Neurobiological Mechanisms of Cognitive Inhibition in Trauma-Exposed Adolescents

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、发育性神经成像研究路线，检查认知和情感处理过程中的神经生物学变化，这些变化可能会对经历过童年虐待的青少年未来的精神病理学产生风险。其他长期目标包括利用这些信息为治疗进展提供信息，并使用神经成像评估治疗效果。拟议的培训将使PI能够发展五个主要领域的技能和专门知识：纵向方法学、儿科创伤研究、发育神经成像、高级神经成像技术和研究道德行为。拟议的研究研究为PI提供实践培训，以便在对有童年人际关系创伤(CIT；例如性虐待、身体虐待)的青少年进行功能性磁共振成像(FMRI)研究的背景下，利用这些新学到的技能。众所周知，有CIT病史的人表现出与威胁反应和处理相关的大脑机制的改变。创伤暴露的个体对中性和威胁信息的认知改变的发现表明，除了增强的威胁反应外，可能还存在核心缺陷。确定核心缺陷的特征是重要的，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，从而导致高共病发生率。抑制被认为是创伤暴露个体的一种可能的核心缺陷。然而，在创伤暴露的年轻人中，人们对包括抑制加工在内的认知加工变化的发展轨迹知之甚少。青春期可能是一个特别关键的研究阶段，因为进一步的神经成熟正在发生，童年创伤对大脑过程的一些影响直到青春期才明显。这项拟议的研究考察了有CIT(身体或性虐待)史的青少年样本(13-17岁)与年龄匹配的没有创伤史的青少年样本在认知抑制方面的变化。认知抑制涉及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fMRI扫描的同时完成中性和情绪版本的任务切换范式。在需要认知抑制的条件下，激活将在两组之间进行对比，并将检查涉及中性和情绪信息的认知抑制的重叠和不同区域。此外，还将探讨年龄与激活之间的交互作用，以及创伤暴露年龄对任务激活的影响。我们将在初步数据中探讨抑制期间的激活对未来临床症状的预测能力。此外，还将对有CIT病史的青少年的静息状态、功能连通性和脑白质微结构进行探索性分析。

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.