A real electro-magnetic placebo (REMP) device for sham transcranial magnetic stimulation (TMS)☆
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.
References (25)
- et al.
Physical interaction between induced electrical fields can have substantial effects on neuronal excitation during simultaneous TMS of two brain areas
Clin Neurophysiol
(2005) - et al.
Sham TMS: intracerebral measurement of the induced electrical field and the induction of motor-evoked potentials
Biol Psychiatry
(2001) - et al.
Transcranial magnetic stimulation (TMS) in controlled treatment studies: are some “sham” forms active?
Biol Psychiatry
(2000) - et al.
Transcranial magnetic stimulation in cognitive neuroscience – virtual lesion, chronometry, and functional connectivity
Curr Opin Neurobiol
(2000) - et al.
TMS in cognitive plasticity and the potential for rehabilitation
Trends Cogn Sci
(2004) - et al.
Hypofunctioning of sensory gating mechanisms in patients with obsessive-compulsive disorder
Biol Psychiatry
(2005) - et al.
Non-invasive electrical and magnetic stimulation of the brain, spinal cord and roots: basic principles and procedures for routine clinical application. Report of an IFCN committee
Electroencephalogr Clin Neurophysiol
(1994) - et al.
A theoretical calculation of the electric field induced in the cortex during magnetic stimulation
Electroenceph Clin Neurophysiol
(1991) - et al.
Transcranial magnetic stimulation – a sandwich coil design for a better sham
Clin Neurophysiol
(2006) - et al.
Therapeutic application of transcranial magnetic stimulation in Parkinson’s disease: the contribution of expectation
Neuroimage
(2006)
The measurement of electric field and the influence of surface charge in magnetic stimulation
Electroencephalogr Clin Neurophysiol
Report on risk and safety of repetitive transcranial magnetic stimulation (rTMS): suggested guidelines from the International Workshop on Risk and Safety of rTMS. June 5–7 1996
Electroencephalogr Clin Neurophysiol
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Italian patent number: n. RM2006A000514.