Mean (±SD) age and gender distribution and clinical variables for control groups and WFS group for DTI scans.

<p>Abbreviation. HC: healthy controls; T1C: diabetic controls; WFS: Wolfram Syndrome group; SD: standard deviation.</p><p>There were no differences between groups for age (p = .24) or gender (p = .28) but there was a significant. difference in duration of diabetes between T1C and WFS (p = .001).</p

Regional subcortical brain volumes by significance level.

<p>Regions were segmented in Freesurfer. Left and right volumes were averaged and are shown on the right side of the brain only. The brainstem, cerebellar gray matter and cerebellar white matter were significantly reduced in the WFS compared to controls and survived Bonferroni multiple comparison correction (in red; p<.0038). In addition, the thalamus and pallidum were also reduced in WFS compared to controls, but did not survive correction (p<.05, in yellow). Finally, the corpus callosum, hippocampus, amygdala, caudate, putamen and accumbens were not different between groups (p>.05, in purple).</p

Voxel-based morphometry (VBM) findings.

<p>Gray and white matter clusters where WFS have lower volumes than controls. (A) Gray matter clusters included right cerebellum (p = .0008), and left cerebellum (p = .0125), while (B) white matter clusters included a large cluster consisting of much of the cerebellum, brainstem, and subcortex (p<.001), and a small cluster in the parietal-occiptal cortex (p = .0239). Glass brain (all results shown collapsed on a single slice) view shown on left, and the significant cluster on an average MR overlay is shown on the right. Cross hairs are placed in the voxel with a peak t value in the cluster.</p

Volume of brainstem segments by diagnosis and age.

<p>(A) The WFS group has reduced volumes in all three brainstem segments after adjusting for intracranial volume. A repeated measures general linear model analysis found a segmental volume by diagnosis interaction (F(4,112) = 7.6, p<.001). Volume in the WFS group was significantly different from the control groups for all three segments (*), but the effect was most striking in the pons. (B) The pons appeared to be reduced in volume in almost all WFS individuals even after adjusting for intracranial volume. This figure shows the relationship between pontine volume and age. HC  =  healthy controls; T1C  =  diabetic controls; WFS  =  Wolfram group.</p

Mean (±SD) age and gender distribution and clinical variables for control groups and WFS group for MPRAGE scans.

<p>Abbreviation. HC: healthy controls; T1C: diabetic controls; WFS: Wolfram Syndrome group; SD: standard deviation.</p><p>There were no differences between groups for age (p = .23), gender (p = .51) or duration of diabetes between T1C and WFS (p = .12).</p

Mean (±SEM) DTI measures from selected brain regions and adjusted for age and gender.

<p>Abbreviation. HC: healthy controls; T1C: diabetic controls; WFS: Wolfram Syndrome group; SEM: standard error of the mean; PLIC: posterior limb of the internal capsule.</p><p>P values shown are for the main effect of group in univariate GLM analyses for each measure.</p><p>Values in <b>bold</b> survived Bonferroni correction (p<.005) for multiple comparisons.</p>a<p>different from HC group; ^bdifferent from T1C group.</p

Results from tract-based spatial statistics (TBSS) analysis.

<p>Fractional anisotropy (FA) and axial diffusivity (AD), but not radial diffusivity, were reduced in the WFS group compared to controls (healthy and diabetic control groups combined), even after multiple comparison correction. There were no significant findings in the opposite direction (WFS > controls). White matter tracts in the cerebellum, brainstem, and optic radiations were prominently affected, but changes were also noted in other areas as well. The multiple comparison corrected p values are represented in the color coding. Z  =  the Talairach coordinate for the transverse plane.</p