Connectivity-enhanced diffusion analysis reveals white matter density disruptions in first episode and chronic schizophrenia
Reduced fractional anisotropy (FA) is a well-established correlate of schizophrenia, but it remains unclear whether these tensor-based differences are the result of axon damage and/or organizational changes and whether the changes are progressive in the adult course of illness. Diffusion MRI data we...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2018-01-01
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| Series: | NeuroImage: Clinical |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2213158218300494 |
| _version_ | 1819092935376896000 |
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| author | Rachael G. Grazioplene Carrie E. Bearden Kenneth L. Subotnik Joseph Ventura Kristen Haut Keith H. Nuechterlein Tyrone D. Cannon |
| author_facet | Rachael G. Grazioplene Carrie E. Bearden Kenneth L. Subotnik Joseph Ventura Kristen Haut Keith H. Nuechterlein Tyrone D. Cannon |
| author_sort | Rachael G. Grazioplene |
| collection | DOAJ |
| description | Reduced fractional anisotropy (FA) is a well-established correlate of schizophrenia, but it remains unclear whether these tensor-based differences are the result of axon damage and/or organizational changes and whether the changes are progressive in the adult course of illness. Diffusion MRI data were collected in 81 schizophrenia patients (54 first episode and 27 chronic) and 64 controls. Analysis of FA was combined with “fixel-based” analysis, the latter of which leverages connectivity and crossing-fiber information to assess both fiber bundle density and organizational complexity (i.e., presence and magnitude of off-axis diffusion signal). Compared with controls, patients with schizophrenia displayed clusters of significantly lower FA in the bilateral frontal lobes, right dorsal centrum semiovale, and the left anterior limb of the internal capsule. All FA-based group differences overlapped substantially with regions containing complex fiber architecture. FA within these clusters was positively correlated with principal axis fiber density, but inversely correlated with both secondary/tertiary axis fiber density and voxel-wise fiber complexity. Crossing fiber complexity had the strongest (inverse) association with FA (r = −0.82). When crossing fiber structure was modeled in the MRtrix fixel-based analysis pipeline, patients exhibited significantly lower fiber density compared to controls in the dorsal and posterior corpus callosum (central, postcentral, and forceps major). Findings of lower FA in patients with schizophrenia likely reflect two inversely related signals: reduced density of principal axis fiber tracts and increased off-axis diffusion sources. Whereas the former confirms at least some regions where myelin and or/axon count are lower in schizophrenia, the latter indicates that the FA signal from principal axis fiber coherence is broadly contaminated by macrostructural complexity, and therefore does not necessarily reflect microstructural group differences. These results underline the need to move beyond tensor-based models in favor of acquisition and analysis techniques that can help disambiguate different sources of white matter disruptions associated with schizophrenia. Keywords: Schizophrenia, Diffusion imaging, DWI, DTI, First episode, Chronic, White matter, Fiber density, Fiber organization |
| first_indexed | 2024-12-21T23:03:31Z |
| format | Article |
| id | doaj.art-4a0790a097604daca402075abf09f1ad |
| institution | Directory Open Access Journal |
| issn | 2213-1582 |
| language | English |
| last_indexed | 2024-12-21T23:03:31Z |
| publishDate | 2018-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | NeuroImage: Clinical |
| spelling | doaj.art-4a0790a097604daca402075abf09f1ad2022-12-21T18:47:13ZengElsevierNeuroImage: Clinical2213-15822018-01-0118608616Connectivity-enhanced diffusion analysis reveals white matter density disruptions in first episode and chronic schizophreniaRachael G. Grazioplene0Carrie E. Bearden1Kenneth L. Subotnik2Joseph Ventura3Kristen Haut4Keith H. Nuechterlein5Tyrone D. Cannon6Yale University, USA; Corresponding author at: 2 Hillhouse Avenue, Department of Psychology, New Haven, CT 06520, USA.University of California Los Angeles, USAUniversity of California Los Angeles, USAUniversity of California Los Angeles, USARush University, USAUniversity of California Los Angeles, USAYale University, USAReduced fractional anisotropy (FA) is a well-established correlate of schizophrenia, but it remains unclear whether these tensor-based differences are the result of axon damage and/or organizational changes and whether the changes are progressive in the adult course of illness. Diffusion MRI data were collected in 81 schizophrenia patients (54 first episode and 27 chronic) and 64 controls. Analysis of FA was combined with “fixel-based” analysis, the latter of which leverages connectivity and crossing-fiber information to assess both fiber bundle density and organizational complexity (i.e., presence and magnitude of off-axis diffusion signal). Compared with controls, patients with schizophrenia displayed clusters of significantly lower FA in the bilateral frontal lobes, right dorsal centrum semiovale, and the left anterior limb of the internal capsule. All FA-based group differences overlapped substantially with regions containing complex fiber architecture. FA within these clusters was positively correlated with principal axis fiber density, but inversely correlated with both secondary/tertiary axis fiber density and voxel-wise fiber complexity. Crossing fiber complexity had the strongest (inverse) association with FA (r = −0.82). When crossing fiber structure was modeled in the MRtrix fixel-based analysis pipeline, patients exhibited significantly lower fiber density compared to controls in the dorsal and posterior corpus callosum (central, postcentral, and forceps major). Findings of lower FA in patients with schizophrenia likely reflect two inversely related signals: reduced density of principal axis fiber tracts and increased off-axis diffusion sources. Whereas the former confirms at least some regions where myelin and or/axon count are lower in schizophrenia, the latter indicates that the FA signal from principal axis fiber coherence is broadly contaminated by macrostructural complexity, and therefore does not necessarily reflect microstructural group differences. These results underline the need to move beyond tensor-based models in favor of acquisition and analysis techniques that can help disambiguate different sources of white matter disruptions associated with schizophrenia. Keywords: Schizophrenia, Diffusion imaging, DWI, DTI, First episode, Chronic, White matter, Fiber density, Fiber organizationhttp://www.sciencedirect.com/science/article/pii/S2213158218300494 |
| spellingShingle | Rachael G. Grazioplene Carrie E. Bearden Kenneth L. Subotnik Joseph Ventura Kristen Haut Keith H. Nuechterlein Tyrone D. Cannon Connectivity-enhanced diffusion analysis reveals white matter density disruptions in first episode and chronic schizophrenia NeuroImage: Clinical |
| title | Connectivity-enhanced diffusion analysis reveals white matter density disruptions in first episode and chronic schizophrenia |
| title_full | Connectivity-enhanced diffusion analysis reveals white matter density disruptions in first episode and chronic schizophrenia |
| title_fullStr | Connectivity-enhanced diffusion analysis reveals white matter density disruptions in first episode and chronic schizophrenia |
| title_full_unstemmed | Connectivity-enhanced diffusion analysis reveals white matter density disruptions in first episode and chronic schizophrenia |
| title_short | Connectivity-enhanced diffusion analysis reveals white matter density disruptions in first episode and chronic schizophrenia |
| title_sort | connectivity enhanced diffusion analysis reveals white matter density disruptions in first episode and chronic schizophrenia |
| url | http://www.sciencedirect.com/science/article/pii/S2213158218300494 |
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