Representational code and causal mechanisms of prefrontal regulation of emotion

项目总结 情绪调节缺陷是情绪和焦虑症的标志。因此，监管的能力 根据一个人的目标做出情绪反应，并有效地超越对情绪的自动反应 事件对心理健康和幸福至关重要。前额叶外侧皮质的功能 被证明在支持目标导向和灵活的行为方面发挥着关键作用。此外，现有的数据意味着 LPFC功能障碍在抑郁和焦虑的病理生理学中的作用。然而，研究确定了具体的 LPFC功能对情绪调节的因果贡献严重缺乏。这项建议将使我们明白 LPFC表征在情绪加工和目标定向行为调控中的因果作用 确定调节神经机制。拟议的研究将检验与任务相关的中心假设 情绪调节目标在LPFC中期被动态地表示，它们从那里被传达到 背内侧PFC(DmPFC)与来自杏仁核的情感信号整合。 这一假设是基于对PFC组织的最新见解和有文献记载的神经解剖学 投射。实验将采用对LPFC函数和索引敏感行为任务 主要情绪刺激对行为的影响程度取决于任务目标。LPFC- 将使用先进的神经成像多体素的组合来检查dmPFC-杏仁核回路 模式分析(MVPA)与经颅磁刺激(TMS)相结合的行为研究 有局灶性PFC病变的患者。这种新的数据采集方法和分析方法的结合 将揭示特定PFC区域的功能因果贡献，并提供精确的机制 LPFC如何对适应性情绪反应做出贡献。因此，拟议的研究将填补 情绪调节研究中的重大差距，以及进一步开发可应用于 为患有情绪和焦虑症的患者优化和个性化治疗 PFC功能障碍。

PROJECT SUMMARY Emotion-regulatory deficits are a hallmark of mood and anxiety disorders. Thus, the ability to regulate emotional responses according to one's goals and to effectively override automatic responses to emotional events is paramount to mental health and wellbeing. Function of the lateral prefrontal cortex (LPFC) has been shown to play a pivotal role in supporting goal-oriented and flexible behavior. Moreover, extant data implicates LPFC dysfunction in the pathophysiology of depression and anxiety. However, studies establishing the specific and causal contributions of LPFC function to emotion regulation are sorely lacking. This proposal will illuminate the causal role of LPFC representations for goal-oriented behavioral regulation during affective processing and identify mediating neural mechanisms. The proposed studies will test the central hypothesis that task-relevant emotion-regulatory goals are dynamically represented in mid-LPFC, from which they are conveyed to topographically organized dorsomedial PFC (dmPFC) and integrated with affect signals from the amygdala. This hypothesis is based on recent insights into PFC organization and documented neuroanatomical projections. The experiments will employ a behavioral task that is sensitive to LPFC function and that indexes the degree of influence of prepotent emotional stimuli on behavior depending on the task goal. The LPFC- dmPFC-amygdala circuitry will be examined using a combination of advanced neuroimaging multi-voxel pattern analysis (MVPA) combined with transcranial magnetic stimulation (TMS), and behavioral studies of patients with focal PFC lesions. This combination of novel data acquisition methods and analytic approaches will reveal the functional causal contributions of specific PFC regions and provide a precise mechanistic account of how the LPFC contributes to adaptive emotional responding. The proposed studies will thus fill a substantial gap in emotion regulation research, and further the development of a model that can be applied to optimize and personalize treatment for individuals who suffer from mood and anxiety disorders associated with PFC dysfunction.