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.

抽象的 儿童创伤在美国高度普遍，可以大大增加发展的风险 年轻人的焦虑症。创伤的经历促进了对潜在威胁的情绪反应的增强， 反过来可能会影响认知能力。情绪和认知过程之间的失衡可能 有助于焦虑症的标志性象征，例如过度恐惧和功能受损。这是 至关重要的是研究认知神经传加的生化机制以识别新颖 治疗靶标并开发出旨在维持认知控制能力的靶向靶向方法更好 在弱势群体中，例如暴露于创伤的青年。 功能性MRI研究表明，背前扣带回皮层（DACC）是关键 维持认知控制和负面影响的视觉提示的组成部分可能会干扰这些 功能。但是，推进这种机械理解的关键障碍是绝大多数 当前的研究利用功能性MRI，该功能MRI依赖于血液动力学响应函数，并且是一种 神经发动的不精确指标。可以使用更精确的神经收益衡量 体内功能性MR光谱学（FMR），这是对谷氨酸暂时变化敏感的新工具 在对比的任务条件下。 该提案的目的是调查儿童创伤对DACC神经的影响 与具有和没有负面影响的认知控制有关的参与及其与小儿焦虑的关联 症状。我们将从城市环境中注册60名青少年（11-15岁，女性50％） 创伤暴露（30个受创伤暴露，30控制）。参与者在完成一个 专门设计的认知控制任务是允许直接表征DACC神经发动的 在认知控制期间，负面影响干扰。该任务包括针对不同的两种模式 认知组成部分：持续的注意力和抑制作用。两种模式将在上下文中进行测试 威胁面孔（负面影响状况）以及中性形状（无影响条件）。这个建议 假设童年创伤将潜在的负面影响干扰DACC神经参与 认知控制功能所必需的 - 在降低的DACC谷氨酸调制过程中证明 负面影响任务的条件。 这种创新的方法将促进对维持认知过程的神经过程的调查 在暴露于创伤的青少年存在威胁的情况下进行控制。该培训项目将为法国Pi提供 概念性培训（创伤和动画的神经生物学）和方法论方法（¹fmrs和 心理评估）。它还将为成功的F32提交和未来学术准备PI准备 研究职业。