Diffusion tensor imaging (DTI) and fiber tractography are useful tools for reconstructing white matter tracts (WMT) in the brain. Previous tractography studies have sought to segment reconstructed WMT into anatomical structures using several approaches, but quantification has been limited to extracting mean values of diffusion indices. Delineating WMT in schizophrenia is of particular interest because schizophrenia has been hypothesized to be a disorder of disrupted connectivity, especially between frontal and temporal regions of the brain. In this study, we aim to differentiate diffusion properties of thalamo-frontal pathways in schizophrenia from normal controls. We present a quantitative group comparison method, which combines the strengths of both tractography-based and voxel-based studies. Our algorithm extracts white matter pathways using whole brain tractography. Functionally relevant bundles are selected and parsed from the resulting set of tracts, using an internal capsule (IC) region of interest (ROI) as "source", and different Brodmann area (BA) ROIs as "targets". The resulting bundles are then longitudinally parameterized so that diffusion properties can be measured and compared along the WMT. Using this processing pipeline, we were able to find altered diffusion properties in male patients with chronic schizophrenia in terms of fractional anisotropy (FA) decreases and mean diffusivity (MD) increases in precise and functionally relevant locations. These findings suggest that our method can enhance the regional and functional specificity of DTI group studies, thus improving our understanding of brain function.

Objective-Impairment of white matter connecting frontal and temporal cortices has been reported in schizophrenia. Yet, not much is known about the effects of age on fibers connecting these brain regions. Using diffusion tensor imaging tractography, we investigated the relationship between age and fiber integrity in patients with schizophrenia vs. healthy adults.Methods-DTI tractography was used to create 3D reconstructions of the cingulum, uncinate and inferior occipito-frontal fasciculi in 27 patients with schizophrenia and 34 healthy volunteers (23-56 years of age, group-matched on age). Fractional anisotropy (FA), describing fiber integrity, was then calculated along the entire length of these tracts, and correlated with subjects' age.Results-Patients revealed a significant decline in FA with age in both the cingulum and uncinate, but not in the inferior occipito-frontal fasciculi. No statistically significant correlations were found in these fiber bundles in controls. ContributorsRosenberger G. and Kubicki M. designed the study. Connor E., Bushell G., and Markant D. collected some of the data and did PUBMED searchers. Nestor P.G., Niznikiewicz M., and Saykin A., undertook the statistical analyses. Rosenberger G.wrote the first draft of the manuscript. Shenton M.,Kikinis R.,Westin C-F., and McCarley R.W. had substantial input on aspects of the design of the study and Shenton M. and Saykin A. had substantial input in editing multiple versions of the manuscript. Shenton M. and McCarley R.W. also had input on clinical aspects of the design including the selection of diagnostic and clinical measures. All other authors contributed to and have improved the final manuscript. Conflict of interestThere are no conflicts of interest. Conclusions-These results suggest an age-associated reduction of frontal-temporal connectivity in schizophrenia, but not in healthy controls. NIH Public Access