Thalamo‐frontal white matter alterations in chronic schizophrenia

Abstract

Diffusion tensor imaging (DTI) and fiber tractography are useful tools for reconstructing white matter tracts (WMT) in the brain. Previous tractography studies have sought to segment reconstructed WMT into anatomical structures using several approaches, but quantification has been limited to extracting mean values of diffusion indices. Delineating WMT in schizophrenia is of particular interest because schizophrenia has been hypothesized to be a disorder of disrupted connectivity, especially between frontal and temporal regions of the brain. In this study, we aim to differentiate diffusion properties of thalamo-frontal pathways in schizophrenia from normal controls. We present a quantitative group comparison method, which combines the strengths of both tractography-based and voxel-based studies. Our algorithm extracts white matter pathways using whole brain tractography. Functionally relevant bundles are selected and parsed from the resulting set of tracts, using an internal capsule (IC) region of interest (ROI) as "source", and different Brodmann area (BA) ROIs as "targets". The resulting bundles are then longitudinally parameterized so that diffusion properties can be measured and compared along the WMT. Using this processing pipeline, we were able to find altered diffusion properties in male patients with chronic schizophrenia in terms of fractional anisotropy (FA) decreases and mean diffusivity (MD) increases in precise and functionally relevant locations. These findings suggest that our method can enhance the regional and functional specificity of DTI group studies, thus improving our understanding of brain function.

Investigation of Anatomical Thalamo-Cortical Connectivity and fMRI Activation in Schizophrenia

“…In this small sample, we could not detect a difference in the average FA or mean diffusivity for the tract connecting the thalamus to the LPFC (Supplementary Table S6), however, more subtle local differences in diffusion properties may exist along the tract that were not detected in the analysis of average values (Oh et al, 2009).…”

“…This is not the first study pointing to altered diffusion parameters in the thalamus or thalamocortical pathways. DTI findings supporting altered integrity of thalamocortical connectivity in schizophrenia include controversial alterations of fractional anisotropy in the anterior limb of the internal capsule (ALIC) Kubicki et al, 2005;Mamah et al, 2010;Sprooten et al, 2009;Sussmann et al, 2009;Zhang et al, 2010;Zhou et al, 2008, but see Ashtari et al, 2007;Kito et al, 2009;Kyriakopoulos et al, 2008;Szeszko et al, 2005;White et al, 2007 for negative findings in younger individuals and Beasley et al, 2009 for lack of evidence of myelin abnormalities post-mortem), of the tracts connecting to the LPFC (Kim et al, 2008;Oh et al, 2009) and altered FA (Hashimoto et al, 2009) or mean diffusivity in the thalamus itself (Agarwal et al, 2008;Rose et al, 2006;Spoletini et al, 2011). Kim et al (2007) have performed a similar DTI study, with an identical a-priori hypothesis, but found only differences in the thalamic CDR defined by connectivity to the orbitofrontal, parietal, and medial prefrontal cortices.…”

Graph theoretical analysis of structural and functional connectivity MRI in normal and pathological brain networks

“…Several regions have been demonstrated to have decreased functional or structural connectivity in associative cortices (prefrontal, temporal and parietal) and the limbic system notably [87][88][89]. Beyond these specific features of brain "dysconnectivity", very recent studies have also demonstrated a disruption of the small-world network organization in these regions as well as in the whole brain associated with this disease [90].…”

Conserved Functional Connectivity but Impaired Effective Connectivity of Thalamocortical Circuitry in Schizophrenia

“…Although some studies have found differences in measures of white matter integrity in schizophrenia (Oh et al, 2009;Rose et al, 2006), others have not (Foong et al, 2002;Steel et al, 2001). Our null finding may be a result of several factors.…”

“…Some studies have suggested that schizophrenia may be characterized by abnormal resting state connectivity (Welsh et al, 2010), structural white matter connectivity (Oh et al, 2009;Rose et al, 2006), and grey matter morphometry (Corradi-Dell'acqua et al, 2011;Ellison-Wright and Bullmore, 2010;Saze et al, 2007;Takahashi et al, 2004) measures. To better understand whether the decreased spTMS-evoked thalamic response in patients with schizophrenia may be related to such abnormalities, here we examine resting state fMRI and structural (white and grey matter) data from the same subjects who participated in the spTMS-fMRI study described above (Guller et al, 2012).…”