Cerebellar Structure and Function in Alcoholism

酒精中毒的小脑结构和功能

• 批准号: 9302605
• 负责人: EDITH VIONI SULLIVAN
• 金额: $ 49.47万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 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/9302605
• 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; Impairment; Injury; Instruction; Intelligence; Knowledge; Length; Magnetic Resonance; Maintenance; Measures; Methods; Motor; Neuroanatomy; Parietal Lobe; Participant; Pattern; Performance; Perfusion; Pharmacological Treatment; Physiologic pulse; Posture; Prefrontal Cortex; Problem Solving; Public Health; Recovery; Recruitment Activity; 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; graph theory; gray matter; human subject; indexing; neuroimaging; novel; problem drinker; rehabilitation strategy; sex; sobriety; success; therapy development

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.

酒精使用障碍对美国的公共卫生造成了巨大的损失，尤其是在大脑方面 结构及其功能。这项扩展的研究计划的目的是确定酒精中毒的机制 - 使用高级磁共振脑成像（MRI）诱导脑损伤，可以指导康复 策略并最终为药理学治疗开发提供信息。酒精中毒的动态周期 缓解和复发可能导致功能妥协，有选择地破坏了解决问题， 工作记忆，视觉空间能力以及步态和平衡。融合证据强烈暗示 额叶电路电路的破坏是酒精中毒特征模式的主要贡献者 相关障碍。当前研究产生的发现揭示了该电路包括多个 可隔离的环，每个循环都依靠不同的认知或运动功能。我们还建立了哪些循环 受到影响并在酒精中毒中幸免的，并发现了新功能的启动 与良好的性能相关的连接和在恢复酗酒者方面更长的清醒相关。此外 这些任务激活的发现，我们的静止状态（RS）fMRI研究确定了内在功能连接性 受到影响的网络以及其他在酗酒者中幸免的网络。我们现在的追求将是测试是否 网络募集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。提出的是3个特定目标，带有可检验的假设： 特定目的1：以短期戒酒和持续的戒酒或变化来阐明地位 休息状态的内在和任务激活的小脑网络的复发； 特定目的2：确定持续清醒或复发对酒精中毒引起的降解的影响 在任务激活和内在连通性网络上的神经解剖学和大脑血液灌注 涉及前脑电路； 特定目的3：检查与清醒有关或与Reiapse相关的电动机和认知后果 用RSFMRI识别的内在网络连接中测量的变化。