Modulation of the Direction and Magnitude of Hebbian Plasticity in Human Motor Cortex by Stimulus Intensity and Concurrent Inhibition

Background The mechanisms mediating the efficacy and variability of paired associative stimulation (PAS), thought to be mediated by Hebbian plasticity, remain incompletely understood. The magnitude and direction of Hebbian plasticity may be modulated by the level of neural depolarisation, which is influenced by stimulation intensity and interactions with cortical circuits. Hypothesis PAS effects would be influenced by the intensity of transcranial magnetic stimulation (TMS) and interaction with other circuits. In particular, PAS would be inhibited by concurrent inhibitory input following median nerve stimulation, known as short latency afferent inhibition (SAI). Methods PAS was tested at an interstimulus interval (ISI) 2 ms or 6 ms longer than the N20 peak of the median nerve somatosensory-evoked potential (PAS_N20+2, PAS_N20+6). PAS_N20+2 was tested at three different TMS intensities. Short interval intracortical facilitation and inhibition were tested in the presence of SAI (SICF_SAI, SICI_SAI). Results The propensity for long term potentiation like effects increased with higher PAS_N20+2 TMS stimulus intensity, whereas long term depression like effects ensued at subthreshold intensity. Stronger SAI correlated with weaker PAS LTP-like effects across individuals. PAS_N20+2 (maximal SAI) was less effective than PAS_N20+6 (weak SAI). SICF_SAI or SICI_SAI did not influence PAS response. Conclusion Inter-individual differences in SAI contribute to the variability in PAS efficacy. The magnitude and direction of PAS effects is modulated by TMS intensity. Together, these findings indicate that the level of neural activity induced by stimulation likely plays a crucial role in determining the direction and magnitude of Hebbian plastic effects evoked by PAS in human cortex.