Abstract
Altered cerebral connectivity is one of the core pathophysiological mechanism underlying the development and progression of information-processing deficits in schizophrenia. To date, most diffusion tensor imaging (DTI) studies used fractional anisotropy (FA) to investigate disrupted white matter connections. However, a quantitative interpretation of FA changes is often impeded by the inherent limitations of the underlying tensor model. A more fine-grained measure of white matter alterations could be achieved by measuring fiber density (FD) - a novel non-tensor-derived diffusion marker. This study investigates, for the first time, FD alterations in schizophrenia patients. FD and FA maps were derived from diffusion data of 25 healthy controls (HC) and 21 patients with schizophrenia (SZ). Using tract-based spatial statistics (TBSS), group differences in FD and FA were investigated across the entire white matter. Furthermore, we performed a region of interest (ROI) analysis of frontal fasciculi to detect potential correlations between FD and positive symptoms. As a result, whole brain TBSS analysis revealed reduced FD in SZ patients compared to HC in several white matter tracts including the left and right thalamic radiation (TR), superior longitudinal fasciculus (SLF), corpus callosum (CC), and corticospinal tract (CST). In contrast, there were no significant FA differences between groups. Further, FD values in the TR were negatively correlated with the severity of positive symptoms and medication dose in SZ patients. In summary, a novel diffusion-weighted data analysis approach enabled us to identify widespread FD changes in SZ patients with most prominent white matter alterations in the frontal and subcortical regions. Our findings suggest that the new FD measure may be more sensitive to subtle changes in the white matter microstructure compared to FA, particularly in the given population. Therefore, investigating FD may be a promising approach to detect subtle changes in the white matter microstructure of altered connectivity in schizophrenia.
Highlights
In the last decades, advanced magnetic resonance imaging (MRI) techniques have started to shed light on the complex brain abnormalities observed across all stages of schizophrenia[1,2,3]
Based on previous findings[13,14], we investigated the relation between fiber density (FD) changes in the frontal fasciculi and positive psychotic symptoms to explore the association between microstructural changes and symptom expression
With a more liberal threshold of p < 0.1, fractional anisotropy (FA) difference between chronic SZ patients and healthy controls (HC) were detectable in the similar brain regions of our FD analysis
Summary
In the last decades, advanced magnetic resonance imaging (MRI) techniques have started to shed light on the complex brain abnormalities observed across all stages of schizophrenia[1,2,3]. It has been shown that the tensor model and FA measures are inadequate to characterize the underlying tissue structure in regions with complex fiber geometries and multiple fiber populations[20,21,22,23,24,25]. Higher order diffusion models based on acquisition schemes with high number of diffusion directions and new reconstruction methods as the constrained spherical deconvolution technique[35] were developed These advances enable the resolution multiple fiber directions within a single voxel and improved the performance of fiber tractography significantly[36,37,38]. The FD is calculated by multiplying each streamline contribution (fiber weight) by the streamline length
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