Transcranial magnetic stimulation

Transcranial magnetic stimulation (TMS) is a 20-year-old technique originally introduced to noninvasively investigate nervous propagation along the corticospinal tract, spinal roots, and peripheral nerves in humans. TMS is extensively used in clinical neurophysiology, including rehabilitation and intraoperative monitoring. Single-pulse TMS and other more recent versions (paired-pulse TMS, repetitive TMS, integration with structural and functional MRI, and neuronavigation) allow motor output to be mapped precisely to a given body district. Moreover, TMS can be used to evaluate excitatory/inhibitory intracortical circuits and to provide information on brain physiology and pathophysiology of various neuropsychiatric diseases as well as on the mechanisms of brain plasticity and of neuroactive drugs. TMS applied over nonmotor areas made it possible to extend research applications (often complementary with other functional neuroimaging techniques) in several fields of psychophysiology, causally testing brain–behavior relationships. Being able to induce relatively long-lasting excitability changes, repetitive TMS has made the treatment of neuropsychiatric diseases linked with brain excitability dysfunctions possible. These uses, however, warrant further large-scale studies. In emerging fields of research, TMS-EEG co-registration is considered a promising approach to evaluate corticocortical connectivity and brain reactivity with high temporal resolution. However, safety and ethical limitations of TMS technique need a high level of vigilance. NEUROLOGY 2007;68:484–488 Transcranial magnetic stimulation (TMS), that is, a brief and intense magnetic field, created by a strong electric current circulating within a coil resting on the scalp, penetrates human tissue painlessly and, if the current amplitude, duration, and direction are appropriate, induces in the brain (or in spinal roots, or in nerves) electric currents that can depolarize neurons or their axons.1 When TMS is delivered over the primary motor cortex with adequate intensity, it induces efferent volleys along the corticospinal pathway. Several measures of distinct physiologic importance can be recorded and measured (table), besides the “classic” electromyographic (EMG) motor evoked potentials (MEPs) from the muscles contralateral to the stimulated motor cortex.2 These different measures allow a comprehensive evaluation of the functional state of the corticospinal pathway useful for investigating both physiologic and pathologic conditions.3-5 TMS was first presented at the London Congress of the International Federation of Clinical Neurophysiology (IFCN) in 1985 by Anthony Barker. The number of TMS papers published in peer-reviewed journals has increased progressively and steadily over the last 20 years (figure). Many of these papers crossed the boundary of the specialized-field journals and appeared in scientific publications of wider interest, such as Science, Nature, Nature Neuroscience, and Neuron. Diagnosis. Both excitability and viability of the corticospinal paths to nearly every body muscle (including sphincters) can be tested. Hence, TMS is now routinely used whenever an objective evaluation of the motor system is required.6,7 Following the report of IFCN,6 however, an updated, official priority list relating to the diagnostic use of MEPs based on literature contributions is still lacking. Diagnostic process and grading of many diseases (multiple sclerosis, posttraumatic, neoplastic and compressive myelopathies, ALS, stroke, epilepsy, and dystonia)7,8 may benefit from TMS investigations.4,5 In the field of movement disorders, corticospinal evaluation may help in the differential diagnosis between idiopathic Parkinson disease, in which central conduction time (CCT) is normal, and other parkinsonisms,9 in which the corticospinal tract can be involved. The presence of normal MEPs in the paretic arm is of clinical From AFaR–Dipartimento di Neuroscienze (P.M.R.), S. Giovanni Calibita, Ospedale Fatebenefratelli Isola Tiberina, and Clinica Neurologica (P.M.R.), Universita Campus Biomedico, Roma, Unita di Neuroscienze Cognitive (P.M.R.), IRCCS S. Giovanni di Dio, Brescia, and Dipartimento di Neuroscienze (S.R.), Sezione Neurologia, University of Siena, Policlinico “Le Scotte,” Siena, Italy. Disclosure: The authors report no conflicts of interest. Received February 16, 2006. Accepted in final form September 15, 2006. Address correspondence and reprint requests to Dr. P.M. Rossini, Dipartimento di Neuroscienze, Ospedale Fatebenefratelli Isola Tiberina, I-00186, Roma, Italy; e-mail: paolomaria.rossini@afar.it 484 Copyright © 2007 by AAN Enterprises, Inc. Table Most utilized TMS measures following stimulation of the motor cortex Pulses Parameter Definition Physiologic significance Use Single Resting motor threshold (RMT) Intensity required to get a 50V MEP appearing with 50% probability Excitability and local density of a central core of excitatory interneurons and corticospinal neurons (“hot spot”); excitability threshold of small and slow-propagating pyramidal neurons Clinical, research, pharmacology Averaged Active motor threshold (AMT) Intensity required to obtain a MEP of about 100–200 V in a slightly contracting muscle Similar physiologic significance of RMT (possibily with the contribution of fastpropagating pyramidal neurons) Clinical, research Single or averaged Central conduction time (CCT) Estimation of the transit time from the cortex to spinal anterior horn motoneurons Corticospinal impulse propagation Clinical: the most useful clinical parameter Single or averaged Motor evoked potential (MEP) Stimulus-locked (latency) peak-to-peak amplitude or area of the negative phase Integrity of the corticospinal tract and excitability of the corticospinal system Clinical, research Single Input–output (I-O) curve Relationships between the intensity of TMS and the MEP amplitude Progressive recruitment of less excitable or surrounding neurons with respect to those of the hot spot Research,