Klinische Neurophysiologie 2013; 44 - P31
DOI: 10.1055/s-0033-1337172

Increasing static motor corticospinal excitability and concomitant blockade of PAS-induced facilitation by combining NMDA-R and L-VGCC blockade

JJ Mann 1, D Weise 1, JJ Rumpf 1, J Claßen 1
  • 1Uniklinikum Leipzig, Neurologie, Leipzig, Deutschland

Introduction: Paired associative stimulation (PAS) induced motor cortex plasticity may be blocked by administration of the NMDA-R-antagonist Dextromethorphan (DXM, Stefan et al 2002) or the L-type-Ca-channel-blocker Nimodipine (NDP, Wolters et al 2003). Here we tested the effect of the combined application of DXM and NDP on static corticospinal excitability (SCSE) and PAS-induced plasticity.

Methods: 11 healthy subjects (six women, aged 18 – 29 years, mean 21.8 ± 3.1 years) were tested in four pseudorandomized, single-blinded sessions each. In three sessions premedication (Exp. 1: placebo (PBO), Exp. 2: 120 mg DXM (DXM120) + PBO, Exp. 3: DXM120 + NDP 30 mg (NDP30)) was administered before performing PAS25 (combination of electrical median-nerve-stimulation and suprathreshold TMS [130% resting motor threshold] over the contralateral motor cortex, 90 pairs, frequency 0.1 Hz, interstimulus interval (ISI) 25 ms). In Exp. 4, again DXM120+NDP30 was administred, but PAS was performed using an ISI of 5000 ms (PAS5000), which has been demonstrated previously to not change corticospinal excitability (Stefan et al 2000). Excitability changes were monitored by changes of MEP-amplitudes of the M. abductor pollicis brevis before and up to 32 min following PAS. Input-output-curves (IOC) of 11 different stimulation intensities (90, 95, ..., 140% of RMT) were recorded in a pseudorandomized order before and after medication to probe SCSE.

Results: DXM+NDP changed SCSE as IOCs were increased (ANOVARM time*intensity, p = 0.020), whereas DXM alone and PBO had no influence on IOC. Following PAS25, corticospinal excitability changed as a function of medication (ANOVA time*medication, p = 0.006), MEP-amplitudes increased under PBO (150%) and under DXM+NDP (139%), but the increase was blocked under DXM+PBO (93%). Under DXM+NDP changes in corticospinal excitability were similar following PAS25 and PAS5000 (ANOVA time*intervention p = 0.751), suggesting that the combination of DXM+NDP blocked the PAS effect, but increased SCSE.

Discussion: Our findings are in line with the hypothesis that PAS induced plasticity depends on calcium entry via different calcium channels. Furthermore, they suggest that the combination of DXM and NDP, which – if given alone – are each able to block PAS-induced potentiation, leads to an increase in SCSE. The increase of SCSE by the combination of DXM and NDP may be explained by medication-induced blockade of NMDA-R and compensatorily increased glutamatergic transmission (Di Lazarro et al 2003).