Short-interval intracortical inhibition as a function of inter-stimulus interval: Three methods compared

Abstract

Background: Short-interval intracortical inhibition (SICI), as measured by threshold-tracking as a function of inter-stimulus interval (ISI), has been proposed as a useful biomarker for amyotrophic lateral sclerosis (ALS), but its relationship to conventional amplitude measurements has not been established. Methods: Serial tracking of SICI at increasing ISIs from 1 to 7 ms (T-SICIs) was compared in 50 healthy control subjects with the same ISIs tracked in parallel (T-SICIp), and with conventional amplitude measurements (A-SICI). For T-SICIp and A-SICI, pairs of conditioning and test stimuli with different ISIs were pseudo-randomised and interspersed with test-alone stimuli given at regular intervals. Thresholds were estimated by regression of log peak-to-peak amplitude on stimulus. Results: T-SICIp and A-SICI were closely related: a tenfold reduction in amplitude corresponding to an approximately 18% increase in threshold. Threshold increases were greater for T-SICIs than for T-SICIp at 3.5e5 ms (P < 0.001). This divergence depended on the initial settings and whether ISIs were progressively increased or decreased, and was attributed to the limitations of the serial tracking protocol. SICI variability between subjects was greatest for T-SICIs estimates and least for A-SICI, and only A-SICI estimates revealed a significant decline in inhibition with age. Conclusions: The serial tracking protocol did not accurately show the dependence of inhibition on ISI. Randomising ISIs gives corresponding SICI measures, whether tracking thresholds or measuring amplitude measurements. SICI variability suggested that A-SICI measurements may be the most sensitive to loss of inhibition.

Early diagnosis of amyotrophic lateral sclerosis by threshold tracking and conventional transcranial magnetic stimulation

“…Parallel T-SICI also estimated inhibition with less variability than serial T-SICI, although not as little as was achieved by A-SICI [21].…”

Test-Retest Reliability of Short-Interval Intracortical Inhibition Assessed by Threshold-Tracking and Automated Conventional Techniques

“…Earlier studies have compared parallel TT-TMS with cTMS for SICI with either multiple conditioning stimulus intensities and single ISI (Samusyte et al, 2018) or a single conditioning stimulus intensity and multiple ISIs (Tankisi et al, 2021a).…”

“…More recently, a good correlation of automated A-SICI and T-SICI at a single CS intensity and ISIs of 1-7 ms with a parallel tracking strategy and important limitations of serial tracking were demonstrated in healthy subjects (Tankisi et al, 2021a). It was proposed that due to a smaller between-subject variability among healthy individuals, A-SICI may be better at demonstrating a pathological loss of inhibition, which has been observed as an early feature of motor neuron disease .…”

Conventional and Threshold-Tracking Transcranial Magnetic Stimulation Tests for Single-handed Operation

“…RMT for a 200 µV (RMT200) or a 1000 µV (RMT1000) peakto-peak response were detected by a '4→2→1' tracking rule and logarithmic regression as previously described 18 . The RMT200 was 52.1% MSO, and the RMT1000 was 59.8%…”

“…The serial approach is efficient when reference thresholds are stable, as in peripheral nerves. However, when thresholds fluctuate widely, as is the case for corticospinal excitability, serial tracking has been found to have the disadvantage of seriously distorting the ISI-dependence of SICI 18 . Therefore, an alternative 'parallel' threshold-tracking paradigm may be more appropriate for SICI (T-SICIp) 18 , 19 The equipment used here includes a TMS machine, an isolated linear bipolar constant-current stimulator, a noise eliminator to remove 50-60 Hz electrical interference, an electromyography amplifier, and a data acquisition system.…”