Combined White Matter Imaging Suggests Myelination Defects in Visual Processing Regions in Schizophrenia

Diverse pathological changes occur in the white matter (WM) of patients with schizophrenia. Various microstructural alterations including a reduction in axonal number or diameter, reduced myelination, or poor coherence of fibers could account for these changes. Abnormal integrity of macromolecules such as myelin ('dysmyelination') can be studied by applying multiple modalities of WM imaging such as diffusion tensor imaging (DTI) and magnetization transfer imaging (MTI) in parallel. Using ultra-high field (7 Tesla) MTI in 17 clinically stable patients with schizophrenia and 20 controls, we evaluated the voxelwise distribution of macromolecular WM abnormalities. Patients had a significant reduction in magnetization transfer ratio (MTR) in WM adjacent to visual processing regions and inferior temporal cortex (Cohen's d = 1.54). Among the regions showing MTR reduction, a concurrent reduction in fractional anisotropy (FA) occurs proximal to the lingual gyrus. Multiple regression analysis revealed that the degree of FA reduction in the putatively 'dysmyelinated' regions in patients predicted impaired processing speed (PS; beta = 0.74; P = 0.003), a core cognitive dysfunction in schizophrenia. In controls, MTR/FA in the occipito-temporal regions were not associated with PS. Our findings suggest that dysmyelination in visual processing regions is present in patients with schizophrenia with greatest cognitive and functional impairment. Combined DTI/MTI deficits in the occipito-temporal region may be an important variable when considering potential treatment targets for improving cognitive function in schizophrenia.