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N ew Trends and Advanced Techniques in Clinical Neurophysiology EDITED BY PAOLO M. ROSSINI Associate Professor of Clinical Neurophysiology, Second University of Rome 'Tor Vergata/ Rome (Italy) and FRANgOIS MAUGUIERE Professor of Neurology, Claude Bernard University, Lyon (France) ELECTROENCEPHALOGRAPHY AND CLINICAL NEUROPHYSIOLOGY SUPPLEMENT NO. 41 1990 ELSEVIER AMSTERDAM · NEW YORK · OXFORD Electroenceph. din. Neurophysiol., 1990, Suppl. 41 © 1990, ELSEVIER SCIENCE PUBLISHERS B.V. (BIOMEDICAL DIVISION) All rights reserved. No part of this publication may be reproduced, stored in a retrieval system or transmitted in any form or by any means, electronic, mechanical, photocopying, recording or otherwise without the prior written permission of the publisher, Elsevier Science Publishers B.V. (Biomedical Division), P.O. Box 1527, 1000 BM Amsterdam, The Netherlands. No responsibility is assumed by the publisher for any injury and/or damage to persons or property as a matter of products liability, negligence or otherwise, or from any use or operation of any methods, products, instructions or ideas contained in the material herein. Because of the rapid advances in the medical sciences, the publisher recommends that independent verification of diagnoses and drug dosages should be made. Special regulations for readers in the USA: This publication has been registered with the Copyright Clearance Center Inc. (CCC), Salem, Massachusetts. Infor­ mation can be obtained from the CCC about conditions under which the photocopying of parts of this publication may be made in the USA. All other copyright questions, including photocopying outside of the USA, should be referred to the publisher. ISBN 0-444-81352-7 (volume) Published by: Elsevier Science Publishers B.V. (Biomedical Division) P.O. Box 211, 1000 AE Amsterdam, The Netherlands. Sole distributors for the USA and Canada: Elsevier Science Publishing Company. Inc. 52 Vanderbilt Avenue, New York, NY 10017, USA. Library of Congress Cataloglng-ln-PublIcatlon Data Advanced evoked potentials and related techniques In clinical neurophysiology / edited by Paolo M. Rossini and Frangols Mauguiere. p. cm. — (Electroencephalography and clinical neurophysiology. Supplement ; no. 41) Includes bibliographical references. Includes Index. ISBN 0-444-Č1352-7 1. Evoked potentials (Elecirophyslology)—Diagnostic use. I. Rossini, Paolo M. II. Mauguiere, Franfols. III. Series. [DNLM: 1. Evoked Potentials. 2. Neurophysiology—methods. WI EL3251 no. 41 / WL 102 A2443] RC386.6.E86A35 1990 616.8'047'547—dc20 DNLM/DLC for Library of Congress 90-14150 CIP Printed in The Netherlands New Trends and Advanced Techniques in Clinical Neurophysiology (EEG Suppl. 41) Editors: P.M. Rossini and F. Mauguiere © 1990, Elsevier Science Publishers, B.V. (Biomedical Division) Foreword When the contributors to this volume met at the International Symposium on Evoked Potentials and Related Techniques, held in Rome in May 1989, they converged onto the opinion that the time had come to publish a book updating the reader with review articles on the newest techniques of Clinical Neurophysiology and their diagnostic applications. The authors, whose expertise in their field is outstanding, were entirely free to organise their chapter and to add as much review and original material as they needed in order to cover their topic exhaustively. This resulted in a volume of reasonable length, neither excessively heavy, to avoid discouraging the naive readers, nor too light in substance, so as to hold the interest of the most experienced ones. Clinical neurophysiologists will discover in this volume comprehensive reviews which could not have been included in the Journal of EEG and Clinical Neurophysiology because of the considerable and growing pressure for printing space; in that respect it corresponds to what a Supplement Volume to the Journal of EEG and Clinical Neurophysiology should be. The book was divided into sections to highlight the topics that have been the most actively debated for the past two years in the Clinical Neurophysiology literature. Indeed there is no doubt that new methods of signal processing, magneto-encephalography, brain stimulation, reflexology, neuro-monitoring, as well as clinical neurophysiology of pain, spasticity, motor and sensory deficits, movement disorders, cognition and language belong in this category. There is no doubt either that the clinical utility of evoked potential studies in AIDS deserved two review chapters in this book. The editors are indebted to all the contributors for their efforts in transmitting their knowledge of the treated topics and in also providing, where necessary, original unpublished data to more clearly define and to complete their individual chapters. We hope that the readers will experience the same pleasure as we did when editing the manuscripts. Paolo M. Rossini Frangois Mauguiere New Trends and Advanced Techniques in Clinical Neurophysiology (EEG Suppl. 