Cerebellar Structure and Function in Alcoholism

酒精使用障碍对美国公众健康造成重大损害，特别是对大脑 结构及其功能。这一扩展研究计划的目标是确定酒精中毒的机制- 用先进的磁共振脑成像(MRI)技术指导康复治疗引起的脑损伤 战略，并最终为药物治疗的发展提供信息。酒精中毒的动态循环 缓解和复发会导致功能受损，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。不断涌现的证据强烈表明 作为酒精中毒特征模式的主要贡献者的额小脑回路中断- 相关损害。目前的研究结果显示，这种电路包括多个 可分离的环路，每个环路都有不同的认知或运动功能。我们还确定了哪些环路 是受影响的，在酒精中毒中幸免于难，并发现了新的功能 在戒酒患者中，良好的表现和更长时间的清醒有关。除了……之外 这些任务激活的发现，我们的静息状态(Rs)功能磁共振研究确定了内在的功能连接。 受影响的网络和其他幸免于酗酒者的网络。我们现在的目标是测试 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 克服选择性功能障碍。提出了3个具体目标，并提出了可检验的假设： 具体目标1：阐明短期戒酒的状态和持续戒酒或持续戒酒的变化 静息状态下固有的和任务激活的功能小脑网络复发； 具体目标2：确定持续戒酒或复发对酒精中毒引起的退化的影响 任务激活和内在连接网络的神经解剖学和脑血流灌注的研究 累及额小脑回路； 具体目标3：研究与戒酒或戒酒相关的运动和认知分支 RsfMRI确定的固有网络连接性中测量的变化。 相关性(请参阅说明)： 酒精使用障碍对美国公共健康造成了巨大的损失，特别是在 对大脑结构和功能的不良影响。使用先进的神经成像技术，我们预计将获得 了解哪些大脑系统因酒精中毒而受损，并区分受影响的人和受影响的人 未受影响的系统。这项研究的成功可以指导康复策略，提供信息 药物治疗的发展，以及帮助启动和维持清醒。

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.