Changes in intracortical excitability induced by stimulation of wrist afferents in man

Abstract

1. Inhibitory and facilitatory neuronal circuits may be explored in the human motor cortex by double pulse transcranial magnetic stimulation (TMS). At short interstimulus intervals (2-5 ms), conditioned motor-evoked potentials (MEPs) are reduced (intracortical inhibition, ICI), whereas they are facilitated at longer interstimulus intervals (8-25 ms; intracortical facilitation, ICF). The aim of this study was to investigate the effects of homonymous and antagonist nerve stimulation on the intracortical inhibition and facilitation in the cortical areas that control the wrist extensor and flexor radialis muscles. 2. Sixteen subjects were asked to contract either their wrist extensor or flexor muscles. The MEP evoked by a test TMS (at 1.2 x MEP threshold) and recorded in the target muscle was then conditioned by subthreshold TMS (at 0.8 x MEP threshold) 2 and 14 ms before the test TMS. The median and radial nerves were stimulated at 0.8 x motor threshold (MT). 3. In both flexor and extensor muscles, antagonist nerve stimulation 40 ms before the test TMS decreased ICI and increased ICF. In contrast, homonymous nerve stimulation had no effect on ICI and ICF. 4. The intensity of the antagonist nerve stimulation required to alter ICI and ICF was as low as 0.6 x MT, which suggests that thick diameter afferents may be involved. The nerve stimulation had to be applied 35-45 ms prior to the test TMS to alter significantly the intracortical excitability. 5. Cutaneous afferents were probably not responsible for the alterations of intracortical excitability, since cutaneous stimulation had no effect on either ICI or ICF at the investigated intervals. 6. The present data suggest that antagonist muscular afferent inputs may evoke reciprocal facilitation or disinhibition at the cortical level. This pattern of antagonist sensory afferent effects may be of significance for control of the wrist extensor and flexor muscles when used as synergists during manipulatory finger movements and gripping tasks.

Figure 1. Demonstration of intracortical inhibition (ICI) and intracortical facilitation (ICF) by paired-pulse TMS technique

A, experimental set-up. B, time course of the effect of subthreshold TMS (0.8 × MEP threshold) on MEPs evoked in the ECR muscle by suprathreshold TMS (1.2 × MEP threshold). The abscissa is the conditioning-test interval (in ms) and the ordinate is the size of the conditioned MEP as a percentage of the control MEP size. Asterisks designate that the conditioned MEP was significantly different from the control MEP with a P value below 0.05. Each error bar is one standard error of the mean. The data are from a single subject. C, description of the different alternatives used. The different alternatives combined test and conditioning (Cond.) TMS (conditioning-test interval of 2 and 14 ms) with and without different nerve stimulations applied from 27 to 60 ms prior the test TMS.

Figure 2. Effect of median nerve stimulation on ICI and ICF estimated from the ECR MEP

The data are from a single subject and show averaged traces of ECR EMG (n = 10) following different combinations of TMS and median nerve stimulation. A-C show the ECR MEP in the control situation without conditioning stimuli (A), with conditioning subthreshold TMS at an interval of 2 ms (B) and with conditioning subthreshold TMS at an interval of 14 ms (C). In D-F median nerve stimulation was applied 40 ms before TMS, but otherwise the three traces represent the same combinations of TMS as A-C. The intensity of the median nerve stimulation was 0.8 × MT. The values to the right of each trace give the size of the MEP recorded in that situation as a percentage of the control MEP (in A).