41) Editors: P.M. Rossini and F. Mauguiere © 1990, Elsevier Science Publishers, B.V. (Biomedical Division) Vll List of Contributors Abbruzzese, G., 145 Crisci, C, 292 Abbruzzese, M., 73 Cruccu, G., 140 Amabile, G., 216 Amassian, V.E., 134 D'Alessio, C, 216 Arendt, G., 370 Dall'Agata, D., 145 Deacon, D.L., 202 Balbi, P., 149 De Lean, J., 223 Baratto, F., 330 Desmedt, J.E., 22 Barzi, E., 172 Deuschl, G., 84 Bazzano, S., 183 Dillmann, U., 314 Begleiter, Ç., 177 Dolenc, V.V., 348 Berardelli, Á., 140 Dona, B., 330 Beretta, Ĺ., 172 Bemardi, G., 286 Edgar, M.A., 342 Bertrand, 0., 51 Eghbal, R., 314 Besser, R., 314 Elidan, J., 119 Bianchi, Á., 28 Elsing, C, 370 Bohorquez, J., 51 Boom, H.B.K., 34 Facco, E., 330 Bouchard, J.P., 223 Famarier, G., 355 Buettner, U.W., 309 Fattapposta, F., 216 Favale, E., 73, 145 Caekebeke, J.F.V., 168 Ferracci, F., 183 Campbell, K.B., 202 Forest, L., 236 Caramia, M.D., 286 Fomara, C, 28 Caruso, G., 149, 292 Foti, Á., 216 Cathala, H.P., 243 Freeman, S., 119 Cerutti, S., 28 Freund, H.-J., 370 Chiarenza, G.A., 172 Fulgente, Ô., 183 Cicinelli, P., 286 Comi, G., 28 Gäbet, J.Y., 223 Cracco, J.B., 134 García-Larrea, L., 102 Cracco, R.Q., 134 Ghilardi, M.F., 183 Girón, G.P., 330 Opsomer, R.J., 298 Guérit, J.M., 298 Ozaki, I., 22 Halonen, J.-P., 342 Pauletti, G., 140 Hari, R., 3 Pelosi, L., 149, 292 Hefter, Ç., 370 Penicaud, Á., 243 Hoemberg, V., 370 Pemier, J., 51 Perretti, Á., 292 Ibañez, V., 274 Peters, M.J., 34 Inghilleri, M., 140 Pierrot-Deseilligny, E., 264 Porjesz, B., 177 Jones, S.J., 342 Prestor, B., 348 Ptito, M., 236 Kimura, J., 13 Koehler, J., 314 Rang, M., 306 Kutas, M., 155 Ransford, A.O., 342 Reni, L., 73, 145 Laffont, F., 243 Rimpel, J., 306 Lafreniére, L., 236 Romani, G.L., 298 Lanzillo, B., 292 Rossini, P.M., 124, 286, 298 Laureau, E., 236 Rothwell, J.C, 251 Le Canuet, P., 243 Lehmann, H.J., 306 Sabouraud, P., 223 Leibner, Ĺ., 119 Sela, M., 119 Liberati, D., 28 Sohmer, H., 119, 323 Locatelli, Ô., 28 Somma-Mauvais, H., 355 Lopes da Silva, F.H., 34 Spekreijse, H.J., 34 Lucking, C.H., 84 Stanzione, P., 216 Ludwig, B., 314 Stok, C.J., 34 Suffield, J.B., 202 Maccabee, P.J., 134 Malatesta, G., 183 Tagliati, M., 216 Malessa, R., 306 Terwort, Á., 306 Manfredi, M., 140 Timmann, D., 309 Marciani, M.G., 216 Tomberg, C, 22 Mathieu, J., 223 Trivelli, G., 145 Mauguiere, F., 102, 223, 274 Meunier, S., 243 Vanasse, M., 223, 236 Meyer, S.T., 306 Van Cangh, P.J., 298 Morena, Ě., 145 Van Dijk, J.G., 168 Munari, Ě., 330 Van Petten, C, 155 Van Sweden, Â., 168 Nelles, H.-W., 370 Villa, Ě., 172 Nitzan, M., 119 Nobilio, D., 183 Yamada, Ô., 13 Noel, P., 22 Zarola, F., 286, 298 2gur, T., 348 Onofrj, M.C, 183 New Trends and Advanced Techniques in Clinical Neurophysiology (EEG Suppl. 41) Editors: P.M. Rossini and F. Mauguiere © 1990. Elsevier Science Publishers, B.V. (Biomedical Division) Magnetic Evoked Fields of the Human Brain: Basic Principles and Applications RIITTA HARI Low Temperature Laboratory, Helsinki University of Technology, SF-02150 Espoo (Finland) Introduction the model, the electric potentials are dispersed and smeared whereas the magnetic pattern is unchanged. In magnetoencephalography, MEG (Williamson and Since the electric potential distributions are influenced Kaufman 1981; Had and Lounasmaa 1989), weak by the location of the reference electrode, inteφreta- magnetic fields, typically 100-1000 fT, are de­ tion of the patterns in terms of generators is difficult tected non-invasively outside the head. The best- whereas no corresponding problem exists in the mag­ quality recordings are carried out within magnetically netic recordings. Consequently, MEG has good spatial shielded rooms, usually made of mu-metal and alu­ resolution; under favourable conditions the location of minium. Superconducting SQUIDs, immersed within the equivalent dipole, best explaining the measured liquid helium, are used as detectors of the magnetic magnetic field pattern, can be determined with a pre­ field. cision of a few millimeters (Hari et al. 1988). The Fig. 1 illustrates a typical experimental situation. physiological inteφretation of the single-dipole model The subject is lying with his head supported by a is synchronous activation of a cortical layer with a di­ vacuum cast and the dewar, containing the detectors, ameter of up to 2 cm. is placed close to the head. All moving magnetic ma­ Only tangential