Norrholm Seth D, Anderson Kemp M, Olin Ilana W, Jovanovic Tanja, Kwon Cliffe, Warren Victor T, McCarthy Alexander, Bosshardt Lauren, Sabree Justin, Duncan Erica J, Rothbaum Barbara O, Bradley Bekh
Trauma Recovery Program, Mental Health Service Line, Atlanta Veterans Affairs Medical Center Decatur, GA, USA.
Front Behav Neurosci. 2011 Nov 21;5:77. doi: 10.3389/fnbeh.2011.00077. eCollection 2011.
Fear conditioning methodologies have often been employed as testable models for assessing learned fear responses in individuals with anxiety disorders such as post-traumatic stress disorder (PTSD) and specific phobia. One frequently used paradigm is measurement of the acoustic startle reflex under conditions that mimic anxiogenic and fear-related conditions. For example, fear-potentiated startle is the relative increase in the frequency or magnitude of the acoustic startle reflex in the presence of a previously neutral cue (e.g., colored shape; termed the conditioned stimulus or CS+) that has been repeatedly paired with an aversive unconditioned stimulus (e.g., airblast to the larynx). Our group has recently used fear-potentiated startle paradigms to demonstrate impaired fear extinction in civilian and combat populations with PTSD. In the current study, we examined the use of either auditory or visual CSs in a fear extinction protocol that we have validated and applied to human clinical conditions. This represents an important translational bridge in that numerous animal studies of fear extinction, upon which much of the human work is based, have employed the use of auditory CSs as opposed to visual CSs. Participants in both the auditory and visual groups displayed robust fear-potentiated startle to the CS+, clear discrimination between the reinforced CS+ and non-reinforced CS-, significant extinction to the previously reinforced CS+, and marked spontaneous recovery. We discuss the current results as they relate to future investigations of PTSD-related impairments in fear processing in populations with diverse medical and psychiatric histories.
恐惧条件反射方法经常被用作可测试的模型,以评估患有创伤后应激障碍(PTSD)和特定恐惧症等焦虑症的个体的习得性恐惧反应。一种常用的范式是在模拟焦虑和恐惧相关条件的情况下测量听觉惊跳反射。例如,恐惧增强惊跳是指在存在先前中性线索(如彩色形状;称为条件刺激或CS+)时,听觉惊跳反射的频率或幅度相对增加,该中性线索已与厌恶非条件刺激(如向喉部吹气)反复配对。我们小组最近使用恐惧增强惊跳范式来证明患有PTSD的平民和战斗人员的恐惧消退受损。在当前的研究中,我们在一个已验证并应用于人类临床情况的恐惧消退方案中,研究了使用听觉或视觉条件刺激。这代表了一个重要的转化桥梁,因为许多恐惧消退的动物研究(许多人类研究都基于这些动物研究)使用的是听觉条件刺激而非视觉条件刺激。听觉组和视觉组的参与者对CS+均表现出强烈的恐惧增强惊跳,对强化的CS+和未强化的CS-有明显区分,对先前强化的CS+有显著的消退,以及明显的自发恢复。我们将当前结果与未来对具有不同医学和精神病史人群中与PTSD相关的恐惧处理障碍的研究相关联进行讨论。