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ANA_21918_sm_SupDocument.doc80KSUPPLEMENTAL METHODS
ANA_21918_sm_SupFig1.tif4824KSUPPLEMENTARY FIGURE 1: Main Effects of Diagnosis in Surface Analyses and VPW in All Participants and in Children Only Rotational views, further abbreviations, and color coding are as in Figure 1. The statistical model included the main effect of diagnosis of TS and covaried for age, sex, OCD, ADHD, and an age-by-sex interaction. VPW images are not GRF-corrected. VPW = Volume Preserved Warping; GRF = Gaussian Random Fields; Cr = Crus. The TS group exhibits local volume reductions in the lateral cerebellar hemispheres relative to healthy controls. VPW analysis further localized the volume reductions to Crus I and lobules VI/VIIB/VIIIA. These effects are most prominent in TS children younger than 13 years of age (right).
ANA_21918_sm_SupFig2.tif4701KSUPPLEMENTARY FIGURE 2: Age and Sex Effects on Surface Morphology Effects of (a) the age-by-sex interaction in all participants, (b) the age-by-sex-by-diagnosis interaction in all participants, (c) correlations of age with surface morphology in males, and (d) correlations of age with surface morphology in females. The statistical model for the age-by-sex-by-diagnosis effect included the main effect of a diagnosis of TS and covaried for age, sex, OCD, ADHD, age-by-sex, diagnosis of TS-by-sex, and diagnosis of TS-by-age. The statistical model for the effect of age on surface morphology in (c) males and (d) females included the main effect of diagnosis of TS and covariates for OCD, ADHD, and sex. These maps are not GRF-corrected. No significant age-by-sex-by-diagnosis effects are noted in regions where age-by-sex interaction effects were noted (b), indicating that age-by-sex effects do not vary with diagnosis. Males (n = 203) demonstrate increasing surface indentation of the lateral cerebellar hemispheres with age (c), whereas females (n = 107) do not vary in surface morphology with age in this region.
ANA_21918_sm_SupFig3.tif5145KSUPPLEMENTARY FIGURE 3: Effects of Comorbid OCD and ADHD on Surface Morphology Rotational views, further abbreviations, and color coding are as in Figure 1. The statistical model was run only for TS participants and covaried for age, sex, the age-by-sex interaction, and either a diagnosis of ADHD (when investigating OCD effects) or OCD (when investigating ADHD effects). Analyses were run separately for all TS participants (top) and for TS children younger than 13 years of age. A: A diagnosis of comorbid OCD imparts local volume increases over the lateral cerebellar hemispheres relative to a diagnosis of TS without OCD. B: A diagnosis of comorbid ADHD has minimal effects on morphological features of the cerebellar surface. OCD = Obsessive-Compulsive Disorder; ADHD = Attention-Deficit/Hyperactivity Disorder.
ANA_21918_sm_SupFig4.tif3556KSUPPLEMENTARY FIGURE 4: Correlation of Symptom Severity with VPW Measures The statistical models assessing the correlations of symptom severity with VPW measures were identical to those used in the analysis of surface morphology (Fig 2). The main effects of a diagnosis of TS (Fig 1) and comorbid OCD on VPW measures are shown for comparison. The color bar indicates the color coding for P values for the correlations of symptom severity with VPW measures, with warmer colors (red and yellow) indicating increasing symptom severity scores with local increases in volume and cooler colors (purple and blue) indicating increasing symptom severity scores with local volume reductions. These images are not GRF-corrected. YGTSS scores increase with greater volume reductions in regions of the lateral cerebellar hemispheres, in the same location of volume reductions in the TS group. The severity of comorbid OCD symptoms correlated with relative volume increases in Crus I and lobules VI, VIIB, and VIIIA. YBOCS scores increased with volume expansion in the regions of Crus I as well as lobules VI, VIIB, and VIIIA, in the same location of volume increases for those with comorbid OCD.
ANA_21918_sm_SupFig5.tif4407KSUPPLEMENTARY FIGURE 5: Surface Morphology in TS Patients with Comorbid OCD Effects of (a) a diagnosis of TS in all participants, (b) a diagnosis of TS in TS patients who have comorbid OCD (n = 57) compared to healthy controls (n = 147), (c) a diagnosis of TS in TS patients without comorbid OCD (n = 106) compared to healthy controls (n = 147), and (d) correlations of YGTSS with surface morphology in TS participants who have comorbid OCD (n = 50). The statistical model for the diagnosis of TS in healthy controls compared to TS with comorbid OCD (b) and without comorbid OCD (c) included the main effect of diagnosis of TS as well as covariates for ADHD, age, sex, and the age-by-sex interaction. The statistical model for the correlation of YGTSS scores with surface morphology in TS subjects with OCD (d) included covariates for ADHD, age, sex, and the age-by-sex interaction term. These maps are not GRF-corrected. Patients with TS and comorbid OCD (b) did not differ significantly in cerebellar surface morphology compared with healthy controls, whereas surface indentation of the lateral cerebellar hemispheres was significant in those with a diagnosis of TS but without comorbid OCD (c). In TS patients with comorbid OCD, YGTSS scores did not correlate significantly with surface morphology in the lateral aspects of the cerebellar hemispheres (d).

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