INVESTIGATING THE ROLE OF THE LATERAL PREFRONTAL CORTEX IN MODULATION EMOTION

我们的工作表明，恒河猴提供了一个很好的模型来研究人类焦虑和恐惧的机制。在我们对恒河猴的研究中，我们发现了与焦虑相关的稳定的大脑（右额叶脑电图不对称），内分泌（皮质醇和CRH增加）和行为（长期的倾向性冻结）特征，我们称之为焦虑的内在表型。这些发现与理解人类精神病理学的发展特别相关，因为具有极端抑制气质和相似生物特征的儿童患焦虑症的风险增加。我们在猴子身上最相关的发现之一是极端右额叶脑电图活动与极端焦虑之间的关系。这些发现与人类研究一致，表明不对称的右前额叶脑电活动与负面情绪之间存在关联。很可能焦虑的内表型的不同方面是由边缘系统、脑干和皮质区域的相互作用介导的。在以前的工作中，我们系统地研究了杏仁核在介导焦虑内表型中的作用。使用选择性鹅膏蕈氨酸损伤，我们发现杏仁核在介导急性恐惧相关反应中的重要作用， 新颖的刺激;然而，数据表明杏仁核在介导与焦虑的内表型相关的稳定的生物学和行为特征中不起主要作用。虽然外侧前额叶皮层（LPFC）与注意力、预期和工作记忆等认知过程有关，但最近的研究表明，LPFC在整合情感和认知信息方面发挥作用，这些信息对指导目标相关行为至关重要。来自我们和其他实验室的证据支持LPFC参与情绪处理，并指出大脑半球的专门化。我们相信，研究LPFC在情绪处理中的作用，将提供新的和重要的见解前额叶皮层机制的焦虑内表型的基础上，并将提供一个机会，整合相关的研究结果，该地区的认知功能与情绪调节。因此，在恒河猴中，我们将使用各种技术（情绪探针，选择性鹅膏蕈氨酸病变，PET成像，脑内特定部位给药药理学策略）系统地评估LPFC在情绪处理中的贡献。

Our work demonstrates that the rhesus monkey provides an excellent model to study mechanisms underlying human anxiety and fear. In our studies with rhesus monkeys, we found stable, brain (right frontal EEG asymmetry), endocrine (increased cortisol and CRH), and behavioral (prolonged dispositional freezing) characteristics related to anxiety that we termed the anxious endophenotype. These findings are particularly relevant to understanding the development of human psychopathology, since children with extremely inhibited temperament and similar biological features are at increased risk to develop anxiety disorders. One of our most pertinent findings in the monkeys was the relation between extreme right frontal EEG activity and extreme anxiety. These findings are consistent with human studies demonstrating an association between asymmetric right prefrontal brain electrical activity and negative affect. It is likely that different aspects of the anxious endophenotype are mediated by the interactions of limbic, brain stem, and cortical regions. In previous work, we systematically investigated the role of the amygdala in mediating the anxious endophenotype. Using selective ibotenic acid lesions, we found an important role for the amygdala in mediating acute fear-related responses to novel stimuli; however the data suggested that the amygdala does not play a major role in mediating the stable biological and behavioral traits associated with the anxious endophenotype. While lateral prefrontal cortex (LPFC) has been implicated in cognitive processes such as attention, anticipation, and working memory, recent studies suggest a role for LPFC in integrating emotional and cognitive information important in directing goal-related behavior. Evidence from our, and other, laboratories supports LPFC involvement in emotion processing and points to hemispheric specialization. We believe that studies examining the role of LPFC in emotion processing will provide new and important insights into prefrontal cortical mechanisms underlying the anxious endophenotype and will provide an opportunity to integrate findings related to the cognitive functions of this region with emotion regulation. Therefore, in rhesus monkeys, we will use a variety of techniques (emotion probes, selective ibotenic acid lesions, PET imaging, and intra-cerebral site specific administration pharmacology strategies) to systematically evaluate the contributions of LPFC in emotion processing.