Disrupted development of neural connections by alcohol initiation in adolescence

青春期酒精引发的神经连接发育受到破坏

• 批准号: 8693876
• 负责人: Monica Luciana
• 金额: $ 52.64万
• 依托单位: UNIVERSITY OF MINNESOTA
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-09-20 至 2016-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8693876
• 关键词: Adolescence; Adolescent; Adult; Adverse effects; Age; Alcohol consumption; Alcoholic beverage heavy drinker; Alcohols; Anterior; Atrophic; Attention; Automobile Driving; Basal Ganglia; Behavior; Behavior Control; Behavioral; Brain; Brain region; Child; Chronic; Clinical; Communities; Complex; Corpus striatum structure; Corticospinal Tracts; Critical Pathways; Cues; Data; Data Collection; Decision Making; Development; Developmental Process; Diffusion; Disease; Drug usage; Education; Electrophysiology (science); Enrollment; Esthesia; Fiber; Functional Magnetic Resonance Imaging; Funding; General Population; Genetic; Health behavior; Heavy Drinking; Incentives; Individual; Justice; Legal; Longitudinal Studies; Magnetic Resonance Imaging; Measures; Medial; Mediating; Memory; Methods; Modeling; National Institute on Alcohol Abuse and Alcoholism; Nature; Neurocognitive; Neurosciences; Nucleus Accumbens; Parahippocampal Gyrus; Parents; Parietal; Participant; Pathway interactions; Patient Self-Report; Pattern; Play; Predisposition; Prefrontal Cortex; Pregnancy in Adolescence; Prevention; Problem behavior; Process; Protocols documentation; Psychiatry; Public Health; Questionnaires; Reporting; Research; Research Personnel; Resistance; Rest; Rewards; Risk; Role; Sampling; Scanning; Societies; Structure; Substance abuse problem; Testing; Thick; Time; Touch sensation; Weight; adolescent alcohol initiation; adverse outcome; age related; alcohol effect; alcohol exposure; alcohol use disorder; alcohol use initiation; behavior test; cognitive control; critical period; discounting; early adolescence; emerging adult; executive function; follow-up; frontal lobe; functional disability; gray matter; indexing; meetings; memory process; neurodevelopment; neuroimaging; neuropsychological; peer influence; relating to nervous system; response; social; substance abuse prevention; trait; underage drinking; white matter

DESCRIPTION (provided by applicant): This application is a resubmitted R01 proposal in response to PA-09-097 Alcohol, Decision- Making, and Adolescent Brain Development (NIAAA). The project capitalizes upon an existing longitudinal sample of adolescents who were enrolled starting in 2004 in a longitudinal brain development study. Participants, ages 9 to 23, underwent an extensive structural neuroimaging protocol that included T1-weighted and diffusion-weighted scans, and also completed a comprehensive behavioral testing battery and a set of self- report questionnaires. Most participants were free of alcohol and drug use at study enrollment. Participants completed one follow-up assessment, two years after the baseline enrollment, using similar data collection methods as at baseline. [A third assessment wave was completed on approximately half the sample since this proposal was reviewed]. Here, funds are requested to conduct two additional longitudinal assessments of the full sample (n=170), many of whom have transitioned from no alcohol use to significant use over time. To date, found age-related improvements were found in numerous frontal lobe-mediated functions, including planning, delay discounting, inhibitory control, and motivated decision making. These functions are associated with white matter integrity throughout the brain, but particularly within tracts that connect the frontal lobe with striatal brain regions. Preliminary findings indicate that individuals who initiated alcohol use, and/or increased their use over time, showed signs of reduced white matter development, specifically with respect to fiber pathways that provide connectivity among cortical regions (superior parietal, anterior temporal, prefrontal) involved in high-level associative processes as well as inhibitory cognitive and behavioral control. Additionally, longitudinal effects of alcohol use include reduced volume of neural fibers connecting the key subcortical structure involved in mediating incentive-reward activation, the nucleus accumbens, with the key cortical region involved in providing descending inhibitory control over behavioral responses to reward cues, the medial orbitofrontal cortex. [Preliminary findings from the partial Time 3 data collection include reductions in white matter integrity of brain regions directly involved in memory processes (hippocampal gyrus, temporal polar cortex) in association with escalating alcohol use from Time 2 to Time 3.] Additional longitudinal assessment will permit a more sophisticated modeling, using linear mixed models, of the effects of adolescent alcohol initiation on ongoing neural connectivity development, together with parallel analyses on associations between behavioral and brain development and how alcohol initiation impacts them. Within the proposed study, the investigators will be able to assess brain connectivity via structural MRI, electrophysiology, resting state fMRI, and a broad range of behavioral tasks. Thus, this application meets NIAAA funding objectives, because the scientific inquiry into the question of alcohol's effects on the developing brain will be advanced.

描述（由申请人提供）：本申请是针对PA-09-097酒精、决策和青少年大脑发育（NIAAA）重新提交的R01提案。该项目利用了现有的青少年纵向样本，这些青少年从2004年开始参加纵向大脑发育研究。9至23岁的参与者接受了广泛的结构神经成像方案，包括t1加权和弥散加权扫描，并完成了全面的行为测试和一套自我报告问卷。大多数参与者在研究登记时都没有饮酒和吸毒。参与者在基线入组两年后完成了一次随访评估，使用与基线时相似的数据收集方法。[自该提案被审查以来，对大约一半的样本进行了第三轮评估]。在这方面，要求资金对全部样本（n=170）进行两次额外的纵向评估，其中许多人随着时间的推移从不饮酒转变为大量饮酒。到目前为止，在许多额叶介导的功能中发现了与年龄相关的改善，包括计划、延迟折扣、抑制控制和动机性决策。这些功能与整个大脑的白质完整性有关，特别是在连接额叶和纹状体的脑束内。初步研究结果表明，开始饮酒和/或随着时间的推移而增加饮酒的个体，表现出白质发育减少的迹象，特别是在皮层区域（顶叶上、颞叶前部、前额叶）之间提供连接的纤维通路方面，这些区域涉及高级联想过程以及抑制性认知和行为控制。此外，酒精使用的纵向影响包括神经纤维体积的减少，神经纤维连接着调节奖励-奖励激活的关键皮层下结构伏隔核，以及对奖励线索的行为反应提供下行抑制控制的关键皮层区域，内侧眶额皮质。[部分时间3数据收集的初步发现包括直接涉及记忆过程的大脑区域（海马回、颞极皮质）的白质完整性减少，这与从时间2到时间3的酒精使用升级有关。]额外的纵向评估将允许更复杂的建模，使用线性混合模型，青少年酒精开始对正在进行的神经连接发展的影响，以及平行分析行为和大脑发育之间的关系以及酒精开始如何影响它们。在拟议的研究中，研究人员将能够通过结构MRI，电生理学，静息状态fMRI和广泛的行为任务来评估大脑连接。因此，这项申请符合NIAAA的资助目标，因为酒精对大脑发育影响的科学研究将得到推进。