History & FDA Approval

The first known instance of TMS can be traced back to 1896 when Jacques-Arsène d'Arsonval reported phosphenes (an entoptic phenomenon characterized by the experience of seeing light without light actually entering the eye, very likely due to retinal stimulation) when placing a coil (110 volts, 30 amperes) around his head. Then in 1985, it was demonstrated by Anthony Barker et al. that an electric coil placed on the scalp could stimulate a region of the underlying brain. In this case, magnetic stimulation was demonstrated to conduct nerve impulses from the motor cortex to the spinal cord.1 Prior to this in 1980, Merten and Morton showed that it was possible to stimulate the motor areas of the human brain electrically through the intact scalp and skull using transcranial electrical stimulation (TES), in which a brief, high voltage electric shock was used to activate the motor cortex.2 This produced a relatively synchronous muscle response, which is known as the motor evoked potential (MEP). Although it was clear that this would be useful for many purposes, TES had a number of practical limitations: it is a painful technique for subjects because the electrical shocks activate the pain fibers in the scalp and can burn the scalp itself. Additionally, another difficulty is posed by the issue of conduction through the scalp and the skull. The TMS technique however circumnavigates these problems. TMS benefits from the fact that it is unimpeded and undistorted by the physical barrier posed by the scalp and skull, which is a problem in TES, and is relatively painless.

TMS is a useful tool in neuroscience for “knockout” studies of the brain to determine what regions of the cortex are associated with certain tasks. Also, it allows for mapping connections from regions on the cortex to various motor responses as well as region-to-region connections within the cortex. The initial clinical application of TMS was to demonstrate the integrity of the motor system by testing connections between the motor cortex and limb muscles such as during spinal surgery. This application has since expanded to include potential diagnosis and therapy for a plethora of disorders, from depression to epilepsy. None of these clinical applications, however, have received FDA approval but many continue to garner much attention in the biomedical research community. FDA approval has only been granted to TMS/rTMS devices for stimulation of peripheral nerves. Brain stimulation using TMS and rTMS is performed off label. The most commonly used form of TMS is single-pulse TMS, which is very safe. Repetitive TMS devices are available that can deliver high-frequency (1–30 Hz) stimulation and have greater effects than single-pulse TMS. rTMS also has the potential to cause seizures, so safety guidelines have been published to help prevent this.3