Physiological Investigations of Movement Disorders

Background:

* Previous studies have given researchers information on how the brain controls movement, how people learn to make fine, skilled movements, and why some people have movement disorders. However, further research is needed to learn more about the causes of most movement disorders, such as Parkinson's disease.
* By using small, specialized studies to evaluate people with movement disorders and compare them with healthy volunteers, researchers hope to learn more about the changes in the brain and possible causes of movement disorders.

Objectives:

* To better understand how the brain controls movement.
* To learn more about movement disorders.
* To train movement disorder specialists.

Eligibility:

* Individuals 18 years of age or older who have had a movement disorder diagnosed by a neurologist and are able to participate based on the specific requirements of the small study.
* Healthy volunteers 18 years of age or older.

Design:

* Participants will have a screening visit with medical history, physical examination, and questionnaire to determine eligibility. Eligible participants will give consent to participate in up to seven additional outpatient visits for study procedures. The number of sessions and the procedures needed for participation depend on specific symptoms.
* Participants must avoid drinking alcohol or caffeinated drinks (sodas, coffee, and tea) for at least 2 days (48 hours) before each session.
* Potential studies may include magnetic resonance imaging (MRI) scans, functional MRI scans, electroencephalography, magnetoencephalography, transcranial magnetic stimulation, nerve and sensory stimulation, or movement and mental tasks during any of the above procedures.
* This study does not provide treatment for movement disorders. Participants will not have to stop any treatment in order to participate.

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.

Eligibility Criteria:
* INCLUSION CRITERIA:

INCLUSION CRITERIA FOR MOVEMENT DISORDER PATIENTS:

* Patients will either have a well-defined diagnosis or be a diagnostic dilemma, depending upon the sub-study
* Age 18 or older
* Able to give informed consent
* Agree to not drink caffeine or alcohol for 48 hours before certain study sessions because both agents can modify brain activity and may confound outcome measures.

INCLUSION CRITERIA FOR HEALTHY VOLUNTEERS:

* Age 18 or older.
* Able to give informed consent.
* Agree to not drink caffeine or alcohol for 48 hours before certain study sessions because both agents may modify the activity of the brain during the study.

EXCLUSION CRITERIA:

EXCLUSION CRITERIA FOR MOVEMENT DISORDER PATIENTS:

* Have used illegal drugs within the past 6 months
* Have more than 7 alcoholic drinks a week in the case of a woman or 14 alcoholic drinks a week in the case of a man.
* Have had a brain tumor, a stroke, head trauma, epilepsy or a history of seizures.
* Have a psychotic disorder, Bipolar Disorder or a current depressive episode.
* Have another neurologic disorder than a movement disorder
* Have had a head injury where there was a loss of consciousness for more than a few seconds.

EXCLUSION CRITERIA FOR HEALTHY VOLUNTEERS:

* Have abnormal findings on a neurological examination that we will perform
* Have used illegal drugs within the past 6 months
* Have more than 7 alcoholic drinks a week in the case of a woman or 14 alcoholic drinks a week in the case of a man
* Have had a brain tumor, a stroke, head trauma, epilepsy or a history of seizures.
* Have major depression or any major mental disorders (axis I disorders)
* Have had a head injury where there was a loss of consciousness for more than a few seconds.

ADDITIONAL EXCLUSION CRITERIA FOR MOVEMENT DISORDER PATIENTS AND HEALTHY VOLUNTEERS SPECIFICALLY FOR fMRI:

We will follow the NMR Center guidelines for MR safety.

Some of the exclusions are:

* Have non-MRI compatible metal in the body, such as a cardiac pacemaker, brain stimulator, shrapnel, surgical metal, clips in the brain or on blood vessels, cochlear implants, artificial heart valves or metal fragments in the eye as these make having an MRI unsafe.
* Unable to lie flat on the back for the expected length of the experiment up to 3 hours
* Have uncontrolled movements of the head
* Have an abnormality on the brain imaging or neurologic examination not related to the diagnosis
* Uncomfortable being in a small space for the expected length of the experiment up to 3 hours
* Pregnancy

ADDITIONAL EXCLUSION CRITERIA FOR MOVEMENT DISORDER PATIENTS AND HEALTHY VOLUNTEERS SPECIFICALLY FOR TMS:

* Have metal in the eye or skull area, brain stimulator, shrapnel, surgical metal, clips in the brain, cochlear implants, metal fragments in the eye, as these make TMS unsafe. Having a cardiac pacemaker, intracardiac lines, implanted pumps or stimulators are also exclusion criteria.
* Have hearing loss.