基于颅内脑电的人类恐惧记忆注意偏向神经机制研究

Attention bias to threat information in fear memory can lead to a variety of emotional diseases. Brain network involved in this process and its working mechanism remain to be elucidated. According to animal experiments and brain imaging studies, amygdala, hippocampus and medial prefrontal cortex are proved to be the core nodes of fear memory network. However, the interaction mechanism among the network remains unclear. Dorsolateral prefrontal cortex is the key structure of attention system, which is also involved in the process of fear memory. However, the interaction mechanism is still unknown. The rationale is to use Pavlovian fear conditioning as a well-established model of fear memory study. We have collected the EEG of epilepsy patients during intracranial EEG monitoring and discovered that the network nodes interacted each other by multiple frequencies in the above-mentioned paradigm. The interaction mechanism was considered in association with the neural activities of dorsolateral prefrontal cortex. In the present study, by means of intracranial electroencephalogram with high spatiotemporal resolution, we will study the interaction mechanism of human fear memory network nodes during classical Pavlovian fear conditioning using graph theory, directional transfer function and other methods. Meanwhile, we’ll use cortico-cortical evoked potential to further clarify the neural effective correlates in these nodes. Moreover, based on network working mechanism, we’ll observe the working mechanism of dorsolateral prefrontal cortex in attention bias and fear memory extinction under cortical electrical pulse train stimulation of it. The present study attempts to find the mechanisms of fear memory network, to elucidate the regulating mechanism of attention system in it, and to provide an important basis for neuromodulation therapy for related diseases.

恐惧记忆中对威胁信息的注意偏向可导致多种情感相关疾病，参与此过程的脑网络及其工作机制有待阐明。动物实验和脑功能成像研究提示杏仁核、海马、内侧前额叶是恐惧记忆网络核心节点，节点间交互作用机制不清；背外侧前额叶是注意系统核心结构，也参与恐惧记忆加工，但其机理未明。基于巴甫洛夫恐惧条件反射的范式是研究恐惧记忆的典范，前期我们采集到埋置颅内电极治疗癫痫患者的脑电，发现此范式作业中网络节点通过多个频段震荡交互影响，且与背外侧前额叶活动有关。我们计划利用此高时空分辨率颅内脑电技术，采用图论、方向传递函数等方法分析恐惧记忆建立时上述网络节点的交互影响；采用皮质-皮质间诱发电位技术确定节点间有效连接；在明确网络工作机制的基础上，通过施加电脉冲串干扰背外侧前额叶功能，观察该脑区在注意偏向及恐惧记忆消除中的作用。本研究可揭示恐惧记忆网络工作机制、明确注意系统对其调节机制，为神经调控治疗相关疾病提供依据。

恐惧记忆中对威胁信息的注意偏向可导致多种情感相关疾病，参与此过程的脑网络及其工作机制有待阐明。动物实验和脑功能成像研究提示杏仁核、海马、内侧前额叶是恐惧记忆网络核心节点，节点间交互作用机制不清；背外侧前额叶是注意系统核心结构，也参与恐惧记忆加工，但其机理未明。基于巴甫洛夫恐惧条件反射的范式是研究恐惧记忆的典范，前期我们采集到埋置颅内电极治疗癫痫患者的脑电，发现此范式作业中网络节点通过多个频段震荡交互影响，且与背外侧前额叶活动有关。我们利用高时空分辨率颅内脑电技术，采用图论、方向传递函数等方法分析恐惧记忆建立时上述网络节点的交互影响。与先前的啮齿类动物研究一致，我们的研究结果显示杏仁核参与恐惧记忆提取而不参与中性记忆提取，海马参与恐惧记忆提取和中性记忆提取。我们发现杏仁核和海马在β频段（14-30Hz）存在同步化活动增强，提示杏仁核和海马之间的β频段同步化活动的增强在人类恐惧记忆的提取过程中起着关键作用。因此，我们的研究结果，杏仁核-海马系统参与人类恐惧记忆提取并具有频率依赖特异性，为恐惧机制提供了新的见解，并具有潜在的临床相关性。