Marusak Hilary A, Peters Craig, Hehr Aneesh, Elrahal Farrah, Rabinak Christine A
Department of Pharmacy Practice, Wayne State University College of Pharmacy and Health Sciences, Detroit, MI, United States.
Department of Pharmacy Practice, Wayne State University College of Pharmacy and Health Sciences, Detroit, MI, United States.
Neurobiol Learn Mem. 2018 Dec;156:86-95. doi: 10.1016/j.nlm.2018.10.007. Epub 2018 Oct 19.
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.
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.
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 hippocampal-cingulate coupling during recall, suggesting that avoidant behavior interferes with extinction retention.
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.
在健康成年人中，成功的消退学习会话间回忆依赖于海马体和腹内侧前额叶皮质（vmPFC），尤其是在消退情境中进行测试时。消退回忆不佳以及海马体 - vmPFC 神经回路功能障碍与基于恐惧的疾病（如焦虑症、创伤后应激障碍）有关。尽管几乎所有基于恐惧的疾病发病年龄都较早，且海马体和 vmPFC 在生命的头二十年中持续发育，但对于儿童的消退回忆及其潜在的神经关联知之甚少。
在此，我们通过将功能磁共振成像和虚拟现实与一种新型的人际威胁相关的为期两天的（ABBA）恐惧消退范式相结合，对 43 名青春期前儿童（6 - 11 岁）进行了消退回忆测试。在行为、主观、生理和神经水平上评估条件性恐惧反应。
尽管儿童在会话内表现出完整的消退，但消退学习的会话间回忆较差（保持指数：13.56%），表现为皮肤电导率升高、回避行为反应和主观评分升高。条件性恐惧反应的升高伴随着海马体和脑岛的激活，以及海马体与脑岛和背侧前扣带回皮质之间连接性的增加——在成人研究中，这些区域与恐惧的恢复有关。在消退过程中与消退线索保持更远距离的儿童在回忆过程中随后表现出海马体 - 扣带回耦合增强，这表明回避行为会干扰消退记忆。
儿童消退回忆不佳可能对基于恐惧的疾病的发育易感性以及将依赖消退原则的治疗策略（如暴露疗法）应用于儿科样本有影响。
