Focal magnetic coil stimulation reveals motor cortical system reorganized in humans after traumatic quadriplegia

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Brain Resear~h i l I) t 199(1) 13(i - ~34 Elsevicr

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Focal m

netic coil stimulation reveals motor cortical system reorganized in humans after traumatic quadriplegia

Walter J. Levy Jr.1, Vahe E. Amassian 2, Monique

Traad 3

and John

Cadwell 4

t Department of Neurosurgery, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213 (U.S.A.), 2Department of Physiology, State University of New York Health Science Center at Brooklyn, Brooklyn, NY 11203 (U.S.A.), 3Department of Biomedical Engineering, College of Engineering, University of Miami, Miami, FL 33124 (U.S.A.) and 4Cadwell Laboratories, Kennewick, WA 99336 (U.S.A.) (Accepted 7 November 1989) Key words: Magnetic coil; Human motor cortex; Reorganization after lesion; Quadriplegia

A figure of '8' magnetic coil (MC) was used to stimulate focally the motor cortex of two adult, traumatic quadriplegics and three normal adults. The two patients were injured approximately 2 years previously and had intensive physiotherapy, including biofeedback training of biceps and deltoid muscles, respectively, which were the most caudal muscles spared. The focal MC elicited compound motor action potentials (CMAPs) from these muscles from a much wider area of scalp than in the normal subjects. Latency of biceps and deltoid CMAPs were inversely related to CMAP amplitude. A reorganization of the motor cortical projection system is inferred, in which areas normally eliciting digit m o v e m e n t s instead activate muscles in quadriplegics just above the spinal level. The reorganization applies also to the central sense of movement normally elicited by focal frontal cortex stimulation. Possible mechanisms of the reorganization and an implication for rehabilitation are discussed. The introduction of the magnetic coil (MC) stimulator made possible transcranial stimulation of human motor cortex with minimal discomfort 6'7. Initially, the coil was round and large (diameter 14 cm) relative to the structures to be stimulated. When conventionally applied tangentially to the scalp at or near the vertex, the MC elicited reliably widespread activation of peripheral muscles 5'17A9. However, by appropriate orientation of the M C laterally and more vertically, the motor cortex could be focally activated, movements predominantly of a single contralateral digit then being obtainable 1'3. Changes in design of the MC, e.g. by Cadwell Laboratories, resulted in linked dual coils, such as the double square MC, each coil being 7 x 7 cm (Fig. 1 in ref. 2); the M C pulse induces a current under the junction region 2.5x greater than that under each lateral portion. As a result, focal m o t o r cortical stimulation was readily obtained under the junction when tangentially applied over lateral m o t o r cortex, making it possible to identify a central sense of distal movement in ischemically paralyzed limb 2. Further improvement resulted in the figure of '8' design, each coil being 5.0 × 4.8 cm and slightly diverging at the handle end of the junction (Fig. 1 left). The locality of cortical excitation by this design is evidenced by the marked reduction in the compound m o t o r potential ( C M A P ) of abductor digiti minimi when

the MC energized a little above threshold was shifted 0.5 cm on the scalp (Fig. 1 in ref. 4). Our initial purpose in mapping the motor cortex after traumatic quadriplegia was to study the central sense of movement in paralyzed limbs, without the time constraint imposed by having to block the m o v e m e n t ischemically. However, the motor maps obtained were so different from those of normal subjects as to become the main focus of our study. The series included two adult, traumatic quadriplegics and three of the authors, who served as controls. All subjects complied with a detailed consent procedure approved by the Miami University Institutional Review Board. The Cadwell MES-10 stimulator was used with a tape-wrapped figure '8' MC. The stimulator output was kept at 100% to reveal the maximum motor representation under each scalp site. Even so, moving this M C by 2 cm could elicit a marked reduction in the CMAP, which permitted the scalp field to be delineated (Fig. 1 middle and right). Subjects were not asked to contract their muscles during MC stimulation to equalize, as far as possible, higher level facilitation in controls and in quadriplegics. Cz was identified and marked with an eye shadow pencil. Scalp sites were marked at intervals of 2 cm from 6 - 8 cm posterior to 4 - 8 cm anterior to C z and from C~ along the interaural line to 8-12 cm laterally, etc. The MC was held tangential to

