The Role for in vivo Glutamate Modulation in Maintaining Cognitive Control in Trauma-Exposed Adolescents

体内谷氨酸调节在维持创伤青少年认知控制中的作用

• 批准号: 10748757
• 负责人: John France
• 金额: $ 4.66万
• 依托单位: WAYNE STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-08-17 至 2025-08-16
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10748757
• 关键词: Adolescence; Adolescent; Affect; Age; Amygdaloid structure; Anterior; Anxiety; Anxiety Disorders; Biochemical; Biochemistry; Caring; Childhood; Cognition; Cognitive; Collaborations; Control Groups; Cues; Dedications; Development; Dorsal; Eligibility Determination; Emotional; Enrollment; Ensure; Equilibrium; Exposure to; Face; Female; France; Fright; Functional Magnetic Resonance Imaging; Future; Glutamates; Goals; Hyperactivity; Impairment; Investigation; Link; Magnetic Resonance Spectroscopy; Measures; Mental disorders; Mentorship; Methodology; Neurobiology; Neurons; Participant; Pharmacotherapy; Process; Psychopathology; Qualifying; Research; Risk; Risk Factors; Role; Scanning; Shapes; Synapses; Technology; Testing; Therapeutic; Training; Trauma; United States; Visual; Vulnerable Populations; Youth; anxiety symptoms; anxious; career; childhood anxiety; cingulate cortex; cognitive ability; cognitive control; cognitive process; cohort; community center; design; experience; hemodynamics; improved; in vivo; innovation; negative affect; neural; neurobiological mechanism; neuroimaging; neuromechanism; neurotransmission; new therapeutic target; novel; pediatric trauma; psychologic; recruit; response; sustained attention; therapeutic target; tool; training project; trauma exposure; urban setting

Abstract Childhood trauma is highly prevalent in the United States, and can greatly increase the risk for developing anxiety disorders in youth. Experiences of trauma promote heightened emotional responses to potential threats, which in turn may impact cognitive ability. The imbalance between emotional and cognitive processes may contribute to hallmark symptoms of anxiety disorders, such as excessive fear and impaired functioning. It is critical to investigate the biochemical mechanisms underlying cognitive neural engagement to identify novel therapeutic targets and develop better targeted pharmacotherapies aimed at maintaining cognitive control ability in vulnerable populations like trauma-exposed youth. Functional MRI studies demonstrate that the dorsal anterior cingulate cortex (dACC) is a critical component of maintaining cognitive control, and that visual cues of negative affect may interfere with these functions. However, the key barrier to advancing this mechanistic understanding is that the vast majority of current investigations utilize functional MRI, which relies on the hemodynamic response function, and is an imprecise indicator of neural engagement. A more precise measure of neural engagement can be obtained using in vivo ¹H functional MR spectroscopy (¹H fMRS), which is a novel tool sensitive to temporal changes in glutamate under contrasting task-conditions. The objective in this proposal is to investigate the impact of childhood trauma on dACC neural engagement related to cognitive control with and without negative affect, and its association with pediatric anxiety symptoms. We will enroll 60 adolescents (ages 11-15, 50% female) from an urban setting with high rates of trauma exposure (30 trauma-exposed, 30 control). Participants undergo ¹H fMRS scanning while completing a cognitive control task specifically designed to allow direct characterization of the dACC neural engagement during cognitive control following negative affect interference. The task includes two modes that target different components of cognition: sustained attention and response inhibition. Both modes will be tested in the context of threatening faces (negative affect condition), as well as neutral shapes (no affect condition). This proposal hypothesizes that childhood trauma will potentiate negative affect interference with dACC neural engagement necessary for cognitive control functioning – demonstrated by reduced dACC glutamate modulation during the negative affect conditions of the task. This innovative approach will facilitate investigation into the neural processes which maintain cognitive control in the presence of threat in trauma-exposed adolescents. This training project will provide PI France with training in conceptual (neurobiology of trauma and anxiety) and methodological approaches (¹H fMRS and psychological assessments). It will also prepare the PI for a successful F32 submission and future academic research career.

摘要 童年创伤在美国非常普遍，并且可以大大增加发展的风险。 青少年焦虑症创伤的经历会促使人们对潜在的威胁做出更强烈的情绪反应， 这反过来又会影响认知能力。情感和认知过程之间的不平衡可能 导致焦虑症的标志性症状，如过度恐惧和功能受损。是 对于研究认知神经参与的生化机制以识别新的神经元至关重要 治疗目标，并开发更好的针对性药物治疗，旨在维持认知控制能力 在易受伤害的人群中，比如遭受创伤的年轻人。 功能磁共振成像研究表明，背侧前扣带皮层（dACC）是一个关键的， 维持认知控制的组成部分，负面影响的视觉线索可能会干扰这些 功能协调发展的然而，推进这种机械理解的关键障碍是， 目前的研究利用功能性MRI，它依赖于血流动力学反应功能，是一种 神经活动的不精确指标。神经参与的更精确的测量可以通过使用 体内<$H功能磁共振波谱（<$H fMRS），这是一种对谷氨酸时间变化敏感的新工具， 在不同的任务条件下。 本提案的目的是调查儿童期创伤对dACC神经元的影响。 参与与有无负面影响的认知控制相关，及其与儿科焦虑的相关性 症状我们将招募60名来自城市环境的青少年（年龄11-15岁，50%为女性）， 创伤暴露组30例，对照组30例。参与者在完成一项 专门设计的认知控制任务，允许直接表征dACC神经参与 在负性情绪干扰后的认知控制中该任务包括两种模式， 认知的组成部分：持续的注意力和反应抑制。这两种模式都将在上下文中进行测试 威胁性面孔（消极情感条件），以及中性形状（无情感条件）。这项建议 假设童年创伤会加强负面情绪干扰dACC神经参与 这是认知控制功能所必需的-通过在大脑皮层中减少dACC谷氨酸调节来证明。 任务的负面影响。 这种创新的方法将有助于研究维持认知的神经过程。 在创伤暴露的青少年中存在威胁时的控制。该培训项目将为PI法国提供 概念（创伤和焦虑的神经生物学）和方法论（üH fMRS和 心理评估）。它还将为PI成功提交F32和未来的学术 研究生涯。