A comparative study of the effects of repetitive paired transcranial magnetic stimulation on motor cortical excitability

doi:10.1016/j.jneumeth.2007.06.002

Journal of Neuroscience Methods

Volume 165, Issue 2, 30 September 2007, Pages 265-269

https://doi.org/10.1016/j.jneumeth.2007.06.002 Get rights and content

Abstract

Objectives

Various methods of application of repetitive transcranial magnetic stimulation (TMS) have been evaluated for their potential capacity to alter motor cortical excitability. Initial research suggests that the repetitive application of paired TMS pulses (repetitive paired pulse TMS (rppTMS)) may have greater effects on cortical excitability, perhaps through the facilitation of I-wave interaction. We aimed to compare the post-train effects of 15 min trains of rppTMS to investigate the potential therapeutic application of this technique as well as to compare it to a standard high frequency repetitive TMS paradigm.

Methods

Ten normal subjects received three 15 min sessions of rppTMS, 5 Hz high frequency rTMS and sham TMS in randomised order. rppTMS consisted of a single train of 180 pulse pairs (0.2 Hz, 1.5 ms inter-stimulus interval, supra-threshold intensity) administered over 15 min. The rTMS condition involved 750 pulses provided in 5 s 5 Hz trains with a 25 s inter-train interval at 90% of the RMT. Motor evoked potential size and cortical silent period duration were assessed before and after each session.

Results

There were no significant changes in cortical excitability produced by any of the stimulation conditions. Five hertz rTMS produced an increase in cortical silent period duration (p = 0.004) which was not affected by rppTMS.

Conclusions

Fifteen minutes trains of 1.5 ms rppTMS do not substantially increase post train cortical excitability. Repetitive brief trains of 5 Hz rTMS also do not alter excitability but appear to effect cortical inhibition.

Introduction

A considerable number of studies have investigated the effects of repetitive transcranial magnetic stimulation (rTMS) trains at various frequencies on the excitability of the motor cortex (Fitzgerald et al., 2006a). Generally, high frequency trains have been shown to produce transiently increased cortical excitability, as assessed by a post-train increase in evoked motor potential (MEP) size (Fitzgerald et al., 2006a). In contrast, low frequency trains (usually ∼1 Hz) have been shown to reduce MEP size (Fitzgerald et al., 2006a). These forms of stimulation are being widely assessed for use in the treatment of a number of psychiatric and neurological disorders (for example (Fitzgerald et al., 2003, George et al., 1995, Hoffman et al., 2003)). More recently a number of novel forms of TMS have been developed for the purpose of enhancing stimulation effects. One of these approaches has been the repetitive application of pairs of pulses (repetitive paired pulse TMS (rppTMS)). This involves the application of the pairs at very low frequency (for example 0.2 Hz). The first rppTMS study involved pulses at a 3 ms interval that were shown to produce a substantial decrease in cortical excitability (Khedr et al., 2004, Sommer et al., 2002). More recently, Thickbroom et al. have shown that pairs at a 1.5 ms interval and frequency of 0.2 Hz produce an increase in motor cortical excitability that appears to be substantially greater than that previously seen with high frequency rTMS protocols (Thickbroom et al., 2006). In particular, this study reported increases in MEP size of the order of 400% during the train and of similar magnitude in the 10 min post-train. However, this study did not directly compare the effects of rppTMS to a standard high frequency condition.

If repetitive paired stimulation is able to be used to markedly enhance cortical excitability, it would have some significant advantages over high frequency stimulation. This method would result in considerably less stress on equipment used and should be substantially more comfortable for individual subjects. However, further confirmation of the strengths of these effects is required prior to the conduct of therapeutically oriented trials. In addition, the 30 min of rppTMS utilised in the study of Thickbroom et al. is considerably longer than the duration of rTMS provided in most previous rTMS trials. Although the ‘in train’ data provided by Thickbroom et al. suggest that cortical excitability is markedly increased after only 15 min (Thickbroom et al., 2006; see Fig. 1), it is not clear if these changes would be apparent if post-train effects were measured at this time. Therefore, we conducted a study to assess the post-train effects of a shorter duration of rppTMS (15 min) on cortical excitability to investigate if this is potentially useful as a therapeutic intervention. We also included a high frequency (5 s trains of 5 Hz rTMS) comparator condition as well as a sham stimulation condition. This was chosen as it is a commonly used application of rTMS used in treatment trials (for example Fitzgerald et al., 2006b, George et al., 2000, Rumi et al., 2005). The conditions were not fully matched in pulse number or intensity but chosen to be matched in time and be provided as approximate potential treatment protocols, for example as may be used in TMS treatment of depression.

Section snippets

Subjects

Ten normal subjects were studied (mean age 27.3 ± 3.97 years, six females, four males). The Human Subject and Ethics Committee of Bayside Health, The Alfred Hospital approved the study and all subjects gave written informed consent. All subjects were screened with a brief clinical interview for current or past psychiatric or neurological disorders and were free of any psychoactive drugs or medication. Menstrual cycle stage was not controlled in the female subjects.

Study procedure

All subjects were studied on

Results

All participants completed each phase of the study and there were no adverse events. The CSP data from one subject was not able to be analysed due to technical problems with the data collection.

All study data is presented in Table 1. With regards to MEP size, we found no changes produced by either 5 Hz or the paired stimulation condition. For MEP size measured with the Magstim 200 system, there was no significant difference produced by the two active conditions over time: there was no effect of

Discussion

In this randomised comparison study, we did not find any significant effects of 15 min of rppTMS on cortical excitability or cortical inhibition as measured by MEP size and CSP duration. A number of TMS methods have been described which may be used to alter the excitability of motor cortex and potentially other cortical regions. These paradigms require exploration and replication prior to the testing their therapeutic potential in neuropsychiatric diseases such as depression and schizophrenia.

Acknowledgements

PF was supported by a Practitioner Fellowship grant from National Health and Medical Research Council (NHMRC) and a NARSAD Young Investigator award. ZJD was supported by the Canadian Institutes of Health Research (CIHR) Clinician Scientist award, by the Ontario Mental Health Foundation (OMHF) and by Constance and Stephen Lieber through a National Alliance for Research on Schizophrenia and Depression (NARSAD) Lieber Young Investigator award.

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A comparative study of the effects of repetitive paired transcranial magnetic stimulation on motor cortical excitability

Abstract

Objectives

Methods

Results

Conclusions

Introduction

Section snippets

Subjects

Study procedure

Results

Discussion

Acknowledgements

Clin Neurophysiol

Biol Psychiat

Clin Neurophysiol

Clin Neurophysiol

Clin Neurophysiol

Clin Neurophysiol

Biol Psychiat

Neurosci Lett

Clin Neurophysiol