Homeostatic and nonhomeostatic modulation of learning in human motor cortex

Motor learning is important throughout life for acquisition and adjustment of motor skill. The extent of motor learning may be modulated by the history of motor cortex activity, but little is known which metaplasticity rule (homeostatic vs nonhomeostatic) governs this interaction. Here, we explored in nine healthy adults the effects of three different paired associative stimulation (PAS) protocols on subsequent learning of rapid thumb flexion movements. PAS resulted in either a long-term potentiation (LTP)-like increase in excitability of the stimulated motor cortex (PAS(LTP)), or a long-term depression (LTD)-like decrease (PAS(LTD)), or no change (control condition, PAS(CON)). Learning was indexed by the increase in peak acceleration of the trained movement. Delays of 0 and 90 min between PAS and motor practice were tested. At the 0 min delay, PAS(LTD) strongly facilitated motor learning (homeostatic interaction), and PAS(LTP) also facilitated learning, although to a lesser extent (nonhomeostatic interaction). At the 90 min delay, PAS(LTD) facilitated learning, whereas PAS(LTP) depressed learning (interactions both homeostatic). Therefore, facilitation of learning by previous brain stimulation occurs primarily and most effectively through homeostatic interactions, but at the 0 min delay, nonhomeostatic mechanisms such as LTP-induced blockade of LTD and nonsaturated LTP-induced facilitation of learning might also play a role. The present findings demonstrate that motor learning in humans can be modulated by noninvasive brain stimulation and suggest the possibility of enhancing motor relearning in defined neurological patients.