CME Copyright 2014 SLACK Inc. The Science of Transcranial Magnetic Stimulation William M. Sauvé, MD; and Lawrence J. Crowther, MEng ABSTRACT Transcranial magnetic stimulation (TMS) is a noninvasive method for stimu- lating neural tissue based on the prin- ciples of electromagnetic induction. The technique is becoming an established treatment for drug-resistant major de- pressive disorder and is a promising tool for a variety of psychiatric and neurologi- cal disorders. Stimulation is achieved by pulsed magnetic !elds inducing electric !elds with the necessary characteristics to depolarize neurons, generating action potentials. In this article, the underlying principles and mechanisms of TMS are explored and an overview of the devel- opment of stimulator devices is provided. [Psychiatr Ann. 2014; 44(6):279–283.] William M. Sauvé, MD, is Medical Direc- tor, TMS NeuroHealth Centers, Richmond. © Shutterstock Lawrence J. Crowther, MEng, is Graduate Research Assistant, Department of Electri- ince the days of Pliny, humans have phenomenon has only recently been used cal and Computer Engineering, Iowa State been curious about the effects of as a therapeutic modality in psychiatry. University. Selectrical stimulation on the body, Known as repetitive transcranial magnetic Address correspondence to: William M. and since Michael Faraday famously de- stimulation (rTMS), it was approved for Sauvé, MD, TMS NeuroHealth Centers, 5231 veloped the concept of electromagnetic the treatment of major depressive disorder Hickory Park Drive, Suite C, Glen Allen, VA induction, it has been understood that by the U.S. Food and Drug Administration 23059; email: [email protected]. changing magnetic fields can cause current in 2008. What follows is a very basic over- Disclosure: Dr. Sauvé is employed by TMS to flow in conductive material,1 including view of the underlying physics of TMS, NeuroHealth Centers. Mr. Crowther has no the brain. Although the ability to stimulate how it impacts the neurons in the brain, relevant financial relationships to disclose. the brain using magnetic pulses was estab- some of the methods of application, and doi:10.3928/00485713-20140609-05 lished by Jacques d’Arsonval in 1896,2 this the various stimulation devices in use. 039#()!42)#!..!,3s6OL .O 279 CME Copyright 2014 SLACK Inc. FARADAY’S LAW OF a neuron, two major factors include chro- be an important part of learning.6 LTP was ELECTROMAGNETIC INDUCTION naxie and rheobase. Chronaxie is defined first described by Terje Lømo in 1966, Both Michael Faraday and Joseph as the minimum time for an electric cur- showing that while a single electric stimu- Henry independently discovered the con- rent to double the strength of the rheobase lus delivered to presynaptic fibers resulted cept of electromagnetic induction in 1831, of a neuron; rheobase is defined as the in excitatory postsynaptic potentials in the but Faraday was the first to publish his lowest intensity of current that can cause postsynaptic cells, high-frequency trains findings. Simply put, a magnetic field that an action potential in said neuron.4 of stimuli delivered to the same resulted is in motion relative to a conductor brings Thus, when a magnetic field pulses in an enhanced response over an extended about a current in said conductor. Hence, adjacent to the volume conductor, which period of time. He called this phenom- a changing magnetic field induces a flow in this case is the brain, an electrical field enon “long-lasting potentiation,”7 which of electric current in nearby conductors is generated at sufficient strength and du- was later changed to “long-term potentia- that, for the purposes of this article, in- ration to cause the neuron to depolarize, tion” by Douglas and Goddard in 1975.8 clude human tissue.3 The most commonly resulting in an action potential. When the LTD is the opposing process to LTP, used form of expression for this concept motor cortex is stimulated in this way, with the efficacy of neuronal synapses be- is the Maxwell-Faraday equation, also re- the result is a motor evoked potential ing decreased after certain stimuli. LTD is ferred to as Faraday’s Law. (MEP), leading to motor activity. Simi- thought to result mainly from a decrease Electromagnetic induction is the key lar single or paired pulse TMS delivered in postsynaptic receptor density, with L- principle in transcranial magnetic stimu- over the occipital cortex has also resulted glutamate interacting with multiple re- lation (TMS), taking advantage of the fact in flashes of light being perceived by the ceptors to selectively weaken receptor that every electric current has a magnetic subject. Pulses delivered over other parts strength. Some examples of the utility of field surrounding it, with alternating cur- of the brain may not be experienced on LTD can be the possible clearing of old rents bringing about fluctuating magnetic the conscious level but have resulted in memory