Klinische Neurophysiologie 2012; 43 - P051
DOI: 10.1055/s-0032-1301601

Induction of LTD-like plasticity by paired associative stimulation is blocked by intracortical inhibition

DT Weise 1, MC Ridding 2, R Gentner 3, JJ Rumpf 1, J Classen 1
  • 1Department of Neurology, University of Leipzig, Leipzig
  • 2Neuromotor Plasticity & Development (NeuroPAD) School of Paediatrics and Reproductive Health The University of Adelaide, Adelaide, AU
  • 3Neurologische Klinik der Universitätsklinik Würzburg, Würzburg

Objective/Aims: Paired associative stimulation (PAS) of the hand motor cortex (M1) may induce depressant effects on corticospinal excitability. It has been likened to the long-term depression of excitatory synapses as studied in vivo animal work. We hypothesized that activation of inhibitory and/or facilitatory interneurons during PAS may modulate LTD-like plasticity.

Methods: 60 subjects were examined (20 in every condition). PAS10 was performed by combining repetitively electric stimulation of the median nerve with subsequent TMS of the contralateral M1 (interstimulus interval 10 ms, 180 pairs, 0.1 Hz). Effects of PAS on MEP amplitude were normalized to baseline. PAS alone (PAS10) was compared to four conditioned PAS protocols in which the TMS pulse was conditioned by a preceding subthreshold (0.8*RMT) TMS pulse (CS) at either 3 ms (CS3) or 13 ms (CS13). The intensity of the second TMS pulse (TS) was either 1.3 * RMT (CS3-PAS10 or CS13-PAS10) or adapted to generate a MEP response matching in size that elicited by a single TMS-pulse at 1.3*RMT in the absence of a conditioning TMS pulse (CS3-PAS10adj or CS13-PAS10adj).

Results: Excitability in M1 changed as a function of the condition (ANOVA TIME*CONDITION F=3.833; P=0.005). MEP amplitudes decreased following CS13-PAS10 and CS13-PAS10adj similarly to PAS10 (around –15%). The depressant PAS10 effect, however, was abolished in the presence of a CS at –3ms (PAS10 vs. CS3-PAS10, P=0.047), even if the TS was adjusted (PAS10 vs. CS3-PAS10adj, P=0.006).

Conclusion: These results show that activation of inhibitory interneurons blocked the induction of LTD-like plasticity in M1 and may support the view that PAS-induced effects are tightly controlled by GABAergic inhibition.