Transcranial Magnetic Stimulation

Transcranial Magnetic Stimulation (TMS), by providing a method of stimulating human brain without the need for surgical exposure or significant discomfort, facilitated the study of cerebral functions in both normal subjects and patients. The aspects of TMS treated include: (1) The part(s) of neurons readily direct excited by TMS; (2) the optimal relationship between the orientations of the electric field induced by TMS and the directly excited neurons; (3) the transynaptic effects of the directly excited neurons that are either distant or local; (4) the effects of repetitive versus single pulse TMS. I. INTRODUCTION Electrophysiological exploration of the human brain was restricted during the late XIX and early XX Centuries to patients with cerebral cortex surgically exposed. The extent to which the remaining properties of such brains may have been altered by disease could not be reliably investigated. Remarkably, Penfield and Roberts (1) removed frontal lobe areas that included the speech expressive region (Broca's Area), in two patients with seizures and both were speaking within 24 hrs. The first major advance occurred when Merton and Morton (2) found that a high voltage electrical pulse applied to the head could penetrate sufficiently the high skull resistance to excite the motor cortex. This made possible experiments on normal subjects, in addition to patients. Specifically, central motor conduction time could now be measured. However, such electrical stimulation of motor cortex, although safe, was quite painful, feeling like a blow to the head. The introduction in 1985 of transcranial magnetic stimulation (TMS) by Barker and Associates (3) caused little discomfort to normal subjects and patients, thereby greatly enhancing its applicability in investigation. When first introduced, a brief, large current pulse was sent through a round coil of wire (o.d. 12.5 cm) centered on the head, generating a magnetic flux that readily penetrated the skull. The magnetic flux induced a current in the brain volume conductor in the reverse direction to that in the coils. The current intensity was maximal under the windings, i.e. stimulation of neurons theoretically could occur anywhere under the windings. Restricting the site of stimulation was first attempted by applying only the edge of the round coil to the head, requiring a tilt so that sufficient magnetic flux entered the brain. Such localized stimulation elicits preferential movements of individual digits and localized projected sensations (4,5). An important technical advance was introduced by joining 2 round coils in a figure 8 such that the currents flowed in the same direction only in the junction region of the two coils. The induced electric field under the junction region is approximately 2x that elsewhere under the coils. Especially when stimuli a little above threshold are used, displacement of a figure 8 coil by as little as 0.5 cm, or a slight change in tilt if the coil is flat on the rounded head, can markedly change the physiological response. Such spatial resolving power should be distinguished from identification of the actual site of excitation (see below). The use of TMS to excite neurons raises a number of questions, including: (1) What part(s) of neurons are directly excited at threshold intensity? (2) What is the optimal relationship between the orientations of the induced electric field and the directly excited neurons? (3) What are the transynaptic effects of the directly excited neurons? 1. The part of the neuron directly excited by TMS at lowest threshold