Rodrigues Julian P, Walters Susan E, Stell Rick, Mastaglia Frank L, Thickbroom Gary W
Centre for Neuromuscular and Neurological Disorders, University of Western Australia, Australia.
Neurosci Lett. 2008 Dec 19;448(1):29-32. doi: 10.1016/j.neulet.2008.10.048. Epub 2008 Oct 21.
We sought to investigate the effects of dopamine on motor cortical plasticity in Parkinson's disease (PD) using a novel interventional transcranial magnetic stimulation protocol that targets spike-timing-dependent plasticity (iTMS). Six patients (3F, mean age 62 years) with mild-moderate PD (mean disease duration 6 years, UPDRS-off 13, UPDRS-on 3, H&Y stage 2, daily levodopa dosage 450 mg) were studied off and on levodopa on separate days. Paired TMS pulses at resting motor threshold with an inter-stimulus interval of 1.5 ms were given over the hand area of the motor cortex for 20 min at 0.2 Hz. Single-pulse motor evoked potential (MEP) amplitude and visually cued simple reaction time (SRT) were measured before and after iTMS. When on levodopa, MEP amplitude increased to 278+/-36% of baseline (p<0.01), and when off levodopa to 157+/-13% of baseline (p=0.02). All patients showed a significantly greater increase in MEP amplitude when on levodopa than off levodopa (p=0.01). SRT was reduced to 95% baseline after iTMS off levodopa (p=0.02), but did not change on levodopa. These findings indicate that motor cortex plasticity to iTMS is preserved in mild-moderate PD. The effects of this spike-timing-related TMS protocol on cortical excitability were consistent and were enhanced by levodopa. The results support the important role of dopamine in regulating synaptic plasticity and justify a larger crossover study to assess the therapeutic effects of iTMS in PD.
我们试图采用一种针对峰时依赖可塑性的新型介入性经颅磁刺激方案（iTMS），来研究多巴胺对帕金森病（PD）运动皮质可塑性的影响。对6例轻度至中度PD患者（3例女性，平均年龄62岁）进行了研究，平均病程6年，未服用左旋多巴时统一帕金森病评定量表（UPDRS）评分为13分，服用左旋多巴时为3分， Hoehn-Yahr分级为2级，每日左旋多巴剂量为450 mg。在不同日期分别在患者服用和未服用左旋多巴的情况下进行研究。在运动皮质手部区域以0.2 Hz的频率给予间隔1.5 ms的成对TMS脉冲，强度为静息运动阈值，持续20分钟。在iTMS前后测量单脉冲运动诱发电位（MEP）幅度和视觉提示简单反应时间（SRT）。服用左旋多巴时，MEP幅度增加至基线的278±36%（p<0.01），未服用左旋多巴时增加至基线的157±13%（p=0.02）。所有患者服用左旋多巴时MEP幅度的增加均显著大于未服用左旋多巴时（p=0.01）。未服用左旋多巴时，iTMS后SRT降至基线的95%（p=0.02），但服用左旋多巴时未发生变化。这些发现表明，轻度至中度PD患者运动皮质对iTMS的可塑性得以保留。这种与峰时相关的TMS方案对皮质兴奋性的影响是一致的，且左旋多巴可增强该影响。结果支持了多巴胺在调节突触可塑性中的重要作用，并证明有必要开展更大规模的交叉研究以评估iTMS对PD的治疗效果。
