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Subtle white matter alterations in schizophrenia identified with a new measure of fiber density.

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.

SUBMITTER: Stampfli P

PROVIDER: S-EPMC6420505 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature

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Subtle white matter alterations in schizophrenia identified with a new measure of fiber density.

Stämpfli Philipp P Sommer Stefan S Manoliu Andrei A Burrer Achim A Schmidt André A Herdener Marcus M Seifritz Erich E Kaiser Stefan S Kirschner Matthias M

Scientific reports 20190315 1

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 coul ...[more]

PMID: 30874571

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Project description:Remote neurodegenerative changes in supraspinal white matter (WM) can manifest after central lesions such as spinal cord injury (SCI). The majority of diffusion tensor imaging (DTI) studies use traditional metrics such as fractional anisotropy (FA) and mean diffusivity (MD) to investigate microstructural changes in cerebral WM after SCI. However, interpretation of FA readouts is often challenged by inherent limitations of the tensor model. Recent developments in novel diffusion markers, such as fiber density (FD), allows more accurate depictions of WM pathways and has shown more reliable quantification of WM alterations compared to FA in recent studies of neurological diseases. This study investigated if FD provides useful characterization of supraspinal WM integrity after SCI in addition to the traditional DTI readouts. FA, MD, and FD maps were derived from diffusion datasets of 20 patients with chronic SCI and compared with 19 healthy controls (HC). Group differences were investigated across whole brain WM using tract-based spatial statistics and averaged diffusion values of the corticospinal tract (CST) and thalamic radiation (TR) were extracted for comparisons between HC and SCI subgroups. We also related diffusion readouts of the CST and TR with clinical scores of sensorimotor function. To investigate which diffusion markers of the CST and TR delineate HC and patients with SCI a receiver operating characteristic (ROC) analysis was performed. Overall, patients with an SCI showed decreased FA of the TR and CST. ROC analysis differentiated HC and SCI based on diffusion markers of large WM tracts including FD of the TR. Furthermore, patients' motor function was positively correlated with greater microstructural integrity of the CST. While FD showed the strongest correlation, motor function was also associated with FA and MD of the CST. In summary, microstructural changes of supraspinal WM in patients with SCI can be detected using FD as a complementary marker to traditional DTI readouts and correlates with their clinical characteristics. Future DTI studies may benefit from utilizing this novel marker to investigate complex large WM tracts in patient cohorts with varying presentations of SCI or neurodegenerative diseases.

Project description:Diffusion tensor imaging (DTI) studies of human brain development have consistently shown widespread, but nonlinear increases in white matter anisotropy through childhood, adolescence, and into adulthood. However, despite its sensitivity to changes in tissue microstructure, DTI lacks the specificity to disentangle distinct microstructural features of white and gray matter. Neurite orientation dispersion and density imaging (NODDI) is a recently proposed multi-compartment biophysical model of brain microstructure that can estimate non-collinear properties of white matter, such as neurite orientation dispersion index (ODI) and neurite density index (NDI). In this study, we apply NODDI to 66 healthy controls aged 7-63 years to investigate changes of ODI and NDI with brain maturation, with comparison to standard DTI metrics. Using both region-of-interest and voxel-wise analyses, we find that NDI exhibits striking increases over the studied age range following a logarithmic growth pattern, while ODI rises following an exponential growth pattern. This novel finding is consistent with well-established age-related changes of FA over the lifespan that show growth during childhood and adolescence, plateau during early adulthood, and accelerating decay after the fourth decade of life. Our results suggest that the rise of FA during the first two decades of life is dominated by increasing NDI, while the fall in FA after the fourth decade is driven by the exponential rise of ODI that overcomes the slower increases of NDI. Using partial least squares regression, we further demonstrate that NODDI better predicts chronological age than DTI. Finally, we show excellent test-retest reliability of NODDI metrics, with coefficients of variation below 5% in all measured regions of interest. Our results support the conclusion that NODDI reveals biologically specific characteristics of brain development that are more closely linked to the microstructural features of white matter than are the empirical metrics provided by DTI.

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Subtle white matter alterations in schizophrenia identified with a new measure of fiber density.

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Subtle white matter alterations in schizophrenia identified with a new measure of fiber density.

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