dipoles produce magnetic field out­ terials must be avoided near the subject. Otherwise side the sphere, whereas both tangential and radial cur­ the situation resembles conventional EEG or evoked rents cause potentials on the surface. This means that potential recordings, and the signal-to-noise ratios of MEG suits well for studies of fissural cortex. When EEG and MEG are at present comparable. To lo­ the depth of the source increases, the magnetic sig­ cate sources, signals must be recorded from 30 to 50 nals decrease relatively more rapidly in amplitude than locations to determine the field pattern. Multichan­ the electric potentials. A source in the centre of the nel instrumentation is rapidly improving, allowing the sphere does not cause any external magnetic field at whole field pattern to be measured with a single shot all, whereas electric potentials can still be recorded on (Kajola et al. 1989). the surface. Therefore, MEG should be considered a To understand some important differences between tool to mainly study cortical activity. EEG and MEG, let us consider a current dipole, i.e., This review illustrates applicability of MEG to stud­ current condensed within a small area, in a conduct­ ies of auditory and somatosensory systems, with ex­ ing sphere. Fig. 2 shows that there are important dif­ amples of results obtained by the neuromagnetism ferences between the resulting EEG and MEG. The group at the Low Temperature Laboratory of Helsinki electric and magnetic field patterns are rotated by University of Technology. At present, 30-40 labora­ 90° with respect to each other. When concentric elec­ tories all over the world are carrying out MEG mea­ tric inhomogeneities, simulating extracerebral tissues surements. (cerebrospinal fluid, skull and scalp), are added to Somatomotor system preamplifiers (1) Action fields The probable sources of cerebral magnetic fields are postsynaptic currents in synchronously activated pyramidal neurones of fissural cortex. However, it has become recently possible to also record magnetic fields associated with compound action potentials of human peripheral nerves (Wikswo et al. 1985; Eme et al. 1988; Hari et al. 1989a). SQUIDS within niobium shields Fig. 3 shows non-invasively recorded compound gradiometer action fields (CAEs) of one subject at cubita, about coils 6 msec after median nerve stimulation at the wrist. The response is at most locations monophasic, with opposite polarities on the medial and lateral sides of the nerve, and the onset and peak latencies increase from distal to proximal channels. channel configuration Currents associated with an action potential can be described with a current quadrupole consisting of 2 Fig. 1. Schematic illustration of a typical experimental situation opposite intracellular dipoles, one at the depolariza­ for auditory measurements with a 7-channel 1st order SQUID tion and the other at the repolarization front (Fig. 3). gradiometer. The dewar, containing the flux transformers and The polarities of our CAEs correspond to the direction the SQUIDs, is placed close to the subject. Adapted from Hari of the intracellular current flow at the leading front of and Lounasmaa (1989). the action potential volley, whereas the other phase, if present, is very flat and lasts longer than the first. It is probable that spatial asynchrony of AFs in fi­ bres of different calibers leads to an asymmetry of the quadrupole source and therefore to dominance of the dipole term when the field is measured at a distance (Stegeman and De Weerd 1982). Clear responses were also detected at the brachial plexus, and conduction velocities calculated from the magnetic signals were in good agreement with the conventional surface elec­ trode recordings. Since CAEs are less contaminated by non-uniform resistivities of the volume conductor than the corresponding CAEs, they can give more di­ rect information about neural currents and might be useful when response amplitudes are of importance. (2) Responses from SI The first cortical magnetic response, N20m, peaks MAGNETIC FIELD ELECTRIC POTENTIAL 18-20 msec after median nerve stimulation (Fig. 4). Fig. 2. Above: a current dipole produces a magnetic field with field The responses have opposite polarities at the upper lines following the right hand rule. Below: magnetic field pattern and lower end of the rolandic fissure, suggesting a over the sphere and electric potential distribution over the surface tangential current source at the primary somatosen­ due to a current dipole in a 4-layer sphere model simulating the sory hand area (Brodmann area 3b). N20m is rather head. The patterns are rotated by 90° with respect to each other. The insensitive