CEREBELLAR STRUCTURE AND FUNCTION IN ALCOHOLISM

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 目的：使用核磁共振成像和行为测试来解释额小脑系统在高级认知和运动功能中的作用以及它们在慢性酒精中毒中的破坏。 方法：我们测量了来自20名酗酒者(51-75岁)和15名年龄匹配的对照组男性的T1(SPGR)和T2(FSE)加权图像的小脑半球、蚯蚓和小脑投射系统结节的体积，这些投射系统是桥小脑额束的一部分。确定前连合(AC)和后连合(PC)，并用于将所有数据与共同方向对齐。然后将SPGR数据重采样到200x200×200、1.0mm3的各向同性数据集，并使用12参数仿射函数将FSE数据注册到重采样的SPGR数据。切除非脑组织，辨认小脑半球边缘。然后用双通道(SPGR和FSE)、隐马尔可夫随机场和带偏场校正的期望最大化模型(Mfast)对分离的小脑半球进行分割。最后的分析单位是被分割成灰质、白质和脑脊液的区域体积。 结果：采用线性回归校正正常的颅内体积(ICV)和年龄变化的小脑体积，我们观察到与对照组相比，酒精患者的小脑皮质灰质体积减少了近1SD，而脑脊液体积增大了约8SD。此外，在酗酒者中，年龄校正后的灰质体积随着年龄的增长而下降(r=-.48，p=。03)，复制了我们之前观察到的年龄与酒精的相互作用。对这些数据的大脑结构-功能分析为我们关于小脑对更高认知功能以及姿势稳定性的贡献的假设提供了初步支持。特别是，酗酒者在痴呆症评定量表、数字广度、数字符号以及轨迹A和B上的较差表现与较大的小脑脑脊液容量(根据年龄和ICV进行调整)相关。此外，更大的开环姿势控制活动，无论有多少可用于稳定性的感觉运动线索，都与较小的小脑灰质体积有关(S的范围从-.42到-.62)。 结论：小脑与开环而不是闭环控制机制的关系符合开环活动可以被预先存在的生理条件改变的模型，并且相对不受意识或环境输入的影响。 尽管酗酒者额小脑回路的所有主要节点都会出现体积缺陷，但这些节点可以独立中断，这表明慢性酒精中毒影响的区域大脑结构模式是不同的。回路中断可能是通常观察到的与酒精中毒相关的认知和运动障碍的基础，要么是个别节点本身存在的异常，要么是由于选择性回路中断而导致的连接中断。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Aims: Use MRI and behavioral tests to explicate the role of the fronto-cerebellar system in higher order cognitive and motor functioning and their disruption in chronic alcoholism. Methods: We measured volumes of the cerebellar hemispheres, vermis, and nodes of cerebellar projection systems that are part of the pontocerebellar-frontal tract from T1 (SPGR) and T2 (FSE) weighted images acquired from 20 alcoholic (51-75 years) and 15 age-matched control men. The anterior commissure (AC) and posterior commissure (PC) were identified and used to align all data with a common orientation. The SPGR data were then resampled into a 200x200x200, 1.0 mm3 isotropic dataset and the FSE data registered to the resampled SPGR data with a 12-parameter affine function. The non-brain tissue was removed and the margins of the cerebellar hemispheres were identified. The isolated cerebellar hemispheres were then segmented with a dual channel (SPGR and FSE), hidden Markov random field and Expectation-Maximization model with bias field correction, "mfast." The final unit of analysis was a regional volume segmented into gray matter, white matter, and CSF. Results: Using linear regression to adjust the cerebellar volumes for normal variation in intracranial volume (ICV) and age, we observed nearly a 1 SD volume deficit in cerebellar cortical gray matter and .8 SD enlargement of CSF volume in alcoholics compared with controls. Further, the age-corrected gray matter volumes declined with age in alcoholics (r=-.48, p=. 03), replicating our previously observed age-alcohol interaction. Brain structure-function analysis of these data provides initial support of our hypotheses regarding the contribution of the cerebellum to higher cognitive function as well as to postural stability. In particular, poorer performance on the Dementia Rating Scale, digit span, digit symbol, and Trails A and B correlated with greater cerebellar CSF volumes, adjusted for age and ICV, in the alcoholics. Further, greater open-loop postural control activity, regardless of number of sensorimotor cues available for stability, was related to smaller cerebellar gray matter volumes (r?s range from -.42 to -.62). Conclusions: The cerebellar relationship with the open-loop rather than the closed-loop control mechanism is consistent with the model that open-loop activity can be modified by pre-existing physiological conditions and is relatively immune to conscious or environmental input. Although volume deficits occur in all major nodes of frontocerebellar circuitry in alcoholics, these nodes can be independently disrupted, suggesting heterogeneity in the pattern of regional brain structures affected by chronic alcoholism. Disruption in circuits may underlie commonly observed alcoholism-related cognitive and motor deficits, either by abnormalities present in individual nodes themselves or by disconnection via interruption of selective circuitry.