The treatment of Parkinson's disease (PD) needs further improvement, particularly in the area 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. We hypothesize that rTMS will have a beneficial effect on gait and freezing in medicated patients, and propose to test this in a controlled trial. Specifically, we propose to look at the effect of 25 Hz stimulation since this type of stimulation has been shown to increase the excitability of the cerebral cortex. Over a one-year period, we will enroll 40 adults with PD and evaluate the effects 8 treatments over a period of 4 weeks. We will investigate effects on the motor cortex and the dorsolateral prefrontal cortex since both of these regions may be underactivated in PD and recent data suggest a change in diencephalic dopamine function with rTMS of the prefrontal cortex. Symptoms will be evaluated with standard tests of motor function including the Unified Parkinson's Disease Rating Scale and specific tests of gait and freezing. We will look for acute effects of stimulation and for cumulative effects.
INCLUSION CRITERIA: Men and women aged forty to eighty five years with DOPA-responsive, akinetic-rigid PD. Patients who have not participated in Human Motor Control Section (HMCS) protocols for PD in the past will be interviewed and examined by either the PI or a Brain Stimulation Unit (BSU) or HMCS physician in order to establish the diagnosis of PD and rule out any neurologic condition. Only patients with a Hoehn and Yahr grade of 3 to 5 while "off" will be accepted. Patients must be on a regimen including levodopa, and have a total dose of medication equal to more than 375 mg of levodopa equivalent including their dopamine agonist agents. Patients should have problems with walking, including freezing, so that their gait time for a 10-meter distance will be 5 seconds or more. Any patient whose record does not contain a neurological examination from the past year will be reexamined before enrollment. The study will be explained and informed consent obtained by a protocol investigator. EXCLUSION CRITERIA: Any significant medical or psychiatric illness (other than PD), pregnancy (urine sample for the pregnancy test will be obtained prior to the rTMS start, at the day of the initial interview and signing the consent form), history of epilepsy, concurrent use of tricyclic antidepressants, neuroleptic agents, or any other licit or illicit drugs other than antiparkinsonian agents that could lower the seizure threshold. Persons with surgically or traumatically implanted foreign bodies such as a pacemaker, implanted medication pump, metal plate in the skull, and metal inside the skull or eyes (other than dental appliances or fillings) that may pose a physical hazard during magnetic stimulation. 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 frailty, or excessive apprehensiveness. Mentally impaired patients having no capacity to provide their own consent will be excluded from the study. The physician establishing the diagnosis and applying UPDRS will evaluate patient's mental capacity using conventional clinical interview. No psychological tests will be used. Formal reevaluation will not be done. Children are excluded since Parkinson's disease is not, generally, a disorder of children.