Neurobiological Mechanisms of Cognitive Inhibition in Trauma-Exposed Adolescents

描述（由申请人提供）：该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，检查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学风险。其他长期目标包括使用这些信息来告知治疗开发和使用神经影像学评估治疗有效性。拟议的培训将使PI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，先进的神经影像学技术和研究的道德行为。拟议的研究为PI提供了实践培训，以在有儿童人际创伤史的青少年的功能性磁共振成像（fMRI）研究中利用这些新学到的技能（CIT;例如，性虐待、身体虐待）。已经确定的是，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改变。在创伤暴露个体中，中性和威胁信息的认知改变的结果表明，除了增强的威胁反应外，可能存在核心缺陷。表征核心缺陷是重要的，将使我们能够确定改变的机制：1）可能是治疗靶点，2）可能与其他临床疾病重叠，因此导致高合并症发生率。抑制被认为是创伤暴露个体可能的核心缺陷。然而，很少有人知道的发展轨迹改变认知加工，包括抑制加工，在创伤暴露的青年。青春期可能是研究的一个特别关键的时期，因为进一步的神经成熟正在发生，而童年创伤对大脑过程的一些影响直到青春期才明显。该研究将研究有CIT（身体或性虐待）史的青少年（年龄13-17岁）样本与无创伤史的年龄匹配青少年样本相比，在认知抑制方面的变化。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，青少年将完成一个中立的和情感版本的任务转换范式，同时接受功能磁共振成像扫描。在需要认知抑制的条件下的激活将在两组之间进行对比，并将检查涉及中性和情感信息的认知抑制的重叠和不同区域。此外，年龄和激活之间的相互作用以及创伤暴露年龄对任务激活的影响也将被研究。在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探索。将对有CIT病史的青少年进行静息状态功能连接和白色微结构的额外探索性分析。

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.