NEURAL SUBSTRATES OF EMOTION IN BORDERLINE PATIENTS

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 交界性人格障碍(BPD)是一种持续存在的严重精神障碍，具有高死亡率、高发病率和高痛苦程度。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一个定义特征。这一障碍几乎没有受到调查研究的审查，异常情绪处理的神经关联也没有被理解。惊恐眨眼修正(SEM)方法为情绪加工的研究提供了一种非语言的量化工具。当在令人不快的刺激期间出现短暂的惊吓刺激时，惊吓反应的幅度会增强；愉快的刺激会相对抑制惊吓反应；而中性刺激是中间的。本研究采用扫描电子显微镜和功能神经成像(事件相关功能磁共振成像和FDG-PET)研究了三组严格筛选的BPD患者情绪反应的强度、时间进程、习惯化和功能神经解剖学：26例BPD患者(无共病的A、C类人格障碍)，26例非BPD患者(诊断为分裂型人格障碍，无B、C类人格障碍或A、C类人格障碍)和26名健康对照。在功能磁共振扫描和FDG摄取PET期间，参与者将看到一系列令人不快(例如，憎恨)、令人愉快(例如，快乐)和中性(例如，查看)的单词。在同时摄取FDG期间测量的扫描电子显微镜幅度差分数(例如，不愉快-愉快)将提供对不愉快刺激的情绪处理的强度、时间进程和习惯化的测量，并与局部糖代谢相关。关键大脑区域的fMRI BOLD反应差异分数将提供大脑激活的强度和时间过程的测量。我们专注于三个被认为参与情绪处理的大脑区域：杏仁核、前扣带回和前额叶皮质(眼眶、额叶和背外侧)。这些区域是大脑回路的一部分，被认为是调节情绪体验的一部分，并在BPD症状的表达中发挥重要作用。这一结合心理生理学和功能神经解剖学的方法有可能提供关于情绪处理的规范方面的急需信息，以及对BPD中观察到的情绪失调背后的神经解剖学的洞察。 假设： 假设(1a)：BPD患者在说不愉快的话时，惊吓反应的强度比正常对照组更大，但对于愉快或中性的刺激，组间没有差异。测试：以组内因素为组间因素，以词和探测条件为重复测量：组(BPD患者与对照组)+词条件(不愉快、愉快、中性)+探测位置(3000ms、4000ms、5000ms)。我们预测了一个显著的组+词条件交互作用。接下来，费舍尔LSD测试将被用来确定我们的假设在不愉快的词，但不愉快的或中性的词期间是否被遵守。 假设(1b)：BPD患者在较晚的探测位置，在不愉快的词语时会表现出更大的惊吓情绪，(1c)BPD患者的这种增强将显示出缓慢的习惯化。对1b的测试：1a中的Manova将检验这一假设，我们预测有意义的组+词条件+探测位置交互作用。事后测试显示，BPD&GT；N扫描电子显微镜在令人不快的词的探测位置为5000毫秒，但不是令人愉快的或中性的，这将证实我们的假设。1c检验：我们将在1a中的Manova中加入时间因素(早期试验、后期试验)来检验这一假设。假设存在显著的组+词条件+探测位置+时间交互作用。之后的测试显示，在对令人不快的单词进行后期试验期间，bpd&gt；N扫描电子显微镜的时长为5000毫秒，但不是令人愉快的或中性的，这将证实我们的假设。 假设(2a)： 正常人在前额叶区域比在杏仁核表现出更大的差异激活(令人不快-愉快的词汇条件)。测试2a，前额叶：对于健康对照组，将对Brodmann计划的大胆反应进行重复测量Manova。这一分析将允许检查前额叶皮质对不愉快的词语条件的反应与对愉快词语条件的反应。设计为：词汇条件(不愉快，愉快)+额区(背外侧，眶前区)+Brodmann区(背外侧：BA 44，45，46；眶前区：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,