Correspondence: V. Amassian, Department of Physiology Box 31, State University of New York, Health Science Center at Brooklyn, 450 Clarkson Avenue, Brooklyn, NY 11203, U.S.A. 0006-8993/90/$03.50 © 1990 Elsevier Science Publishers B.V. (Biomedical Division)

131 lateral to C z (Fig. 2 top). With MC stimulation 10 cm and 2 cm lateral to C z, the biceps CMAP still reached 3 mV and 2.2 mV, respectively. Stimulating at other A - P sites disclosed biceps CMAPs of 3 mV at X, Y (+6, 4) and 4.4 mV at (-4, 6). Thus large biceps CMAPs were elicited by focal MC stimulation over a very wide area of scalp whose full extent laterally could not be mapped because of the proximity of the temporalis muscle and stimulation thereof. Triceps CMAPs were much smaller in amplitude, never exceeding 0.6 mV. (By contrast, triceps responses are normally larger than those elicited in biceps.) Biceps and triceps CMAPs elicited at different sites were strongly positively correlated (rank order, r = +0.988, P < 0.001) in amplitude (Fig. 3, top). No responses were obtained from APB or ADM. Latencies of biceps CMAPs were in the range 13.5-16.0 ms and were strongly negatively correlated (r = -0.906, P < 0.001) with amplitude (Fig. 3, bottom). Using the same focal stimulation technique, the largest and most extensive biceps responses recorded among the three of us were approximately 1 mV and 0.4 mV elicited at (0, 4) and (-2, 4), respectively, i.e., extending much less both laterally and in the A - P axis than in the first patient (Fig. 2 bottom). A few other sites (-2, 6), (0, 6), (2, 6) and (2, 8) yielded small responses of amplitude less than 0.2 mV. By contrast, in the same subject, the largest ADM responses reached 6.3 mV, and substantial ADM responses were elicited at sites separated by 8 cm in the A - P axis and 2-4 cm in the mediolateral axis.

the scalp with the junction region parallel to the midline and with the handle pointing anteriorly. When the skull curvature prevented the coils from lying flat on the scalp, the MC was tilted so the medial coil usually conformed. An X, Y coordinate of e.g. (-2, 4) implied that the point of divergence of the 2 coils at the other end of the MC lay 2 cm posterior and 4 cm lateral to Cz. Given that the junction region extended anteriorly for nearly 5 cm from this point, the zone of strongest cortical excitation lay anterior to any coordinates given. The CMAPs were recorded with paired disc electrodes from the skin overlying the muscle and were fed into either a Cadweli Spectrum or a Cadwell 7400, for amplification, visual monitoring and data storage. The bandpass was 2 kHz-10 Hz. Either a laser or a dot matrix printer was used to obtain CMAP records. A computer was used for data analysis and construction of histograms, etc. The first patient was a 22-year-old male. An injury 2 years ago initially rendered him quadriplegic, save for some biceps function in the arm, implying a level close to C5. He had extensive physiotherapy, including biofeedback training primarily of the biceps, resulting currently in 4/5 strength in this muscle. Light touch was diminished in the upper arm and absent below. Position sense was absent in the digits. Recordings from biceps, triceps, abductor pollicis brevis (APB) and abductor digiti minimi (ADM) disclosed the largest CMAPs (4.5 mV peakto-peak) in biceps; these were recorded 4, 6 and 8 cm

