Representational code and causal mechanisms of prefrontal regulation of emotion

项目摘要 注意力调节缺陷是情绪和焦虑障碍的标志。因此，监管的能力 根据一个人的目标的情绪反应，并有效地推翻情绪的自动反应， 活动对心理健康和福祉至关重要。外侧前额叶皮层（LPFC）的功能一直是 在支持目标导向和灵活的行为方面发挥着关键作用。此外，现有数据表明， 抑郁症和焦虑症病理生理学中的LPFC功能障碍。然而，研究表明， LPFC功能对情绪调节的因果作用非常缺乏。这一建议将阐明 LPFC表征在情感处理过程中对目标导向行为调节的因果作用， 识别中介神经机制。拟议中的研究将检验任务相关的中心假设， 情绪调节目标在LPFC中期动态地表现出来，从那里它们被传达到 地形组织的背内侧PFC（dmPFC），并与来自杏仁核的情感信号整合。 这一假设是基于最近对PFC组织的了解和记录的神经解剖学 预测。实验将采用对LPFC功能敏感的行为任务， 优势情绪刺激对行为的影响程度取决于任务目标。LPFC- dmPFC-杏仁核回路将使用高级神经成像多体素 模式分析（MVPA）结合经颅磁刺激（TMS）和行为研究， 局灶性PFC病变患者。这种新颖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如何有助于适应性情绪反应。因此，拟议的研究将填补 情绪调节研究的巨大差距，并进一步发展了一个模型，可应用于 优化和个性化治疗的个人谁患有情绪和焦虑症相关的 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.