CEREBELLAR STRUCTURE AND FUNCTION IN ALCOHOLISM

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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.