Muscle Contraction in Patients With Focal Hand Dystonia
| Status: | Completed |
|---|---|
| Conditions: | Neurology, Orthopedic |
| Therapuetic Areas: | Neurology, Orthopedics / Podiatry |
| Healthy: | No |
| Age Range: | 18 - Any |
| Updated: | 4/21/2016 |
| Start Date: | September 2006 |
| End Date: | May 2011 |
The Effect of Surround Inhibition During Phasic Compared to Tonic Voluntary Finger Movement in Focal Hand Dystonia
This study will examine and compare brain activity in people with focal hand dystonia (FHD)
and healthy volunteers to obtain further knowledge about the underlying cause of FHD.
Patients with dystonia have muscle spasms that cause abnormal postures while trying to
perform a movement; FHD affects the hands and fine finger movements. During fine finger
movement, the brain controls muscles in a process called surround inhibition. This process
may be impaired in people with hand dystonia, leading to uncontrolled overactivity in
muscles and impairing motor function.
Healthy volunteers and patients with FHD over 18 years of age may be eligible for this
study. Candidates are screened with a physical and neurological examination.
In a series of three experiments conducted during a single clinic visit, participants
undergo transcranial magnetic stimulation (TMS) while performing a finger movement. A wire
coil is placed on the subject's scalp. A brief electrical current is passed through the
coil, creating a magnetic pulse that travels through the scalp and skull and causes small
electrical currents in the outer part of the brain. The stimulation may cause muscle, hand
or arm twitching, or may affect movement or reflexes. During the stimulation, the subject is
asked to contract one finger.
In addition to TMS, subjects have surface electromyography. For this test, they sit in a
chair with their hands placed on a pillow on their lap. The electrical activity of three
muscles in the right hand is recorded by electrodes (small metal disks) taped to the skin
over the muscles.
and healthy volunteers to obtain further knowledge about the underlying cause of FHD.
Patients with dystonia have muscle spasms that cause abnormal postures while trying to
perform a movement; FHD affects the hands and fine finger movements. During fine finger
movement, the brain controls muscles in a process called surround inhibition. This process
may be impaired in people with hand dystonia, leading to uncontrolled overactivity in
muscles and impairing motor function.
Healthy volunteers and patients with FHD over 18 years of age may be eligible for this
study. Candidates are screened with a physical and neurological examination.
In a series of three experiments conducted during a single clinic visit, participants
undergo transcranial magnetic stimulation (TMS) while performing a finger movement. A wire
coil is placed on the subject's scalp. A brief electrical current is passed through the
coil, creating a magnetic pulse that travels through the scalp and skull and causes small
electrical currents in the outer part of the brain. The stimulation may cause muscle, hand
or arm twitching, or may affect movement or reflexes. During the stimulation, the subject is
asked to contract one finger.
In addition to TMS, subjects have surface electromyography. For this test, they sit in a
chair with their hands placed on a pillow on their lap. The electrical activity of three
muscles in the right hand is recorded by electrodes (small metal disks) taped to the skin
over the muscles.
OBJECTIVE:
In sensory systems, a neural mechanism called surround inhibition (SI) sharpens sensation by
creating an inhibitory zone around the central core of activation. This principle was
described for the visual system first, but there is evidence for similar mechanisms in the
primary motor cortex (M1) involved in movement generation and control, especially in precise
motor tasks. Dystonia is generally regarded as a motor execution abnormality due to a
dysfunction in the cortico-striato-thalamo-cortical motor loop. Using transcranial magnetic
stimulation (TMS), recent findings point to highly task-specific impairment of motor
cortical inhibition in patients with focal hand dystonia (FHD).
The goal for this research proposal is to understand the underlying physiology as it relates
to different inhibitory pathways on movement generation and control. To achieve this goal,
different modes of voluntary contractions will be examined in healthy controls and patients
with FHD with the prospect of having new options for treatment.
STUDY POPULATION:
We intend to study 100 adult patients with FHD and 100 healthy volunteers on an outpatient
basis.
DESIGN:
Participants will perform a contraction of the first dorsal interosseous muscle (FDI). At
rest, before EMG-onset (premotor), during phasic and tonic contraction single TMS pulses
(Experiment 1) or double TMS pulses (Experiment 2) will be applied over the primary motor
cortex to assess activation-induced changes in cortical excitability in the abductor
pollicis brevis muscle (APB), which is not activated. Additionally the influence of visual
feedback on short intracortical inhibition (SICI) will be tested in Experiment 3. In
Experiment 4-8 interhemispheric (IHI), ventral and dorso-lateral premotor-motor
intracortical inhibition will be assessed.
