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

- PAS plastic effects were inhibited by GABAA mediated inhibitory input known as short latency afferent inhibition (SAI). Inter-individual differences in SAI contributed to the variability of PAS effects.
- The magnitude and direction of plastic effects were modulated by TMS intensity, and an anti-Hebbian reversal of plastic effects was achieved at subthreshold intensity.
- The findings are in agreement with cellular studies showing that the magnitude and direction of Hebbian plastic effects are modulated by the level of neural activation.
- The identification of predictors of plasticity (such as SAI) and factors that can enhance plasticity induction (higher TMS intensity) is highly valuable if these protocols are to be applied in clinical populations.
- The modulation of short interval intracortical inhibition and facilitation (SICI, SICF) in the presence of SAI did not appear to relate to the magnitude of PAS effects.

BackgroundThe 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.HypothesisPAS 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).MethodsPAS was tested at an interstimulus interval (ISI) 2 ms or 6 ms longer than the N20 peak of the median nerve somatosensory-evoked potential (PASN20+2, PASN20+6). PASN20+2 was tested at three different TMS intensities. Short interval intracortical facilitation and inhibition were tested in the presence of SAI (SICFSAI, SICISAI).ResultsThe propensity for long term potentiation like effects increased with higher PASN20+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. PASN20+2 (maximal SAI) was less effective than PASN20+6 (weak SAI). SICFSAI or SICISAI did not influence PAS response.ConclusionInter-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.