to the stimulus repetition rate whereas the continuous lines refer to magnetic flux oriented out of the sphere next large deflection P30m, at 27-30 msec, increases or to positive potential. depolarization Fig. 3. Compound action fields after electric stimulation of the right median nerve at the wrist. The measurements were made at 2 sites with the 7-channel gradiometer. Passband is 0.05-2000 Hz and responses from 2 successive measurements are superimposed. Each trace is the average of about 1000 responses. The insert on the left illustrates intracellular current flow in a nerve fibre during an action potential and the associated magnetic field around the nerve; the asymmetry illustrates the fact that repolarization currents are distributed along a wider area than the dense depolarization currents. The insert on the right shows (with a time scale from 2 to 27 msec) responses of the same subject to median nerve stimulation at cubita, plexus, and somatosensory cortex. From Hari et al. (1989a). clearly in amplitude when the repetition rate is de­ The sites of the equivalent dipoles, activated by creased from 5 to 2 Hz (Tiihonen et al. 1989a). Ac­ stimulation of different parts of the body, correspond tivity continues around SI for about 150 msec. to the somatotopic organization of SI. For lower limb The responses in Fig. 4 also illustrate a deflection stimulation, the first response peaks at 40 msec with at 22 msec, the probable magnetic counteφart of the a source at the mesial wall of the hemisphere. For electric P22. P22 is assumed to be generated by radial cutaneous stimulation of fingers, the source is about sources, which would not generate detectable mag­ 1 cm more lateral for the thumb than the little fin netic ñelds outside a sphere. The detection of P22m ger (Hari and Kaukoranta 1985). The distributions of indicates that even a slight tangential component of the early somatosensory evoked fields (SEFs) to ulnar source currents can generate an extracranial magnetic and median nerve stimulation also follow the somato- field, big enough to be measured with a low-noise topical order but during the late deflections, at about instrument. P22m reversed polarity between the up 80 msec, no such differences are observed (Huttunen per and lower measurement locations, but due to the et al. 1987). Interaction between afferent input is ev small size of the response and its superimposition on ident from an experiment where rare (10%) median the N20m-P30m slope, its precise source could not nerve stimuli were presented among frequently (90%) be determined. repeated ulnar nerve stimuli (ISI 1 sec) or vice versa second somatosensory area SII at the upper bank c the sylvian fissure (Hari et al. 1984b; Kaukoranta et al. 1986). This area is activated by both lower and upper limb stimuli, presented either contra- or ipsilaterally. The main response at SII peaks about 100 msec after cutaneous stimulation of the middle finger, and it is significantly increased in amplitude if the site of stimulation is infrequently and unpredictedly changed from one finger to another (Hari et al. 1990). In this 200 fT respect SII differs clearly from SI. (4) Noxious stimulation Selective activation of pain afferents evokes strong magnetic signals. After electric stimulation of the frontal incisor, the response peaks at about 90 msec with an equivalent source in the frontal operculum (Hari et al. 1983b). After carbon dioxide stimulation of the nasal mucosa, a long-latency response is seen at 350 msec with the source near SII (Huttunen et al. 1986), clearly posterior to the source activated by Fig. 4. Magnetic fields at the upper and lower ends of the right dental stimulation. central sulcus after median nerve stimulation at the wrist. The interStimulus interval was 200-220 msec, passband 0.05-2000 Hz, (5) Premovement activity and the sampling frequency 8 kHz. The traces are averages of In monkey motor cortex, preparation for a voluntary about 1000 responses. The first cortical deflection at 19 msec is movement is associated with neural activity several specified, the following deflection of opposite polarity peaks at 30 msec. Modified from Tiihonen et al. (1989a). hundred milliseconds before the movement. In hu­ mans, slow EEG shifts precede voluntary movements. (Huttunen et al. 1987). The response wave forms and It is also possible to record magnetic shifts resem­ amplitudes were similar independently whether the bling in moφhology the electric 'readiness' poten­ stimulus was standard or deviant, indicating that there tials. Fig. 5 shows that magnetic shifts preceding self- is strong interaction between the afferent input from paced plantar flexions of the right foot