This study will use various methods to measure the activity of the motor cortex (the part of the brain that controls hand movements) in order to learn more about focal dystonia Patients with dystonia have muscle spasms that cause uncontrolled twisting and repetitive movement or abnormal postures. In focal dystonia, just one part of the body, such as the hand, neck or face, is involved.

Patients with focal hand dystonia and healthy normal volunteers 18 years of age and older may be eligible for this study. Candidates are screened with a medical history and physical examination.

Participants undergo transcranial magnetic stimulation, nerve conduction studies, and electromyography (described below) four times at four separate visits. If more information is still needed, subjects may be asked to repeat the tests once more time at a fifth visit. At the second visit, subjects receive motor training before undergoing the procedures.

Transcranial magnetic stimulation

This procedure maps brain function. A wire coil is held on the scalp, and a brief electrical current passes through the coil, creating a magnetic pulse that stimulates the brain. During the stimulation, the subject may be asked to tense certain muscles slightly or perform other simple actions to help position the coil properly. The subject may hear a click and feel a pulling sensation on the skin under the coil. In addition, the stimulation may cause a twitch in muscles of the face, arm, or leg, and the Electrodes are placed on the hands to record the twitching.

Nerve conduction studies

Nerve conduction studies measure the speed with which nerves conduct electrical impulses and the strength of the connection between the nerves and the muscle. For these studies, a metal rod placed on the skin delivers a small electrical stimulus to a nerve in an arm or leg, triggering a muscle to tighten or bend. Small wire electrodes taped to the skin record the time it takes for the nerve to move the electrical current from one part of the limb to another. The stimulus produces a stinging or tingling sensation and the muscle may twitch.

Electromyography

Electromyography (EMG) measures the electrical activity of muscles. This study uses surface EMG, in which small metal disks filled with a conductive gel are taped to the skin on the front and back of the elbows.

Motor training

For the motor training at visit 2, subjects are asked to pinch their index finger and thumb together as quickly as possible in response to the sound of a metronome every 2 seconds. There are three pinching sessions, in which subjects pinch their fingers together a total of 600 times. During visits 3 and 4, subjects are asked to perform only 5 to 10 movements.

Further Study Details: 

Expected Total Enrollment:  60

Objectives

The main objectives of this proposal are (1) to characterize motor learning abnormalities in patients with focal dystonia; (2) to show, using transcranial magnetic stimulation, that this abnormal motor learning went together with an impaired modulation by somatosensory inputs of short and long-interval paired-pulse inhibitions (sICI, lICI) and facilitations (sICF, ICF) of MEPs (ICIs and ICFs are thought to reflect activity of inhibitory and excitatory interneuron's in the primary motor cortex M1); (3) to show that abnormalities of long-term potentiation and long-term depression (LTP/LTD)-like mechanisms (tested using a paired associative stimulation (PAS) intervention), thought to play a crucial role in learning, are associated in dystonia with an abnormal modulation of ICIs and ICFs by somatosensory inputs.

Study population

30 patients with a focal upper limb dystonia and 30 healthy volunteers

Design

Subjects will complete 5 different sessions: visit 1: clinical screening, 1 hour; visit PAS session, 3 hours; visit 3: a minimum of 7 days later, motor learning session, 3 hours; visit follow-up 24 hours later, 1hour and half; visit 5, follow-up 48 hours later, 1 hour and half. During the PAS session they will receive 15 minutes of repeated paired stimulations (transcranial magnetic stimulation -TMS- and peripheral stimulation) thought to produce LTP/LTD like phenomena in M1. During the motor learning sessions they will be asked to perform, as fast as possible, a metronome-paced (0.5 Hz) pinch of their index finger and thumb. They will have 3 blocks of motor practice during the motor learning session.

Between each block of motor practice and before and after PAS, while they rest, subjects will receive paired-pulse transcranial magnetic stimulations (TMS) associated or not with peripheral nerve stimulation in order to assess interactions at M1 cortical level between somatosensory incoming volleys and intracortical inhibitory and excitatory interneuron's.

Outcome measures:

The behavioral effect of the motor training or of the PAS intervention will be assessed by measuring the mean peak acceleration (MPA) of thumb movement during the blocks of motor practice and the mean maximal peak force (MPF) between the index finger and thumb before and after the blocks of motor practice.

The activity of different sets of intracortical interneurons (short and long interval GABA related inhibitions: sICI, lICI, intracortical glutamate-related facilitation: ICF and short interval facilitation: sICF) can be tested using paired-pulse TMS paradigms. The effect of learning (or of PAS intervention) on interaction between somatosensory afferent input and intracortical processes will be assessed by comparing the amount of sICI, lICI, ICF and sICF when associated or not with a peripheral nerve stimulation (median and ulnar nerve stimulation) in a trained muscle (flexor pollicis brevis: FPB) and a non-trained muscle (abductor digiti minimi: ADM) at different times during and after the motor learning or the PAS intervention.

Genders Eligible for Study:  Both

Accepts Healthy Volunteers

Criteria

INCLUSION CRITERIA:
-Healthy volunteers (aged 18 or older) who are willing to participate.
-Patients (aged 18 and older) with an idiopathic upper limb dystonia, who are able to practice the motor learning task
EXCLUSION CRITERIA:
-Subjects with a history of neurological or psychiatric disorder, current use or a history of alcohol or drug abuse, psychiatric disorders requiring hospitalization or prolonged treatment such as substance abuser addiction, head injury with loss of consciousness, epilepsy.
-Subjects with significant hearing loss
-Subjects receiving drugs acting primarily on the central nervous system.
-Subjects who have been treated with botulinum toxin injections 3 months prior to their participation in the study.
-Subjects who are taking any medication for dystonia at the time of the study.
-Subjects who have already participated in a protocol using a motor learning task.
-Subjects who practice intensively playing any kind of music instrument
The following exclusion criteria are due to the use of transcranial magnetic stimulation:
-Subjects with cardiac pacemakers, intracardiac lines, implanted medication pumps.
-Subjects with eye, blood vessel, cochlear, or eye implants.
-Subjects with increased intracranial pressure as evaluated by clinical means.
-Subjects with metal in the cranium.
-Subjects with dental braces (but dental fillings are not a problem), metal fragments from occupational exposure or surgical clips in or near the brain.
Women in the last trimester of pregnancy will not be studied because they will likely be uncomfortable maintaining a motionless seated posture during the three hour experiment.

Maryland
      National Institute of Neurological Disorders and Stroke (NINDS), 9000 Rockville Pike,  Bethesda,  Maryland,  20892,  United States; Recruiting

Study ID Numbers:  050094; 05-N-0094
Record last reviewed:  January 24, 2005
Last Updated:  March 5, 2005
Record first received:  February 4, 2005
ClinicalTrials.gov Identifier:  NCT00102999
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08