TMS-induced silent periods: A review of methods and call for consistency

Highlights

• Muscle silent periods provide a valuable in vivo measurement of cortical inhibitory function in the human brain.

• Past silent period studies have implemented widely varying methodology, including subjective analyses.

• The varying methodology and lack of methods details in past work limits comparison across studies and reproducibility.

• Here, we review the impact of methodological choices on silent period outcomes, including considerations for the lower limbs.

• We conclude with recommendations to improve the consistency of data collection, analysis, and reporting in future studies.

Abstract

Transcranial magnetic stimulation (TMS)-induced silent periods provide an in vivo measure of human motor cortical inhibitory function. Cortical silent periods (cSP, also sometimes referred to as contralateral silent periods) and ipsilateral silent periods (iSP) may change with advancing age and disease and can provide insight into cortical control of the motor system. The majority of past silent period work has implemented largely varying methodology, sometimes including subjective analyses and incomplete methods descriptions. This limits reproducibility of silent period work and hampers comparisons of silent period measures across studies. Here, we discuss methodological differences in past silent period work, highlighting how these choices affect silent period outcome measures. We also outline challenges and possible solutions for measuring silent periods in the unique case of the lower limbs. Finally, we provide comprehensive recommendations for collection, analysis, and reporting of future silent period studies.

Introduction

Transcranial magnetic stimulation (TMS) was first introduced in 1985 as a noninvasive method for stimulating the human brain (Barker et al., 1985). Barker et al. demonstrated that a single TMS pulse to the primary motor cortex could elicit responses in the muscles that received corticospinal input from the stimulated cortical region (Barker et al., 1985). Since this time, multiple TMS approaches including single pulse (e.g., Fling and Seidler, 2011; Swanson and Fling, 2018), paired pulse (e.g., Gagnon et al., 2011; Wittenberg et al., 2007), and repetitive TMS (e.g., Brunoni et al., 2017; Chou et al., 2015; Fitzgerald et al., 2006; Galhardoni et al., 2015) have been adopted and applied to a wide variety of tasks and patient populations.

Despite the growing popularity of TMS, there has been a lack of methodological studies for single pulse techniques, including testing of cortical and ipsilateral silent periods (cSPs and iSPs, respectively). TMS-induced silent periods present as a reduction of ongoing electromyography (EMG) activity and provide information regarding intracortical and interhemispheric inhibition during voluntary muscle contraction. Thus, they are particularly suited for studying how the central nervous system controls muscle activity. To date, silent period studies have used varying methodology and many papers fail to report complete methods. This has made it difficult to compare outcome measures across studies and has precluded meta-analyses among patient populations (Major et al., 2015) or in older age (Levin et al., 2014). For instance, older age has been associated with decreased upper limb cSP duration (Beynel et al., 2014; Davidson and Tremblay, 2013a; Oliviero et al., 2006; Sale and Semmler, 2005), no difference in cSP duration (Fujiyama et al., 2009, 2012; Hunter et al., 2008), and increased cSP duration (McGinley et al., 2010) across studies. Methodological differences between these studies make it difficult to understand how age relates to cSP duration.

In the present review, we address the potential impacts of methodological differences on silent period outcome variables and provide recommendations for future work. We begin with a discussion of the mechanisms underlying cSPs and iSPs as well as common silent period outcome measures (Section 2). Next, we outline methodological differences among past silent period work, which make inter-study comparisons difficult (Sections 3–5). Finally, we examine unique methodological considerations for measuring silent periods in the lower limbs (Section 6), and provide recommendations for collection, analysis, and reporting in future silent period studies (Section 7).