Toward a Functional Anatomy of Tourette Syndrome

Abstract & Commentary

By Claire Henchcliffe, MD, DPhil, Assistant Professor, Department of Neurology and Neuroscience, Weill Medical College, Cornell University. Dr. Henchcliffe reports that she is on the speaker's bureau for the following companies: GlaxoSmithKline, Teva, Boehringer Ingelheim, Schwarz Pharma, and Allergan.

Synopsis: Functional MRI (fMRI) measurements in unmedicated children with Tourette syndrome during cognitively difficult tasks suggest increased "direct" pathway activity in the basal ganglia, and possible compensatory mechanisms involving the subthalamic nucleus and prefrontal cortex.

Source: Baym CL, Corbett BA, Wright SB, et al. Neural correlates of tic severity and cognitive control in children with Tourette syndrome. Brain 2008;131(Pt 1):165-179.

This study addresses two critical yet poorly understood issues in Tourette syndrome (TS): the association of cognitive deficits with TS, and the nature of the neuronal networks that are disrupted in this developmental disorder. Eighteen children with TS (mean age 10.42 years, range 7-13 years, 15/18 boys), were recruited through the Tourette Syndrome Association, advertisements, referrals, and UC Davis; and were compared with 19 healthy matched volunteers (mean age 10.33 years, 11/19 boys) recruited via local schools, recreational centers, and fliers. TS diagnosis was based upon DSM-IV criteria. Of the 18 children with TS, 16 had never taken medication for the condition, 1 had taken no medication for 1 month, and 1 had withdrawn medication 40 hours prior. All children with TS scored higher on evaluation of tic severity, executive dysfunction, OCD and ADHD symptomatology, anxiety, and behavioral and social communication. In all subjects, fMRI data were acquired during response to 3 types of tasks representing aspects of cognitive control: 1) task-switching; 2) response selection (ignoring competing information); and 3) rule representation. In TS subjects, tic severity correlated with increased activation of the substantia nigra/ventral tegmental area (SN/VTA), striatum and globus pallidus pars interna (GPi), thalamus, motor cortex, nucleus accumbens, and subthalamic nucleus (STN). Moreover, during task performance, TS subjects displayed higher activation of the left prefrontal cortex compared with control subjects.


TS is a developmental disorder characterized by motor and vocal tics (the latter may be words, phrases, or more complex sentences or simply grunts or throat-clearing). However, individuals with TS typically suffer from an array of "non-motor" symptoms, including ADHD and OCD (in this study using the Conners' and CY-BOCS rating scales, 7/18 TS subjects scored in the clinical range for OCD, 1/18 for ADHD, and 2/18 for OCD/ADHD), and problems with cognitive flexibility and inhibitory control have been particularly evident. The present study builds upon evidence pointing to deficits in TS in processing in the prefrontal cortex and striatum, regions important for cognitive control. Unlike previous studies though, children were unmedicated, arguing against changes simply representing medication effects. fMRI measurements defined several important regions of increased activation correlating with tic severity (i.e., presumed associated with TS and not its comorbid conditions). 1) Increased activation of the SN/VTA (containing abundant dopaminergic neurons) fits with previous data implicating dopamine dysfunction in TS. 2) The authors suggest that heightened activation in the striatum, GPi, thalamus, and motor cortex may be linked, representing activation of the "direct" pathway, important in motor control. 3) The nucleus accumbens demonstrated increased activation in this study, which may be consistent with a role in reinforcing behavior. 4) While activation of the STN might initially seem counterintuitive, the authors hypothesize that the "hyperdirect" pathway from cortex to STN would compensate for "direct" pathway activation. In summary, despite limitations inherent to this type of neuroimaging study, these data represent an important step toward dissecting the complex neural changes occurring in TS. This is critical. Since as novel therapeutic approaches such as deep brain stimulation are now being developed for TS, it is imperative that the neural underpinnings and any cognitive comorbidities are better understood.