Learning modifies subsequent induction of long-term potentiation-like and long-term depression-like plasticity in human motor cortex

Abstract

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.

Figures

Figure 1.

Timeline of experiments (for details, see Materials and Methods).

Figure 2.

Lasting increase of MEP amplitude in the resting APB muscle induced by PAS (PASN20; squares) and MEP decrease induced by PASN20-5 (circles). The times of MEP testing are denoted on the x-axis (compare Fig. 1). MEPs are normalized to MEP amplitude measured at B1. Each subject was tested twice (session 1, black symbols; session 2, white symbols). All data are the means ± 1 SEM from six subjects.

Figure 3.

Changes in MEP amplitude induced by MP alone in the LTP (squares) and LTD (circles) groups. Otherwise, arrangement and conventions are as in Figure 2.

Figure 4.

Interactions between MP and PASN20. Black squares indicate the lasting increase in MEP amplitude induced by PASN20 alone (average of PASN20 sessions 1 and 2 in Fig. 2). Gray and white squares show the changes in MEP amplitude if PASN20 was preceded by MP associated with learning. White squares refer to the control experiment in which any increase in MEP amplitude induced by MP was compensated for by reduction in fTMS intensity (reinstallation of MEP1mV at B1). Otherwise, arrangement and conventions are as in Figure 2. Note that motor learning prevented the lasting increase in MEP amplitude induced by PASN20 alone.

Figure 5.

Interactions between MP and PASN20-5. Arrangement and conventions are as in Figure 4. Note that motor learning enhanced the lasting decrease in MEP amplitude induced by PASN20-5 alone.

Figure 6.

Interactions of MPslow with PASN20 and PASN20-5. Squares show normalized MEP amplitudes in the PASN20 alone (black) and MPslow+PASN20 (gray) conditions, and circles show MEP amplitudes in the PASN20-5 alone (black) and MPslow+PASN20-5 (gray) conditions. Note that MPslow had no effect on either the lasting increase in MEP amplitude induced by PASN20 alone or the lasting decrease in MEP amplitude induced by PASN20-5 alone.