Super rapid transcranial magnetic stimulation (srTMS) is a method of brain stimulation that
may be able to change the electrical activity of the nerve cells of the brain. It has been
proposed and tested as a treatment for brain disorders, including Parkinson's disease.
The purpose of this study is to use a device called the magnetic stimulator to investigate
the safe limit of srTMS, such as intensity of stimulation and the number of magnetic pulses
that may lead to excessive brain stimulation.
Ten patients with Parkinson's disease-whose main problems are slowness of movement and
difficulty walking-will participate in this study. They will be asked to come to the
laboratory for one experiment. Before and after srTMS treatment, investigators will test
participants' brain function with a series of psychological tests and an EEG
(electroencephalogram). The srTMS treatment is performed by placing an insulated coil of
wire on the scalp and passing a very brief electrical current through the wire coil. The
experiment will last 2 to 4 hours.
The treatment of Parkinson's disease (PD) needs further improvement, particularly in the
areas of gait and freezing. A promising technique is repetitive transcranial magnetic
stimulation (rTMS) that, so far, has produced small effects on bradykinesia in drug free
patients in limited trials. The relevant rTMS parameters for the therapeutic effect are
unknown. Use of very high rTMS frequency (50 Hz, maximum output of the modern TMS machines,
super rapid TMS [srTMS] with circular coil design [vs. a figure eight shape]) may further
improve the therapeutic effect in people who have PD. The 50 Hz srTMS frequency proposed
here is in a range that exceeds the currently established guidelines since such high
frequencies have not been investigated. We will look for acute srTMS effects of the primary
motor cortex (M1) stimulation (60% to 100% motor threshold [MT] intensity, 0.5 seconds to 2
seconds train duration). A multi-channel electromyography (EMG) record will be visually
controlled for signs of increasing time-locked EMG activity, EMG correlates of the spread of
excitation through M1, or an increase of M1 excitability to establish the safe superrapid
transcranial magnetic stimulation (srTMS) limit. The electroencephalogram (EEG) Record,
Folstein Mini-Mental Exam, CFL and FAS Letter Production Test (words beginning with letters
'C', 'F' etc), Serial Reaction Time, Grooved Pegboard Test, and Unified PD Rating Scale
(UPDRS) will be done before and after the srTMS session to control possible srTMS side
- INCLUSION CRITERIA:
Subjects will be men and women aged 40 to 80 years with DOPA-responsive, akinetic-rigid
After obtaining the informed consent, patients will be interviewed and examined by either
the prinicipal investigator (PI) or a Brain Stimulation Unit (BSU) or an HMCS physician to
establish the diagnosis of PD and rule out any other neurologic condition.
Only patients with a Hoehn and Yahr grade of 2 to 4 while 'off' will be accepted.
Patients must be on a regimen including L-DOPA, and they must have a total dose of
medication equal to more than 300 mg of L-DOPA equivalent, including their dopamine
Any patient whose record does not contain a neurological examination from the past year
will be reexamined before enrollment.
Any significant medical or psychiatric illness (other than PD), pregnancy, history of
epilepsy, or concurrent use of tricyclic antidepressants, neuroleptic agents, or any other
licit or illicit drugs other than antiparkinsonian agents that could lower the seizure
Persons with surgically or traumatically implanted foreign bodies such as a pacemaker, or
any implanted stimulators, an implanted medication pump, a metal plate in the skull, or
metal inside the skull or eyes (other than dental appliances or fillings) that may pose a
physical hazard during magnetic stimulation will also be excluded.
Most of these exclusions also come under the category of significant medical illness.
Patients for whom participation in the study would, in the opinion of the investigators,
cause undue risk or stress for reasons such as tendency to fall, excessive fatigue,
general fatigue, general frailty, or excessive apprehensiveness will also be excluded.
A urine sample for the pregnancy test will be obtained from any women of childbearing
potential prior to the start of srTMS, on the day of the initial interview and signing of
the consent form. Pregnant women will be excluded from the study.
Mentally impaired patients who have no capacity to provide their own consent will be
excluded from the study.