The Influence of Different Inter-Trial Intervals on the Quantification of Intracortical Facilitation in the Primary Motor Cortex

Abstract

Intracortical facilitation (ICF) is a paired-pulse transcranial magnetic stimulation (TMS) measurement used to quantify interneuron activity in the primary motor cortex (M1) in healthy populations and motor disorders. Due to the prevalence of the technique, most of the stimulation parameters to optimize ICF quantification have been established. However, the underappreciated methodological issue of the time between ICF trials (inter-trial interval; ITI) has been unstandardized, and different ITIs have never been compared in a paired-pulse TMS study. This is important because single-pulse TMS studies have found motor evoked potential (MEP) amplitude reductions over time during TMS trial blocks for short, but not long ITIs. The primary purpose was to determine the influence of different ITIs on the measurement of ICF. Twenty adults completed one experimental session that involved 4 separate ICF trial blocks with each utilizing a different ITI (4, 6, 8, and 10 s). Two-way ANOVAs indicated no significant ITI main effects for test MEP amplitudes, condition-test MEP amplitudes, and therefore ICF. Accordingly, all ITIs studied provided nearly identical ICF values when averaged over entire trial blocks. Therefore, it is recommended that ITIs of 4-6 s be utilized for ICF quantification to optimize participant comfort and experiment time efficiency.

Keywords: electromyography; intracortical facilitation; motor evoked potential; short-interval intracortical inhibition; transcranial magnetic stimulation.

Figure 1

Schematic of the experimental protocol. Each experiment comprised 7 steps that included: 3 MVCs (pre), motor hotspot localization, RMT quantification, 1 mV stimulation intensity determination, the 1 mV_4 and 1 mV_10 control blocks, the ICF_4, ICF_6, ICF_8, and ICF_10 blocks, and 3 MVCs (post).

Figure 2

MEP amplitude in the control blocks. (A) The MEP amplitude as a function of Epoch number. MEP amplitude was similar for the 1 mV_4 condition and 1 mV_10 conditions and across the three epochs; (B) The MEP amplitude was similar for the 1 mV_4 and 1 mV_10 control blocks when averaged over the whole block.

Figure 3

MEP amplitude as a function of trial number for the control blocks. Each point represents the average of all twenty participants for a given trial in each of the two blocks. (A) MEP amplitude as a function of trial number for the 1 mV_4 condition; (B) MEP amplitude as a function of trial number for the 1 mV_10 condition.

Figure 4

Test MEPs, condition-test MEPs, and ICF values in the ICF blocks. (A) The MEP amplitude as a function of Epoch number for the test MEP trials only. MEP amplitude was similar for the four test MEP ITI conditions across the three epochs; (B) The MEP amplitude as a function of Epoch number for the condition-test MEP trials only. MEP amplitude was similar for the four condition-test ITI conditions across the three epochs; (C) ICF values as a function of Epoch number. ICF was lower for the ICF_4 condition compared with the ICF_10 condition, but only in the first epoch (p = 0.015). All other ICF values were similar for the four ICF ITI conditions across the 3 epochs. * indicates the significant pairwise comparison between ICF_4 and ICF_10 in Epoch 1.

Figure 5

The overall block averages for test MEPs, condition-test MEPs, and ICF values in the ICF blocks. (A) There were no differences in average MEP values for the test MEPs for any of the ITIs. (B) There were no differences in average MEP values for the condition-test MEPs for any of the ITIs. (C) Thus, there was no difference in ICF for the four ITIs when comparing the overall block averages.

Figure 6

Test MEP and condition-test MEP amplitudes as a function of trial number for the ICF blocks for the four ITIs are depicted for illustration (A–D). Test MEP trials are indicated in red and condition-test MEP trials are indicated in blue. Each data point represents the average MEP amplitudes of all 20 subjects for a given trial.

Figure 7

ICF as a function of trial number for the ICF blocks for the four ITIs are depicted for illustration (A–D). Each data point represents the average ICF values of all 20 subjects for a given trial.

Figure 8

Theoretical mathematical example using created round numbers to illustrate the general concept of how random covariation between the 2 elements of ICF (test MEP, condition-test MEP) for 2 separate epochs (blue and red rows) could influence ICF values and therefore the paired t-test between the ICF values for the 2 epochs. This analysis is best explained through the six following steps: (1) ICF is calculated as the ratio of the condition-test MEP amplitude to the test MEP amplitude and then expressed as a percentage; (2) this means that for the ICF value of a specified epoch (blue or red rows) to be higher or lower relative to the average ICF value of other epochs (black row criteria average values, a few mathematical conditions must be met; (3) relative to the average condition-test/test MEP = ICF value (150%), there are 3 possible outcomes (higher, lower, the same) for each of the 2 ICF inputs (test MEP, condition-test MEP). Thus, there are 3 (test MEP) × 3 (condition-test MEP) = 9 combinations that can uniquely influence the value of ICF; (4) 3 leads to a lower ICF vs. the average, 3 leads to a higher ICF vs. the average, and 3 lead to the same ICF vs. the average. Note criteria average test MEP and condition-test MEP absolute values (columns 4–5 from left) were multiplied by 20% (delta 20%) to give a lower or higher change; (4) Epoch 1 of the ICF_4 condition (blue) had a higher test MEP and a lower condition-test MEP than average and therefore lower ICF than average; (5) Epoch 1 of the ICF_10 condition had a lower test MEP and a higher condition-test MEP than average and therefore higher ICF than average; and (6) the low ICF in ICF_4 and high ICF in ICF_10 combined to cause the significant difference in ICF in Epoch 1 between ICF_4 and ICF_10.