Tract-based analysis of magnetization transfer ratio and diffusion tensor imaging of the frontal and frontotemporal connections in schizophrenia

Abstract

Background: In the pathophysiology of schizophrenia, aberrant connectivity between brain regions may be a central feature. Diffusion tensor imaging (DTI) studies have shown altered fractional anisotropy (FA) in white brain matter in schizophrenia. Focal reductions in myelin have been suggested in patients using magnetization transfer ratio (MTR) imaging but to what extent schizophrenia may be related to changes in MTR measured along entire fiber bundles is still unknown.

Methods: DTI and MTR images were acquired with a 1.5-T scanner in 40 schizophrenia patients and compared with those of 40 healthy participants. The mean FA and mean MTR were measured along the genu of the corpus callosum and the left and right uncinate fasciculus.

Results: A higher mean MTR of 1% was found in the right uncinate fasciculus in patients compared with healthy participants. A significant negative correlation between age and mean FA in the left uncinate fasciculus was found in schizophrenia patients but not in healthy participants.

Conclusions: Decreased FA in the left uncinate fasciculus may be more prominent in patients with longer illness duration. The increased mean MTR in the right uncinate fasciculus could reflect a compensatory role for myelin in these fibers or possibly represent aberrant frontotemporal connectivity.

Fig. 1.

(a) Transverse Slice of the Model Brain (Top) and the Corresponding Slice of the Color-Coded Directional Group Map of the Main Direction of the Tensors Computed Over All Subjects (Bottom). In this color-coded directional map, the left-right direction in model space is encoded with red, the anterior-posterior direction is encoded with green, and blue encodes the inferior-superior direction. (b) ROIs used for the selection of the tracts representing the left uncinate fasciculus. Note that the ROIs are overinclusive to ensure that they comprise the specific fiber bundles for all subjects. One ROI (light blue) was positioned in the prefrontal region, and the other ROI (yellow) was positioned in the temporal region. The positioning of the ROIs for the right uncinate fasciculus was done in a similar fashion. (c) ROIs used for the selection of the genu of the corpus callosum. The first ROI (red) was placed in the left prefrontal region, and the second ROI (yellow) was placed in the right prefrontal region. A third ROI (light blue) was added at the midline anterior to the ventricles to remove spurious tracts. Computation of the average fiber for the right uncinate fasciculus (d). The spline representation (e) of the fiber bundle was divided in 2-mm regular intervals starting from the center of the spline (denoted by the red disk). (f) The radius of the average fiber denotes the variance of the cross-sectioned coordinates.

Fig. 2.

Fractional Anisotropy (FA) and Magnetization Transfer Ratio (MTR) Measurements along the Uncinate Fasciculi. (a) FA and MTR values in patients (red rectangle up) and healthy participants (blue rectangle down) with a 2-mm interval along the left uncinate fasciculus (left) and right uncinate fasciculus (right). Note that the bars represent +1 and −1 standard error of the mean. For both uncinate fasciculi, no differences in FA were found between patients and healthy participants. The MTR in the right uncinate fasciculus measured along the complete fiber was significantly higher in patients than in healthy participants. In contrast, comparison at a local level (ie, per 2-mm interval) did not reveal significant differences in MTR or FA (after Bonferroni correction for multiple comparisons with the number of comparisons set to 43). (b) Local differences in MTR between patients and healthy participants along the average group fiber of the right uncinate fasciculus (more reddish color represents higher local MTR in patients).

Fig. 3.

Correlation Between Age and Fractional Anisotropy for Patients (r = −0.36, P = .02) (Red Rectangle Up) and Healthy Participants (r = −0.15, P = .36) (Blue Rectangle Down) in the Left Uncinate Fasciculus (Left) and Right Uncinate Fasciculus (Right).