start even 1 both nerves. sec before muscular activity (Hari et al. 1983a). The The somatosensory cortex also seems to have an idle recording, made along the line connecting the ampli­ rhythm comparable to the alpha activity of the visual tude extrema, shows polarity reversal in the middle, cortex. This rhythm consists of about 10 Hz and 21.5 over the motor representation area of the ankle. Simi­ Hz activity with a source area close to the source larly, MEG shifts preceding finger extensions reverse of N20m for median nerve stimulation (Tiihonen et in polarity between the upper and lower ends of the al. 1989b). The high-frequency rhythm resembles the rolandic fissure suggesting a source in the hand rep­ electric mu rhythm in reactivity: it is blocked by resentation area. clenching the fist, but not by opening the eyes. That the mu rhythm seems to be mainly generated at the SI hand area may be explained by the fact that the hand Auditory system (especially the thumb) occupies a relatively large area in the somatosensory homunculus, in accordance with (I) General its importance to human behaviour. Due to the anatomical location of the auditory cortex, the electric activity is best recorded in the midline (3) Responses from SI I of the scalp. It is thus very difficult to differentiate It is also possible to detect MEG responses from the between responses of each hemisphere, unless source peaks at 19 msec with an equivalent source deep within the sylvian fissure, probably at the primary auditory cortex (Scherg et al. 1989). The activity in the supratemporal cortex continues for a few hundred O.SpT milliseconds, with slightly varying source areas. (2) Steady-state responses When the interstimulus interval is shortened below about 200 msec, 'steady-state responses' are formed. If the system under study is non-linear, steady-state and transient responses give complementary informa tion. The best known steady-state response is the 40 Hz response, first described by Galambos et al. (1981) in the electric recordings. This potential was largest in amplitude for stimulus rates of 40 Hz. The mag netic 40 Hz response has been detected to trains of clicks and to continuous presentation of clicks and noise bursts (Mäkelä and Hari 1987; Hari et al. 1989b; Tiihonen et al. 1989c). The field patterns indicate a 10 "^^^^^ ^ source at the supratemporal auditory cortex, 20-35 mm beneath the scalp. This source explains the major part of the electric potential on the scalp suggesting that the electric response achieves its major contribu tion from cortical currents. Two explanations can be presented for the ampli tude enhancement around 40 Hz (see Fig. 6). First, Fig. 5. Magnetic fields preceding self-paced plantar flexions of the right foot. The recordings were made along a line connecting the field extrema of the slow shift. The vertical bars on the right hand side of the curves indicate the average standards errors of the mean for each curve. The schematic figure shows a simple current dipole model for the measured field. Adapted from Hari et al. (1983a). The vertical lines indicate the onset of the movement. modelling is used (Scherg 1990). The special advan tage of MEG in the study of the auditory system is that ,¡1 activity of both hemispheres can be detected selec 40.1 50 fT tively. Neuromagnetic studies of the auditory cortices in 1 1 have demonstrated in humans some functional fea 0 20 40 60 0 25 50 75 100 tures, earlier observed only in animals, and have also Repetition rate (Hz) Time (nis) given information about new functional principles. Fig. 6. Left: mean (± S.E.M.; 10 subjects) amplitudes of the steady- Further, recordings of both electrically evoked poten state responses to clicks as a function of stimulus repetition rate. Right: responses of 1 subject to clicks presented at 10.1, 20.1, and tials and magnetic fields under identical conditions 40.1 Hz. The recordings are from the posterior field extremum over have been important in identifying neural sources of the right hemisphere. The passband is 0.05-250 Hz, and 1500-1800 auditory evoked responses (for a recent review, see responses were averaged for each curve. The dotted lines illustrate Hari 1990). 'synthetic responses' calculated from the 10.1 Hz responses by multiplying the repetition rate by 2 and 4. The vertical line at 40 When stimuli are presented at slow rates, typically msec illustrates the 'apparent latency' of the steady-state response below 3 Hz, 'transient responses' are elicited. The deduced from the phase/repetition rate dependence. From Hari et earliest transient magnetic auditory response to a click al. (1989b).

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