Clinical and Physiological Studies of Tremor Syndromes

Background: Researchers have some data on how the brain controls movement and why some people have tremor. But the causes of tremor are not fully known. Researchers want to study people with tremor to learn about changes in the brain and possible causes of tremor. Objective: To better understand how the brain controls movement, learn more about tremor, and train movement disorder specialists. Eligibility: People ages 18 and older with a diagnosed tremor syndrome Healthy volunteers ages 18 and older Design: Participants will be screened with: * Medical history * Physical exam * Urine tests * Clinical rating scales * Health questions * They may have electromyography (EMG) or accelerometry. Sensors or electrodes taped to the skin measure movement. Participation lasts up to 1 year. Some participants will have a visit to examine their tremor more. They may have rating scales, EMG, and drawing and writing tests. Participants will be in 1 or more substudies. These will require up to 7 visits. Visits could include the following: * EMG with accelerometry * Small electrodes taped on the body give small electric shocks that stimulate nerves. * MRI: Participants lie on a table that slides into a cylinder that takes pictures of the body while they do simple tasks. * Small electrodes on the scalp record brain waves. * A cone with detectors on the head measures brain activity while participants do tasks. * A wire coil held on the scalp gives an electrical current that affects brain activity. * Tests for thinking, memory, smell, hearing, or vision * Electrodes on the head give a weak electrical current that affects brain activity. * Photographs or videos of movement Participant data may be shared with other researchers.

Objectives The purpose of this protocol is to study the phenotypic spectrum and the pathophysiology of tremor syndromes by performing small behavioral, electrophysiological and neuroimaging sub-studies. The protocol includes techniques with minimal risk (standard clinical evaluation, MRI, EEG, peripheral nerve stimulation, single and paired pulse TMS) and certain sub-studies may involve healthy volunteers. This protocol aims to study neurophysiological and behavioral outcomes in defined groups of patients with tremor syndromes, to inform future hypothesis-driven and confirmatory studies, which will be developed and submitted as separate protocols. For this purpose, we aim to conduct 1) pilot sub-studies, 2) individual patient investigations, 3) technical development studies. Study population We intend to enroll up to 300 patients with essential tremor and other isolated action tremor syndromes, as well as 150 healthy volunteers. Design This is a non-hypothesis driven study involving standardized phenotyping After patients and healthy volunteers complete a screening visit, patients will undergo a standardized phenotyping visit including clinical rating scales as well as electrophysiological tremorworkup. Patient and healthy controls may then be enrolled in sub-studies, and if a substudy leads to results of interest, a separate protocol will be submitted with a priori hypotheses, specific study design and power analysis adapted from the pilot or exploratory sub-studies performed in the present protocol. Outcome measures Outcome measures applied in this protocol involve methods for tremor phenotyping such as clinical rating scales and questionnaires, electrophysiological tremor studies, videotaped exam, as well as digitizing based tasks. During the sub-studies focused on the neurophysiological characterization of tremor syndromes, the following outcome measures will be applied: EMG: we will analyze tremor signals using spectral analyses, coherence analyses, and in combination with accelerometry, EEG, MEG, and TMS to explore tremor-networks. MRI: we will analyze measures such as the amplitude of the BOLD signal (fMRI); tractography between seed and target regions of interest (using DTI); morphometry of brain regions (using VBM); and different neurotransmitter levels in brain regions of interest (using MRS). EEG and MEG: we will quantify measures such as corticomuscular coherence, event- or task-related potentials, synchronization/desynchronization, and coherence between sensors or sources located close to the brain areas of interest. TMS: we will analyze measures such as MEP amplitude and central conduction time, as well as measures of cortical excitability and inhibition paradigms. Behavioral measures: we will quantify measures of voluntary movement involving tremor, reaction times to initiate movements, EMG patterns, movement kinematics (position, velocity, acceleration, curvature), eye movement. Actigraphy: We will quantify continuous recordings of motion sensors involving multiaxial accelerometers and gyroscopes. Furthermore, we may measure autonomic data during the course of experiments (such as blood pressure, skin co ductance, and respiratory rate) which would correlate to the outcome measures.