Plasticity and Motor Cortial Excitability in Tourette’s Syndrome: Response to Therapy and Natural History

Grant Type
Clinical
Grant Year
2010-2011
Institution Location
Foreign
Institution Organization Name
University College of London UK
Investigators Name
Rothwell, John C., PhD

The tics of Tourette syndrome (TS) have a surprising variation in clinical history and response to treatment. In many cases, the tics disappear in adolescence and early adulthood. However, in others, the tics persist and although they often respond to treatment with dopamine antagonists; the effect in individual cases is notoriously difficult to predict. The aim of this proposal is to use physiological tools to probe individual differences in brain organization that might be responsible for these effects. Our current understanding of the neurobiology of TS suggests that tics arise from a combination of two factors: reduced excitability of GABAergic inhibition in striatum coupled with changes in plasticity of corticostriatal synapses. The former leads to release of unwanted movements by reducing inhibitory output of basal ganglia, whereas the latter may promote long term plastic changes in the strength of synapses that impact on the learning processes responsible for development of complex tics and behaviors. Cortico- striatal plasticity is heavily influenced by dopaminerigic projections, which may account for the clinical effect of dopaminergic antagonists in treating tics. It is difficult to study directly the corticostriatal system in awake humans. However work suggests that the postulated abnormalities in these deep circuits may also be reflected in organization of cortical circuits that are much more amenable to study. In the present project we will employ a range of newly developed non-invasive electrophysiological tests of synaptic plasticity and inhibition in motor cortex of subgroups of patients who show different characteristics of individual history and response to treatment. We hypothesize that these will provide objective biomarkers to quantify and even predict effects of treatment in individual patients. John C. Rothwell, Ph.D., Diane Ruge, M.D., Eileen Joyce, M.D. Institute of Neurology, University College, London, England Award: $74,959 Commentary: Individuals with Tourette syndrome can have a surprising range of clinical characteristics. Some patients have tics in childhood that spontaneously disappear when they reach adolescence or adulthood, whereas other patients may have tics that persist and have to be treated with medications that change levels of chemicals in the brain. Many patients respond well, but in others, treatment is extremely difficult. Our understanding of the mechanisms of how tics are generated has now reached the stage where we think that it will be possible to identify the reasons for differences between individuals. We will use a variety of approaches to record and stimulate important pathways in the brain in order to characterize differences between individual cases. This should enable us to identify the mechanisms that cause tics to disappear and predict which medications may be most effective in treating patients whose tics persist. Tourette Association of America Inc. – Research Grant Award 2010-2011