Alterations of superficial white matter in schizophrenia and relationship to cognitive performance

Abstract

Post-mortem studies have demonstrated alterations in superficial white matter (SWM) in schizophrenia patients. Diffusion tensor imaging (DTI) can be used to assess SWM in vivo, and compare SWM fractional anisotropy (FA) in schizophrenia patients vs healthy controls. The assessment of SWM in vivo also provides an opportunity to identify novel neural correlates of cognitive performance, and potential cognitive impairment in schizophrenia patients. Forty-four patients with schizophrenia and 44 matched healthy controls underwent neuroimaging and cognitive protocols. Using an SWM mask and tract-based spatial statistics, differences in SWM-FA were examined between groups. SWM-FA clusters different between groups were then used to predict cognitive performance with multiple linear regression. The relative contribution of SWM fiber subtypes (deep white matter extensions vs U-fibers and intraregional fibers) from significantly different clusters was examined. Compared to controls, patients with schizophrenia had reduced FA in five SWM clusters: the largest a left posterior parieto-occipital cluster, followed by four clusters in the left frontal lobe. SWM-FA in the frontal lobe clusters predicted attention, working memory, and processing speed performance in healthy controls, but not in patients with schizophrenia. The majority of streamlines tracked from these clusters were restricted to U-fibers and intraregional fibers, rather than deep white matter extensions. Our analyses revealed prominent SWM disruption in patients with schizophrenia compared to controls. SWM-cognition relationships shown in healthy individuals were disrupted in patients with schizophrenia. SWM may be an important neurobiological substrate of cognitive performance and a novel cortical treatment target for cognitive deficits in schizophrenia patients.

Figure 1

The top row demonstrates the final superficial white matter (SWM) skeleton mask (yellow) on different slices from the FMRIB58_FA standard-space. The bottom row shows the SWM skeleton mask in association with different deep white-matter labels (in purple spectrum) from Johns Hopkins University Diffusion Tensor Imaging Atlas that had been deleted from the skeleton. FA, fractional anisotropy.

Figure 2

Clusters from tract-based spatial statistical analysis showing decreased fractional anisotropy (FA) in the patients with schizophrenia compared to healthy controls (p_FWE<0.05). On the FMRIB58_FA standard-space image (gray scale), the white matter skeleton is projected (green). Some of the associated cortical regions from the Harvard Oxford Cortical Atlas are also demonstrated. IFG, inferior frontal gyrus; LOC, lateral occipital cortex (superior division); MFG, middle frontal gyrus; PCC, posterior cingulate cortex; PrC, precuneus; PrG, precentral gyrus.

Figure 3

Relationships between mean fractional anisotropy values extracted from clusters (horizontal axis) and scores on specific cognitive tasks (vertical axis). Red squares and blue diamonds represent patients with schizophrenia and healthy controls, respectively.