LTD-like plasticity induced by paired associative stimulation: direct evidence in humans.

Paired associative stimulation (PAS), in which peripheral nerve stimuli are followed by transcranial magnetic stimulation (TMS) of the motor cortex, may produce a long lasting change in cortical excitability. At an interstimulus interval slightly shorter than the time needed for the afferent inputs to reach cerebral cortex (10 ms), motor cortex excitability decreases. Indirect data support the hypothesis that PAS at this interval (PAS10) involves LTD like-changes in cortical synapses. The aim of present paper was to investigate more directly PAS10 effects. We recorded corticospinal descending volleys evoked by single pulse TMS before and after PAS10 in two conscious subjects who had a high cervical epidural electrode implanted for pain control. These synchronous volleys provide a measure of cortical synaptic activity. PAS10 significantly reduced the amplitude of later descending waves while the earliest descending wave was not modified. Present results confirm the cortical origin of the effect of PAS10.