Evidence of frontotemporal structural hypoconnectivity in social anxiety disorder: A quantitative fiber tractography study

Abstract

Investigation of the brain's white matter fiber tracts in social anxiety disorder (SAD) may provide insight into the underlying pathophysiology. Because models of pathological anxiety posit altered frontolimbic interactions, the uncinate fasciculus (UF) connecting (orbito-) frontal and temporal areas including the amygdala is of particular interest. Microstructural alterations in parts of the UF have been reported previously, whereas examination of the UF as discrete fiber tract with regard to more large-scale properties is still lacking. Diffusion tensor imaging was applied in 25 patients with generalized SAD and 25 healthy control subjects matched by age and gender. By means of fiber tractography, the UF was reconstructed for each participant. The inferior fronto-occipital fasciculus (IFOF), originating from the frontal cortex similarly to the UF, was additionally included as control tract. Volume and fractional anisotropy (FA) were compared between the groups for both tracts. Volume of left and right UF was reduced in patients with SAD, reaching statistical significance for the left UF. Bilateral IFOF volume was not different between groups. A similar pattern was observed for FA. Reduced volume of the left UF in SAD fits well into pathophysiological models of anxiety, as it suggests deficient structural connectivity between higher-level control areas in the orbitofrontal cortex and more basal limbic areas like the amygdala. The results point to a specific role of the left UF with regard to altered white matter volume in SAD. However, results should be replicated and functional correlates of altered UF volume be determined in future studies.

Figure 1

The uncinate fasciculus (red) and the inferior fronto‐occipital fasciculus (yellow): Example of their relative locations, shown for one subject, lateral view onto the left hemisphere. [Color figure can be viewed in the online issue, which is available at wileyonlinelibrary.com.]

Figure 2

Tracking procedure and examples. A. Tracking of the uncinate fasciculus (UF): Placement of ROIs within one coronal slice (left) and localization of this slice in a lateral view (right) are shown. For illustration purposes, six examples of the left UF are shown in red. B. Tracking of the inferior fronto‐occipital fasciculus (IFOF): Placement of ROIs within two different coronal slices (left) and respective localization of these slices in a lateral view (right) are shown. For illustration purposes, three examples of the left IFOF are shown in yellow. [Color figure can be viewed in the online issue, which is available at wileyonlinelibrary.com.]

Figure 3

Volume of the reconstructed fiber tracts in patients with social anxiety disorder and healthy subjects. Mean (bars) and standard deviation (error bars) of absolute volume values are shown for each tract and group; SAD: social anxiety disorder. ^bAccording to a t‐test contrasting relative volume values (ratio of tract volume and global WM volume). [Color figure can be viewed in the online issue, which is available at wileyonlinelibrary.com.]