Placebo-Controlled Study of rTMS for the Treatment of Parkinson’s Disease Mikhail P. Lomarev, PhD, MD, 1 * Sulada Kanchana, MD, PhD, 1 William Bara-Jimenez, MD, 2 Meena Iyer, PhD, 3 Eric M. Wassermann, MD, 3 and Mark Hallett, MD 1 1 Human Motor Control Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland, USA 2 Experimental Therapeutic Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland, USA 3 Brain Stimulation Unit and Cognitive Neuroscience, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland, USA Abstract: The objective of this study is to assess the safety and efficacy of repetitive transcranial magnetic stimulation (rTMS) for gait and bradykinesia in patients with Parkinson’s disease (PD). In a double-blind placebo-controlled study, we evaluated the effects of 25 Hz rTMS in 18 PD patients. Eight rTMS sessions were performed over a 4-week period. Four cortical targets (left and right motor and dorsolateral prefrontal cortex) were stimulated in each session, with 300 pulses each, 100% of motor threshold intensity. Left motor cortex (MC) excitability was assessed using motor evoked potentials (MEPs) from the abductor pollicis brevis. During the 4 weeks, times for execut- ing walking and complex hand movements tests gradually decreased. The therapeutic rTMS effect lasted for at least 1 month after treatment ended. Right-hand bradykinesia im- provement correlated with increased MEP amplitude evoked by left MC rTMS after individual sessions, but improvement overall did not correlate with MC excitability. rTMS ses- sions appear to have a cumulative benefit for improving gait, as well as reducing upper limb bradykinesia in PD patients. Although short-term benefit may be due to MC excitability enhancement, the mechanism of cumulative benefit must have another explanation. © 2005 Movement Disorder So- ciety Key words: Parkinson’s disease; rTMS; motor cortex Parkinson’s disease (PD) is typically easy to treat early in the disease, but later, the response declines and complications develop. Postural instability associated with gait disorder is usually very disabling, less treatable, and represents a major contributing factor in progression from mild bilateral disease to wheelchair confinement. 1 Gait and postural disturbances are less responsive to deep brain stimulation compared to other PD symptoms. 2 Repetitive transcranial magnetic stimulation (rTMS) is a tool that allows noninvasive stimulation of the cerebral cortex. Many researchers have used TMS to understand PD pathophysiology, but only a few have used it in therapeutic trials. In the initial study, repetitive 5 Hz TMS (rTMS) applied to the primary motor cortex (MC), contralateral to the performing hand, shortened the time for PD patients on levodopa/carbidopa therapy to com- plete the Grooved Pegboard test. 3 However, these results were not reproducible in drug-free patients. 4 In a different PD study, MC rTMS at a 1 Hz frequency for 15 minutes increased the velocity of finger tapping. 5 Siebner and colleagues found that 5 Hz rTMS over the MC improved ballistic movements for 20 minutes and improved contralateral arm motor scores 1 hour after the TMS session. 6 One-month-long improvement of the Uni- fied Parkinson’s Disease Rating Scale (UPDRS) score, walking speed, and a self-assessment scale were reported in drug-free PD patients after 10 sessions of 5 Hz rTMS of leg and hand projections in the MC. 7 The reported improvement was an impressive 13.9 points of the total *Correspondence to: Dr. Mikhail Lomarev, NIH Building 10, Room 5N240, 10 Center Dr MSC 1428, Bethesda MD 20892-1428. E-mail: lomarevm@ninds.nih.gov Received 11 January 2005; Revised 29 March 2005; Accepted 28 June 2005 Published online 6 October 2005 in Wiley InterScience (www. interscience.wiley.com). DOI: 10.1002/mds.20713 Movement Disorders Vol. 21, No. 3, 2006, pp. 325–331 © 2005 Movement Disorder Society 325