Imaging Cognitive Motor Control in Tourette Syndrome

Grant Type
Grant Year
Institution Location
Institution Organization Name
Yale University
Investigators Name
Li, Chiang-shan Ray, MD, PhD

Tourette syndrome (TS) has long been regarded as a disorder of involuntary movement. That is, the “tics” are thought to be the result of a deficit in motor response inhibition. On the other hand, many patients with TS report a premonitory feeling or an “urge” to move prior to the generation of tics. This observation has led to some investigators to liken TS to Obsessive Compulsive Disorder (OCD) and to conceptualize shared neural processes between TS and OCD. The present study is designed to distinguish between two hypotheses: Is TS a disorder of impaired motor response inhibition or an OC spectrum disorder? By combining functional magnetic resonance imaging (fMRI) and a stop signal task, we propose to investigate the neural processes of cognitive motor control in patients with TS. In previous studies we examined the neural processes of motor response inhibition and error processing during the stop signal task. Deficits of motor response inhibition manifest as diminished activation of a dorsomedial prefrontal cortical region, while error processing engages a distinct circuit of dorsal anterior cingulate and subcortical regions. These results provided a unique platform to distinguish the two hypotheses. In our preliminary findings, we observed that patients with TS demonstrated decreased error-related activations in the thalamus, similar to that seen in patients with OCD. In this proposal, we will investigate the molecular bases of the altered error-related thalamic activation in TS patients. Specifically, we will use positron emission tomography (PET) imaging to examine whether the altered activation is related to differences in norepinephrine transporter (NET) availability in the thalamus. We will use a PET radioligand (S,S)-[11C]O-methyl reboxetine to compare NET availability in 12 TS patients and 12 demographics matched control participants. We believe that the potential results could provide information instrumental in the development of novel therapeutics for TS. Chiang-shan Ray Li, M.D., Ph.D., James Leckman, M.D., Yu-Shin Ding, Ph.D. Yale University School of Medicine, New Haven, CT Award: $75,000 (2nd Year) Commentary: Tourette syndrome is a chronic, debilitating neurological illness. The etiology of Tourette syndrome remains unclear and current treatments are only partially effective. With previous funding we showed that a part of the brain called the thalamus is affected in patients with Obsessive Compulsive Disorder as well as in patients with Tourette syndrome. In this study we will continue to examine the bases of this dysfunction in the thalamus. We anticipate that the results could provide information instrumental in the development of novel therapies for Tourette syndrome. Tourette Association of America Inc. – Research Grant Award 2010-2011