健康与遗传心理学研究室知识库

恐惧作为个体为应对内外界危险因素所形成的的自我保护机制的一部分，在众多高级生命的生存与发展中发挥着重要作用。适当的恐惧能帮助个体躲避可能存在的威肋、从而顺利生存下来，而过度的恐惧不仅于生存无益，反而易引发恐惧反应的过度表达，在人类身上甚至容易引发如创伤后应激障碍、焦虑症、惊恐障碍等精神疾病，严重影响个体的生活质量，同时也为社会带来巨大的经济负担。临床上通常采用基于行为研究结果发展而来的暴露疗法对恐惧相关疾病进行治疗，然而在患者处在治疗环境之外的安全情境中时，上述疾病常常复发。因此，解析恐惧记忆相关脑区内部及脑区之间信息处理的神经机制，对于理解这些疾病的发生发展，寻求切实有效的治疗方案至关重要。

研究表明与恐惧记忆消退相关的脑区主要涉及杏仁核、内侧前额叶和海马三个脑区，而杏仁核、内侧前额叶尤其是腹内侧前额叶在其中发挥了极其关键的作用。在恐惧消退的过程中，这两个脑区表现出特定的神经活动模式，并构成了恐惧记忆成功消退的神经基础。在神经振荡层面，大量研究发现theta}2-8 Hz)和gamma(30-120 Hz)频段的活动参与到恐惧记忆消退加工过程当中。然而这些证据大都是基于动物实验的结果，以人类为对象的研究所提供的大多是行为或脑成像实验的证据，目前并没有非常全面和直接的电生理证据证明这些神经振荡模式也存在于人类大脑中。因此，本研究聚焦于杏仁核和腹内侧前额叶两个脑区，旨在探讨人类大脑在恐惧记忆消退中的神经振荡机制，讨论动物神经振荡模型在人类身上的可重复性，从而为恐惧记忆的消退和情绪相关精神障碍的进一步研究提供科学证据。

本研究分为两个部分，研究一以健康人为研究对象，采用经典的恐惧条件化范式，通过记录被试在恐惧习得、消退以及消退效果提取过程中的皮肤电活动，探讨条件化线索数量对恐惧记忆消退的影响，并以此为依据设计后续实验;研究二中，利用颅内立体电极定位技术记录恐J俱记忆消退过程中杏仁核和内侧前额叶的神经振荡活动，探讨不同脑区对条件化恐惧记忆消退的调控作用，研究一中我们发现被试在单线索和多线索任务中都能够成功习得并消退恐惧记忆，并且在消退提取发生了恐惧恢复，但单线索任务中恐惧泛化程度更低;在研究二中，我们发现杏仁核与腹内侧前额叶的theta振荡活动都参与到恐惧记忆的消退中，且这种活动强度随着恐惧记忆的消退而降低，而脑区间连接则随着消退学习的进行而增强。本研究的结果说明，与动物相似，人类的杏仁核与腹内侧前额叶也能通过调控theta振荡参与到恐惧记忆的消退中在一定程度上为寻找更有效促进恐惧记忆消退的方法提供了科学依据。

As part of the self-protection mechanism that individuals use to deal with internal and external risk factors, fear plays an important role in the survival of organisms. However, excessive fear is not only detrimental to the survival of the individual, but also easy to cause mental illness such as post-traumatic stress disorder and anxiety, which seriously affects the quality of life. Clinically, exposure therapy based on behavioral findings are often used to treat fear-related diseases, but these symptoms often recur when the patient break away from the treatment environment. Therefore, the investigation of the information processing in the neural circuits related to fear memory is essential for understanding the occurrence and development of these diseases and establishing new treatments. Numerous studies have demonstrated that amygdala and medial prefrontal cortex (mPFC) perform a key role in the extinction of fear memory. In the process of fear extinction, these brain regions show specific patterns of neural oscillations especially of theta (4-12Hz) and gamma (30-120Hz) frequency bands, which constitutes the neural basis for the successful extinction of fear memory. However, most of these results were rooted from animal experiment, it is still unknown that whether human brain acts similarly in the process of fear extinction.

Our study constitutes two parts. The first part is to collect healthy participants' data to observe the behavioural reaction in natural fear extinction. In the second part we perform the experiment in conbine with SEEG dynamically recording. This step aim to explore the oscillatory pattern of amygdala and mPFC neurons during fear extinction. In the present research we found that subjects are able to learn and extinguish conditional fear memory successfully, but the single-cue task lead to less fear generalization. On the other hand, the EEG analysis reveals that theta (2-8 Hz) oscillation in amygdala and vmPFC participated in the extinction of conditional fear memory. The findings from this research promote the understanding of the neural oscillation mechanism about fear memory in humans.