Cerebellar morphology in Tourette syndrome and obsessive-compulsive disorder

Abstract

Objective: Neuroanatomical and functional imaging studies have identified the cerebellum as an integral component of motor and language control. Few studies, however, have investigated the role of the cerebellum in Tourette syndrome (TS), a condition defined by the presence of semi-involuntary movements and sounds.

Methods: Magnetic resonance imaging was conducted in 163 persons with TS and 147 control participants. Multivariate linear regression models were used to explore effects on cerebellar surface morphology and underlying volumes for the main diagnosis effects of TS as well as comorbid obsessive-compulsive disorder (OCD) and attention-deficit/hyperactivity disorder. Additionally, the correlations of symptom severity with cerebellar morphology were also assessed.

Results: The TS group demonstrated reduced volumes of the cerebellar hemispheres bilaterally that derived primarily from reduced gray matter in crus I and lobules VI, VIIB, and VIIIA. These decreased regional volumes accompanied increasing tic symptom severity and motoric disinhibition as demonstrated by a finger tapping test. Males had reduced volumes of these same regions compared with females, irrespective of diagnosis. Comorbid OCD was associated with relative enlargement of these regions in proportion to the increasing severity of OCD symptoms.

Interpretation: The cerebellum is involved in the pathogenesis of TS and tic-related OCD. Baseline gender differences in cerebellar morphology may in part account for the more prevalent expression of TS in males.

FIGURE 1

Tourette syndrome (TS) effect and age-by-sex interaction effects in surface morphology and volume preserved warping (VPW). Rotational views and representative transverse slices (radiologic views, right=left) of the cerebellum are shown. Left: The statistical model included the main effect of diagnosis of TS and covaried for age, sex, obsessive-compulsive disorder (OCD), attention-deficit/hyperactivity disorder (ADHD), and an age-by-sex interaction. The color bar indicates the color coding for p values associated with the main effect of diagnosis. Warmer colors (red and yellow) indicate protrusion in surface morphology and volume expansion in VPW analyses, whereas cooler colors (purple and blue) indicate indentation in surface morphology and volume contraction in VPW analyses. The TS group exhibits local volume reductions in the lateral cerebellar hemispheres relative to healthy controls and is further localized to crus (Cr) I and lobules VI/VIIB/VIIIA on volumetric analysis. Right: The statistical model for the age-by-sex interaction included the main effect of a diagnosis of TS and covaried for age, sex, OCD, and ADHD. The color bar indicates the color coding for p values associated with significant interaction effects of age and sex (where males = 1 and females = 0 in statistical modeling), with warmer and cooler colors indicating different interaction effects on surface morphology and regional volumes. Significant age-by-sex interactions are present in the lateral cerebellar hemispheres in a territory that overlaps anatomically with that of the main effect of diagnosis. Volumetric analysis localizes this interaction effect to crus I and lobule VI. Gaussian random field (GRF)-corrected images indicate which voxels in the image survive rigorous correction for multiple comparisons. VPW images are not GRF-corrected.

FIGURE 2

Symptom severity effects on surface morphology. The main effect of diagnosis of Tourette syndrome (TS) (see Fig 1) is shown in the left-most column for comparison. The statistical model for obsessive-compulsive disorder (OCD) effects in the TS group covaried for age, sex, age by sex, and attention-deficit/hyperactivity disorder (ADHD). A diagnosis of comorbid OCD imparts local volume increases over the lateral cerebellar hemispheres relative to a diagnosis of TS without OCD. Warmer colors (red and yellow) indicate protrusion in surface morphology, and cooler colors (purple and blue) indicate indentation in surface morphology. The statistical models assessing correlations with TS symptom severity were conducted in only the TS group and covaried for age, sex, OCD, ADHD, and the age-by-sex interaction term. Yale Global Tic Severity Scale (YGTSS) scores (n = 289) correlated inversely with local volumes in regions of the lateral cerebellar hemispheres, where the local volume reductions were located in the TS group. This correlation with severity was most prominent for vocal tics, particularly in the right cerebellar hemisphere. Yale Brown Obsessive Compulsive Scale (YBOCS) scores (n = 291) correlated positively with local volumes in regions of the lateral cerebellar hemispheres where the local increases in volume were located for those who had a diagnosis of comorbid OCD. For all correlation analyses, the color bar indicates the color coding for p values associated with the symptom severity effect, with warmer colors (red and yellow) indicating increasing symptom severity scores with protruding surfaces in surface morphology images and cooler colors (purple and blue) indicating increasing symptom severity scores with indented surfaces in surface morphology images. These images are not Gaussian random field-corrected. Obs = obsession; Comp = compulsion.

FIGURE 3

Correlations of finger tapping speed with surface morphology and volume preserved warping (VPW). The main effect of a diagnosis of Tourette syndrome (TS) on surface morphology and VPW is presented in the top row for comparison (see Fig 1). The statistical model for the correlation of finger tapping speed with surface morphology was assessed in 69 control subjects and 96 TS subjects for whom this measure was available. Analysis for the control group included covariates for age, sex, and the age-by-sex interaction. Analysis for the TS group included covariates for ADHD, OCD, age, sex, and the age-by-sex interaction. The color bar indicates the color coding for p values associated with the effect of finger tapping speed, with warmer colors (red and yellow) indicating protruding surfaces in surface morphology images or local volume expansion with improved finger tapping performance, whereas cooler colors (purple and blue) indicate indented surfaces in surface morphology images or local volume contraction with greater finger tapping speed. These images are not Gaussian random field-corrected. Increasing performance of right finger tapping accompanies progressively more prominent volume reductions of the right lateral cerebellar hemisphere and less substantial volume reduction of the left lateral cerebellar hemisphere in both control and TS participants. This finding localizes to right crus (Cr) I and lobule VI, overlapping anatomic regions where a local volume reduction is present in those with a diagnosis of TS.