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132 Stimulation at a few sites in the first patient elicited a sense of digit movement, especially flexion. Significantly, these sensations were elicited by stimulation at X, Y (5, 6) and (8, 7.5), i.e., anterior to the main biceps representation. Paresthesias described as 'pins and needles' were felt when C~ and (-2, 0) were stimulated. Probably the paresthesias were derived from motor cortex, because large biceps responses were elicited still more posteriorly. (Paresthesias elicited in an intact subject were previously shown to result from motor cortical stimulation4.) The second patient was a 47-year-old male who was rendered quadriplegic nearly 2 years ago by a wave while swimming. Initially, the level was at C~-C e requiring that he be artificially ventilated. He had extensive physiotherapy and biofeedback training, especially for the deltoid, which currently has 4/5 power. Some recovery of muscle function occurred both in the arm and the leg muscles. Using the left hand, he could control the joystick of a power wheelchair, but could not use an eating utensil. Bilaterally, position sense was absent in the digits and at the wrist. Crude touch sensation was present in the digits, but a sharp point was not felt. Recordings from the

anterior deltoid, biceps and A P B disclosed that C M A P s in the deltoid could be elicited from a wide area on the scalp. Deltoid CMAPs, ranging in amplitude from 0.7 to 1.5 mV, were elicited over an A - P extent of +2 to - 4 cm and mediolaterally from 2 to 8 cm (Fig. 4, top). When elicited at different sites (Fig. 1, right), the deltoid C M A P exhibited only a first, early wave (latency 10.515.0 ms), or only a second, later wave (latency 31-39 ms), or both waves. The largest, first responses were not followed by second waves and the largest second waves were usually not preceded by significant first waves (Fig. 5, top; r = -0.460, P < 0.025). No biceps responses were recorded and only miniscule responses (less than 25 HV) were elicited in APB to the focal MC stimulation. Latency and amplitude of first deltoid CMAPs were weakly inversely correlated (Fig. 5, bottom; r = -0.465, P < 0.025). In the same normal control, first deltoid C M A P s of amplitude 0.64 mV, 1.1 mV, 0,25 mV and 0.2 mV were elicited only at four nearby sites, (-2, 4), (0, 4) (0, 6) and (0, 8) respectively, i.e., over a much smaller area than in the second patient (Fig. 4, bottom). Distally projected sensations were rarely elicited in the

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second patient. A tingle in the palm was elicited at one site, but sensations of finger movement were not elicited. Our use of a focal MC is important in interpreting the findings; increased amplitudes and representations of C M A P s of proximal muscles such as biceps and the deltoid would be expected when using the larger, round MC, which excites a larger area of motor cortex under the windings. In the quadriplegic patients, focal motor cortical stimulation elicited substantial responses in proximal muscles from many sites that elicit distal responses in the normal subject. The ease with which responses were elicited in proximal muscles innervated just above the spinal cord lesion parallels the ease with which focal MC stimulation normally elicits distal responses, e.g., in the hand. Therefore, our findings imply that following the traumatic myelopathy, the motor cortex and/or its projection system has undergone a 'reorganization'. Reorganization of somatosensory cortex following deprivation of sensory input by nerve block or amputation has been inferred in several species, including rats 22, cats 8'16, raccoons ~, monkeys ~5 and humans 2°. More recently, an increased motor cortical representation of muscles prox-

imal to an amputated forelimb has been demonstrated in rats l° and in humans u. The categories of explanation for reorganization after loss of sensory input have differing time courses, including: (1) Increased efficacy of preexisting synapses ~4, e.g. an immediate effect through loss of presynaptic inhibition or denervation supersensitivity of the target neuron requiring at least a few days. With traumatic myelopathy, a special possibility is an immediate loss of tonic inhibitory input from below the lesion. The mechanism could be reduced presynaptic inhibition of corticospinal input to motoneurons innervating proximal muscles, or reduced postsynaptic inhibition of motoneurons or corticospinal neurons. (2) Collateral sprouting of axons requiring at least many days ~3'21. Collateral sprouting of corticospinal axons could occur just above the spinal lesion. Alternatively, the sprouting could occur in motor cortex perhaps as a result of loss of afferent input or through biofeedback training. (3) Other longer-latency pathways may be immediately disinhibited by the sensory deprivation ~. However, in the patients with traumatic myelopathy, the response latencies were not elevated.

