To investigate the treatment effect of continuous transcranial magnetic stimulation on patients with Parkinson disease, and the underlying neural mechanism by functional MRI

All patients underwent a medical evaluation that included physical examination and routine laboratory studies before and after repetitive transcranial magnetic stimulation (rTMS) treatment. Patients were randomly allocated to rTMS group and the sham group by coin toss. There are at least 20 patients in each group. The decision to enroll a patient was always made prior to randomization. Patients were studied using a double-blind design. Study participants, clinical raters, and all personnel responsible for the clinical care of the patient remained masked to allocated condition and allocation parameters. Only rTMS administrators had access to the randomization list; they had minimal contact with the patients, and no role in assessing clinical symptoms. Each patient would be treated for continuous 14 days by rTMS.

Before the rTMS treatment, the Unified Parkinson's Disease Rating Scale, and the Non-motor Symptom Scale were obtained by a trained investigator to assess baseline severity. The patients had receiving a battery measure of neuropsychological tests(mini-mental state examination, Montreal cognitive assessment, digital span test, verbal fluency test, Hamilton depression/anxiety scale, Stroop test, Iowa gambling test, game of dice test, stop signal test, and delay discount), magnetic resonance imaging scan in multimodalities, and electroencephalography (EEG) record.

In the second day after the last treatment, all the tests were reassessed. Patients were instructed to focus their answers on the past 14 days. The patients had also receiving a battery measure of neuropsychological tests, magnetic resonance imaging scan in multimodalities, and EEG record.

The clinical symptom and cognition of participants were followed in two month after the last treatment. They were instructed to focus their answers on the past week. Additionally, they were also asked to assess the battery of neuropsychological tests, and have magnetic resonance imaging scan in multimodalities, and EEG record. Afterwards, they were unblinded by the study coordinator.

Inclusion Criteria:

• Diagnosis of Parkinson disease (PD) according to the United Kingdom Brain Bank Criteria, confirmed by a neurologist with expertise in movement disorders.
• Minimum of 3 years since the formal diagnosis of PD, and requiring dopaminergic therapy (at a minimum, on levodopa and/or dopamine agonist therapy).
• On a stable dose of all medications for 2 months; and no anti-PD medication adjustments in the next 3 months.
• Age 40 years or older.
• Mini-mental state examination > 27.

Exclusion Criteria:

• Any history or clinical signs of other severe psychiatric illnesses (like major depression, psychosis or obsessive compulsive disorder).
• History of head injury, stroke, or other neurologic disease.
• Organic brain defects on T1 or T2 images.
• History of seizures or unexplained loss of consciousness.
• Implanted pacemaker, medication pump, vagal stimulator, deep brain stimulator.
• Family history of medication refractory epilepsy.
• History of substance abuse within the last 6 months.