Effects of volitional contraction on intracortical inhibition and facilitation in the human motor cortex

Abstract

Short-interval intracortical inhibition (SICI), intracortical facilitation (ICF) and short-interval intracortical facilitation (SICF) were assessed in the cortical motor area of the first dorsal interosseous muscle (FDI) of 16 healthy subjects. Paired-pulse TMS was delivered to the left hemisphere at the following interstimulus intervals (ISIs): 2 and 3 ms for SICI, 10 and 15 ms for ICF and 1-5 ms for SICF. Motor-evoked potentials were recorded from the resting and active right FDI. The effects exerted on SICI and ICF by four intensities (60-90% of active motor threshold, AMT) of the conditioning stimulus (S1) and by three levels of muscle contraction (10%, 25%, 50% of maximal voluntary contraction, MVC) were evaluated. The effects exerted on SICF were evaluated with two intensities (90% and 70% of AMT) of the test stimulus (S2) and with the same levels of muscle contraction. Results showed that: (i) during 10% MVC, maximum SICI was observed with S1 = 70% AMT; (ii) the amount of SICI obtained with S1 = 70% AMT was the same at rest as during 10% MVC, but decreased at higher contraction levels; (iii) ICF was observed only at rest with S1 = 90% AMT; (iv) SICF was facilitated at 10% and 25% MVC, but not at 50% MVC. We conclude that during muscle activation, intracortical excitability reflects a balance between activation of SICI and SICF systems. Part of the reduction in SICI during contraction is due to superimposed recruitment of SICF. Low intensity (70% AMT) conditioning stimuli can test SICI independently of effects on SICF at low contraction levels.

Figure 1. SICI and ICF assessed in the cortical representation of the first dorsal interosseus (FDI) muscle in resting and active conditions

Mean data obtained from 16 subjects are reported. The effects of four different intensities of the conditioning stimulus (S1) (90% AMT (♦), 80% AMT (▪), 70% AMT (▴), 60% AMT (•)) on the size of the conditioned MEP were evaluated in the FDI muscle relaxed (A) and activated at 10% MVC (B). At rest the best inhibition was obtained delivering a S1 of 90% AMT while during contraction the most efficacious S1 was 70% AMT. At ICF ISIs the highest S1 intensity was able to induce a significant facilitation only in the relaxed muscle. The abscissa indicates interstimulus intervals (ISIs) while the ordinate indicates mean MEP amplitude expressed as a percentage of the S2 given alone. The thin horizontal lines indicate the 100% level. Error bars represent s.e.m.

Figure 2. Time course of SICI studied in the resting FDI (A) and during slight (10% MVC) muscular contraction (B)

Data were obtained from 8 subjects and four intensities of the conditioning stimulus (S1) (90% AMT (♦), 80% AMT (▪), 70% AMT (▴), 60% AMT (•)) were used. S2 was set to induce a test MEP of 1 mV peak to peak. At rest the inhibition was bigger with a S1 of 90% AMT at all ISIs tested, the deepest inhibition being observed at 1 and 2.5 ms. During contraction, the 70% AMT was confirmed to be the optimal S1 intensity to obtain the maximal SICI. Ordinate indicates mean conditioned MEP amplitude expressed as a percentage of the test MEP amplitude, taken as 100% (thin horizontal line) and abscissa reports ISIs. Error bars represent s.e.m.

Figure 3. Comparison of SICI induced by a conditioning stimulus of 90% AMT (A) and of 70% AMT (B) in the resting and active conditions

Note that while with a S1 of 90% AMT there was a big discrepancy in SICI curves between these two muscular conditions, when 70% AMT was used, the two curves overlapped. Abscissa indicates interstimulus intervals (from 1 to 5 ms in steps of 0.5 ms). MEP size after paired stimulation is expressed as a percentage of the control MEP in the ordinate. The thin horizontal line indicates the 100% level. Error bars represent s.e.m.

