Cerebellar Structure and Function in Alcoholism

酒精使用障碍对美国的公共健康造成了重大影响，特别是在大脑方面 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）诱导脑损伤，可以指导康复 战略，并最终告知药理学治疗的发展。酒精中毒的动态循环 缓解和复发可能导致功能受损，选择性地破坏问题解决， 工作记忆、视觉空间能力、步态和平衡。证据表明 额小脑回路的破坏是酒精中毒的主要原因， 相关损害。从目前的研究中得出的结果显示，这种电路包括多个 可分离的回路，每个回路都服务于不同的认知或运动功能。我们还确定了 受影响，并幸免于酒精中毒，并已发现新的功能性 与良好的表现和更长的清醒在恢复酗酒者的连接。除了 这些任务激活的发现，我们的静息状态（rs）fMRI研究确定了内在功能连接 受影响的网络和其他在酗酒者中幸免的网络。我们现在要做的是 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 来克服选择性功能障碍提出了3个具体目标和可检验的假设： 具体目标1：阐明短期戒烟的状态和持续戒烟的变化， 静息态固有和任务激活的功能性小脑网络复发; 具体目标2：确定持续清醒或复发对酒精中毒引起的退化的影响 神经解剖学和脑血流灌注对任务激活和内在连接网络的影响 涉及额小脑回路; 具体目标3：检查清醒相关或苏醒相关的运动和认知分支 rsfMRI确定的内在网络连接测量的变化。

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.