The goal of this project is to understand the underlying physiological mechanisms of different involuntary movement disorders. The tools we use include clinical neurophysiological methods such as electroencephalography, electromyography, and transcranial magnetic stimulation and neuroimaging with positron emission tomography and functional magnetic resonance imaging. Currently active projects in the Section include studies of tremor and tic. New drugs are needed for treatment of essential tremor. Using tremor accelerometry and clinical tremor testing we showed that 1-Octanol, as a single dose, can be safely used (up to 64 mg/kg) and that it significantly reduces tremor in benign essential tremor. We are now planning a study using Octanol for longer periods of time. We have been approaching the physiology of tics in many different ways. After optimizing parameters for single voxel magnetic resonance spectroscopy (MRS), we started acquiring spectra from three locations in the frontal lobes and one location from basal ganglia, bilaterally, of normal volunteers and patients. Simultaneously, high-resolution anatomical images were acquired for a voxel based morphometry (VBM) study. Using BOLD fMRI, we are examining what brain regions are activated during tics and tic imitations in patients with Tourette's syndrome and chronic tic disorder. Previous studies have used neuroimaging to show brain activation during tics as well as tic suppression. By studying both the patient's natural tics as well as the patient's voluntary imitation of the tic, we hope to find what brain areas may be activated in generating the urge to tic and the automatic movement that follows. We are also using blood flow PET to try to define the anatomy for tic generation. In this situation, we are using a sleep state for baseline so that we can have a state largely free of both tics and urge to tic.