Cortical Excitability Motor Threshold With Single-Pulse TMS Conduction Latency With Single-Pulse TMS Intracortical Inhibition and Facilitation With Paired-Pulse TMS Frequency-Dependent Effects on Cortical Excitability With rTMS

In the 1990s, it is difficult to open a newspaper or watch television and not find someone claiming that magnets promote healing.Rarely do these claims stem from double-blind, peer-reviewed studies, making it difficult to separate the wheat from the chaff. The current fads resemble those at the end of the last century, when many were falsely touting the benefits of direct electrical and weak magnetic stimulation. Yet in the midst of this popular interest in magnetic therapy, a new neuroscience field has developed that uses powerful magnetic fields to alter brain activity-transcranial magnetic stimulation. This review examines the basic principles underlying transcranial magnetic stimulation, and describes how it differs from electrical stimulation or other uses of magnets. Initial studies in this field are critically summarized, particularly as they pertain to the pathophysiology and treatment of neuropsychiatric disorders. Transcranial magnetic stimulation is a promising new research and, perhaps, therapeutic tool, but more work remains before it can be fully integrated in psychiatry's diagnostic and therapeutic armamentarium. Arch Gen Psychiatry.1999;56:300-311 Since the work of Penfield, the possibility of noninvasive and focal stimulation of the brain has been an appealing vision that now seems to be realized. Transcranial magnetic stimulation (TMS) holds special promise as a tool to study localization of function, connectivity of brain regions, and pathophysiology of neuropsychiatric disorders. It may also have potential as a therapeutic intervention. For more than a century, it has been recognized that electricity and magnetism are interdependent. Passing current through a coil of wire generates a magnetic field perpendicular to the current flow in the coil. If a conducting medium, such as the brain, is adjacent to the magnetic field, current will be induced in the conducting medium. The flow of the induced current will be parallel but opposite in direction to the current in the coil. Thus, TMS has been referred to as "electrodeless" electrical stimulation, to emphasize that the magnetic field acts as the medium between electricity in the coil and induced electrical currents in the brain. [1] PROCEDURES 9/5/03 2:37 PM Ovid: George: Arch Gen Psychiatry, Volume 56(4).April 1999.300-311 Page 2 of 22 http://80-gateway1.ovid.com.ezp1.harvard.edu/ovidweb.cgi Fo r p ers on al an d r es ea rch us e o nly Transcranial magnetic stiumulation involves placing an electromagnetic coil on the scalp ( ). Highintensity current is rapidly turned on and off in the coil through the discharge of capacitors. This produces a time-varying magnetic field that lasts for about 100 to 200 microseconds. The magnetic field typically has a strength of about 2 T (40,000 times the earth's magnetic field, or about the same intensity as the static magnetic field used in clinical magnetic resonance imaging). The proximity of the brain to the time-varying magnetic field results in current flow in neural tissue. The technological advances made in the last 15 years led to the development of magnetic stimulators that produce sufficient current in brain to result in neuronal depolarization. Figure 1 Figure 1. Example of transcranial magnetic stimulation (TMS) application. Ziad Nahas, MD, demonstrates a TMS figure-8 coil applied over the left prefrontal cortex of Ananda Shastri, PhD. Note that the subject is awake and alert, and is wearing earplugs for safety. The electromyography machine in the lower left corner (B) is used to determine the motor threshold for dosing of stimulation intensity. Several TMS devices and coils are pictured: A, Medtronic-Dantec (Copenhagen, Denmark); C, Cadwell (Kennewick, Wash) with watercooled figure-8 coil; D, Neotonus (Atlanta, Ga); and E, Magstim (Sheffield, England). Neuronal depolarization can also be produced by electrical stimulation, with electrodes placed on the scalp (referred to as transcranial electric stimulation). Electroconvulsive therapy (ECT) is an example of this. Importantly, unlike electrical stimulation, where the skull acts as a massive resistor, magnetic fields are not deflected or attenuated by intervening tissue. This means that TMS can be more focal than electric stimulation. Furthermore, for electrical stimulation to achieve sufficient current density in brain to result in neuronal depolarization, pain receptors in the scalp must be stimulated. [2,3] Transcranial magnetic stimulation is usually performed in outpatient settings, and, unlike ECT, does not require anesthesia or analgesics. Subjects usually notice no adverse effects except for occasional mild headache and discomfort at the site of the stimulation. A striking effect of TMS occurs when one places the coil on the scalp over primary motor cortex. A single TMS pulse of sufficient intensity causes involuntary movement. The magnetic field intensity needed to produce motor movement varies considerably across individuals, and is known as the motor threshold. Placing the coil over different areas of the motor cortex causes contralateral movement in different distal muscles, corresponding to the well-known homunculus. Transcranial magnetic stimulation can be used to map the representation of body parts in the motor cortex on an individual basis. Subjectively, this stimulation feels much like a tendon reflex movement. Thus, a TMS pulse produces a powerful but brief magnetic field that passes through the skin, soft tissue, and skull, and induces electrical current in neurons, causing depolarization that then has behavioral effects (body movement). The TMS magnetic field declines logarithmically with distance from the coil. This limits the area of depolarization with current technology to a depth of about 2 cm below the brain's surface. [4]