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.

项目概要 情绪调节缺陷是情绪和焦虑障碍的一个标志，超过 20% 的人患有这种疾病 在美国的成年人。情绪调节不良的特点通常是与情境不相适应 情绪的表达，包括外部消极状态的无端持续和影响 时间背景。因此，在时间和情境中对情绪事件做出反应的能力 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 表明外侧前额皮质 (LPFC) 的功能，包括外侧额极和中 LPFC， 对于暂时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， 尽管有强烈的迹象表明 LPFC 在情绪中的功能，但仍缺乏对 LPFC 功能的机制研究。 LPFC 在促进适应性情绪功能方面发挥着突出但鲜为人知的作用，包括 情绪和焦虑障碍中低激活和 LPFC 连接性减少，LPFC 之间的关联 重度抑郁症的病变和发病率，以及使用经颅磁刺激（TMS）对 LPFC 进行治疗 治疗抑郁症。因此，该提案的中心目标是阐明组织、代表性 以及不同 LPFC 区域对适应性时间和情境敏感情绪反应的因果贡献。 该提案测试了人类额外侧极（FPl）整合情感的中心假设 和时间信息，通过下游中 LPFC 促进目标导向和上下文敏感的响应 功能。这一假设是通过记录的神经解剖学预测、对 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。 采用功能磁共振成像数据多变量分析和信息引导 TMS 的创新组合， 拟议的研究检查了不同 LPFC 区域的代表性和因果作用：(1) 目标导向 需要准确跟踪时间扩展的情感信息的动作（目标 1）和（2）时间- 情感的情境敏感调节（目标 2）。全因子代表性相似性分析将允许 量化情绪效价、时间和情境目标信号，以及重要的是它们的相互作用。 信息引导的 TMS，随后进行任务 fMRI 采集，将建立功能性和代表性 不同 LPFC 区域（FPl 和 mid-LPFC）的特异性以及因果推断（目标 1b-2b）。基于任务的 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-时间整合和情感调节相关（目标 3）。 总的来说，这些目标将推进 LPFC 功能和杏仁核-LPFC 功能的定向模型 面对情绪挑战时，互动支持根据时间和情境做出适当的反应。