Poor between-session recall of extinction learning and hippocampal activation and connectivity in children
Poor between-session recall of extinction learning and hippocampal activation and connectivity in children
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DOI：
10.1016/j.nlm.2018.10.007
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发表时间：
2018-12-01
影响因子：
2.7
通讯作者：
Rabinak, Christine A.
中科院分区：
文献类型：
--
作者：
Marusak, Hilary A.;Peters, Craig;Rabinak, Christine A.
背景：在健康成年人中，消退学习的成功的会话间回忆取决于海马体和腹内侧前额叶皮层（vmPFC），尤其是在消退背景下进行测试时。海马-vmPFC 回路内的消退记忆不良和功能障碍与基于恐惧的疾病（例如焦虑、创伤后应激障碍）有关。尽管几乎所有基于恐惧的疾病都在早期发病，并且海马体和 vmPFC 在生命的前 20 年中长期发育，但人们对儿童的灭绝回忆及其潜在的神经相关性知之甚少。方法：在这里，我们通过将功能磁共振成像和虚拟现实与新型人际威胁相关两天 (ABBA) 结合起来，测试了 43 名青春期前儿童（6-11 岁）的灭绝回忆。恐惧-灭绝范式。在行为、主观、生理和神经层面评估条件性恐惧反应。结果：尽管儿童在会话内表现出完整的消退能力，但在会话间对消退学习的回忆很差（保留指数：13.56%），皮肤电导、回避行为反应和主观评分的升高证明了这一点。在成人研究中，条件性恐惧反应的升高伴随着海马体和岛叶的激活，以及海马体与岛叶和背侧前扣带皮层区域的连接性增加，这与成人研究中恐惧的回归有关。在消退过程中与消失线索保持更远距离的儿童随后在回忆过程中表现出更高的海马扣带回耦合，这表明回避行为会干扰消退保留。结论：儿童的消退记忆不良可能会影响其对基于恐惧的疾病的发育脆弱性，以及对儿科样本应用依赖于消退原理（例如暴露疗法）的治疗策略。
Background: In healthy adults, successful between-session recall of extinction learning depends on the hippocampus and ventromedial prefrontal cortex (vmPFC), especially when tested in the extinction context. Poor extinction recall and dysfunction within hippocampal-vmPFC circuitry are associated with fear-based disorders (e.g., anxiety, posttraumatic stress disorder). Despite the early age of onset of virtually all fear-based disorders and the protracted development of the hippocampus and vmPFC across the first two decades of life, little is known about extinction recall and the underlying neural correlates in children.Methods: Here, we tested extinction recall in 43 pre-adolescent children (ages 6-11 yrs) by coupling functional magnetic resonance imaging and virtual reality with a novel interpersonal threat-related two-day (ABBA) fear-extinction paradigm. Conditioned fear responding was assessed at behavioral, subjective, physiological, and neural levels.Results: Although children demonstrated intact within-session extinction, there was poor between-session recall of extinction learning (retention index: 13.56%), evidenced by elevations in skin conductance, avoidant behavioral responses, and subjective ratings. Elevations in conditioning fear responding were accompanied by activation in the hippocampus and insula, and increased connectivity of the hippocampus with the insula and dorsal anterior cingulate cortex-regions implicated in the return of fear in adult studies. Children who kept more distance from the extinguished cue during extinction subsequently demonstrated heightened hippocampalcingulate coupling during recall, suggesting that avoidant behavior interferes with extinction retention.Conclusions: Poor extinction recall in children may have implications for developmental vulnerability to fear-based disorders, and for the application of therapeutic strategies that rely on principles of extinction (e.g., exposure therapy) to pediatric samples.