Abnormal anatomical connectivity between the amygdala and orbitofrontal cortex in conduct disorder

Abstract

Objective: Previous research suggested that structural and functional abnormalities within the amygdala and orbitofrontal cortex contribute to the pathophysiology of Conduct Disorder (CD). Here, we investigated whether the integrity of the white-matter pathways connecting these regions is abnormal and thus may represent a putative neurobiological marker for CD.

Methods: Diffusion Tensor Imaging (DTI) was used to investigate white-matter microstructural integrity in male adolescents with childhood-onset CD, compared with healthy controls matched in age, sex, intelligence, and socioeconomic status. Two approaches were employed to analyze DTI data: voxel-based morphometry of fractional anisotropy (FA), an index of white-matter integrity, and virtual dissection of white-matter pathways using tractography.

Results: Adolescents with CD displayed higher FA within the right external capsule relative to controls (T = 6.08, P<0.05, Family-Wise Error, whole-brain correction). Tractography analyses showed that FA values within the uncinate fascicle (connecting the amygdala and orbitofrontal cortex) were abnormally increased in individuals with CD relative to controls. This was in contrast with the inferior frontal-occipital fascicle, which showed no significant group differences in FA. The finding of increased FA in the uncinate fascicle remained significant when factoring out the contribution of attention-deficit/hyperactivity disorder symptoms. There were no group differences in the number of streamlines in either of these anatomical tracts.

Conclusions: These results provide evidence that CD is associated with white-matter microstructural abnormalities in the anatomical tract that connects the amygdala and orbitofrontal cortex, the uncinate fascicle. These results implicate abnormal maturation of white-matter pathways which are fundamental in the regulation of emotional behavior in CD.

Figure 1. Voxel based whole-brain Diffusion Tensor Imaging analysis.

The right external capsule was the only white matter area that emerged as significant when comparing FA maps from individuals with CD relative to age- and IQ-matched healthy controls (two-sample t test, P<0.05, corrected for the entire volume of the white-matter in the whole brain). The CD group showed increased FA values in this region relative to the healthy control group. MNI: Montreal Neurological Institute (x, y, z) coordinates. The color bar ranging from red (bottom) to yellow (top) represents T statistics.

Figure 2. Examples of reconstructions of the right Uncinate Fascicle (left panel) or the left Inferior Frontal-Occipital Fascicle (right panel) pathways in two individual subjects.

Figure 3. Plots of the fractional anisotropy (FA) values within the bilateral Uncinate Fascicle and the Inferior-Frontal-Occipital Fascicle in individuals with Conduct Disorder (CD) and healthy controls as obtained from tractography analyses.

Error bars represent the standard error of the mean.