Effect of physiological activity on an NMDA-dependent form of cortical plasticity in human

Retention of motor learning can be enhanced or degraded by subsequent performance of a different task. Neurophysiologically this may reflect interference in synaptic plasticity by ongoing neural activity in the brain. Here we demonstrate that N-methyl-D-aspartate (NMDA) dependent aftereffects of repetitive transcranial magnetic stimulation (rTMS) also are subject to interference effects, suggesting that it may be possible to investigate these basic mechanisms in the intact human brain. We measured the motor-evoked potential (MEP) amplitude and short-interval intracortical inhibition (SICI) in the first dorsal interosseous (FDI) muscle after continuous or intermittent theta burst (cTBS/iTBS) forms of rTMS. In resting subjects, cTBS depressed MEPs and reduced SICI for about 20 min, whereas iTBS had the opposite effect. However, if subjects contracted the FDI during TBS, then effects on the MEP were abolished, although effects of cTBS on SICI remained. Contraction immediately after TBS enhanced the facilitatory effect of iTBS and reversed the usual inhibitory effect of cTBS into facilitation. Contraction 10 min after cTBS (iTBS not tested) had only a transient (3-4 min) effect on MEPs. These interactions with behavior may relate to mechanisms of interference between learning paradigms in human and be similar to effects on synaptic long-term potentiation/depression described in animal experiments.