Neurobiological Mechanisms of Cognitive Inhibition in Trauma-Exposed Adolescents

遭受创伤的青少年认知抑制的神经生物学机制

• 批准号: 8805740
• 负责人: Kristen L Mackiewicz Seghete
• 金额: $ 18.12万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-09-23 至 2018-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8805740
• 关键词: Adolescence; Adolescent; Adult; Affective; Age; Amygdaloid structure; Area; Awareness; Behavioral; Brain; Brain imaging; Brain region; Child Abuse; Childhood; Clinical; Cognition; Cognitive; Comorbidity; Control Groups; Data; Development; Diffusion Magnetic Resonance Imaging; Disease; Early Intervention; Early-life trauma; Emotional; Ethics; Exposure to; Functional Magnetic Resonance Imaging; Future; Goals; Hippocampus (Brain); Individual; Inferior frontal gyrus; Knowledge; Learning; Life Stress; Magnetic Resonance Imaging; Measures; Medial; Methodology; Methods; Neurobiology; Prefrontal Cortex; Process; Psychopathology; Recording of previous events; Recruitment Activity; Regulation; Research; Research Methodology; Rest; Risk; Sampling; Sexual abuse; Short-Term Memory; Stimulus; Structure; Symptoms; Techniques; Training; Trauma; Trauma Research; Treatment Effectiveness; Youth; cognitive control; density; depressive symptoms; experience; follow-up; intervention program; neurobiological mechanism; neuroimaging; pediatric trauma; physical abuse; public health relevance; research study; response; skills; therapy development; white matter

DESCRIPTION (provided by applicant): This K23 application advances the PI's long-term research goal of establishing an independent line of longitudinal, developmental neuroimaging research examining neurobiological alterations in cognitive and affective processing that may confer risk for future psychopathology in youth who have experienced childhood abuse. Additional long-term goals include using this information to inform treatment development and evaluate treatment effectiveness using neuroimaging. The proposed training will enable the PI to develop skills and expertise in five primary areas: longitudinal methodology, pediatric trauma research, developmental neuroimaging, advanced neuroimaging techniques, and ethical conduct of research. The proposed research study provides the PI with hands-on training to utilize these newly learned skills in the context of a functional magnetic resonance imaging (fMRI) study of adolescents with a history of childhood interpersonal trauma (CIT; e.g., sexual abuse, physical abuse). It has been well-established that individuals with a history of CIT demonstrate altered brain mechanisms related to threat responding and processing. Findings of altered cognition for both neutral and threat information in trauma-exposed individuals suggest possible core deficits may exist, in addition to enhanced threat responding. Characterizing core deficits is important and would allow us to identify altered mechanisms that: 1) could be treatment targets, and 2) may overlap with other clinical disorders and therefore contribute to high comorbidity rates. Inhibition has been proposed as a possible core deficit in trauma-exposed individuals. However, little is known about the developmental trajectory of altered cognitive processing, including inhibitory processing, in trauma-exposed youth. Adolescence may be a particularly crucial period to study, as further neuromaturation is occurring and some effects of childhood trauma on brain processes is not evident until adolescence. The proposed study examines alterations in cognitive inhibition in a sample of adolescents (age 13-17 years) with a history of CIT (physical or sexual abuse) compared to a sample of age-matched adolescents with no history of trauma. Cognitive inhibition involves clearing no longer relevant information from working memory. In order to examine cognitive inhibition, adolescents will complete a neutral and emotional version of a task-switching paradigm while undergoing an fMRI scan. Activation during conditions requiring cognitive inhibition will be contrasted between the two groups and overlapping and disparate regions involved in the cognitive inhibition of neutral and emotional information will be examined. Additionally, the interaction between age and activation as well as the impact of age of trauma-exposure on task activation will be investigated. The ability of activation during inhibition to predict future clinical symptoms will e explored in preliminary data. Additional exploratory analyses of resting state functional connectivity and white matter microstructure in adolescents with a history of CIT will be conducted.

描述（由申请人提供）：这项K23申请推进了PI的长期研究目标，即建立一条独立的纵向发育神经影像学研究路线，研究认知和情感处理中的神经生物学改变，这些改变可能会给经历过童年虐待的青少年带来未来精神病理的风险。额外的长期目标包括利用这些信息为治疗发展提供信息，并利用神经影像学评估治疗效果。拟议的培训将使PI能够在五个主要领域发展技能和专业知识：纵向方法，儿科创伤研究，发育神经影像学，高级神经影像学技术和伦理研究行为。拟议的研究为PI提供了实践培训，以便在功能磁共振成像（fMRI）研究有童年人际创伤史（CIT，例如性虐待，身体虐待）的青少年的背景下利用这些新学到的技能。有CIT病史的个体表现出与威胁反应和处理相关的大脑机制的改变，这已经得到了证实。创伤暴露个体对中性和威胁信息的认知改变的研究结果表明，除了增强的威胁反应外，可能存在核心缺陷。描述核心缺陷是很重要的，这将使我们能够确定改变的机制：1)可能是治疗目标，2)可能与其他临床疾病重叠，因此导致高合并率。抑制被认为可能是创伤暴露个体的核心缺陷。然而，在创伤暴露的青少年中，认知加工（包括抑制性加工）改变的发展轨迹知之甚少。青春期可能是一个特别重要的研究时期，因为神经正在进一步成熟，而童年创伤对大脑过程的一些影响直到青春期才显现出来。提出的研究考察了有CIT（身体或性虐待）史的青少年样本（13-17岁）与没有创伤史的同龄青少年样本的认知抑制变化。认知抑制包括从工作记忆中清除不再相关的信息。为了检查认知抑制，青少年将在接受功能磁共振成像扫描时完成任务转换范式的中性和情感版本。在需要认知抑制的条件下，两组之间的激活将进行对比，并将检查涉及中性和情绪信息认知抑制的重叠和不同区域。此外，本研究还探讨了年龄与任务激活的相互作用以及创伤暴露年龄对任务激活的影响。抑制期间的激活预测未来临床症状的能力将在初步数据中进行探索。将对有CIT病史的青少年的静息状态功能连通性和白质微观结构进行进一步的探索性分析。