Person:

Savadjiev, Peter

The cingulum bundle (CB) connects gray matter structures of the limbic system and as such has been implicated in the etiology of schizophrenia. There is growing evidence to suggest that the CB is actually comprised of a conglomeration of discrete sub-connections. The present study aimed to use Diffusion Tensor tractography to subdivide the CB into its constituent sub-connections, and to investigate the structural integrity of these sub-connections in patients with schizophrenia and matched healthy controls. Diffusion Tensor Imaging scans were acquired from 24 patients diagnosed with chronic schizophrenia and 26 matched healthy controls. Deterministic tractography was used in conjunction with FreeSurfer-based regions-of-interest to subdivide the CB into 5 sub-connections (I1 to I5). The patients with schizophrenia exhibited subnormal levels of FA in two cingulum sub-connections, specifically the fibers connecting the rostral and caudal anterior cingulate gyrus (I1) and the fibers connecting the isthmus of the cingulate with the parahippocampal cortex (I4). Furthermore, while FA in the I1 sub-connection was correlated with the severity of patients' positive symptoms (specifically hallucinations and delusions), FA in the I4 sub-connection was correlated with the severity of patients' negative symptoms (specifically affective flattening and anhedonia/asociality). These results support the notion that the CB is a conglomeration of structurally interconnected yet functionally distinct sub-connections, of which only a subset are abnormal in patients with schizophrenia. Furthermore, while acknowledging the fact that the present study only investigated the CB, these results suggest that the positive and negative symptoms of schizophrenia may have distinct neurobiological underpinnings.

Background—Structural abnormalities in the callosal fibers connecting the heteromodal association areas of the prefrontal and temporoparietal cortices bilaterally have been suggested to play a role in the etiology of schizophrenia. Aims—To investigate for geometric abnormalities in these callosal fibers in schizophrenia patients using a novel Diffusion-Tensor Imaging (DTI) metric of fiber geometry named ShapeNormalized Dispersion (SHD). Methods—DTIs (3T, 51 gradient directions, 1.7 mm isotropic voxels) were acquired from 26 schizophrenia patients and 23 matched healthy controls. The prefrontal and temporoparietal fibers of the corpus callosum were extracted by means of whole-brain tractography, and their mean SHD calculated. Results—The schizophrenia patients exhibited subnormal levels of SHD in the prefrontal callosal fibers when controlling for between-group differences in Fractional Anisotropy. Reduced SHD could reflect either irregularly turbulent or inhomogeneously distributed fiber trajectories in the corpus callosum. Conclusions—The results suggest that the transcallosal misconnectivity believed to be associated with schizophrenia could arise from abnormalities in fiber geometry. These abnormalities in fiber geometry could potentially be underpinned by irregularities in the normative processes of neurodevelopment.

We introduce a fibre tractography framework based on a particle filter which estimates a local geometrical model of the underlying white matter tract, formulated as a `streamline flow' using generalized helicoids. The method is not dependent on the diffusion model, and is applicable to diffusion tensor (DT) data as well as to high angular resolution reconstructions. The geometrical model allows for a robust inference of local tract geometry, which, in the context of the causal filter estimation, guides tractography through regions with partial volume effects. We validate the method on synthetic data and present results on two types in vivo data: diffusion tensors and a spherical harmonic reconstruction of the fibre orientation distribution function (fODF).

We introduce a mathematical framework for computing geometrical properties of white matter fibres directly from diffusion tensor fields. The key idea is to isolate the portion of the gradient of the tensor field corresponding to local variation in tensor orientation, and to project it onto a coordinate frame of tensor eigenvectors. The resulting eigenframe-centered representation then makes it possible to define scalar indices (or measures) that describe the local white matter geometry directly from the diffusion tensor field and its gradient, without requiring prior tractography. We derive new scalar indices of (1) fibre dispersion and (2) fibre curving, and we demonstrate them on synthetic and in vivo data. Finally, we illustrate their applicability to a group study on schizophrenia.

Many studies have observed altered neurofunctional and structural organization in the aging brain. These observations from functional neuroimaging studies show a shift in brain activity from the posterior to the anterior regions with aging (PASA model), as well as a decrease in cortical thickness, which is more pronounced in the frontal lobe followed by the parietal, occipital, and temporal lobes (retrogenesis model). However, very little work has been done using diffusion MRI (dMRI) with respect to examining the structural tissue alterations underlying these neurofunctional changes in the gray matter. Thus, for the first time, we propose to examine gray matter changes using diffusion MRI in the context of aging. In this work, we propose a novel dMRI based measure of gray matter “heterogeneity” that elucidates these functional and structural models (PASA and retrogenesis) of aging from the viewpoint of diffusion MRI. In a cohort of 85 subjects (all males, ages 15–55 years), we show very high correlation between age and “heterogeneity” (a measure of structural layout of tissue in a region-of-interest) in specific brain regions. We examine gray matter alterations by grouping brain regions into anatomical lobes as well as functional zones. Our findings from dMRI data connects the functional and structural domains and confirms the “retrogenesis” hypothesis of gray matter alterations while lending support to the neurofunctional PASA model of aging in addition to showing the preservation of paralimbic areas during healthy aging.