Objective: To assess whether multifocal, high-frequency repetitive transcranial magnetic stimulation (rTMS) of motor and prefrontal cortex benefits motor and mood symptoms in patients with Parkinson disease (PD). Methods:Patients with PD and depression were enrolled in this multicenter, double-blind, shamcontrolled, parallel-group study of real or realistic (electric) sham rTMS. Patients were randomized to 1 of 4 groups: bilateral M1 ( 1 sham dorsolateral prefrontal cortex [DLPFC]), DLPFC ( 1 sham M1), M1 1 DLPFC, or double sham. The TMS course consisted of 10 daily sessions of 2,000 stimuli for the left DLPFC and 1,000 stimuli for each M1 (50 3 4-second trains of 40 stimuli at 10 Hz). Patients were evaluated at baseline, at 1 week, and at 1, 3, and 6 months after treatment. Primary endpoints were changes in motor function assessed with the Unified Parkinson's Disease Rating Scale-III and in mood with the Hamilton Depression Rating Scale at 1 month.Results: Of the 160 patients planned for recruitment, 85 were screened, 61 were randomized, and 50 completed all study visits. Real M1 rTMS resulted in greater improvement in motor function than sham at the primary endpoint (p , 0.05). There was no improvement in mood in the DLPFC group compared to the double-sham group, as well as no benefit to combining M1 and DLPFC stimulation for either motor or mood symptoms. Conclusions:In patients with PD with depression, M1 rTMS is an effective treatment of motor symptoms, while mood benefit after 2 weeks of DLPFC rTMS is not better than sham. Targeting both M1 and DLPFC in each rTMS session showed no evidence of synergistic effects. Parkinson disease (PD) presents with both motor and nonmotor features. Motor symptoms can respond to pharmacologic and other therapies such as deep brain stimulation, 1 but these treatments are often ineffective for nonmotor symptoms. Depression is particularly common, with a prevalence ranging from 40% to 70%.2 Not infrequently, depression in PD is resistant to medication and affects patients' quality of life.

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Freezing of gait (FOG) is 'an episodic inability to generate effective stepping in the absence of any known cause other than parkinsonism or high level gait disorders'. FOG is one of the most disabling symptoms in Parkinson's disease, especially in its more advanced stages. Early recognition is important as FOG is related to higher fall risk and poorer prognosis. Although specific treatments are still elusive, there have been recent advances in the development of new therapeutic approaches. The aim of this review is to present the latest knowledge regarding the phenomenology, pathogenesis, diagnostic assessment and conventional treatment of FOG in Parkinson's disease. A review of the evidence supporting noninvasive brain stimulation will follow to highlight the potential of these strategies.

Background In Parkinson’s disease (PD), skill retention is poor, even when acquisition rate is generally preserved. Recent work in normal subjects suggests that 5 Hz-repetitive transcranial magnetic stimulation (5Hz-rTMS) may induce phenomena of long-term potentiation at the cortical level. Objective/Hypothesis We thus verified whether, in PD, 5Hz-rTMS enhances retention of a visuo-motor skill that involves the activity of the right posterior parietal cortex. Methods A group of patients with PD was tested in two two-day sessions, separated by one week (treatment and placebo sessions). The first day of each session, they learned to adapt their movements to a step-wise 60° visual rotation. Immediately after the task, either real 5Hz-rTMS (treatment) or sham (placebo) stimulation was applied over the right posterior parietal cortex (P6). Retention of this motor skill was tested the following day. Results In patients with PD, adaptation achieved at the end of training was comparable in the treatment and placebo sessions and was similar to that of a group of age-matched controls. However, retention indices tested on the following day were significantly lower in the placebo compared to the treatment session in which retention indices were restored to the level of the controls. Importantly, reaction and movement time as well as other kinematic measures were the same in the treatment and placebo sessions. Conclusion These results suggest that rTMS applied after the acquisition of a motor skill over specific areas involved in this process might enhance skill retention in PD.