Jeremy D Schmahmann - US grants

This application to the National Library of Medicine is to provide short term assistance for the preparation of an atlas of the human cerebellum in printed book form and on CD-ROM. The goal of this project is to develop a detailed atlas of the human cerebellum that will be accessible to clinicians and investigators around the world whether they are dependent upon computer based information systems or not. The atlas is designed so that it may be incorporated into international databases of the human brain accessible through the world wide web, such as the Visible Human Project of the National Library of Medicine, and the International Consortium for Brain Mapping. The intense interest and growth of information about the organization and function of the human brain has focused to a large extent on the cerebral cortex. The understanding of the function of the cerebellum has advanced considerably in recent years, particularly with respect to its involvement in higher brain functions concerned with thought and emotion. Functional neuroimaging studies in particular have shown cerebellar activation by cognitive tasks, but there are only vague notions of which particular cerebellar structures are being activated by these tasks. This is in large measure a reflection of the fact that there is no useful guide for neuroimaging purposes to the landmarks and structures of the human cerebellum. The work that the Principal Investigator has performed to date, and which he plans to publish with his collaborators with the help of the National Library, will remedy this problem. This project uses very high resolution magnetic resonance images, state of the art computer technology, and a universally accepted stereotaxic (Talairach) coordinate system to analyze the data, and it is combined with a thorough revision and simplification of previously confusing cerebellar nomenclature. The book and CD-ROM proposed in this application present the gross morphology of the human cerebellum with previously unattainable clarity and precision. This 3- dimensional atlas of the human cerebellum in Talairach space has the potential to become the standard anatomic reference in the field of anatomic and functional neuroimaging of the cerebellum.

[unreadable] DESCRIPTION (provided by applicant): The traditional notion that cerebellar function is confined to the coordination of voluntary motor activity is in the midst of a paradigm shift. Converging lines of evidence from anatomical, clinical, experimental and functional neuroimaging studies indicate that the cerebellum is necessary for normal psychological and social behavior. At the core of this re-evaluation is the recognition that the cerebellum may contribute a unique modulating role to a wide array of functions, and that loss of cerebellar modulation degrades different behaviors in a unique manner (Schmahmann, 1991, 1996, 2000a). The specific aims of this study are to address two issues central to the evolving understanding of the role of the cerebellum. First, what is the scope of the cerebellar role in non-motor performance, and is there topographic organization within cerebellum of sensorimotor, cognitive and emotional behaviors? Second, what are the mechanisms of the cerebellar contribution to cognition and emotion? This study attempts to answer these questions in adult patients with focal cerebellar injury from stroke. Lesion-deficit correlations will be performed using paradigms that identify defective strategies in cognitive performance, that evaluate language and mood states, and that determine the extent of motor incapacity. These approaches will address the scope and topographic organization of cerebellar function. Fluoro-2- deoxy-D-glucose positron emission tomography will examine whether there is decreased glucose utilization (diaschisis) in areas of the cerebral cortex that are anatomically linked with the cerebellum (prefrontal cortex, posterior parietal cortex, superior temporal region, cingulate gyrus), but not in areas devoid of cerebellar connections (inferotemporal cortex, ventral occipital cortex). This will address the functional relevance of the cerebrocerebellar circuits, and help assess whether a fundamental mechanism of cerebellar function can be discerned. The demonstration of a correlation between the scope of the functional impairment (which cognitive domains are involved), and the underlying mechanism (deprivation of the universal cerebellar transform from the cerebrocerebellar communication), would be a conceptual advance in understanding the cerebellar contribution to cognition, and the functional relevance of the cerebrocerebellar system. This study has implications for the recognition and treatment of disorders of higher order function in cerebellar patients. [unreadable] [unreadable]

Arginine; Arginine, L-Isomer; CRISP; Cerebellar Ataxia; Cerebellar Incoordination; Clinical Trials; Clinical Trials, Unspecified; Computer Retrieval of Information on Scientific Projects Database; Diagnosis; Funding; Grant; Institution; Investigators; L-Arginine; MSA; Multiple System Atrophy; Multiple System Atrophy Syndrome; Multisystem Atrophy; Multisystemic Atrophy; NIH; National Institutes of Health; National Institutes of Health (U.S.); Patients; Research; Research Personnel; Research Resources; Researchers; Resources; Source; TPO gene; TPX; Testing; United States National Institutes of Health; clinical investigation

Project Summary/Abstract The goal of this project is to create noninvasive methodology to image the connectional neuroanatomy of the human brain using diffusion MRI. Two recent developments make this possible. First, we have shown in macaque that every region of the cerebral cortex reliably gives rise to a predictable number of fiber tracts connecting it with unique sets of neuronal subpopulations distributed within cortical and subcortical regions. Second, we have shown, also in macaque, that novel forms of high angular resolution diffusion spectrum MRI (DSI) have the unique capacity to define connectional neuroanatomy non-invasively. The goal of the present project is to define, for the first time, the connectional neuroanatomy of the monkey brain non-invasively, and to build a bridge from the macaque brain to the human brain in order to accomplish a previously impossible goal - the determination of connectional neuroanatomy in the human brain. To achieve this goal, three steps are necessary. First, we will validate diffusion MRI in macaque by comparison to the gold standard of isotope tract tracer injections, the tracer injections and MRI to be performed in the same animals. The technical parameters that optimally and most accurately replicate the findings of the tract tracer studies will be determined, and potential sources of MRI error quantified and minimized. Second, post-mortem human brains will be imaged to achieve the highest possible resolution of these human brains, with the aim of replicating the mandatory principles of organization of the white matter pathways identified as defining the connections of the monkey brain. Next, the brains of living human subjects will be imaged, to attempt to replicate the findings in the post-mortem specimens, in order to establish the limitations of the methodology in vivo. To convey this technology into the broader imaging arena, we will investigate the hypothesis that structural and functional connectivity are correlated by comparing the results with those of resting state connectivity in the living human brain.