Lateral prefrontal organization in emotion: representational and causal mechanisms

项目摘要 注意力调节缺陷是情绪和焦虑障碍的标志， 成年人在美国。不良的情绪调节通常表现为情境不当 情绪的表达，包括不必要的持续和影响的负面状态以外的 时间语境因此，在时间和背景上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。认知控制研究的证据 表明外侧前额叶皮层（LPFC），包括外侧额极和中LPFC， 对时间上有组织的认知控制和对目标和环境敏感的行为至关重要。然而，在这方面， 尽管有强烈的迹象表明，LPFC在情绪中的功能机制研究仍然缺乏， LPFC在促进适应性情绪功能方面的突出但鲜为人知的作用，包括 心境障碍和焦虑症患者LPFC连接功能减退和LPFC连接功能减退之间的关系 病变和抑郁症的发病率，以及使用经颅磁刺激（TMS）对LPFC， 治疗抑郁症因此，本提案的中心目标是阐明组织、代表性和 不同LPFC区域对适应性时间和情境敏感情绪反应的因果贡献。 这项提议验证了一个中心假设，即人类的侧额极（FPl）整合了情感， 和时间信息，以通过下游LPFC中期促进目标导向和环境敏感的响应 功能这一假设是由记录的神经解剖预测，洞察到的 LPFC中时间控制的组织，以及最近揭示不同LPFC功能特异性的工作 情绪依赖性认知控制期间的区域。 使用fMRI数据的多变量分析和信息引导TMS的创新组合， 拟议的研究审查了不同LPFC区域的代表性和因果作用，以（1）目标导向 需要准确跟踪时间上扩展的情感信息的动作（目标1）和（2）时间- 情境敏感的情感调节（目标2）。全因子代表性相似性分析将允许 量化情绪效价，时间和上下文目标信号，以及，关键是，它们的相互作用。 信息引导的TMS，然后是任务功能磁共振成像采集，将建立功能和代表性 不同LPFC区域-FP 1和中LPFC-的特异性，具有因果推断（目的1b-2b）。任务型 功能连接分析将揭示杏仁核-LPFC相互作用的拓扑结构（包括 中间mPFC节点）与情绪-时间整合和情绪调节（目标3）。 总的来说，这些目标将推进LPFC功能和杏仁核-LPFC的方向模型 互动支持在面对情感挑战时做出适应性的时间和背景适当的反应。

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.