Predicting inter-hemispheric transfer time from the diffusion properties of the corpus callosum in healthy individuals and schizophrenia patients: A combined ERP and DTI study

Background: Several theories of schizophrenia have emphasized the role of aberrant neural timing in the etiology of the disease, possibly as a consequence of conduction delays caused by structural damage to the white-matter fasciculi. Consistent with this theory, increased inter-hemispheric transmission times (IHTTs) to unilaterally-presented visual stimuli have been reported in patients with schizophrenia. The present study investigated whether or not these IHTT abnormalities could be underpinned by structural damage to the visual fibers of the corpus callosum. Methods: Thirty three schizophrenia patients and 22 matched controls underwent Event Related Potential (ERP) recording, and a subset of 19 patients and 16 controls also underwent 3 T Diffusion-Tensor Imaging (DTI). Unilateral visual stimuli (squares, 2 x 2 degrees) were presented 6 degrees lateral to either side of a central fixation point IHTTs (ipsilateral minus contralateral latencies) were calculated for the P1 and N1 components at parietal-occipital sites in current source density-transformed ERPs. The visual fibers of the corpus callosum were extracted with streamline tractography and the diffusion metrics of Fractional Anisotropy (FA) and Mode calculated. Results: While both subject groups exhibited highly significant IHTTs across a range of posterior electrode pairs, and significantly shorter IHTTs from left-to-right hemisphere than vice versa, no significant groupwise differences in IHTT were observed. However, participants' IHTTs were linearly related to their FA and Mode, with longer IHTTs being associated with lower FA and more prolate diffusion ellipsoids. Conclusions: These results suggest that IHTTs are estimable from DTI measures of white matter integrity. In light of the range of diffusion abnormalities that have been reported in patients with schizophrenia, particularly in frontal fasciculi, these results support the conjecture that schizophrenia is associated with abnormalities in neural timing. (C) 2010 Elsevier Inc. All rights reserved.