Automated Probabilistic Reconstruction of White-Matter Pathways in Health and Disease Using an Atlas of the Underlying Anatomy

The neurons of the human cerebral cortex are arranged in a highly folded sheet, with the majority of the cortical surface area buried in folds. Cortical maps are typically arranged with a topography oriented parallel to the cortical surface. Despite this unambiguous sheetlike geometry, the most commonly used coordinate systems for localizing cortical features are based on 3-D stereotaxic coordinates rather than on position relative to the 2-D cortical sheet. In order to address the need for a more natural surface-based coordinate system for the cortex, we have developed a means for generating an average folding pattern across a large number of individual subjects as a function on the unit sphere and of nonrigidly aligning each individual with the average. This establishes a spherical surface-based coordinate system that is adapted to the folding pattern of each individual subject, allowing for much higher localization accuracy of structural and functional features of the human brain.

Schizophrenia is hypothesized to involve disordered connectivity between brain regions. Currently, there are no direct measures of brain connectivity; functional and structural connectivity used separately provide only limited insight. Simultaneous measure of anatomical and functional connectivity and its interactions allow for better understanding of schizophrenia-related alternations in brain connectivity. Twenty-seven schizophrenia patients and 27 healthy control subjects underwent magnetic resonance imaging with resting state functional magnetic resonance imaging and diffusion tensor imaging. Separate functional and anatomical connectivity maps were calculated and combined for each subject. Global, regional, and voxel measures and K-means network analysis were employed to identify group differences and correlation with clinical symptoms. A global connectivity analysis indicated that patients had lower anatomical connectivity and lower coherence between the two imaging modalities. In schizophrenia these group differences correlated with clinical symptom severity. Although anatomical connectivity nearly uniformly decreased, functional connectivity in schizophrenia was lower for some connections (e.g., middle temporal gyrus) and higher for others (e.g., cingulate and thalamus). Within the default mode network (DMN) two separate subsystems can be identified. Schizophrenia patients showed decoupling between structural and functional connectivity that can be localized to networks originating in posterior cingulate cortex as well as in the task-positive network and one of the DMN components. Combining two measures of brain connectivity provides more comprehensive descriptions of altered brain connectivity underlying schizophrenia. Patients show deficits in white matter anatomy, but functional connectivity alterations are more complex. Fusion of both methods allows identification of subsystems showing both increased and decreased functional connectivity. Copyright 2010 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Functional imaging with positron emission tomography and functional MRI has revolutionized studies of the human brain. Understanding the organization of brain systems, especially those used for cognition, remains limited, however, because no methods currently exist for noninvasive tracking of neuronal connections between functional regions [Crick, F. & Jones, E. (1993) Nature (London) 361, 109-110]. Detailed connectivities have been studied in animals through invasive tracer techniques, but these invasive studies cannot be done in humans, and animal results cannot always be extrapolated to human systems. We have developed noninvasive neuronal fiber tracking for use in living humans, utilizing the unique ability of MRI to characterize water diffusion. We reconstructed fiber trajectories throughout the brain by tracking the direction of fastest diffusion (the fiber direction) from a grid of seed points, and then selected tracks that join anatomically or functionally (functional MRI) defined regions. We demonstrate diffusion tracking of fiber bundles in a variety of white matter classes with examples in the corpus callosum, geniculo-calcarine, and subcortical association pathways. Tracks covered long distances, navigated through divergences and tight curves, and manifested topological separations in the geniculo-calcarine tract consistent with tracer studies in animals and retinotopy studies in humans. Additionally, previously undescribed topologies were revealed in the other pathways. This approach enhances the power of modern imaging by enabling study of fiber connections among anatomically and functionally defined brain regions in individual human subjects.