杏仁核社会认知功能紊乱的代偿脑机制：基于皮层镜像神经元系统潜在作用的研究

Brain amygdala cognitive dysfunction is widely associated with social and emotional problems observed in both the healthy population as well as in many psychiatric disorders, most notably in terms of impaired emotion recognition and empathy. Recently we have observed in rare patients with bilateral amygdala damage that impaired emotional cognitive processing may be compensated in some cases by increased activity in parts of the cortical mirror neuron system also involved in emotion recognition and thought to play a role in emotional contagion/mimicry and empathy. The main objective of the current proposal is to provide a detailed investigation of functional links between the amygdala and cortical mirror neuron system and the brain mechanisms that can functionally compensate for amygdala dysfunction. To achieve this we will first use healthy human subjects with impaired amygdala function and emotion recognition as a result of having high autistic or anxiety traits, or as a result of reduced amygdala responsivity to emotional stimuli due to pharmacological intervention targeting serotonergic, noradrenergic or oxytocinergic signalling(citalopram/propranolol/oxytocin), or following neurofeedback training using real time functional magnetic imaging/EEG recording methods. Next we will use both behavioral, neurofeedback training and transcranial magnetic stimulation approaches to determine optimal strategies for promoting compensatory changes in different parts of the cortical mirror neuron system which will facilitate emotion recognition and empathy and social interaction skills. A key objective of these studies will be to provide a platform for subsequent therapeutic use in clinical populations, most notably autism, schizophrenia and psychopathy as well as in antisocial disorders such as conduct disorder.

杏仁核认知功能紊乱与人们的社会认知与情绪问题密切相关，尤其是情绪认知加工，这在健康人群与精神疾病患者中都有体现。我们研究发现，杏仁核两侧受损所致的情绪识别障碍患者，其情绪认知加工能力在某些情况下可以通过部分皮层镜像神经元系统的激活增强进行代偿。因此，本项目旨在找到杏仁核与皮层镜像神经元系统之间在功能上的联系，以及在何种程度上镜像神经元系统可以弥补杏仁核的功能紊乱。为此，我们拟通过健康被试，采用行为特质区分法、药物干预法以及神经反馈训练等手段，调节杏仁核功能并识别出其代偿脑机制，从而找到可以提高杏仁核认知功能紊乱代偿作用的最优方案，即通过改变认知改变情绪。这些研究将有望为探索临床患者的治疗方法提供基础，尤其是自闭症、精神分裂症、心理变态及反社会人格障碍等。

本项目旨在探索健康人群和临床患者大脑杏仁核功能紊乱下镜像神经元的代偿机制。围绕该整体目标，项目分为四个研究方向进行开展：（1）揭示杏仁核结构和功能、镜像神经元系统与精神障碍以及人格特质之间的关系；（2）明晰镜像神经元网络和突显网络在情绪认知加工过程中的功能作用及其可能的代偿机制；（3）探索催产素对人类社会行为的调节作用以及与执行网络、情绪网络、突显网络及奖赏加工网络之间的交互影响；（4）探寻与临床心理疾病及精神障碍症状相关的异常神经网络改变以及生物学标记。.本项目多项研究显示，杏仁核与镜像神经元网络及奖赏网络的交互作用在人类的社会行为和情绪加工中发挥着重要作用，并且这些网络相互作用与健康人群的特定人格特质以及自闭症、社会焦虑和抑郁症等社会功能紊乱相关症状关系密切，其中杏仁核与颞上沟之间功能连接的代偿性增加或许对社会功能的改善具有积极潜力。本项目主要通过药理学（催产素-oxytocin、洛沙坦-lorsatan、莫达非尼-modafinil）以及神经反馈干预训练等脑功能干预技术开展了一系列的多模态和大样本研究，发现相比其他干预策略，催产素在促进社会认知和降低焦虑等方面效果更为显著。值得一提的是，催产素的潜在疗效会受到个体性别、个体基因型、给药频次以及给药方式等不同因素的影响，需要进一步探索以确立催产素调节社会功能紊乱的最佳策略。.在本项目的支持下，团队5年来发表同行评议学术成果77篇，其中12篇论文影响因子大于10（含PNAS），另有5篇在审。多项成果发表在Advanced Science (IF = 15.8)、American Journal of Psychiatry (IF = 14.1)、Psychotherapy and Psychosomatics (IF = 14.9)、Biological Psychiatry (IF = 11.5)、 Molecular Psychiatry (IF = 12.0)、(Brain IF = 11.4)、eLife（IF = 6.8）, Cerebral Cortex(IF = 6.3), NeuroImage(IF = 5.8)、Psychological Medicine (IF = 5.8)等国际顶级和一流期刊。举办两次国际会议，并在2018年新加坡举办的OHBM会议中举办两场分会论坛。