A real electro-magnetic placebo (REMP) device for sham transcranial magnetic stimulation (TMS)

doi:10.1016/j.clinph.2006.11.005

Clinical Neurophysiology

Volume 118, Issue 3, March 2007, Pages 709-716

https://doi.org/10.1016/j.clinph.2006.11.005 Get rights and content

Abstract

Objective

There is growing interest in neuropsychiatry for repetitive transcranial magnetic stimulation (rTMS) as a neuromodulatory treatment. However, there are limitations in interpreting rTMS effects as a real consequence of physiological brain changes or as placebo-mediated unspecific effects, which may be particularly strong in psychiatric patients. This is due to the fact that existing sham rTMS procedures are less than optimal. A new placebo tool is introduced here, called real electro-magnetic placebo (REMP) device, which can simulate the scalp sensation induced by the real TMS, while leaving both the visual impact and acoustic sensation of real TMS unaltered.

Methods

Physical, neurophysiological and behavioural variables of monophasic and biphasic single-pulse TMS and biphasic 1 Hz and 20 Hz rTMS procedures (at different intensities) were tested in subjects who were expert or naïve of TMS. Results of the real TMS were compared with those induced by the REMP device and with two other currently used sham procedures, namely the commercially available Magstim sham coil and tilting the real coil by 90°.

Results

The REMP device, besides producing scalp sensations similar to the real TMS, attenuated the TMS-induced electric field (as measured by a dipole probe) to a biologically inactive level. Behaviourally, neither expert nor naïve TMS subjects identified the “coil at 90°” or the “Magstim sham coil” as a real TMS intervention, whilst naïve subjects were significantly more likely to identify the REMP-attenuated TMS as real.

Conclusions

The “goodness of sham” of the REMP device is demonstrated by physical, neurophysiological, and behavioural results.

Significance

Such placebo TMS is superior to the available sham procedures when applied on subjects naïve to TMS, as in case of patients undergoing a clinical rTMS trial.

Introduction

Born about 20 years ago as a tool to investigate the functionality of the corticospinal tract in intact humans, transcranial magnetic stimulation (TMS) is now increasingly employed in several fields of neuropsychiatry and neuroscience in general (Hallett, 2000, Rossini and Rossi, 2006). This is also due to technical advances which allow one to stimulate the brain repetitively. Such an approach is called repetitive TMS (rTMS), and represents, besides an established tool for demonstrating that brain regions are causally involved in a variety of cognitive functions (Walsh and Cowey, 2000, Pascual-Leone et al., 2000, Rossi and Rossini, 2004), even a therapeutic neuromodulatory strategy of increasing clinical relevance. The latter opportunity relies on the evidence that rTMS-induced excitability changes at cortical level may outlast the interventional time and that these modulatory effects may transiently improve symptoms of many neuropsychiatric diseases characterized by dysfunctions of regional excitability (Wasserman and Lisanby, 2001, Hoffman and Cavus, 2002, Fregni and Pascual-Leone, 2005).

However, both psychophysiological investigations and therapeutic trials with TMS require control conditions with sham (placebo) stimulation. Indeed, placebo effects induced by rTMS may be particularly relevant in neuropsychiatric patients (Wasserman and Lisanby, 2001) and even produce clearly detectable changes in brain activity, as recently demonstrated in parkinsonian patients (see Strafella et al., 2006).

None of the available sham conditions are fully satisfactory as to the absence of biological effects and failure to reproduce the scalp sensations induced by real TMS, especially concerning trigeminal afferents activation underneath the stimulation site (see later in the discussion). To obtain a more reliable sham stimulation, we developed the so-called REMP (real electro-magnetic placebo) device, a 3-cm thick wooden tool shaped and coloured as a real 8-shaped coil, and containing a bipolar electrical stimulator on the surface which comes in contact with the scalp. During real TMS, the REMP device lies over the magnetically stimulating coil, whilst during sham stimulation the position of the two coils is inverted, so that the REMP is between the real coil and the scalp. This way, both the acoustic sensation and visual impact are the same and the scalp sensation of the real TMS is synchronously reproduced by the electrical stimulator of the REMP device (Fig. 1). Here we present a series of experiments aimed to demonstrate the physical, physiological and behavioural reliability of the REMP device.

Section snippets

Subjects

All participants were healthy volunteers who gave their written informed consent to participate in the study, which was approved by the local Ethics Committee. They were seated in a comfortable chair with their arms fully supported and were asked to report any potential adverse effect experienced during or after TMS.

The REMP device (Fig. 1)

The REMP device (weight about 230 g) is built in compact wood, and is of the same shape and colour as the 70 mm eight-shaped coil produced by Magstim Co. (Whitland, Dyfed, UK). It is

Results

None of the participants reported adverse reactions during or after the experimental procedures.

Discussion

There is general agreement that an ideal sham TMS should fulfil the following criteria: absence of biological effects on the cortex, same visual impact and position of the real coil on the scalp, and same acoustic and sensory afferent sensations (Loo et al., 2000, Lisanby et al., 2001, Sommer et al., 2006).

Tilting the stimulating coil at less than 90° is biologically active on the brain (Lisanby et al., 2001). Both sham TMS with the coil at 90°, or keeping the coil at a distance from the scalp,

Acknowledgments

Authors thank Drs G. Greco, A. Di Rollo, A. De Capua, and A. Borgheresi for experimental help and constructive criticism.

This research was supported by a Project grant from the Ministero della Salute RF 2005/56.

The Center of Florence was also supported by a grant from “Ente Cassa di Risparmio di Firenze”, Florence, Italy.

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^☆: Italian patent number: n. RM2006A000514.

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A real electro-magnetic placebo (REMP) device for sham transcranial magnetic stimulation (TMS)☆

Abstract

Objective

Methods

Results

Conclusions

Significance

Introduction

Section snippets

Subjects

The REMP device (Fig. 1)

Results

Discussion

Acknowledgments

Clin Neurophysiol

Biol Psychiatry

Biol Psychiatry

Curr Opin Neurobiol

Trends Cogn Sci

Biol Psychiatry

Electroencephalogr Clin Neurophysiol

Electroenceph Clin Neurophysiol

Clin Neurophysiol

Neuroimage

Electroencephalogr Clin Neurophysiol

Electroencephalogr Clin Neurophysiol