Physiological Investigations of Movement Disorders

Brief Summary

Detailed Description

Objectives The purpose of this protocol is to improve understanding of the pathophysiology of movement disorders by performing small behavioral, electrophysiological and neuroimaging sub-studies. This will allow identifying dysfunction of the central nervous system that causes behavioral abnormalities seen in movement disorder patients. This will also help to determine potential diagnostic or therapeutic targets. Some sub-studies will require healthy volunteers. We will conduct: * Pilot Sub-study (previously labeled as Small Pilot Sub-studies) Pilot sub-studies are exploratory in nature, in order to develop enough information to generate a hypothesis. The criterion for transition to a new full protocol will be a sufficient amount of information to generate a power analysis. There are no enrollment limitations for pilot sub-studies.Small substudies to pilot investigations for larger studies, * Hypothesis-Testing Sub-study (previously labeled small number sSub-studies) is defined as a study with a specific hypothesis to be thattested that can be completed with a few subjects healthy volunteers or patients, , Hypothesis-testing sub-studies will undergo statistical and PIRC review after 6 subjects (if there is one group) or after 12 (six per arm) if two groups are studied before additional subjects are recruited. Together, the P.I. and PIRC will decide whether to continue the hypothesis sub-study with more subjects or if a new protocol is necessary. A memo requesting a review of hypothesis-testing sub-studies for possible additional enrollment will be sent to PIRC and the statistical reviewer. If the action to request accrual increase proceeds beyond PIRC to the IRB, then it needs to be submitted in the form of an amendment for prospective review/approval. * Individual patient investigations that may increase knowledge of a disease process or be helpful in patient diagnosis, * Training for investigators who do not have prior experience using electrophysiological and neuroimaging techniques, * Technical development of new experimental paradigms. This protocol includes only non-invasive techniques with minimal risk (MRI, EEG, MEG, peripheral nerve stimulation, TMS). Study population We intend to study 1200 healthy volunteers and 1000 patients with diagnoses of movement disorders. Design We will design small projects as ideas arise in our patient population that are pertinent to the theme of movement disorder pathophysiology. We will investigate patients with movement disorders or healthy volunteers in the resting state or while they perform simple motor or sensory tasks. If a small study leads to results of interest and if a larger population is necessary to reach statistical significance, 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 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 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. Behavioral measures: we will quantify measures such as reaction times to initiate movements, EMG patterns, movement kinematics (position, velocity, acceleration, curvature). We may measure autonomic data during the course of the experiment (such as blood pressure, skin conductance, and respiratory rate) which would correlate to the outcome measures.

Primary Outcomes