Department of Neurology, Xuanwu Hospital, Capital Medical University, Beijing, 100053, China.
The Beijing Key Laboratory of Neuromodulation, Beijing, 100053, China.
Acta Neurochir (Wien). 2020 Oct;162(10):2499-2507. doi: 10.1007/s00701-020-04276-y. Epub 2020 Mar 26.
Fear, as one of the basic emotions, is crucial in helping humans to perceive hazards and adapt to social activities. Clinically, fear memory is also involved in a wide spectrum of psychiatric disorders. A better understanding of the neural mechanisms of fear thereby has both neuroscientific and clinical significance. In recent years, data from animal models have demonstrated the key role of the amygdala-hippocampal circuit in the development of fear. However, the neural processing of fear memory remains unclear in humans, which is mainly due to the limitation of indirect measure of neural activity.
Herein, we investigated fear memory by direct intracranial recordings from 8 intractable epilepsy patients with depth electrodes in both the hippocampus and ipsilateral amygdala. All the patients were subjected to a well-established Pavlovian fear memory paradigm consisted of the familiarization task, conditioning task, and retrieval task, respectively. Simultaneous local field potentials from the hippocampus and amygdala were recorded during different stages. The oscillatory activities from the amygdala and hippocampus were analyzed during fear memory retrieval compared with neutral stages.
Consistent with previous rodent studies, our results showed that the amygdala was involved in fear memory retrieval rather than neutral memory retrieval, while the hippocampus was involved both in fear memory retrieval and neutral memory retrieval. In particular, we found that there was an enhanced synchronized activity between the amygdala and hippocampus at beta frequencies (14-30 Hz), which suggested that enhanced synchronized activity at beta frequencies between the amygdala and hippocampus play a pivotal role during retrieval of fear memory in human.
Thus, our observation that the amygdala-hippocampal system contributing to fear memory retrieval in human with frequency-depended specificity has provided new insights into the mechanism of fear and have potential clinical relevance.
恐惧作为基本情绪之一，对于帮助人类感知危险和适应社会活动至关重要。临床上，恐惧记忆也涉及广泛的精神疾病。因此，更好地理解恐惧的神经机制具有神经科学和临床意义。近年来，动物模型的数据表明，杏仁核-海马回路在恐惧的发展中起着关键作用。然而，人类对恐惧记忆的神经处理仍不清楚，这主要是由于对神经活动的间接测量的限制。
在此，我们通过对 8 名患有深部电极的难治性癫痫患者的海马体和同侧杏仁核进行直接颅内记录，研究了恐惧记忆。所有患者均接受了一个成熟的巴甫洛夫恐惧记忆范式，包括熟悉任务、条件任务和检索任务。在不同阶段记录海马体和杏仁核的局部场电位。分析恐惧记忆检索与中性阶段相比时，来自杏仁核和海马体的振荡活动。
与以前的啮齿动物研究一致，我们的结果表明，杏仁核参与恐惧记忆检索，而不是中性记忆检索，而海马体则参与恐惧记忆检索和中性记忆检索。特别是，我们发现杏仁核和海马体之间在β频带（14-30 Hz）存在增强的同步活动，这表明杏仁核和海马体之间在β频带的增强同步活动在人类恐惧记忆检索中起着关键作用。
因此，我们观察到，在人类中，杏仁核-海马系统在以频率依赖的特异性参与恐惧记忆检索，这为恐惧的机制提供了新的见解，并具有潜在的临床相关性。