traces in the hippocampus9 and fields. Fluctuating magnetic fields in turn measurable changes, such as on the sub- the concept of neuroplasticity in general, cause electric current to flow in conduc- ject’s performance in a cognitive task. with LTP and LTD occurring in concert to tors placed within them; the conductors Practical application of TMS, however, selectively strengthen and weaken synap- in the case of TMS being neurons in the is largely focused on rTMS, where such tic connections in the brain. It is the pos- brain, thus allowing for electrical stimula- pulses are being delivered in trains at cer- sible modulation of these phenomena by tion of neurons within the brain in a non- tain frequencies that have been shown to rTMS that may explain some of its lasting invasive fashion. generate more lasting effects. Generally, effects and clinical utility. by mechanisms that are not well under- DIRECT NEURONAL EFFECTS OF TMS stood, low-frequency stimulation (!1 Hz) DEFINING PULSE SEQUENCES It has been demonstrated that a mag- is thought to bring about reduced corti- Determining pulse sequences requires netic field pulsed adjacent to a volume cal excitability, whereas high-frequency that decisions be made about frequency, conductor (such as the brain) induces an stimulation (>5 Hz) increases cortical intensity, and duration of stimulation. electrical field in that conductor. Although excitability and, in each case, the effect Frequency of stimulation will be chosen the brain is truly a heterogeneous con- is maintained for some time after a num- based on the desired effect, either an in- ductor, with the white and gray matter as ber of pulse trains have been completed. crease or decrease in cortical excitability in well as cerebrospinal fluid all having dif- Again, the mechanism is not well un- the area being stimulated, with an increase ferent conductivities (0.48, 0.7 and 1.79 derstood but may be partly explained by typically brought about by high-frequency siemens/m, respectively),3 the resultant the phenomena of long-term potentiation pulse trains, and a decrease brought about differences in the induced electric field are (LTP) and long-term depression (LTD).5 by low-frequency pulse trains. For exam- small enough that the brain can be thought ple, the approved treatment for depression of as a homogeneous volume conductor. LONG-TERM POTENTIATION/ consists of 4-second pulse trains at 10 Hz Furthermore, the induced current is small DEPRESSION delivered to the left-side dorsolateral pre- enough so as not to have any effect on the LTP refers to a process by which syn- frontal cortex and is thought to generate magnetic field, thus eddy currents are not aptic communication between neurons is an increase in cortical excitability in this significant in this case, making the induc- made more efficient when said neurons area. Conversely, some small studies in the tion of an electric field within the brain via fire in sequence. Often remembered in treatment of Tourette syndrome have used TMS a one-way proposition. school by the saying “neurons that fire to- a frequency of 1 Hz stimulation over the When discussing the effect of TMS on gether, wire together,” LTP is thought to supplementary motor area (SMA), with 280 #OPYRIGHT¹3,!#+)NCORPORATED CME Copyright 2014 SLACK Inc. the expectation that cortical excitability seconds for a total of 191.84 seconds, or a meaning circular coils do not produce a will be decreased as a result.10 total of 600 pulses, with continuous TBS single area of maximum field. Circular Intensity of stimulation is affected by being defined as three pulses at 50 Hz coils do, however, offer the ability to stim- many variables but is largely dictated by repeated every 200 ms for 20 or 40 sec- ulate both hemispheres at the same time the baseline excitability of the cortex, onds for a total of 300 or 600 pulses. TBS to some degree by placing the coil at the which can be measured by the minimum protocols remain in the investigational cranial vertex, although the direction of stimulation required to bring about an stage, with the main potential advantage induced current has an influence over the MEP. In clinical practice, this is often being that similar effects to rTMS may be extent to which neuronal activation can be determined by the observation of muscle achieved with considerably shorter pro- achieved in the motor cortex, with a pref- movement in the subject being stimulated tocols leading to similar or even greater erence for currents flowing from posterior and is called the resting motor threshold duration of either excitatory or inhibitory to anterior. Flat circular coils are still used (RMT). Stimulus intensity in various pro- after effects. and commercially produced15,16 but have tocols will then be expressed as a percent- been succeeded by more complex designs age of RMT (eg, the approved treatment TMS STIMULATOR DESIGN for therapeutic implementation.