Homeostatic plasticity in human motor cortex demonstrated by two consecutive sessions of paired associative stimulation

Long‐term potentiation (LTP) and long‐term depression (LTD) underlie most models of learning and memory, but neural activity would grow or shrink in an uncontrolled manner, if not guarded by stabilizing mechanisms. The Bienenstock–Cooper–Munro (BCM) rule proposes a sliding threshold for LTP/LTD induction: LTP induction becomes more difficult if neural activity was high previously. Here we tested if this form of homeostatic plasticity applies to the human motor cortex (M1) in vivo by examining the interactions between two consecutive sessions of paired associative stimulation (PAS). PAS consisted of repeated pairs of electrical stimulation of the right median nerve followed by transcranial magnetic stimulation of the left M1. The first PAS session employed an interstimulus interval equalling the individual N20‐latency of the median nerve somatosensory‐evoked cortical potential plus 2 ms, N20‐latency minus 5 ms, or a random alternation between these intervals, to induce an LTP‐like increase in motor‐evoked potential (MEP) amplitudes in the right abductor pollicis brevis muscle (PASLTP), an LTD‐like decrease (PASLTD), or no change (PASControl), respectively. The second PAS session 30 min later was always PASLTP. It induced an moderate LTP‐like effect if conditioned by PASControl, which increased if conditioned by PASLTD, but decreased if conditioned by PASLTP. Effects on MEP amplitude induced by the second PAS session exhibited a negative linear correlation with those in the first PAS session. Because the two PAS sessions activate identical neuronal circuits, we conclude that ‘homosynaptic‐like’ homeostatic mechanisms in accord with the BCM rule contribute to regulating plasticity in human M1.