Research ReportThe effects of alterations in conditioning stimulus intensity on short interval intracortical inhibition
Introduction
Cortical excitability can be assessed using a paired-pulse transcranial magnetic stimulation [TMS] paradigm. In the conventional constant stimulus paradigm, a subthreshold conditioning stimulus [CS] exerts an effect on a subsequent test stimulus [TS], such that when the interstimulus interval [ISI] is between 1 and 5 ms the motor evoked potential [MEP] amplitude produced by the test response is inhibited, a process referred to as short interval intracortical inhibition [SICI] (Di Lazzaro et al., 1998, Hanajima et al., 1998a, Kujirai et al., 1993, Nakamura et al., 1997).
Recently, a paired-pulse threshold-tracking TMS technique was developed to overcome the potential limitations of the constant stimulus method (Awiszus et al., 1999, Fisher et al., 2002, Vucic et al., 2006). Specifically, the utility of the constant stimulus technique may be limited by variability in the motor evoked potential [MEP] amplitude with consecutive stimuli (Kiers et al., 1993). This variability results from spontaneous fluctuations in the resting threshold of cortical neurons. The threshold-tracking technique attempts to control for variability in cortical excitability by assessing RMT every stimulus sequence (see Experimental procedures), but even so, resting threshold has to be reasonably stable for a reliable assessment of SICI. Using the threshold-tracking technique, two phases of SICI at ISIs of 1 and 2.5–3 ms were identified (Fisher et al., 2002, Vucic et al., 2006), and the presence of two phases of SICI has been confirmed using the constant stimulus method (Roshan et al., 2003). While there is supportive evidence to suggest that the later SICI peak at 2.5 ms is mediated by synaptic mechanisms, the physiological basis underlying the first peak [at 1 ms] is less clear. Fisher et al. (2002) proposed that refractoriness of axons of cortical interneurons subliminally activated by a subthreshold CS underlies the first phase of SICI, a suggestion also argued by Chen (2004). In contrast, Roshan et al. (2003) argued that axonal refractoriness could not entirely account for the first phase of SICI and suggested a role for synaptic processes. It has been argued that SICI is a complex neurophysiological measure, mediated in part by the interaction of multiple cortical circuits, reflecting a balance between inhibition and facilitation (Ni and Chen, 2008, Peurala et al., 2008). The present study used novel threshold-tracking TMS techniques to shed further light on the mechanisms underlying SICI by investigating the effects of variable CS intensity, in addition to correlating SICI at different CS intensities and interstimulus intervals.
Section snippets
Results
A complete sequence of recordings was obtained from all subjects. The peak-to-peak amplitude of the CMAP for the APB muscle was 9.1 ± 1.3 mV, while the neurophysiological index was 2.7 ± 0.5, both within the normal range (de Carvalho and Swash, 2000, Vucic et al., 2006). In addition, the mean distal motor latency to the APB was 4.0 ± 0.1 ms, and the minimal F-wave latency was 29.2 ± 0.9 ms, within previously established control ranges (Kimura, 2001, Vucic et al., 2006).
Discussion
In the present study, a threshold-tracking TMS technique was applied using a paired-pulse paradigm to investigate the mechanisms underlying SICI when the intensity of the conditioning stimulus was varied. With the conditioning stimulus set to 70% RMT, SICI lasted for 7 ms and had two distinct phases, a small peak at 1 and a large peak at 2.5 ms. Reducing the CS intensity to 40% RMT resulted in disappearance of the small peak at 1 ms and less SICI overall. Increasing the CS intensity to 90% RMT
Experimental procedures
Studies were undertaken on 10 right-handed healthy volunteers [4 men and 6 women, mean 44 years, age range 24–73 years]. It is noted that in our control data for SICI for conditioning stimulus 70% (Vucic et al., 2006), no age-related changes were evident between younger and older subjects [SICI age < 40 years, 8.3 ± 1.3%; SICI > 40 years, 9.7 ± 1.1%, P = 0.2]. None of the subjects had symptoms or clinical signs of central or peripheral nerve dysfunction. Subjects gave written informed consent to the
Acknowledgments
Funding support from the Brain Foundation, Motor Neuron Disease Research Institute of Australia and National Health and Medical Research Council of Australia [Project grant number 510233] is gratefully acknowledged. The authors thank Professor Hugh Bostock for helpful comments concerning the manuscript.
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2020, Clinical NeurophysiologyCitation Excerpt :Anatomical and physiological differences in the interneuronal cortical circuitry could account for AP-to-LM latency spread and thereby SICI variability between individuals (Vucic et al., 2006a, Matamala et al., 2018). In addition, SICI may also be influenced the linear increment in CS stimulus intensity, being optimal when CS intensity is set to 70 or 80% RMT (Vucic et al., 2009, Lackmy et al., 2010, Samusyte et al., 2018). While the CS stimulus intensity was not varied in the present study, the increase in SICI with linear increment of CS intensity [from 40 to 80% RMT] suggests that I3 waves are most optimally recruited with CS intensity set to 70 or 80% RMT.