Modeling sex-differences in trauma-related neural organization conferring resilience against addiction

模拟创伤相关神经组织中的性别差异，赋予其抗成瘾的能力

• 批准号: 9317079
• 负责人: George Andrew James
• 金额: $ 22.35万
• 依托单位: UNIV OF ARKANSAS FOR MED SCIS
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-01 至 2019-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9317079
• 关键词: 15 year old; Acute; Adolescent; Adult; Age; Anterior; Attention; Behavior; Behavior Control; Behavioral; Biological Neural Networks; Child Abuse and Neglect; Childhood; Clinical; Cognition; Cognitive; Conflict (Psychology); Cues; Data; Development; Disease; Dorsal; Drug Addiction; Drug Use Disorder; Drug usage; Early-life trauma; Emotional; Enrollment; Event; Exposure to; Female Adolescents; Functional Magnetic Resonance Imaging; Future; Goals; Impaired cognition; Impairment; Impulsivity; Individual; Individual Differences; Inferior; Informal Social Control; Intervention; Knowledge; Left; Life; Life Stress; Literature; Maps; Measures; Mental disorders; Modeling; Motivation; Motor; Neural Pathways; Outcome; Pattern; Predisposition; Prevention program; Preventive Intervention; Process; Psychopathology; Public Health; Recording of previous events; Recruitment Activity; Reproducibility; Research; Research Proposals; Risk; Risk Factors; Role; Sampling; Severities; Sex Characteristics; Signal Transduction; Stimulus; Stress; Symptoms; Testing; Time; Translating; Trauma; Woman; Work; addiction; assault; attentional bias; base; cingulate cortex; drug development; emotional stimulus; evidence base; frontal lobe; girls; innovation; men; motor control; neural correlate; neurobehavioral; neurodevelopment; neuromechanism; neuroregulation; pediatric trauma; potential biomarker; psychologic; psychosocial; relating to nervous system; resilience; response; sex; therapy development; young adult

ABSTRACT While childhood adversity is a recognized risk factor for the development of drug use and other psychiatric disorders, many individuals are resilient against the negative consequences of childhood trauma. Searches for the mechanisms of resilient adaptation have largely sought to characterize psychological and psychosocial protective factors. However, inhibitory motor control and its inferior frontal cortex (IFC) mechanisms represent risk and protective factors for drug use disorders. The motivation for the proposed exploratory/developmental project is our fMRI demonstration that – for women without drug use or other psychiatric disorders – an increasing severity of childhood maltreatment was associated with increasing negative modulation of dorsal anterior cingulate cortex (dACC) activity by the left IFC (LIFC). Furthermore, this LIFC to dACC influence predicted both better response inhibition for a Stop Signal task and less impaired attention/impulsivity, suggesting it may be a construct encoding resilience to trauma. Our finding stands in contrast of existing literature implicating right IFC function in inhibitory control among healthy individuals. The proposed project would use further characterize the role of IFC-dACC connectivity in encoding sex-differences in resiliency against trauma. Aim 1 would use fMRI to independently replicate this adaptive response for motor control (Stop Signal task) by comparing task responses for men and women without drug use or other disorders and with (“resilient”) and without (“control”) childhood maltreatment histories. Aim 2 would assess the generalization of this neural pathway to cognitive conflict for emotionally distracting stimuli (the emotional Stroop task). Aim 3 would explore neurodevelopment of resilience through re-enrollment of female adolescents with trauma histories whom previously underwent the Stop Signal fMRI task to associate longitudinal changes in the neural mechanisms of inhibitory control to post-trauma clinical and drug use trajectories. The proposed model-based and hypothesis-driven research plan would explore further the role of a hypothetical neural network response related to behavioral control as a mechanism of adaptive cognitive resilience and develop potential biomarkers of resilience and neurobehavioral targets for intervention in at-risk individuals.

抽象的 虽然童年逆境是吸毒和其他精神疾病发展的公认危险因素 疾病，许多人能够抵御童年创伤的负面后果。 弹性适应机制在很大程度上试图描述心理和社会心理的特征 然而，抑制性运动控制及其下额皮质（IFC）机制代表了保护因素。 药物使用障碍的风险和保护因素。拟议的探索/发展的动机。 项目是我们的功能磁共振成像演示——对于没有吸毒或其他精神疾病的女性—— 儿童虐待的严重程度增加与背侧负调节的增加有关 前扣带皮层 (dACC) 活动受左 IFC (LIFC) 此外，LIFC 对 dACC 的影响。 预测了对停止信号任务的更好的反应抑制和更少的注意力/冲动受损， 表明它可能是一种编码创伤复原力的结构，我们的发现与现有的形成鲜明对比。 涉及健康个体抑制控制中正确的 IFC 功能的文献。 将进一步描述 IFC-dACC 连接在编码弹性性别差异方面的作用 目标 1 将使用功能磁共振成像来独立复制这种运动控制的适应性反应（停止） 信号任务）通过比较没有吸毒或其他疾病的男性和女性以及有吸毒或其他疾病的男性和女性的任务反应 （“有弹性”）和没有（“控制”）儿童虐待史的目标 2 将评估儿童虐待史的普遍性。 这种因情绪分散刺激而导致认知冲突的神经通路（情绪斯特鲁普任务）。 将通过重新招募患有创伤的女性青少年来探索复原力的神经发育 之前接受过停止信号 fMRI 任务以关联神经元纵向变化的历史 对创伤后临床和药物使用轨迹的抑制控制机制。 假设驱动的研究计划将进一步探索假设的神经网络响应的作用 与行为控制相关作为适应性认知弹性的机制并开发潜在的生物标志物 对高危个体进行干预的复原力和神经行为目标。