Transcranial magnetic stimulation (TMS) is a noninvasive brain stimulation technology that can focally stimulate the human cortex.1,2
Several studies have found that rTMS delivered over motor cortex can affect the perception of laboratory-induced pain in healthy adults as well as chronic neuropathic pain in clinical samples. 3–12
Additionally, a few studies have demonstrated anti-nociceptive effects with TMS over the prefrontal cortex TMS.13–17
One significant limitation of much of the research on the effects of TMS on pain perception to date concerns the nature of the placebo or sham conditions employed. When TMS pulses are delivered repetitively (especially prefrontal TMS) it is often experienced as painful (and at a minimum it produces noticeable scalp and/or facial sensations; see Borckardt18
). Most sham TMS techniques (whether they involve tilting the coil away from the scalp or whether a specially designed sham TMS coil is used) produce identical sounds to active TMS, but they do not cause much, if any, scalp or facial sensation or discomfort. This is a serious problem when investigators are attempting to evaluate the effects of TMS using traditional sham techniques for several reasons including: 1) introduction of unintended systematic differences between real and sham TMS groups (i.e., confounds), 2) participants may be able to correctly guess the condition to which they have been randomized (introducing demand characteristics), and 3) real TMS may lead to changes in pain perception independent of the intended cortical stimulation. A typical TMS session lasts 20-minutes, and it is possible that the painfulness of the experience triggers pain modulatory activity in research subjects (e.g., endogenous opioid activity, cognitive changes, activation of other descending pain inhibitory mechanisms). Thus, when comparing the effects of real TMS to sham TMS on pain perception, any observed antinociceptive effects of real TMS may be simply due to exposing subjects to a 20-minute painful procedure. These effects may have little or nothing to due with changes in cortical activation. Until a simple, affordable sham TMS system is available that produces facial/scalp sensations comparable to real TMS, valid inferences about the effects of TMS on pain perception will be limited.
A few studies have begun to address the limitations associated with traditional approaches to sham TMS. Okabe et al (2003) implemented an electrical sham system in a controlled trial of rTMS for Parkinson’s Disease. A 0.2 ms electrical pulse was delivered in-time with TMS coil clicks at twice the intensity of participants’ sensory thresholds for skin stimulation. However, it is unclear based on the material presented in this paper, what kind of equipment was used to produce the electrical stimulation, what methods were implemented to sync the electrical pulses with the TMS coil noises, what TMS coils the system would work with, and what costs were associated with building and implementing the system. Very recently, Rossi et al (2007) has introduced a sophisticated sham system (real electro-magnetic placebo; REMP) in which a compact wood component (contoured to the shape of a Magstim figure-8 coil) is attached to the active surface of a real Magstim coil with Velcro strips. The thickness of the component (3 cm) is likely sufficient to attenuate most of the induced electrical currents by the TMS coil. An electric stimulator is connected to round copper metal disks embedded in the surface of the REMP attachment. Electrical pulses are then delivered in sync with the TMS pulses. While it is likely possible to develop REMP attachments for different coil types and shapes, at present, it appears that this device has only been developed and tested for the 70mm figure-eight shaped Magstim coil. One potential problem that might arise with this otherwise very elegant system, is that it would be difficult to truly blind the TMS administrator as to whether a participant was receiving real or sham TMS because the REMP device changes the weight and appearance of the handheld coil. Thus, the present REMP design would permit the implementation of excellent single-blind research methods but double-blind studies would prove considerably more difficult.
One emerging issue regarding TMS systems in general is related to portability. Recently, Borckardt et al (2006a) has found that 20-minutes of 10Hz prefrontal TMS (at 100% of resting motor threshold) is associated with a reduction in patient-controlled analgesia use post-operatively (a total of 4000 pulses were delivered in the 20-minute session). In this study, a Neuronetics TMS machine was wheeled into the post-anesthesia care unit (PACU) and TMS was delivered to patients immediately following bariatric surgery. The available Magstim coils are not be capable of stimulating at a frequency of 10Hz for 20 minutes (4000 pulses) without problems related to coil overheating. Thus, the sham systems described above (for use with Magstim coils) would not work for this type of TMS application. In order to have provided sham stimulation that matched real TMS with respect to facial and scalp sensations with currently available technology using our Neuronetics machine, we would have had to transport an expensive CPU along with a monitor, and large electric pulse-generator to the PACU along with the TMS machine (as per the James-Long sham TMS system described in the Methods section). Additionally, we would have had to set-up this rather bulky and elaborate system for each participant in the study, which would have added considerable time and effort.
In this paper, we first describe the development of a simple, portable, and relatively inexpensive sham TMS system designed to mimic real TMS with respect to perceived facial/scalp sensations, and painfulness. This system is designed to work with any TMS machine that has a TTL output port. It is small enough to sit atop the TMS machine, and is inexpensive enough to implement in trials that have limited funding. Additionally, we present data from a small pilot trial in which the sensations and location (scalp and/or facial) produced by the sham system are compared to those produced by real TMS.