Reduced interhemispheric connectivity in schizophrenia-tractography based segmentation of the corpus callosum

Abstract

Background A reduction in interhemispheric connectivity is thought to contribute to the etiology of schizophrenia. Diffusion Tensor Imaging (DTI) measures the diffusion of water and can be used to describe the integrity of the corpus callosum white matter tracts, thereby providing information concerning possible interhemispheric connectivity abnormalities. Previous DTI studies in schizophrenia are inconsistent in reporting decreased Fractional Anisotropy (FA), a measure of anisotropic diffusion, within different portions of the corpus callosum. Moreover, none of these studies has investigated corpus callosum systematically, using anatomical subdivisions. Methods DTI and structural MRI scans were obtained from 32 chronic schizophrenic subjects and 42 controls. Corpus callosum cross sectional area and its probabilistic subdivisions were determined automatically from structural MRI scans using a model based deformable contour segmentation. These subdivisions employ a previously generated probabilistic subdivision atlas, based on fiber tractography and anatomical lobe subdivision. The structural scan was then co-registered with the DTI scan and the anatomical corpus callosum subdivisions were propagated to the associated FA map. Results Results revealed decreased FA within parts of the corpus interconnecting frontal regions in schizophrenia compared with controls, but no significant changes for callosal fibers interconnecting parietal and temporo-occipital brain regions. In addition, integrity of the anterior corpus was statistically significantly correlated with negative as well as positive symptoms, while posterior measures correlated with positive symptoms only. Conclusions This study provides quantitative evidence for a reduction of interhemispheric brain connectivity in schizophrenia, involving corpus callosum, and further points to frontal connections as possibly disrupted in schizophrenia.

Altered Interhemispheric and Temporal Lobe White Matter Microstructural Organization in Severe Chronic Schizophrenia

“…Not accounted for in these analyses are the few negative studies that exist. Two previous studies reported no differences in FA throughout the brain (Foong et al, 2002;Murakami et al, 2011); others have reported widespread lower FA but did not detect significant differences in the genu of the corpus callosum specifically (Agartz et al, 2001;Foong et al, 2000;Karlsgodt et al, 2008;Kubicki et al, 2008;Seal et al, 2008).…”

“…Postmortem studies have shown a genderdiagnosis effect of reduced axonal number (Highley et al, 1999a), oligodendrocyte density loss (Hof et al, 2003), and lower levels of immunoreactivity of oligodendrocyte-associated proteins in the genu of the corpus callosum (Flynn et al, 2003). Diffusion-weighted imaging has been relatively consistent in reporting reduced callosal FA in chronic schizophrenia (Douaud et al, 2007;Koch et al, 2010;Kubicki et al, 2008;Miyata et al, 2010;Mori et al, 2007b;RotarskaJagiela et al, 2008), including during remission (Koch et al, 2010) and less consistently in studies examining individuals at the first episode (Cheung et al, 2008;Gasparotti et al, 2009;Perez-Iglesias et al, 2010b;Peters et al, 2008;Price et al, 2005;Szeszko et al, 2005) or in earlier stages of illness (Davenport et al, 2010;Douaud et al, 2007;Kyriakopoulos and Frangou, 2009). Directly comparing first episode and chronic groups supports more severe changes in FA in the genu of the corpus callosum (Friedman et al, 2008;Kong et al, 2011), the left ILF (Friedman et al, 2008), and ALIC (Bora et al, 2011) in the chronic group including relative to the first episode group.…”

“…The most consistently implicated WM bundles in chronic schizophrenia samples include the genu of the corpus callosum (Kong et al, 2011;Kubicki et al, 2008;RotarskaJagiela et al, 2008;Whitford et al, 2010), the splenium of the corpus callosum (Agartz et al, 2001;Foong et al, 2000), anterior cingulate (Camchong et al, 2011;Sun et al, 2003;Wang et al, 2004), and anterior limb of the internal capsule (ALIC) (Buchsbaum et al, 1998;Sussmann et al, 2009). However, none of these studies were specifically carried out on a treatment-resistant clozapine-naive group, and clozapine has previously been reported to cause structural changes in the brain (Ho et al, 2003;Molina et al, 2005;Scheepers et al, 2001).…”

Complementary diffusion tensor imaging study of the corpus callosum in patients with first-episode and chronic schizophrenia

“…40 A study of patients with chronic schizophrenia also reported similar results: specifically, that fractional anisotropy decreased in the areas of the corpus callosum interconnecting with frontal regions and that the integrity of the anterior corpus callosum was significantly correlated with negative and positive symptoms. 41 Mitelman and colleagues 35,42,43 found that patients with schizophrenia and poor outcomes showed greater decline in fractional anisotropy and smaller corpus callosum size compared with patients with good outcomes. All these studies suggest that fractional anisotropy values may be an indicator of illness severity and outcome in patients with schizophrenia.…”

Anatomical Distance Affects Functional Connectivity in Patients With Schizophrenia and Their Siblings

“…17 Further, interhemispheric connections form a major portion of the functional connectivity in the resting brain 18 ; aberrant interhemispheric connectivity has also been prominently observed in schizophrenia. 19,20 Despite this consistency, there is a significant heterogeneity among patients in both the degree and the distribution of dysconnectivity. So far, it is unclear whether common mechanistic factors underlie the distributed pattern of dysconnectivity observed in patients.…”