Ziemann U, Muellbacher W, Hallett M, Cohen L G
Clinic of Neurology, J. W. Goethe University, Schleusenweg 2-16, D-60590 Frankfurt am Main, Germany.
Brain. 2001 Jun;124(Pt 6):1171-81. doi: 10.1093/brain/124.6.1171.
Motor practice may lead to expansion of trained representations in the motor cortex, but it is unknown whether this practice-dependent plasticity can be purposefully enhanced or depressed. Evidence, mainly based on animal experiments, indicates that the activity of GABA-related cortical inhibition is important in controlling the extent to which plasticity may occur. We tested the role of GABA in modulating practice-dependent plasticity in the human motor cortex. A decrease in GABA-related cortical inhibition was achieved by ischaemic nerve block (INB) in the hand by deafferentation/deefferentation and an increase was achieved by administration of the GABA(A) receptor agonist lorazepam. In Experiment 1, healthy subjects performed motor practice (MP), consisting of repeated ballistic contractions of the biceps muscle in the absence (MP alone) or presence of INB (MP+INB). Changes in the biceps motor cortex representation were assessed by transcranial magnetic stimulation (TMS). MP+INB resulted in a dramatic increase in the size of the motor evoked potential (MEP) and in paired-pulse excitability compared with mild or no changes in the MP-alone and INB-alone conditions. In Experiment 2, this dramatic increase in biceps representation induced by MP+INB was replicated when subjects were pretreated with placebo, but this increase was prevented or even switched to a decrease when subjects were pretreated with lorazepam. These findings indicate that a decrease in GABA-related inhibition facilitates practice-dependent plasticity in the human motor cortex, whereas an increase depresses it. In Experiment 3, practice-dependent plasticity (assessed by TMS, as in the first two experiments) was also tested at the behavioural level. The dramatic increase in biceps MEP size induced by MP+INB was paralleled by an increase in peak acceleration of the fastest elbow flexion movements. Similarly, the lack of change in MEP size in the MP-alone condition was paralleled by a lack of change in peak acceleration. We propose that changes in GABA activity may be instrumented to modulate plasticity purposefully; for instance, to enhance plastic change and recovery of function after a lesion in neurological patients.
运动练习可能会导致运动皮层中经过训练的表征扩展，但尚不清楚这种依赖于练习的可塑性是否能够被有意地增强或抑制。主要基于动物实验的证据表明，与GABA相关的皮层抑制活动在控制可塑性可能发生的程度方面很重要。我们测试了GABA在调节人类运动皮层中依赖于练习的可塑性方面的作用。通过手部缺血性神经阻滞（INB）使传入神经/传出神经切断来降低与GABA相关的皮层抑制，通过给予GABA(A)受体激动剂劳拉西泮来增加这种抑制。在实验1中，健康受试者进行运动练习（MP），包括在不存在（仅MP）或存在INB（MP + INB）的情况下对肱二头肌进行重复的爆发性收缩。通过经颅磁刺激（TMS）评估肱二头肌运动皮层表征的变化。与仅MP和仅INB条件下的轻微或无变化相比，MP + INB导致运动诱发电位（MEP）的大小以及成对脉冲兴奋性显著增加。在实验2中，当受试者用安慰剂预处理时，MP + INB诱导的肱二头肌表征的这种显著增加得以重现，但当受试者用劳拉西泮预处理时，这种增加被阻止甚至转变为减少。这些发现表明，与GABA相关的抑制的降低促进了人类运动皮层中依赖于练习的可塑性，而增加则会抑制它。在实验3中，还在行为水平上测试了依赖于练习的可塑性（如前两个实验中通过TMS评估）。MP + INB诱导的肱二头肌MEP大小的显著增加与最快的肘部屈曲运动的峰值加速度增加并行。同样，仅MP条件下MEP大小缺乏变化与峰值加速度缺乏变化并行。我们提出，可以通过改变GABA活性来有意地调节可塑性；例如，在神经疾病患者发生损伤后增强可塑性变化和功能恢复。
