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

基本信息

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
项目类别：
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

项目摘要

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.

抽象的童年创伤在美国非常普遍，并且会大大增加罹患此病的风险青少年的焦虑症经历会促进对潜在威胁的情绪反应，这反过来可能会影响认知能力。情绪和认知过程之间的不平衡可能会影响认知能力。导致焦虑症的标志性症状，例如过度恐惧和功能受损。研究认知神经参与背后的生化机制以识别新的特征至关重要治疗目标并开发更好的靶向药物疗法，旨在维持认知控制能力弱势群体，例如遭受创伤的青少年。功能性 MRI 研究表明，背侧前扣带皮层 (dACC) 是一个关键的区域。维持认知控制的组成部分，并且负面影响的视觉线索可能会干扰这些然而，推进这种机制理解的关键障碍是绝大多数目前的研究利用功能性 MRI，它依赖于血流动力学反应函数，并且是一种神经参与度的不精确指标可以通过使用获得更精确的神经参与度测量。体内 1H 功能磁共振波谱 (1H fMRS)，这是一种对谷氨酸的时间变化敏感的新型工具在对比任务条件下。本提案的目的是调查童年创伤对 dACC 神经的影响与有或没有负面影响的认知控制相关的参与度及其与儿科焦虑的关系我们将招募 60 名来自发病率较高的城市的青少年（11-15 岁，50% 为女性）。创伤暴露（30 名创伤暴露，30 名对照）参与者在完成测试时接受 1H fMRS 扫描。专门设计用于直接表征 dACC 神经参与的认知控制任务在负面情绪干扰后的认知控制期间，该任务包括针对不同目标的两种模式。认知的组成部分：持续注意力和反应抑制将在上下文中进行测试。威胁面孔（负面影响条件），以及中性形状（无影响条件）。认为童年创伤会增强对 dACC 神经参与的负面干扰认知控制功能所必需的——通过在负面条件会影响任务。这种创新方法将有助于研究维持认知的神经过程该培训项目将为 PI France 提供在面临威胁时的控制。概念（创伤和焦虑的神经生物学）和方法学方法（1H fMRS 和它还将为 PI 成功提交 F32 和未来的学术做好准备。研究生涯。