White matter hemisphere asymmetries in healthy subjects and in schizophrenia: A diffusion tensor MRI study

Clinical Neuroscience Division, Laboratory of Neuroscience, Boston VA Health Care System-Brockton Division, Department of Psychiatry, Harvard Medical School, Boston, MA 02301, USA.
NeuroImage (Impact Factor: 6.36). 10/2004; 23(1):213-23. DOI: 10.1016/j.neuroimage.2004.04.036
Source: PubMed


Hemisphere asymmetry was explored in normal healthy subjects and in patients with schizophrenia using a novel voxel-based tensor analysis applied to fractional anisotropy (FA) of the diffusion tensor. Our voxel-based approach, which requires precise spatial normalization to remove the misalignment of fiber tracts, includes generating a symmetrical group average template of the diffusion tensor by applying nonlinear elastic warping of the demons algorithm. We then normalized all 32 diffusion tensor MRIs from healthy subjects and 23 from schizophrenic subjects to the symmetrical average template. For each brain, six channels of tensor component images and one T2-weighted image were used for registration to match tensor orientation and shape between images. A statistical evaluation of white matter asymmetry was then conducted on the normalized FA images and their flipped images. In controls, we found left-higher-than-right anisotropic asymmetry in the anterior part of the corpus callosum, cingulum bundle, the optic radiation, and the superior cerebellar peduncle, and right-higher-than-left anisotropic asymmetry in the anterior limb of the internal capsule and the anterior limb's prefrontal regions, in the uncinate fasciculus, and in the superior longitudinal fasciculus. In patients, the asymmetry was lower, although still present, in the cingulum bundle and the anterior corpus callosum, and not found in the anterior limb of the internal capsule, the uncinate fasciculus, and the superior cerebellar peduncle compared to healthy subjects. These findings of anisotropic asymmetry pattern differences between healthy controls and patients with schizophrenia are likely related to neurodevelopmental abnormalities in schizophrenia.

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Available from: Carl-Fredrik Westin
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    • "More recently, a research interest in WM fibre tracts subserving anatomical connections between distinct brain regions and its lateralized manifestation in schizophrenia is emerging (Kubicki M et al. 2007), coinciding with the recent advent of structural DTI technique. Convergent evidence has shown a reduced leftward asymmetry in particular WM tracts, including the anterior cingulum (Park HJ et al. 2004; Wang F et al. 2004), the uncinate fasciculus (Kubicki M et al. 2002; Ribolsi M et al. 2009; Miyata J et al. 2012), the inferior occipito-frontal fasciculi (Miyata J et al. 2012), and the superior occipito-frontal fasciculi (Kunimatsu N et al. 2008; Carletti F et al. 2012). In one recent meta-analysis of DTI studies in hemispheric asymmetries of various brain regions as well as WM tracts (Ribolsi M et al. 2009; Oertel- Knochel V and DE Linden 2011; Miyata J et al. 2012; Ribolsi M et al. 2014) and impaired structural connectivity in schizophrenia (Ellison-Wright I and E Bullmore 2009; Stephan KE et al. 2009; Pettersson-Yeo W et al. 2011; Zalesky A et al. 2011; Kubicki M and ME Shenton 2014), determining the status of broader structural network asymmetries between the hemispheres may lead to a better understanding of the underlying nature of altered laterality and potentially help to elucidate the etiology of the disorder. "
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    ABSTRACT: Despite convergent evidence indicating a variety of regional abnormalities of hemispheric asymmetry in schizophrenia, patterns of wider neural network asymmetry remain to be determined. In this study,we investigated alterations in hemispheric white matter topology in schizophrenia and their association with clinical manifestations of the illness.Weighted hemispheric brain anatomical networks were constructed for each of 116 right-handed patients with schizophrenia and 66 matched healthy participants. Graph theoretical approaches were then employed to estimate the hemispheric topological properties.We found that although small-world properties were preserved in the hemispheric network, a significant hemispheric-independent deficit of global integration was found in schizophrenia. Furthermore, a significant group-by-hemisphere interaction was revealed in the characteristic path length and global efficiency, attributing to significantly reduced hemispheric asymmetry of global integration in patients compared with healthy controls. Specifically, we found reduced asymmetric nodal efficiency in several frontal regions and the hippocampus. Finally, the abnormal hemispheric asymmetry of brain anatomical network topology was associated with clinical features (duration of illness and psychotic psychopathology) in patients. Our findings provide new insights into lateralized nature of hemispheric dysconnectivity and highlight the potential for using brain network measures of hemispheric asymmetry as neural biomarkers for schizophrenia and its clinical features.
    Full-text · Article · Oct 2015 · Cerebral Cortex
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    • "In that context, WM asymmetries have been observed, mainly focusing on the arcuate fasciculus because of its relationship to hemispheric specialization of language [e.g., Buchel et al., 2004; Catani et al., 2007; Nucifora et al., 2005; Rodrigo et al., 2007; Takao et al., 2011; Thiebaut de Schotten et al., 2011; Vernooij et al., 2007]. Other DTI studies have explored fractional anisotropy asymmetry in the cingulum [e.g., Gong et al., 2005; Kubicki et al., 2003; Takao et al., 2011], corticospinal tract [e.g., Park et al., 2004; Westerhausen et al., 2007], and uncinate fasciculus [Kubicki et al., 2002]. Our understanding of structural asymmetries is still largely limited to the level of individual structures. "
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    ABSTRACT: The study on structural brain asymmetries in healthy individuals plays an important role in our understanding of the factors that modulate cognitive specialization in the brain. Here, we used fiber tractography to reconstruct the left and right hemispheric networks of a large cohort of 346 healthy participants (20–86 years) and performed a graph theoretical analysis to investigate this brain laterality from a network perspective. Findings revealed that the left hemisphere is significantly more “efficient” than the right hemisphere, whereas the right hemisphere showed higher values of “betweenness centrality” and “small-worldness.” In particular, left-hemispheric networks displayed increased nodal efficiency in brain regions related to language and motor actions, whereas the right hemisphere showed an increase in nodal efficiency in brain regions involved in memory and visuospatial attention. In addition, we found that hemispheric networks decrease in efficiency with age. Finally, we observed significant gender differences in measures of global connectivity. By analyzing the structural hemispheric brain networks, we have provided new insights into understanding the neuroanatomical basis of lateralized brain functions. Hum Brain Mapp, 2014. © 2014 Wiley Periodicals, Inc.
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    • "For instance, the normal leftward asymmetry of the arcuate fasciculus [16], [17] is disturbed in left, but not right, TLE [4], [15], [18]. In contrast, the uncinate fasciculus has a normal rightward asymmetry with higher FA and more fibers on the right [19], [20], creating the possibility of higher WM risk in those tracts specifically bearing the burden of seizure dispersion (i.e., the uncinate [21]). "
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