DOPAMINERGIC EFFECTS ON CORTICAL FUNCTION IN TOURETTE'S

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. In a recent function imaging study, a cognitive task involving working memory (WM) produced excessive activation of several brain regions in subjects with Tourette syndrome (TS), but the excessive activation normalized after administration of the dopamine precursor levodopa. This drug is well suited for neuroimaging studies as it is well tolerated in TS and (when given with carbidopa) essentially delivers dopamine to the brain only. The current research project aims to clarify the cognitive task components and the clinical variables that combine to produce the abnormal responses to the WM task and levodopa. Adults with TS or chronic tic disorders, and matched controls, will be studied using functional MRI and WM tasks after levodopa or saline infusion on different days. Cognitive tasks will include parametric scaling of working memory load and matched spatial and verbal working memory task. Careful characterization of subjects will allow tests of how the imaging findings are affected by clinical variable such as comorbidity (e.g., ADHD, OCD), severity, or past medication exposure. Additionally, in these or other subjects a mixed (pergolide) and D2-like-selective (pramipexole) dopamine receptor agonist, or placebo, will be given on separate scanning days with the same cognitive tasks. This will help determine the pharmacological mechanism of the levodopa effect. The significance of this research includes its potential to define a biological marker for future development or genetic studies of TS.