Fear learning circuitry is biased toward generalization of fear associations in posttraumatic stress disorder.
Fear learning circuitry is biased toward generalization of fear associations in posttraumatic stress disorder.
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DOI：
10.1038/tp.2015.196
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发表时间：
2015-12-15
影响因子：
6.8
通讯作者：
LaBar KS
中科院分区：
文献类型：
--
作者：
Morey RA;Dunsmoor JE;Haswell CC;Brown VM;Vora A;Weiner J;Stjepanovic D;Wagner HR 3rd;VA Mid-Atlantic MIRECC Workgroup;LaBar KS
恐惧条件反射是研究创伤后应激障碍（PTSD）的一个成熟模型。然而，症状触发可能模糊地类似于最初的创伤事件，在各种感官和情感维度上有所不同。我们扩展了恐惧条件反射模型，以评估PTSD中条件恐惧对恐惧加工神经回路的泛化作用。退伍军人（n=67）组成的创伤后应激障碍（n=32）和创伤暴露的比较（n=35）组进行功能性磁共振成像过程中的恐惧条件反射到一个低的恐惧表达的脸，而一个中立的脸是明确的未加强。刺激变化沿着中性到恐惧的连续体提出前条件反射，以评估基线反应，和条件反射后，以评估经验依赖的神经活动的变化。与创伤暴露的对照组相比，PTSD患者表现出更大的研究后记忆扭曲的恐惧条件刺激的刺激表达最高的恐惧强度。PTSD患者在梭状回（P<0.02）、视皮层（P <0.001）、初级视皮层（P <0.05）、蓝斑（P<0.04）、丘脑（P<0.01）和额下回（P=0.07）等脑区均表现出偏向高强度刺激的激活。除梭状核外，所有区域均受童年创伤的影响。PTSD患者在条件反射后对高强度刺激的杏仁核-距状核（P=0.01）和杏仁核-丘脑（P=0.06）功能连接选择性增加。相比之下，杏仁核腹内侧前额叶皮层（P=0.04）连接选择性增加创伤暴露对照组相比，创伤后应激障碍患者的低强度刺激后条件，代表安全学习。总之，PTSD中的恐惧泛化倾向于比原始条件性恐惧刺激具有更高情绪强度的刺激。脑功能差异为恐惧泛化提供了一个假定的神经生物学模型，即PTSD症状是由仅仅类似于指数创伤的威胁线索触发的。
Fear conditioning is an established model for investigating posttraumatic stress disorder (PTSD). However, symptom triggers may vaguely resemble the initial traumatic event, differing on a variety of sensory and affective dimensions. We extended the fear-conditioning model to assess generalization of conditioned fear on fear processing neurocircuitry in PTSD. Military veterans (n=67) consisting of PTSD (n=32) and trauma-exposed comparison (n=35) groups underwent functional magnetic resonance imaging during fear conditioning to a low fear-expressing face while a neutral face was explicitly unreinforced. Stimuli that varied along a neutral-to-fearful continuum were presented before conditioning to assess baseline responses, and after conditioning to assess experience-dependent changes in neural activity. Compared with trauma-exposed controls, PTSD patients exhibited greater post-study memory distortion of the fear-conditioned stimulus toward the stimulus expressing the highest fear intensity. PTSD patients exhibited biased neural activation toward high-intensity stimuli in fusiform gyrus (P<0.02), insula (P<0.001), primary visual cortex (P<0.05), locus coeruleus (P<0.04), thalamus (P<0.01), and at the trend level in inferior frontal gyrus (P=0.07). All regions except fusiform were moderated by childhood trauma. Amygdala–calcarine (P=0.01) and amygdala–thalamus (P=0.06) functional connectivity selectively increased in PTSD patients for high-intensity stimuli after conditioning. In contrast, amygdala–ventromedial prefrontal cortex (P=0.04) connectivity selectively increased in trauma-exposed controls compared with PTSD patients for low-intensity stimuli after conditioning, representing safety learning. In summary, fear generalization in PTSD is biased toward stimuli with higher emotional intensity than the original conditioned-fear stimulus. Functional brain differences provide a putative neurobiological model for fear generalization whereby PTSD symptoms are triggered by threat cues that merely resemble the index trauma.
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影响因子：
16.2
作者：
Breiter, HC;Etcoff, NL;Rosen, BR
通讯作者：
Rosen, BR
影响因子：
19.9
作者：
Etkin, Amit;Egner, Tobias;Kalisch, Raffael
通讯作者：
Kalisch, Raffael
影响因子：
120.7
作者：
Binder, Elisabeth B.;Bradley, Rebekah G.;Ressler, Kerry J.
通讯作者：
Ressler, Kerry J.
影响因子：
5.9
作者：
Elliott, DM
通讯作者：
Elliott, DM
DOI：
10.1037/0097-7403.1.1.3
发表时间：
1975-01-01
期刊：
JOURNAL OF EXPERIMENTAL PSYCHOLOGY-ANIMAL BEHAVIORAL PROCESSES
影响因子：
--
作者：
BLOUGH, DS
通讯作者：
BLOUGH, DS