STRESS-INDUCED STARTLE MODULATION IN PTSD

这项提议的目的是阐明 夸张的惊吓反应，这是Post的标志之一 创伤应激障碍(PTSD)。不可避免的休克的动物研究 越南战争退伍军人的心理生理调查 创伤后应激障碍表明，有条件和无条件的机制都必须 在创伤后应激障碍的发病机制中被考虑。概念框架 因为这项拟议的研究是基于条件性和条件性的动物模型 无条件的应激诱导惊吓调制，即恐惧- 加强惊吓、惊吓的休克敏感化和应激诱导 脉冲前抑制消失。退伍军人的高反应性也可能 指出在处理环境刺激方面普遍存在缺陷。我们 发现创伤后应激障碍退伍军人过度关注 外部刺激。我们将试图进一步描述这一不足之处 使用事件相关电位(ERP)。我们还将进行一项研究 应用脑干听觉诱发电位(BAEP)探索感觉 正在处理。任何信息损伤之间的关系 还将检查处理和异常惊吓调制。 惊吓调制和处理外部刺激将是 在基线和实验诱导的应激期间进行调查 患有创伤后应激障碍的退伍军人(N=44)和适当的平民(N=82)和 退伍军人(N=81)对照组。应力条件将包括 对电击的期待和对创伤场景的观看。 强烈的惊吓反射的眨眼成分 将测量突然发作的声刺激 肌电图仪。对外部刺激的认知加工将 使用由各种类型的刺激引起的事件相关电位进行调查 旨在吸引受试者的注意。BAEP将会是 仅在基线上测量。 拟议研究的结果将澄清是否增加了 创伤后应激障碍患者对感觉刺激的反应性反映慢性升高 唤醒或刺激诱导的状态。这些实验可能会提供一种 为更客观的诊断方法和更好的 通过核心特征来评估治疗结果 创伤后应激障碍的症状。此外，我们目前的知识状况来自 应激相关惊厥神经生物学底物的研究 在动物中的调制可能导致识别出 大脑调节失调与创伤后应激障碍有关，并可能最终导致 更好的行为和药物治疗的发展 治疗这种疾病的方法。

The aim of this proposal is to elucidate the mechanisms underlying the exaggerated startle response which is one of the hallmarks of Post Traumatic Stress Disorder (PTSD). Animal studies of inescapable shock and psychophysiological investigations in Vietnam war veterans with PTSD suggest that both conditioned and unconditioned mechanisms must be considered in the pathogenesis of PTSD. The conceptual framework for the proposed study is based on animal models of conditioned and unconditioned stress-induced startle modulation, namely, fear- potentiated startle, shock sensitization of startle, and stress-induced loss of prepulse inhibition. Hyperreactivity of PTSD veterans may also point to a general deficit in processing environmental stimuli. We have found that PTSD veterans engaged excessive attention toward external stimuli. We will attempt to further characterize this deficit using event-related potentials (ERP). We will also conduct a study using brainstem auditory evoked potentials (BAEP) to explore sensory processing. The relationship between any impairments in information processing and abnormal startle modulation will also be examined. Startle modulation and processing of external stimuli will be investigated both at baseline and during experimentally-induced stress in veterans with PTSD (N=44) and appropriate civilian (N=82) and veteran (N=81) control subjects. The stress conditions will consist of anticipation of electric shocks and the viewing of traumatic scenes. The eyeblink component of the startle reflex elicited by an intense acoustic stimulus with abrupt onset will be measured electromyographically. Cognitive processing of external stimuli will be investigated with ERPs elicited by various types of stimuli that are designed to attract the subject's attention. The BAEPs will be measured at baseline only. The results of the proposed study will clarify whether the increased reactivity to sensory stimulation in PTSD reflects a chronic elevated arousal or a stimulus-induced state. These experiments may provide a foundation for more objective diagnostic approaches and a better assessment of treatment outcome through the characterization of core symptoms of PTSD. In addition, our current state of knowledge from the delineation of the neurobiological substrates of stress-related startle modulation in animals could lead to the identification of patterns of brain dysregulation involved in PTSD and could ultimately result in the development of better behavioral and pharmacological treatment approaches for this disorder.