Figure 3. Effect of median and radial nerve stimulation on ICI and ICF measured from ECR and FCR MEPs in all tested subjects

The graphs give the effect of median (A,C, F and H) and radial (B, D, E and G) stimulation on ICI (A, B, E and F) and ICF (C, D, G and H) estimated from the ECR (A-D) and FCR (E-H) MEPs. A comparison is made of the size of ICI or ICF with (right-hand side of graph) and without peripheral nerve stimulation (left-hand side of graph). Each small circle (extensor MEPs) or square (flexor MEPs) and thin line represents one subject. In addition the mean size of ICI and ICF with and without peripheral nerve stimulation is shown as large circles or squares and thick lines in each of the graphs. In all experiments ICI was estimated at an interval of 2 ms between conditioning and test TMS, whereas ICF was measured at an interval of 14 ms. The interval between peripheral nerve stimulation and TMS was 40 ms. The intensity of peripheral nerve stimulation was 0.8 × MT. ns, not significant.

Figure 4. Threshold of the effect of peripheral nerve stimulation on ICI and ICF estimated from the extensor and flexor MEPs

The data are from a single subject. A and B show the effect of peripheral nerve stimulation on ICI and ICF, respectively, estimated from changes in the amplitude of extensor MEPs. C and D show the effect of peripheral nerve stimulation on ICI and ICF, respectively, estimated from changes in the amplitude of flexor MEPs. Open columns show the size of ICI or ICF in the control situation without peripheral nerve stimulation, whereas grey columns show the effect of radial nerve stimulation and black columns the effect of median nerve stimulation. The intensity of the peripheral nerve stimulation was varied from 0.5 to 1.0 × MT. ICI was measured at an interval of 2 ms between the conditioning subthreshold TMS and the test TMS and ICF was measured at an interval of 14 ms. The interval between the peripheral nerve stimulation and TMS was 40 ms in all cases. The ordinate is the size of the conditioned MEP as a percentage of the control MEP size. Each error bar is one standard error of the mean. The asterisks designate statistical significance at P < 0.05.

Figure 5. Time course of the effect of median nerve stimulation on ICI and ICF estimated from the extensor MEPs

The data are from a single subject. A, ICI was measured at an interval of 2 ms between the conditioning subthreshold and the test TMS. B, ICF was measured at an interval of 14 ms between the conditioning subthreshold and the test TMS. Open circles show the size of the conditioned MEP without peripheral nerve stimulation whereas filled circles show the size when preceded by median nerve stimulation at 0.8 × MT. The ordinate is the size of the conditioned MEP expressed as a percentage of the control MEP and the abscissa is the interval between the nerve stimulation and the test TMS. Each error bar is one standard error of the mean. The asterisks indicate statistical significance at P < 0.05.

Figure 6. Effect of cutaneous stimulation on ICI and ICF estimated from the ECR MEP

The data are from a single subject. The figure is arranged in the same way as Fig. 2. Upper traces show the test MEP alone (A and G) and with brushing of the hand (D) or stimulation of the median nerve at the wrist (J). The middle traces show the test MEP when conditioned by subthreshold TMS at a 2 ms interval alone (B and H) and in combination with brushing of the hand (E) or stimulation of the median nerve at the wrist (K). The lower traces show the test MEP when conditioned by subthreshold TMS at an interval of 14 ms alone (C and I) and in combination with hand brushing (F) or median nerve stimulation at the wrist (L). The cutaneous stimulation of the palmar side of the hand was applied by a rotating brush. The intensity of the median nerve stimulation was 5 × perception threshold. The stimulation was applied 45 ms prior to TMS. All traces are the mean of 10 stimuli.

Figure 7. Effect of median nerve stimulation on the ECR EMG activity

The data are from the same subject as in Fig. 5.A, extensor MEP evoked by TMS (1.2 × MEP threshold). The trace is the mean of 10 stimuli. B, rectified extensor EMG activity following median nerve stimulation. The trace is the mean of 100 stimuli. C, the effects of the same median nerve stimulation on the extensor MEP. The latency of the MEP has been added to the interval between median nerve stimulation and the test TMS, so that the intervals correspond to the effects of the stimulation in the EMG (B). The size of the MEP conditioned by median nerve stimulation is expressed as a percentage of the control MEP size. Each error bar is one standard error of the mean.