期刊
MOVEMENT DISORDERS
卷 26, 期 10, 页码 1913-1921出版社
WILEY
DOI: 10.1002/mds.23731
关键词
dystonia; deep brain stimulation; plasticity; longitudinal; human; excitability; mechanism
资金
- Dystonia Medical Research Foundation (DMRF)
- Action Medical Research
- Department of Health's NIHR Biomedical Research Centres
- Medtronic
- National Institutes of Health [RO1-NS40902 (PI:DC)]
- Medical Research Council UK
- Brain Research Trust
- Medtronic UK
- Parkinson's Appeal
- Dystonia Society UK
- Halley Stewart Trust
Deep brain stimulation to the internal globus pallidus is an effective treatment for primary dystonia. The optimal clinical effect often occurs only weeks to months after starting stimulation. To better understand the underlying electrophysiological changes in this period, we assessed longitudinally 2 pathophysiological markers of dystonia in patients prior to and in the early treatment period (1, 3, 6 months) after deep brain stimulation surgery. Transcranial magnetic stimulation was used to track changes in short-latency intracortical inhibition, a measure of excitability of GABA(A)-ergic corticocortical connections and long-term potentiation-like synaptic plasticity (as a response to paired associative stimulation). Deep brain stimulation remained on for the duration of the study. Prior to surgery, inhibition was reduced and plasticity increased in patients compared with healthy controls. Following surgery and commencement of deep brain stimulation, short-latency intracortical inhibition increased toward normal levels over the following months with the same monotonic time course as the patients' clinical benefit. In contrast, synaptic plasticity changed rapidly, following a nonmonotonic time course: it was absent early (1 month) after surgery, and then over the following months increased toward levels observed in healthy individuals. We postulate that before surgery preexisting high levels of plasticity form strong memories of dystonic movement patterns. When deep brain stimulation is turned on, it disrupts abnormal basal ganglia signals, resulting in the absent response to paired associative stimulation at 1 month. Clinical benefit is delayed because engrams of abnormal movement persist and take time to normalize. Our observations suggest that plasticity may be a driver of long-term therapeutic effects of deep brain stimulation in dystonia. (C)2011 Movement Disorder Society
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