Supplementary motor area stimulation for Parkinson disease A randomized controlled study
ABSTRACT OBJECTIVE: To explore the efficacy and stimulation frequency dependence of repetitive transcranial magnetic stimulation (rTMS) over the supplementary motor area (SMA) in Parkinson disease (PD). METHODS: In this randomized, double-blind, sham-controlled, multicenter study with a parallel design, a weekly intervention was performed 8 times. The effects were monitored up to 20 weeks. By central registration, participants were assigned to 1 of 3 arms of the study: low-frequency (1-Hz) rTMS, high-frequency (10-Hz) rTMS, and realistic sham stimulation. The primary end point was the score change of the Unified Parkinson's Disease Rating Scale (UPDRS) part III from the baseline. Several nonmotor symptom scales such as the Hamilton Rating Scale for Depression, apathy score, and nonmotor symptoms questionnaire were defined as secondary end points. RESULTS: Of the 106 patients enrolled, 36 were allocated to 1-Hz rTMS, 34 to 10-Hz rTMS, and 36 to realistic sham stimulation. Results show 6.84-point improvement of the UPDRS part III in the 1-Hz group at the last visit of the 20th week. Sham stimulation and 10-Hz rTMS improved motor symptoms transiently, but their effects disappeared in the observation period. Changes in nonmotor symptoms were not clear in any group. No severe adverse event was reported. CONCLUSIONS: The 1-Hz rTMS over the SMA was effective for motor, but not nonmotor, symptoms in PD. LEVEL OF EVIDENCE: This study provides Class I evidence that 1-Hz rTMS over the SMA is effective for motor symptoms in PD.
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ABSTRACT: Brain stimulation, a therapy increasingly used for neurological and psychiatric disease, traditionally is divided into invasive approaches, such as deep brain stimulation (DBS), and noninvasive approaches, such as transcranial magnetic stimulation. The relationship between these approaches is unknown, therapeutic mechanisms remain unclear, and the ideal stimulation site for a given technique is often ambiguous, limiting optimization of the stimulation and its application in further disorders. In this article, we identify diseases treated with both types of stimulation, list the stimulation sites thought to be most effective in each disease, and test the hypothesis that these sites are different nodes within the same brain network as defined by resting-state functional-connectivity MRI. Sites where DBS was effective were functionally connected to sites where noninvasive brain stimulation was effective across diseases including depression, Parkinson's disease, obsessive-compulsive disorder, essential tremor, addiction, pain, minimally conscious states, and Alzheimer's disease. A lack of functional connectivity identified sites where stimulation was ineffective, and the sign of the correlation related to whether excitatory or inhibitory noninvasive stimulation was found clinically effective. These results suggest that resting-state functional connectivity may be useful for translating therapy between stimulation modalities, optimizing treatment, and identifying new stimulation targets. More broadly, this work supports a network perspective toward understanding and treating neuropsychiatric disease, highlighting the therapeutic potential of targeted brain network modulation.Proceedings of the National Academy of Sciences 09/2014; 111(41). DOI:10.1073/pnas.1405003111 · 9.81 Impact Factor
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ABSTRACT: To investigate whether a period of continuous theta burst stimulation (cTBS) over the supplementary motor area (SMA) induces cortical plasticity and thus improves bradykinesia in Parkinson's disease (PD) in the medication ON and OFF state. In total, 26 patients with Parkinson's disease were tested with both real and sham stimulation. The group was divided into an OFF-medication (4 females, mean age 65 years, disease duration 6 years) and an ON-medication group (7 females, mean age 61 years, disease duration 7 years) with each containing 13 individuals. Both groups were evaluated in terms of electrophysiological (motor-evoked potentials) and behavioural [Purdue Pegboard test (PPT), UPDRS motor subscore] parameters before (baseline condition) and after a 40-second period of real or sham continuous theta burst stimulation over the SMA ON and OFF dopaminergic drugs. Patients in the OFF group demonstrated an improved UPDRS III score (p < 0.05) and a better performance in the PPT for the less affected side (p < 0.025) compared to baseline after real stimulation. However, electrophysiological parameters did not change in either the ON or the OFF state. cTBS over the SMA has a mild effect on motor symptoms of the upper limb in the OFF state of PD patients. In contrast, stimulation did not change cortico-spinal excitability. A lack of change (i.e. no plasticity) to brain stimulation protocols is a known finding in PD. A clinical improvement in the OFF state, however, contrasts with this and the mechanism of these induced changes is worth further exploration.Journal of Neurology 11/2014; 262(2). DOI:10.1007/s00415-014-7572-8 · 3.84 Impact Factor
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ABSTRACT: Transcranial magnetic stimulation (TMS) is a valuable technique for assessing the underlying neurophysiology associated with various neuropathologies, and is a unique tool for establishing potential neural mechanisms responsible for disease progression. Recently, repetitive TMS (rTMS) has been advanced as a potential therapeutic technique to treat selected neurologic disorders. In healthy individuals, rTMS can induce changes in cortical excitability. Therefore, targeting specific cortical areas affected by movement disorders theoretically may alter symptomology. This review discusses the evidence for the efficacy of rTMS in Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, and multiple sclerosis. It is hoped that gaining a more thorough understanding of the timing and parameters of rTMS in individu-als with neurodegenerative disorders may advance both clinical care and research into the most effective uses of this technology.