Ziemann Ulf, Ilić Tihomir V, Pauli Christian, Meintzschel Frank, Ruge Diane
Motor Cortex Laboratory, Clinic of Neurology, Johann Wolfgang Goethe-University, D-60528 Frankfurt am Main, Germany.
J Neurosci. 2004 Feb 18;24(7):1666-72. doi: 10.1523/JNEUROSCI.5016-03.2004.
Learning may alter rapidly the output organization of adult motor cortex. It is a long-held hypothesis that modification of synaptic strength along cortical horizontal connections through long-term potentiation (LTP) and long-term depression (LTD) forms one important mechanism for learning-induced cortical plasticity. Strong evidence in favor of this hypothesis was provided for rat primary motor cortex (M1) by showing that motor learning reduced subsequent LTP but increased LTD. Whether a similar relationship exists in humans is unknown. Here, we induced LTP-like and LTD-like plasticity in the intact human M1 by an established paired associative stimulation (PAS) protocol. PAS consisted of 200 pairs of electrical stimulation of the right median nerve, followed by focal transcranial magnetic stimulation of the hand area of the left M1 at an interval equaling the individual N20 latency of the median nerve somatosensory-evoked cortical potential (PAS(N20)) or N20-5 msec (PAS(N20-5)). PAS(N20) induced reproducibly a LTP-like long-lasting (>30 min) increase in motor-evoked potentials from the left M1 to a thumb abductor muscle of the right hand, whereas PAS(N20-5) induced a LTD-like decrease. Repeated fastest possible thumb abduction movements resulted in learning, defined by an increase in maximum peak acceleration of the practiced movements, and prevented subsequent PAS(N20)-induced LTP-like plasticity but enhanced subsequent PAS(N20-5)-induced LTD-like plasticity. The same number of repeated slow thumb abduction movements did not result in learning and had no effects on PAS-induced plasticity. Findings support the view that learning in human M1 occurs through LTP-like mechanisms.
学习可能会迅速改变成人大脑运动皮层的输出组织。长期以来一直存在这样一种假说，即通过长时程增强（LTP）和长时程抑制（LTD）来改变皮质水平连接上的突触强度，是学习诱导的皮质可塑性的一种重要机制。通过表明运动学习会降低随后的LTP但增加LTD，为大鼠初级运动皮层（M1）提供了支持这一假说的有力证据。在人类中是否存在类似的关系尚不清楚。在这里，我们通过既定的配对联想刺激（PAS）方案，在完整的人类M1中诱导出类似LTP和类似LTD的可塑性。PAS包括200对右侧正中神经的电刺激，随后以等于正中神经体感诱发电位的个体N20潜伏期（PAS（N20））或N20 - 5毫秒（PAS（N20 - 5））的间隔，对左侧M1手部区域进行局灶性经颅磁刺激。PAS（N20）可重复地诱导从左侧M1到右手拇指外展肌的运动诱发电位出现类似LTP的持久（>30分钟）增加，而PAS（N20 - 5）则诱导出类似LTD的降低。重复尽可能快的拇指外展运动导致了学习，其定义为练习运动的最大峰值加速度增加，并阻止了随后PAS（N20）诱导的类似LTP的可塑性，但增强了随后PAS（N20 - 5）诱导的类似LTD的可塑性。相同次数的重复缓慢拇指外展运动并未导致学习，并且对PAS诱导的可塑性没有影响。这些发现支持了人类M1中的学习是通过类似LTP的机制发生的这一观点。