OUTCOME MEASURES:
The primary outcome measure for Experiment 1 will be the difference in MEP peak-to-peak
amplitude between all motor conditions.
The primary outcome measure for Experiment 2, 5, 6, 7 and 8 will be the difference in
normalized MEP peak-to-peak amplitude between all motor conditions in FHD patients and
healthy volunteers.
In Experiments 1 and 2, the change in MEP peak-to-peak amplitude between different force
levels (10% versus 20%) will be a second outcome parameter.
The primary outcome parameter for Experiment 3 will be change in MEP peak-to-peak between
patients and healthy volunteers during tonic contraction with and without visual feedback.
In Experiment 4, Hmax/Mmax ratio will be the primary outcome parameter.
In sensory systems, a neural mechanism called surround inhibition (SI) sharpens sensation by
creating an inhibitory zone around the central core of activation. This principle was
described for the visual system first, but there is evidence for similar mechanisms in the
primary motor cortex (M1) involved in movement generation and control, especially in precise
motor tasks. Dystonia is generally regarded as a motor execution abnormality due to a
dysfunction in the cortico-striato-thalamo-cortical motor loop. Using transcranial magnetic
stimulation (TMS), recent findings point to highly task-specific impairment of motor
cortical inhibition in patients with focal hand dystonia (FHD).
The goal for this research proposal is to understand the underlying physiology as it relates
to different inhibitory pathways on movement generation and control. To achieve this goal,
different modes of voluntary contractions will be examined in healthy controls and patients
with FHD with the prospect of having new options for treatment.
STUDY POPULATION:
We intend to study 100 adult patients with FHD and 100 healthy volunteers on an outpatient
basis.
DESIGN:
Participants will perform a contraction of the first dorsal interosseous muscle (FDI). At
rest, before EMG-onset (premotor), during phasic and tonic contraction single TMS pulses
(Experiment 1) or double TMS pulses (Experiment 2) will be applied over the primary motor
cortex to assess activation-induced changes in cortical excitability in the abductor
pollicis brevis muscle (APB), which is not activated. Additionally the influence of visual
feedback on short intracortical inhibition (SICI) will be tested in Experiment 3. In
Experiment 4-8 interhemispheric (IHI), ventral and dorso-lateral premotor-motor
intracortical inhibition will be assessed.
OUTCOME MEASURES:
The primary outcome measure for Experiment 1 will be the difference in MEP peak-to-peak
amplitude between all motor conditions.
The primary outcome measure for Experiment 2, 5, 6, 7 and 8 will be the difference in
normalized MEP peak-to-peak amplitude between all motor conditions in FHD patients and
healthy volunteers.
In Experiments 1 and 2, the change in MEP peak-to-peak amplitude between different force
levels (10% versus 20%) will be a second outcome parameter.
The primary outcome parameter for Experiment 3 will be change in MEP peak-to-peak between
patients and healthy volunteers during tonic contraction with and without visual feedback.
In Experiment 4, Hmax/Mmax ratio will be the primary outcome parameter.
- INCLUSION CRITERIA:
PATIENTS:
18 years old or older
Presence of FHD, for Experiment 5, 6, 7 and 8 the affected limb has to be the right and
dominant side
HEALTHY VOLUNTEERS:
18 years old or older
Right handedness
Absence of dystonia or other neurological disorder with any effect on the motor or sensory
systems
EXCLUSION CRITERIA:
PATIENTS AND HEALTHY VOLUNTEERS:
Concurrent significant medical, surgical, neurological or psychiatric condition
Taking the following medications: antidepressants, anxiolytics, anticonvulsants,
antipsychotics, antiparkinson, hypnotics, stimulants, and/or antihistamines
Patients- Received botulinum toxin injection within 3 months of starting the protocol
For TMS: Presence of pacemaker, implanted medical pump, metal plate or metal object in
skull or eye
History of seizure disorder
Known history of hearing loss
For MRI: Presence of pacemakers or other implanted electrical devices, brain stimulators,
dental implants, aneurysm clips, metallic prostheses (including metal pins and rods, heart
valves, and cochlear implants), permanent eyeliner, implanted delivery pumps, or shrapnel
fragments. Welders and metal workers are also at risk for injury because of possible small
metal fragments in the eye of which they may be unaware.
Pregnancy.
We found this trial at
1
site
9000 Rockville Pike
Bethesda, Maryland 20892
Bethesda, Maryland 20892
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