prefrontal: For the healthy control group, a repeated-measures MANOVA on BOLD response from the Brodmann program will be conducted. This analysis will allow an examination of prefrontal cortex response to unpleasant vs. pleasant word conditions. The design will be: Word condition (unpleasant, pleasant)+Frontal region (dorsolateral, orbitofrontal)+Brodmann area (dorsolateral: BA 44, 45, 46; orbitofrontal: BA 11, 12, 47)+Hemisphere (right,