Influence of Short-Interval Intracortical Inhibition on Short-Interval Intracortical Facilitation in Human Primary Motor Cortex

Abstract

Using the paired-pulse paradigm, transcranial magnetic stimulation (TMS) has revealed much about the human primary motor cortex (M1). A preceding subthreshold conditioning stimulus (CS) inhibits the excitability of the motor cortex, which is named short-interval intracortical inhibition (SICI). In contrast, facilitation is observed when the first pulse (S1) is followed by a second one at threshold (S2), named short-interval intracortical facilitation (SICF). SICI and SICF have been considered to be mediated by different neural circuits within M1, but more recent studies reported relations between them. In this study, we performed triple-pulse stimulation consisting of CS-S1-S2 to further explore putative interactions between these two effects. Three intensities of CS (80-120% of active motor threshold: AMT) and two intensities of S2 (120 and 140% AMT) were combined. The SICF in the paired-pulse paradigm exhibited clear facilitatory peaks at ISIs of 1.5 and 3 ms. The second peak at 3 ms was significantly suppressed by triple-pulse stimulation using 120% AMT CS, although the first peak was almost unaffected. Our present results obtained using triple-pulse stimulation suggest that each peak of SICF is differently modulated by different intensities of CS. The suppression of the second peak might be ascribed to the findings in the paired-pulse paradigm that CS mediates SICI by inhibiting later I waves such as I3 waves and that the second peak of SICF is most probably related to I3 waves. We propose that CS might inhibit the second peak of SICF at the interneurons responsible for I3 waves.

Increased primary motor cortical excitability by a single-pulse transcranial magnetic stimulation over the supplementary motor area

“…First, the modulation of SICF was observed when S2 intensity was 1.0 AMT for FDI, but not 1.4 AMT. Our results, as well as other reports (Chen and Garg 2000;Shirota et al 2010), showed that higher S2 intensity produced larger SICF. Therefore, enhancement of SICF might be blurred by large peaks of SICF when S2 intensity was as high as 1.4 AMT, possibly because of modest influence of the SMA stimulation on SICF system.…”

“…2. As previously reported, higher S2 intensity yielded more facilitation (Chen and Garg 2000;Shirota et al 2010). Statistically, three-way repeated-measures ANOVA revealed significant main effect of S2 Intensity (F 1,12 = 25.4, p \ 0.001), ISI (F 2.8,33 = 14.1, p \ 0.001), and their interaction (F 7,84 = 3.5, p = 0.002).…”

“…Because intervals between peaks of SICF are similar to I-wave intervals, SICF is believed to be produced by summation of EPSPs for I-wave generation (Hanajima et al 2002;Peurala et al 2008;Ziemann et al 1998). More recent studies revealed differential modulation of each peak of SICF by another stimulus (Shirota et al 2010;Wagle-Shukla et al 2009); we reported that the second peak of SICF was most probably caused by increase in I3 wave (Shirota et al 2010). Therefore, the simplest explanation of our present findings is that SMA stimulation might enhance SICF through I3 wave summation.…”

Short- and intermediate-interval cortical inhibition and facilitation assessed by navigated transcranial magnetic stimulation

“…This, in turn, makes it unlikely that the inhibition at ISI of 3 ms is due to refractory corticospinal axons and/or after hyperpolarization in the cell body. The inhibition is evoked especially in I3-wave at ISIs 3-5 s (Hanajima et al, 2003;Shirota et al, 2010). Based on these earlier investigations the observed latency change in our study at ISI of 3 ms may be associated with suppression of I3-waves.…”

Age-related changes in short-interval intracortical facilitation and dexterity

“…The first and later SICF peaks are affected differently by manipulation of TMS stimulus parameters, indicating different underlying physiological processes [13]. SICF 1.5 is thought to result from S2-evoked excitation of the initial axonal segments of excitatory interneurons that were subliminally excited by S1, whereas SICF 2.5 and later peaks are thought to result from summation of excitatory synaptic activity [14].…”