Abnormal water diffusivity in corticostriatal projections in children with Tourette syndrome

Abstract

The fronto-striato-thalamic circuit has been implicated in the pathomechanism of Tourette Syndrome (TS). To study white and gray matter comprehensively, we used a novel technique called Tract-Based Spatial Statistics (TBSS) combined with voxel-based analysis (VBA) of diffusion tensor MR images in children with TS as compared to typically developing controls. These automated and unbiased methods allow analysis of cerebral white matter and gray matter regions. We compared 15 right-handed children with TS (mean age: 11.6 ± 2.5 years, 12 males) to 14 age-matched right-handed healthy controls (NC; mean age: 12.29 ± 3.2 years, 6 males). Tic severity and neurobehavioral scores were correlated with FA and ADC values in regions found abnormal by these methods. For white matter, TBSS analysis showed regions of increased ADC in the corticostriatal projection pathways including left external capsule and left and right subcallosal fasciculus pathway in TS group compared to NC group. Within the TS group, ADC for the left external capsule was negatively associated with tic severity (r= -0.586, P = 0.02). For gray matter, VBA revealed increased ADC for bilateral orbitofrontal cortex, left putamen, and left insular cortex. ADC for the right and left orbitofrontal cortex was highly correlated with internalizing problems (r = 0.665; P = 0.009, r = 0.545; P = 0.04, respectively). Altogether, this analysis revealed focal diffusion abnormalities in the corticostriatal pathway and in gray matter structures involved in the fronto-striatal circuit in TS. These diffusion abnormalities could serve as a neuroimaging marker related to tic severity and neurobehavioral abnormalities in TS subjects.

Figure 1

The abnormal corticostriatal projection tracts (red‐yellow, L‐SC: left subcallosal fasciculus, R‐SC: right subcallosal fasciculus, and EC: left external capsule) of the TS subjects with increased ADC values compared to the controls. Green: skeleton voxels. [Color figure can be viewed in the online issue, which is available at wileyonlinelibrary.com.]

Figure 2

Box plot (A) shows the differences in the ADC values for the three regions (L‐SC: left subcallosal fasciculus, R‐SC: right subcallosal fasciculus, and L‐EC: left external capsule) between the two groups (TS and controls). Scatter plot (B–D) shows the distribution of ADC values with age in all the three regions (L‐SC, L‐EC, and R‐SC, respectively) for both the groups.

Figure 3

Partial correlation plot of the ADC values form the left External Capsule (L‐EC) and Tic severity scores (r = −0.586, p = 0.028).

Figure 4

Shows the (estimated marginal mean) ADC value of cortical and subcortical gray matter structures with significant three‐way interaction between regions × side × group (F = 2.4 and p = 0.05). The follow‐up test for individual regions showed increased diffusivity in left and right orbitofrontal (p = 0.035, p = 0.025), left putamen (p = 0.014), and left insular cortex (p = 0.023) compared to the controls. ORB_FRN: orbitofrontal cortex, DOR_FRN: dorsal frontal cortex, Cingulum: anterior cingulate cortex. The error bars denote the standard error of the estimated marginal mean values.

Figure 5

The partial correlation plot between the ADC values of the left (A) (r = 0.545; p = 0.044) and right (B) (r = 0.665; p = 0.009) orbitofrontal cortex with the Internalizing problem scores with controlling for age.