An FMRI study of frontostriatal circuits during the inhibition of eye blinking in persons with Tourette syndrome

Abstract

Objective: The authors sought to study activity in neural circuits that subserve the inhibition of a semi-involuntary motor behavior, eye blinking, in children and adults with Tourette syndrome and in healthy comparison subjects.

Method: Functional magnetic resonance imaging was used to scan 120 participants (51 with Tourette syndrome and 69 comparison subjects) as they either blinked normally or successfully inhibited eye blinking. The authors compared the blood-oxygen-level dependent signal during these two conditions across the Tourette and comparison groups.

Results: Relative to comparison subjects, patients with Tourette syndrome activated more strongly the frontal cortex and striatum during eye blink inhibition. Activation increased more with age in the dorsolateral and inferolateral prefrontal cortex and caudate nucleus in the Tourette group relative to comparison subjects. In addition, the Tourette group more strongly activated the middle frontal gyrus, dorsal anterior cingulate, and temporal cortices. The severity of tic symptoms in the Tourette group correlated inversely with activation in the putamen and inferolateral prefrontal cortex.

Conclusions: Frontostriatal activity is increased in persons with Tourette syndrome during the inhibition of eye blinks. Activation of frontostriatal circuits in this population may help to maintain regulatory control over semi-involuntary behaviors, whether these are tics or eye blinks.

FIGURE 1. Brain Activation During the Inhibition of Eye Blinks in Tourette Syndrome and Healthy Comparison Subjects a

^aImages are axial slices positioned “superiorly to inferiorly” (top to bottom) in radiological convention (the left side of the image represents the right side of the brain). Activation maps were generated using the general linear model in which fMRI signal change during the inhibition of eye blinking was the dependent variable, diagnosis was the independent variable, and age and sex were covariates. The model included a diagnosis-by-age interaction (p < 0.05, cluster size=25, a conjoint requirement that yielded a significance threshold of p < 0.000005). For columns A–F, increases in signal during the suppression of eye blinks are coded in red to yellow, and decreases are coded in blue to purple. In column G, greater activation in the Tourette syndrome group relative to comparison subjects is coded in red to yellow. Column I depicts the general linear model correlating signal change with the severity of tic symptoms in the Tourette group, while covarying for age and sex (p < 0.05, cluster size=25). Positive correlations are shown in red to yellow, and inverse correlations are in blue to purple. Activations in each group did not correlate significantly with motion indices. DACC=dorsal anterior cingulate cortex; STG=superior temporal gyrus; DLPFC=dorsolateral prefrontal cortex; ILPFC=inferolateral prefrontal cortex; SFG=superior frontal gyrus; MFG=middle frontal gyrus; IFG=inferior frontal gyrus; MTG=middle temporal gyrus; Pu=putamen; PCC=posterior cingulate cortex; ACC=anterior cingulate cortex.

FIGURE 2. Regions of Age-Specific Differences in Activation Between Tourette Syndrome and Healthy Comparison Subjects

^a Activation increased with age in persons with Tourette syndrome, declined in the healthy comparison subjects. Correlations of activation with age in the Tourette group (r=0.30, p=0.03) and comparison group (r=−0.22, p=0.07) were compared through Fisher z transformation (z=2.81), with the positive z score indicating a significantly larger correlation coefficient in the Tourette group relative to the comparison subjects (p=0.005). ^b Activation increased with age in persons with Tourette syndrome, declined in the healthy comparison subjects. Correlations of activation with age in the Tourette group (r=0.37, p=0.008) and comparison group (r=−0.17, p=0.16) were compared through Fisher z transformation (z=2.92), with the positive z score indicating a significantly larger correlation coefficient in the Tourette group relative to the comparison subjects (p=0.003). ^c Activation increased with age in persons with Tourette syndrome more than in the healthy comparison subjects. Correlations of activation with age in the Tourette group (r=0.34, p=0.01) and comparison group (r=0.20, p=0.09) were compared through Fisher z transformation (z=2.96), with the positive z score indicating a significantly larger correlation coefficient in the Tourette group relative to the comparison subjects (p=0.003). ^d Activation increased with age in persons with Tourette syndrome, declined in the healthy comparison subjects. Correlations of activation with age in the Tourette group (r=0.51, p < 0.0001) and comparison group (r=−0.24, p=0.04) were compared through Fisher z transformation (z=4.25), with the positive z score indicating a significantly larger correlation coefficient in the Tourette group relative to the comparison subjects (p < 0.0001).