Effects of adolescent alcohol exposure on functional brain connectivity

青少年酒精暴露对大脑功能连接的影响

• 批准号: 10237254
• 负责人: Margaret A Broadwater
• 金额: $ 15.47万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-09-01 至 2021-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10237254
• 关键词: Abstinence; Acute; Address; Adolescence; Adolescent; Adult; Affect; Age; Alcohol consumption; Alcoholism; Alcohols; Animals; Behavior; Behavioral; Brain; Brain region; Cognition; Data; Data Analyses; Data Collection; Development; Ethanol; Exposure to; FOS gene; Female; Frequencies; Functional Magnetic Resonance Imaging; Glutamates; Health; Histologic; Histology; Human; Laboratory Research; Life; MRI Scans; Magnetic Resonance Imaging; Measures; Mediating; Mentored Research Scientist Development Award; Mentors; Neurons; Pathway interactions; Pharmacology Study; Predisposition; Prefrontal Cortex; Rattus; Research; Research Personnel; Research Training; Resolution; Rest; Risk Behaviors; Rodent; Scanning; Scientist; Signal Transduction; Structure; Surrogate Markers; Techniques; Testing; Therapeutic Intervention; Time; Training; United States National Institutes of Health; Water; addiction; adolescent alcohol effect; adolescent alcohol exposure; alcohol exposure; alcohol pharmacology; alcohol research; alcohol response; alcohol use disorder; alcohol use initiation; blood oxygen level dependent; career; career development; chronic alcohol ingestion; cognitive control; executive function; frontal lobe; functional restoration; indexing; insight; magnetic field; male; optogenetics; relating to nervous system; response; targeted treatment; tool; underage drinking

ABSTRACT This is an application for a Mentored Research Scientist Development Award (K01) to support the career development of Dr. Margaret Broadwater as an independent academic research scientist. The candidate is an early stage investigator with a strong background in behavioral alcohol pharmacology studies and is relatively new to the field of magnetic resonance imaging (MRI). The applicant's career and research training will be overseen by a strong mentoring team and supported by strong institutional commitment to the candidate's career development. The training outlined in this proposal will allow the candidate to develop a successful, productive research laboratory that will be at the forefront of alcohol research using functional connectivity MRI (fcMRI) in rodents. In humans and rodents, functional connectivity can be assessed with MRI by correlating fluctuations in blood-oxygen-level-dependent (BOLD) signal, a surrogate marker of neural activity, between brain regions. The proposed studies will use this tool to examine the effects of adolescent alcohol exposure on brain. Alcohol use during adolescence is common and initiation of alcohol use at an early age is associated with development of later alcohol use disorders. Chronic alcohol use during adolescence may result in deficits of inhibitory, top-down control of the prefrontal cortex (PFC) on subcortical brain structures, possibly contributing to compulsive and inflexible behavior typically seen in addiction. Indeed, the prefrontal cortex (PFC) is particularly vulnerable to alcohol use during adolescence, the developmental period of cortical maturation; however, it is unknown how PFC connectivity to other brain regions may be affected by adolescent alcohol exposure. The overarching hypothesis of this proposal is that adolescent alcohol exposure will alter maturation of PFC connectivity, leading to persistent deficits in PFC functional connectivity and altered responding to acute alcohol challenge in adulthood. These results will be informative for ongoing research initiatives from the NIH assessing consequences of adolescent alcohol use in humans, and ultimately will aid in our understanding of potential mechanisms for addiction vulnerability to identify targets for therapeutic intervention and reversal.

摘要