Figure 4. Effects of different levels of muscle contraction on SICI obtained delivering a S1 of 70% AMT

Three levels of contraction (10% MVC, black columns; 25% MVC, grey columns; 50% MVC, white columns) were evaluated in 8 subjects. A significant inhibition of the conditioned MEP was observed during the lowest level of contraction in all the ISIs tested (1, 2 and 3 ms). During 25% MVC a significant inhibition was observed only at 1 ms ISI. During strong contraction (50% MVC) no inhibition of the conditioned MEP was observed. On the ordinate the conditioned MEP amplitude is expressed as a percentage of the control MEP. The thin horizontal line indicates the 100% level. Error bars represent s.e.m. Asterisks indicate significant differences (*P < 0.05; **P < 0.01).

Figure 5. SICF assessed in the cortical representation of the first dorsal interosseus (FDI) muscle in resting and active conditions

A, SICF mean data obtained from 8 subjects keeping the FDI relaxed (black line) or during slight muscular contraction at 10% MVC (grey line). In both conditions, S1 intensity was set to produce a MEP with a mean peak-to-peak amplitude of 1 mV when given alone, while S2 intensity was set at 90% AMT. Only during muscle contraction were significant facilitatory peaks observed (1, 1.5, 2 and 3 ms, respectively). On the contrary no significant peaks were seen at rest. Grey asterisks indicate that in the active state the conditioned MEP was significantly (*P < 0.05; **P < 0.01) bigger than the test MEP (S1). The black asterisk indicates that at 1.5 ms ISI the conditioned MEPs obtained in the resting and active conditions were significantly different (P < 0.05). B, in the same subjects a paired-pulse stimulation in which the S1 stimulus intensity was set at 100% AMT and the S2 at an intensity able to evoke 1 mV MEP amplitude was delivered at rest and during contraction of the FDI at 10% MVC. At rest (black line) the conditioned MEP was inhibited at all ISIs, while during contraction a facilitation was observed at all ISIs, apart from 1 and 2.5 ms. ISIs are reported in abscissa; ordinate indicates mean MEP amplitude expressed as percentage value of the suprathreshold pulse alone (S1 in experiment in A and S2 in experiment in B); thin horizontal lines indicate the 100% level and error bars represent s.e.m.

Figure 6. Effects of different levels of contraction on SICF

Those ISIs where significant facilitatory peaks were previously found (Expt 5a, Fig. 6) were tested in four subjects. Three contraction levels (A: 10% MVC; B: 25% MVC; C: 50% MVC) were evaluated. For each of these levels of contraction, two S2 intensities, 90% AMT (black line) and 70% AMT (grey line), were evaluated. S1 was kept constant at 1 mV. Only using a S2 of 90% AMT was a MEP facilitation seen at 10% and 25% MVC. This facilitation was gradually reduced in amplitude with increasing contraction level and disappeared at 50% MVC. With a S2 of 70% AMT no significant facilitation was observed at any contraction level. Abscissa reports ISIs; the ordinate reports conditioned MEP amplitude which is expressed as a percentage value of the control MEP (S1). The thin horizontal line indicates the 100% level. Error bars represent s.e.m.

Figure 7. The model summarizes the effects of volitional contraction and of the intensity of the conditioning stimulus on SICI and SICF assessed in the FDI motor cortex

A, SICI inhibitory system (black) and SICF facilitatory system (grey) exert their influence on corticospinal neurons (CSN) through the production of IPSPs and EPSPs, respectively. Threshold of both systems, expressed in percentage of AMT was 60% for SICI and 80% for SICF. B, at rest the S1 optimal intensity to obtain maximal SICI was 80% or 90% AMT while for SICF it was around 100% AMT. When the classical SICI paired-pulse protocol was applied using a S1 of 80–90%, only the SICI system was activated, because this intensity was too weak to activate the SICF system. Then a strong pure SICI effect was obtained in this condition. C, during slight contraction (10% MVC) the SICF system was facilitated; then it was susceptible to being affected at lower intensity. A S1 stimulus of 80–90% AMT was then able to activate both SICI and SICF systems. Inhibitory effects on the CSN are antagonized by the facilitatory ones thus resulting in little change in the conditioned MEP amplitude, with a slight preponderance of inhibition. D, during the same level of contraction (10% MVC) the delivery of a S1 of 70% AMT induced only the activation of the SICI system because it was not strong enough to simultaneously activate the SICF system, even if the latter was facilitated by muscular activity. A pure SICI effect was then obtained. The absence of activation of the antagonistic facilitatory system during contraction allowed the same entity of inhibition in the resting and active conditions to be obtained (see text for more details).