134 The two patients in our studies were first stimulated so

Our findings may be significant for optimal rehabili-

late after their lesions that a choice between explanations based on their different time courses is precluded. Nor can the site or sites of the reorganization, i.e., cortical vs

tation of quadriparetic patients. Both patients had intensive biofeedback therapy of the lowest innervated muscles spared by the lesion. If such therapy enhances the 'takeover' of motor cortex, or it projections by the

subcortical, readily be indentified from our present findings. The negative correlation found between latency of the biceps or deltoid C M A P and its amplitude need not imply the development of an alternative pathway with additional, interposed synapses. A n increased latency from peripheral scalp sites of the cortical motor

representation of the trained muscle, then improvement in voluntary control of the weaker, distal arm muscles may be slowed or even hindered, although such muscles are very important in skilled motor activities. Therefore, analysis of the effects of different types of rehabilitation

representation would be expected if small m o t o n e u r o n s , with low peripheral conduction velocities, had the greatest excitability ~2 and therefore the most extensive cortical

on motor cortical representation of distal vs proximal muscle activation may prove useful in guiding therapy.

representation to focal mapping. However, the paucity of

We wish to express our thanks to the Department of Neurological Surgery, University of Miami School of Medicine, where this study was performed and for support by the Miami Project to Cure Paralysis and the Foundation for Investigation of Neurological Disorders. The generous cooperation of the two patients made this study possible.

reports of a central sense of digit movement, normally elicited readily by focal stimulation of motor cortex 2, implies that the substrate of this central sense also has been reorganized, presumably above the spinal level. 1 Amassian, V.E., Cadwell, J., Cracco, R.Q. and Maccabee, P.J., Focal cerebral and peripheral nerve stimulation in man with the magnetic coil, J. Physiol. (Lond.), 390 (1987) 24P. 2 Amassian, V.E., Cracco, R.Q. and Maccabee, P.J., A sense of movement elicited in paralyzed distal arm by focal magnetic coil stimulation of human motor cortex, Brain Research, 479 (1989) 355-360. 3 Amassian, V.E., Cracco, R.Q. and Maccabee, P.J. Focal stimulation of human cerebral cortex with the magnetic coil: a comparison with electrical stimulation, Electroenceph. Clin. Neurophysiol., 74 (1989) 401-416. 4 Amassian, V,E., Cracco, R.Q., Maccabee, P.J. and Somasundaram, M., Focal magnetic coil stimulation near human central sulcus exceptionally elicits localized contralateral paresthesias, J. Physiol. (Lond.), 403 (1989) 75E 5 Barker, A.T., Freeman, I.L., Jalinous, R. and Jarratt, J.A., Magnetic stimulation of the human brain and peripheral nervous system: an introduction and the results of an intitial clinical evaluation, Neurosurgery, 20 (1987) 100-109. 6 Barker, A.T., Freeston, I.L., Jalinous, R., Merton, J.A. and Morton, H.B., Magnetic stimulation of the human brain, J. Physiol. (Lond.), 369 (1985) 3P. 7 Barker, A.T., Jalinous, R. and Freeston, I.L., Non-invasive magnetic stimulation of the human motor cortex, Lancet, i (1985) 1106-1107. 8 Brandenberg, G.A. and Mann, M.D., Sensory nerve crush and regeneration and the receptive fields and response properties of neurons in the primary somatosensory cerebral cortex of cats, Exp. Neurol., 103 (1989) 256-266. 9 Cohen, L.G. and Hallett, M., Changes in human cortical motor representation areas of muscles proximal to the stump after amputations: a study with transcranial magnetic stimulation, Soc. Neurosc. Abstr., 15 (1989) 1239. 10 Donoghue, J.E and Sanes, J.N., Peripheral nerve injury in developing rats reorganizes representation pattern in motor cortex, Proc. Natl. Acad. Sci. U.S.A., 84 (1987) 1123-1126. ll Fadiga, E., Haimann, C., Margnelli, M. and Sogtiu, M.L., Variability of peripheral representation in ventrobasal thalamic nuclei of the cat: effects of acute reversible blockade of the dorsal column nuclei, Exp. Neurol., 60 (1978) 484-498.

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