Lateral prefrontal organization in emotion: representational and causal mechanisms

项目总结 情绪调节缺陷是情绪和焦虑症的标志，超过20%的人患有这种疾病 美国的成年人。情绪调节不良的特点往往是语境不合适 情绪的表达，包括情绪以外的消极状态的无端持续和影响 时间背景。因此，在时间和背景下对情绪事件做出反应的能力 敏感的态度对心理健康和幸福至关重要。来自认知控制研究的证据 提示外侧前额叶皮质(LPFC)的功能，包括额叶外侧极和LPFC中部 对时间上有组织的认知控制和对目标和背景敏感的行为至关重要。然而， 尽管有强烈的迹象表明，LPFC在情绪中的作用，但缺乏机制研究 LPFC在促进适应性情绪功能方面的重要作用，但鲜为人知，包括 情绪和焦虑症患者LPFC活性低下和连接性降低，LPFC之间的关联 主要抑郁的损害和发生率，以及使用经颅磁刺激(TMS)LPFC 治疗抑郁症。因此，这项提案的中心目标是阐明组织、代表性 以及不同LPFC区域对适应时间和语境敏感情绪反应的因果贡献。 这一提议检验了人类额叶外侧极(FPL)整合情绪的中心假说 和时间信息，以通过下游MID-LPFC促进面向目标和上下文敏感的响应 功能。这一假说是由记录在案的神经解剖学投影、对 LPFC中时间控制的组织，以及揭示不同LPFC的功能特异性的最新工作 情绪依赖认知控制中的区域。 使用fMRI数据的多变量分析和信息引导的TMS的创新组合， 建议的研究考察了不同的LPFC区域对(1)目标导向的代表性和因果作用 需要准确跟踪时间延长的情绪信息的行动(目标1)和(2)时间- 情境敏感的情感调控(目标2)。全因素表征相似性分析将允许 量化情绪效价、时间和背景目标信号--以及关键的是，它们之间的相互作用。 信息引导的TMS，然后是任务功能磁共振成像采集，将建立功能性和代表性 具有因果推断的不同LPFC区域的特异性--Fpl和Mid-LPFC(目标1b-2b)。基于任务的 功能连通性分析将揭示杏仁核-LPFC相互作用的拓扑(包括 中间mPFC节点)与情绪-时间整合和情绪调节相关(目标3)。 总而言之，这些目标将推进LPFC功能和杏仁核-LPFC功能的方向性模型 互动支持在面对情绪挑战时根据时间和背景做出适当的适应性反应。

PROJECT SUMMARY Emotion-regulatory deficits are a hallmark of mood and anxiety disorders, which afflict over 20% of adults in the United States. Poor emotion regulation is often characterized by the context-inappropriate expression of emotion, including the unwarranted persistence and influence of negative states outside their temporal context. Therefore, the ability to respond to emotional events in a temporally and contextually sensitive manner is paramount to mental health and wellbeing. Evidence from cognitive control studies indicates that function of the lateral prefrontal cortex (LPFC), including lateral frontal pole and mid-LPFC, is essential for temporally organized cognitive control and behavior sensitive to goals and context. However, mechanistic studies of LPFC function in emotion are lacking, even though there are strong indications of a prominent but little-understood role for LPFC in promoting adaptive emotional functioning, including hypoactivation and reduced LPFC connectivity in mood and anxiety disorders, associations between LPFC lesions and incidence of major depression, and the use of transcranial magnetic stimulation (TMS) to LPFC to treat depression. The central goal of this proposal is therefore to elucidate the organization, representational and causal contributions of distinct LPFC regions for adaptive time and context sensitive emotional responding. This proposal tests the central hypothesis that the human lateral frontal pole (FPl) integrates emotional and temporal information to promote goal-oriented and context-sensitive responses via downstream mid-LPFC function. This hypothesis is informed by documented neuroanatomical projections, insights into the organization of temporal control in LPFC, and recent work unveiling functional specificity in distinct LPFC regions during emotion-dependent cognitive control. Using an innovative combination of multivariate analysis of fMRI data and information-guided TMS, the proposed studies examine the representational and causal roles of distinct LPFC regions for (1) goal-oriented action that requires accurate tracking of temporally extended emotional information (Aim 1) and (2) temporal- context sensitive regulation of affect (Aim 2). Full-factorial representational similarity analysis will permit quantifying emotional valence, temporal, and contextual goal signals—as well as, critically, their interaction. Information-guided TMS, followed by task fMRI acquisition, will establish functional and representational specificity of distinct LPFC regions—FPl and mid-LPFC—with causal inference (Aims 1b-2b). Task-based functional connectivity analysis will uncover the topology of amygdala-LPFC interactions (including intermediary mPFC nodes) associated with emotion-temporal integration and affect regulation (Aim 3). Collectively, these Aims will advance a directional model of how LPFC function and amygdala-LPFC interactions support adaptive time-and-context appropriate responses in the face of emotional challenges.