Comparison between adaptive and fixed stimulus paired-pulse transcranial magnetic stimulation (ppTMS) in normal subjects

Abstract

Objectives: Paired-pulse TMS (ppTMS) examines cortical excitability but may require lengthy test procedures and fine tuning of stimulus parameters due to the inherent variability of the elicited motor evoked potentials (MEPs) and their tendency to exhibit a 'ceiling/floor effects' in inhibition trials. Aiming to overcome some of these limitations, we implemented an 'adaptive' ppTMS protocol and compared the obtained excitability indices with those from 'conventional' fixed-stimulus ppTMS.

Methods: Short- and long interval intracortical inhibition (SICI and LICI) as well as intracortical facilitation (ICF) were examined in 20 healthy subjects by adaptive ppTMS and fixed-stimulus ppTMS. The test stimulus intensity was either adapted to produce 500 μV MEPs (by a maximum likelihood strategy in combination with parameter estimation by sequential testing) or fixed to 120% of resting motor threshold (rMT). The conditioning stimulus was 80% rMT for SICI and ICF and 120% MT for LICI in both tests.

Results: There were significant (p < 0.05) intraindividual correlations between the two methods for all excitability measures. There was a clustering of SICI and LICI indices near maximal inhibition ('ceiling effect') in fixed-stimulus ppTMS which was not observed for adaptive SICI and LICI.

Conclusions: Adaptive ppTMS excitability data correlates to those acquired from fixed-stimulus ppTMS.

Significance: Adaptive ppTMS is easy to implement and may serve as a more sensitive method to detect changes in cortical inhibition than fixed stimulus ppTMS. Whether equally confident data are produced by less stimuli with our adaptive approach (as already confirmed for motor threshold estimation) remains to be explored.

Keywords: Maximum likelihood strategy; Non-invasive brain stimulation; Paired pulse TMS; Parameter estimation by sequential testing; Threshold-tracking; Transcranial magnetic stimulation.

Fig. 1

Resting motor threshold estimation by ML-PEST. The initial deflection of the curve represents a large change in TMS MO% followed by an exponential-like convergence of the rMT estimate towards the final estimate after 20 trials i.e., the TMS MO% for trial number 21. The Y-axis represents the difference (ΔMO%; given in absolute values) between the rMT estimate for each trial and the final estimate after 20 trials. The plot is based on rMT estimation data from all 20 subjects obtained before FS-ppTMS.

Fig. 2

Adaptive ppTMS (A-ppTMS) with unconditioned (ucTS) and conditioned (SICI, ICF and LICI) test stimulus estimates in one subject. After each stimulation, the statistical algorithm (ML-PEST) presents a new and more confident estimate of the TS intensity required to produce MEPs of 0.5 mV for ucTS, SICI, ICF and LICI. The final estimates after 15 trials are shown rightmost in the figure where SICI, ICF and LICI effects are demonstrated as differences in MO% compared to ucTS. The plots for ucTS, SICI and LICI are overlapping for the first 2–3 stimuli (the first stimulus was always set to 50% MO), see text for details.

Fig. 3

Excitability effects (ΔSICI, ΔICF and Δ LICI) in relation to unconditioned test stimulus intensities (ucTS). Data from twenty subjects. The conditioning effect (expressed as the difference (Δ) between the conditioned and unconditioned TS intensities) plotted against ucTS intensities for SICI (A), ICF (B) and LICI (C). Positive values on the y-axis indicate inhibition and negative values indicate facilitation. Eleven out of the 20 subjects did not demonstrate ICF (B). All values on X and Y-axes represent TMS machine output %.

Fig. 4

Correlation between fixed stimulus ppTMS and adaptive ppTMS indices for SICI (A), ICF (B) and LICI (C). Fixed stimulus ppTMS data are presented on the Y-axis where values below 100% indicate inhibition. Normalised adaptive ppTMS indices are presented on the X-axis where values above 0% indicate inhibition.