A local signature of LTP- and LTD-like plasticity in human NREM sleep

Paired associative stimulation (PAS) repeatedly pairs electrical nerve stimulation with transcranial magnetic stimulation of the contralateral motor hand area (M1_HAND). Depending on the interstimulus interval, PAS can induce a long-term potentiation (LTP)-like facilitation or long-term depression (LTD)-like suppression of cortical excitability. In three experimental sessions, 12 awake men received PAS of the right median nerve and left M1_HAND in the evening before sleep. To optimize the timing of paired stimulation in M1_HAND, the interstimulus interval of PAS was adjusted to the individual N20-latency of the somatosensory evoked potential to induce LTP-like effects (PAS_N20+2ms), LTD-like effects (PAS_N20-5ms), or no timing-dependent after-effects (PAS_control). Motor-evoked potentials (MEPs) showed high interindividual variations in the conditioning effects of PAS_N20+2ms and PAS_N20-5ms on cortical excitability. However, PAS_control allowed us to adjust for any unspecific stimulation effects and the MEP increase after PAS_N20+2ms differed significantly from the MEP decrease after PAS_N20-5ms. PAS _N20+2ms and PAS_N20-5ms also had a differential effect on regional expression of slow waves and slow spindle activity during the first hour of subsequent non-rapid eye movement (NREM) sleep. At the electrode sites overlying the conditioned M1_HAND and the adjacent premotor cortex, local expression of slow spindle activity was significantly correlated with interindividual differences in the efficacy of PAS_N20+2ms and PAS_N20-5ms to potentiate or suppress cortical excitability. This correlation indicates that PAS shapes the local regulation of slow sleep spindles during subsequent NREM sleep.