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Fiber tractography reveals disruption of temporal lobe white matter tracts in schizophrenia.

ABSTRACT: Diffusion tensor imaging (DTI) studies have demonstrated abnormal anisotropic diffusion in schizophrenia. However, examining data with low spatial resolution and/or a low number of gradient directions and limitations associated with analysis approaches sensitive to registration confounds may have contributed to mixed findings concerning the regional specificity and direction of results. This study examined three major white matter tracts connecting lateral and medial temporal lobe regions with neocortical association regions widely implicated in systems-level functional and structural disturbances in schizophrenia. Using DTIstudio, a previously validated regions of interest tractography method was applied to 30 direction diffusion weighted imaging data collected from demographically similar schizophrenia (n=23) and healthy control subjects (n=22). The diffusion tensor was computed at each voxel after intra-subject registration of diffusion-weighted images. Three-dimensional tract reconstruction was performed using the Fiber Assignment by Continuous Tracking (FACT) algorithm. Tractography results showed reduced fractional anisotropy (FA) of the arcuate fasciculi (AF) and inferior longitudinal fasciculi (ILF) in patients compared to controls. FA changes within the right ILF were negatively correlated with measures of thinking disorder. Reduced volume of the left AF was also observed in patients. These results, which avoid registration issues associated with voxel-based analyses of DTI data, support that fiber pathways connecting lateral and medial temporal lobe regions with neocortical regions are compromised in schizophrenia. Disruptions of connectivity within these pathways may potentially contribute to the disturbances of memory, language, and social cognitive processing that characterize the disorder.

SUBMITTER: Phillips OR

PROVIDER: S-EPMC2655322 | biostudies-literature | 2009 Jan

REPOSITORIES: biostudies-literature

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Fiber tractography reveals disruption of temporal lobe white matter tracts in schizophrenia.

Phillips Owen R OR Nuechterlein Keith H KH Clark Kristi A KA Hamilton Liberty S LS Asarnow Robert F RF Hageman Nathan S NS Toga Arthur W AW Narr Katherine L KL

Schizophrenia research 20081125 1

Diffusion tensor imaging (DTI) studies have demonstrated abnormal anisotropic diffusion in schizophrenia. However, examining data with low spatial resolution and/or a low number of gradient directions and limitations associated with analysis approaches sensitive to registration confounds may have contributed to mixed findings concerning the regional specificity and direction of results. This study examined three major white matter tracts connecting lateral and medial temporal lobe regions with n ...[more]

PMID: 19028423

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Project description:White matter hyperintensities of presumed vascular origin are frequently observed on magnetic resonance imaging in normal aging. They are typically found in cerebral small vessel disease and suspected culprits in the etiology of complex age- and small vessel disease-related conditions, such as late-onset depression. White matter hyperintensities may interfere with surrounding white matter metabolic demands by disrupting fiber tract integrity. Meanwhile, risk factors for small vessel disease are thought to reduce tissue oxygenation, not only by reducing regional blood supply, but also by impairing capillary function. To address white matter oxygen supply-demand balance, we estimated voxel-wise capillary density as an index of resting white matter metabolism, and combined estimates of blood supply and capillary function to calculate white matter oxygen availability. We conducted a cross-sectional study with structural, perfusion- and diffusion-weighted magnetic resonance imaging in 21 patients with late-onset depression and 21 controls. We outlined white matter hyperintensities and used tractography to identify the tracts they intersect. Perfusion data comprised cerebral blood flow, blood volume, mean transit time and relative transit time heterogeneity-the latter a marker of capillary dysfunction. Based on these, white matter oxygenation was calculated as the steady state cerebral metabolic rate of oxygen under the assumption of normal tissue oxygen tension and vice versa. The number, volume and perfusion characteristics of white matter hyperintensities did not differ significantly between groups. Hemodynamic data showed white matter hyperintensities to have lower blood flow and blood volume, but higher relative transit time heterogeneity, than normal-appearing white matter, resulting in either reduced capillary metabolic rate of oxygen or oxygen tension. Intersected tracts showed significantly lower blood flow, blood volume and capillary metabolic rate of oxygen than normal-appearing white matter. Across groups, lower lesion oxygen tension was associated with higher lesion number and volume. Compared with normal-appearing white matter, tissue oxygenation is significantly reduced in white matter hyperintensities as well as the fiber tracts they intersect, independent of parallel late-onset depression. In white matter hyperintensities, reduced microvascular blood volume and concomitant capillary dysfunction indicate a severe oxygen supply-demand imbalance with hypoxic tissue injury. In intersected fiber tracts, parallel reductions in oxygenation and microvascular blood volume are consistent with adaptations to reduced metabolic demands. We speculate, that aging and vascular risk factors impair white matter hyperintensity perfusion and capillary function to create hypoxic tissue injury, which in turn affect the function and metabolic demands of the white matter tracts they disrupt.

Dataset Information

Fiber tractography reveals disruption of temporal lobe white matter tracts in schizophrenia.

Publications

Fiber tractography reveals disruption of temporal lobe white matter tracts in schizophrenia.

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