Learning Modifies Subsequent Induction of Long-Term Potentiation-Like and Long-Term Depression-Like Plasticity in Human Motor Cortex

TLDR

Learning can rapidly reorganize adult motor cortex output, likely via long‑term potentiation and depression of horizontal cortical connections. The study investigates whether this LTP/LTD relationship also occurs in human motor cortex. The authors induced LTP‑like and LTD‑like plasticity in human M1 using paired associative stimulation (PAS) consisting of 200 median‑nerve stimulations paired with transcranial magnetic stimulation timed to the individual N20 latency or N20‑5 ms. Fast thumb‑abduction learning abolished subsequent PAS‑N20 LTP‑like potentiation and amplified PAS‑N20‑5 LTD‑like depression, whereas slow movements had no effect, indicating that human motor learning depends on LTP‑like mechanisms.

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.