Corpus callosum abnormalities and their association with psychotic symptoms in patients with schizophrenia

Abstract

Background: While the neuroanatomical underpinnings of the functional brain disconnectivity observed in patients with schizophrenia (SZ) remain elusive, white matter fiber bundles of the brain are a likely candidate, given that they represent the infrastructure for long-distance neural communication.

Methods: This study investigated for diffusion abnormalities in 19 patients with chronic SZ, relative to 19 matched control subjects, across tractography-defined segments of the corpus callosum. Diffusion-weighted images were acquired with 51 noncollinear gradients on a 3T scanner (1.7 mm isotropic voxels). The corpus callosum was extracted by means of whole-brain tractography and automated fiber clustering and was parcelled into six segments on the basis of fiber trajectories. The diffusion indexes of fractional anisotropy (FA) and mode were calculated for each segment.

Results: Relative to the healthy control subjects, the SZ patients exhibited mode increases in the parietal fibers, suggesting a relative absence of crossing fibers. Schizophrenia patients also exhibited FA reductions in the frontal fibers, which were underpinned by increases in radial diffusivity, consistent with myelin abnormalities. Significant correlations were observed between patients' degree of reality distortion and their FA and radial diffusivity, such that the most severely psychotic patients were the least abnormal in terms of their frontal fiber diffusivity.

Conclusions: The SZ patients exhibited a variety of diffusion abnormalities in the corpus callosum, which were related to the severity of their psychotic symptoms. To the extent that diffusion abnormalities influence axonal transmission velocities, these results provide support for those theories that emphasize neural timing abnormalities in the etiology of schizophrenia.

Figure 1

A summary of the image processing procedures. Firstly, whole-brain tractography was performed on each subject's Diffusion-Weighted Image (Panel A), and the resultant fibers combined for all subjects. Fibers with similar shapes and spatial positions were then grouped together into one of 400 fiber-clusters (Panel B). The fiber-clusters constituting the Corpus Callosum were then identified for a randomly selected subject (Panel C), and subsequently subdivided into six segments on the basis of which cortical regions the fiber-clusters projected (Panel D). The fiber-clusters constituting each of the six Corpus segments were then automatically extracted for all subjects, and the average FA and Mode of these fiber-clusters calculated. As illustrated in Panel D, the six Corpus segments were: CC1 (red) – Frontal fibers (defined as fibers projecting anterior to the SMA), CC2 (blue) – Premotor fibers (defined as fibers projecting to the SMA or premotor areas), CC3 (green) – Sensorimotor fibers (defined as fibers projecting to the primary motor or primary sensory cortices), CC4 (pink) – Parietal fibers (defined as fibers projecting to the superior or inferior parietal lobules), CC5 (orange) – Occipital fibers (defined as fibers projecting posterior to the parieto-occipital sulcus) and CC6 (yellow) – Temporal fibers (defined as fibers projecting ventrally to the temporal cortices). The Corpus segmentations of four randomly selected subjects are displayed in Panel E.

Figure 2

Scatterplots illustrating the variations in FA (Panel A) and Mode (Panel B), between groups (SZ in red, Controls in blue), and across Corpus segments (CC1 through CC6). The black bars represent CC segment means, and the asterisks represent significant between-group differences in diffusivity.

Figure 3

Scatterplots illustrating the variations in FA (Panel A), Radial Diffusivity (Panel B) and Axial Diffusivity (Panel C) between groups (SZ in red, Controls in blue) for CC1 (frontal fibers). The black bars represent CC segment means, and the asterisks represent significant between-group differences in diffusivity.

Figure 4

Scatterplots illustrating the relationships between SZ patients' Reality Distortion score (i.e., the sum of the PANSS-Hallucinations and Delusions subscales) and their FA (Panel A) and Radial Diffusivity (Panel B) in CC1. The black lines represent the line-of-best-linear-fit for the data. The red dotted lines show the mean values of FA and Radial Diffusivity exhibited by the healthy controls.