Lateral prefrontal organization in emotion: representational and causal mechanisms

情绪中的外侧前额叶组织：表征和因果机制

• 批准号: 10723060
• 负责人: Regina Lapate
• 金额: $ 50.83万
• 依托单位: UNIVERSITY OF CALIFORNIA SANTA BARBARA
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-07-01 至 2028-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10723060
• 关键词: Adult; Advanced Development; Affect; Affective; Amygdaloid structure; Anatomy; Anxiety Disorders; Attenuated; Behavior; Brain imaging; Code; Complex; Data; Disease; Emotional; Emotions; Evaluation; Event; Failure; Functional Magnetic Resonance Imaging; Functional disorder; Goals; Human; Impairment; Incidence; Individual; Lateral; Lesion; Major Depressive Disorder; Mental Depression; Mental Health; Modeling; Mood Disorders; Multivariate Analysis; National Institute of Mental Health; Neuroanatomy; Neurocognitive; Personal Satisfaction; Population; Prefrontal Cortex; Process; Regulation; Role; Science; Signal Transduction; Specificity; Stimulus; Task Performances; Testing; Time; Transcranial magnetic stimulation; United States; With laterality; Work; cognitive control; emotion regulation; emotional functioning; functional MRI scan; imaging modality; innovation; insight; novel; response; showing emotion; treatment optimization

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.

项目摘要 情绪调节定义是情绪和焦虑症的标志，折磨超过20％ 在美国的成年人。不良的情绪调节通常以上下文不适当的特征 情绪的表达，包括在其之外的负面状态的持久性和影响 临时上下文。因此，在暂时和上下文中应对情感事件的能力 敏感的方式对于心理健康和福祉至关重要。认知控制研究的证据 表明外侧前额叶皮层（LPFC）的功能，包括额叶侧极和Mid-LPFC 对于临时组织的认知控制和行为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在促进适应性情感功能中的重要作用，包括 情绪和动画障碍的LPFC连接性降低和LPFC的关联降低 重大抑郁的病变和入射，以及将经颅磁刺激（TMS）用于LPFC的使用 治疗抑郁症。因此，该提案的核心目标是阐明组织，代表性 与自适应时间和上下文敏感情感反应的不同LPFC区域的因果关系。 该提案检验了人类侧额叶（FPL）整合情感的中心假设 和临时信息，以通过下游LPFC促进面向目标和上下文敏感的响应 功能。这一假设是由有记录的神经解剖学项目告知的 组织LPFC中的临时控制，最近的工作揭示了不同LPFC的功能特异性 情绪依赖性认知控制过程中的区域。 使用fMRI数据和信息引导的TMS的多元分析的创新组合， 拟议的研究检查了（1）面向目标的不同LPFC区域的代表性和因果关系 需要准确跟踪暂时扩展情绪信息（AIM 1）和（2）临时的行动 情感敏感的情感调节（目标2）。全因素代表性分析将允许 量化情绪价值，临时和上下文目标信号，以及批判性的相互作用。 信息指导的TMS随后进行fMRI获取，将建立功能和代表性 不同的LPFC区域（FPL和LPFC）的特异性以及因果推断（AIMS 1B-2B）。基于任务 功能连接分析将发现杏仁核-LPFC相互作用的拓扑（包括 中间MPFC节点）与情绪 - 周期性整合并影响调节（AIM 3）。 总的来说，这些目标将推进LPFC功能和杏仁核LPFC的定向模型 在面对情感挑战时，互动支持自适应的时间和篇幅。