Cerebellar Structure and Function in Alcoholism

酒精中毒的小脑结构和功能

基本信息

批准号：
8819186
负责人：
EDITH VIONI SULLIVAN
金额：
$ 50.98万
依托单位：
STANFORD UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2015
资助国家：
美国
起止时间：
2015-07-01 至 2020-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8819186
关键词：
Abstinence Affect Age Alcoholism Americas Atlases Attenuated Behavioral Brain Brain Injuries Brain imaging Cerebellar cortex structure Cerebrum Characteristics Cognitive Data Disease remission Education Equilibrium Exhibits Family history of Frequencies Functional Imaging Functional Magnetic Resonance Imaging Functional disorder Gait Goals Graph Impairment Injury Instruction Intelligence Knowledge Length Magnetic Resonance Maintenance Measures Methods Motor Neuroanatomy Parietal Lobe Participant Pattern Performance Perfusion Pharmacological Treatment Physiologic pulse Prefrontal Cortex Problem Solving Public Health Recovery Regional Perfusion Relapse Research Rest Risk Short-Term Memory Site Smoking History Structure System Testing Thalamic structure Tremor Visuospatial alcohol use disorder base blood perfusion brain volume cognitive task gray matter human subject indexing neuroimaging novel problem drinker rehabilitation strategy sex sobriety success theories therapy development

项目摘要

Alcohol use disorders exact a substantial toll on America's public health especially with respect to brain structure and its functions. The goal of this expanded research plan is to identify mechanisms of alcoholism- induced brain injury using advanced magnetic resonance brain imaging (MRI) that could guide rehabilitation strategies and ultimately inform pharmacological treatment development. Alcoholism's dynamic cycle of remission and relapse can result in compromised functioning, selectively destructive to problem solving, working memory, visuospatial abilities, and gait and balance. Converging evidence strongly implicates disruption of frontocerebellar circuitry as a principal contributor to the characteristic pattern of alcoholism- related impairment. Findings generated from the current research revealed this circuitry comprises multiple dissociable loops, each subserving different cognitive or motor functions. We also established which loops are affected and which are spared in alcoholism and have discovered instatement of novel functional connections associated with good performance and longer sobriety in recovering alcoholics. In addition to these task-activated findings, our resting-state (rs) fMRI studies identified intrinsic functional connectivity networks that are affected and others that are spared in alcoholics. Our pursuit now will be to test whether network recruitment can be redirected from disrupted nodes and networks to alternative functional circuitry for overcoming selective dysfunction. Proposed are 3 specific aims with testable hypotheses: Specific Aim 1: To elucidate the status with short-term abstinence and change with sustained abstinence or relapse of resting-state intrinsic and task-activated functional cerebellar networks; Specific Aim 2: To determine the impact of sustained sobriety or relapse on alcoholism-induced degradation ofthe neuroanatomy and cerebral blood perfusion on task-activated and intrinsic connectivity networks involving frontocerebellar circuitry; Specific Aim 3: To examine the motor and cognitive ramifications of sobriety-related or reIapse-related changes measured in intrinsic network connectivity identified with rsfMRI. RELEVANCE (See instructions): Alcohol use disorders exact a substantial toll on America's public health especially with respect to its untoward effect on brain structure and its functions. Using advanced neuroimaging, we expect to gain knowledge about what brain systems sustain injury from alcoholism and to differentiate the affected from the unaffected systems. Success in this research endeavor could guide rehabilitation strategies, inform pharmacological treatment development, and aid initiation and maintenance of sobriety.

酒精使用障碍对美国的公共卫生造成重大损害，尤其是在大脑方面结构及其功能。这项扩展研究计划的目标是确定酗酒的机制—— 使用先进的磁共振脑成像（MRI）诱发脑损伤，可以指导康复策略并最终为药物治疗的开发提供信息。酗酒的动态循环缓解和复发可能导致功能受损，选择性地破坏问题的解决，工作记忆、视觉空间能力、步态和平衡能力。综合证据强烈暗示额小脑回路的破坏是酒精中毒特征模式的主要原因相关的损害。当前研究的结果表明该电路包含多个可分离的循环，每个循环都促进不同的认知或运动功能。我们还建立了哪些循环受到影响并免受酒精中毒的影响，并发现了新的功能在酗酒者康复过程中，良好的表现和较长时间的清醒与良好的表现有关。此外这些任务激活的发现，我们的静息态 (rs) fMRI 研究确定了内在的功能连接受影响的网络和其他未受到酗酒者影响的网络。我们现在的追求是测试是否网络招募可以从中断的节点和网络重定向到替代功能电路用于克服选择性功能障碍。提出了 3 个具有可检验假设的具体目标：具体目标 1：阐明短期戒断的状况以及持续戒断或戒断后的变化静息态内在和任务激活的功能性小脑网络的复发；具体目标 2：确定持续清醒或复发对酗酒引起的退化的影响任务激活和内在连接网络的神经解剖学和脑血液灌注涉及额小脑回路；具体目标 3：检查清醒相关或复发相关的运动和认知影响通过 rsfMRI 识别的内在网络连接测量的变化。相关性（参见说明）：酒精使用障碍对美国的公共卫生造成了重大损失，特别是在其对大脑结构及其功能产生不良影响。使用先进的神经影像学，我们期望获得了解哪些大脑系统因酗酒而受到损伤，并将受影响者与正常人区分开来不受影响的系统。这项研究工作的成功可以指导康复策略，提供信息药物治疗的开发，以及帮助开始和维持清醒。