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8 - Lesions of the periphery and spinal cord

Published online by Cambridge University Press:  12 August 2009

Michael J. Angel
Affiliation:
Toronto Western Hospital, Ontario, Canada
Nicholas J. Davey
Affiliation:
Department of Sensorimotor Systems, Imperial College School of Medicine, Charing Cross Hospital, London, UK
Peter H. Ellaway
Affiliation:
Department of Sensorimotor Systems, Imperial College School of Medicine, Charing Cross Hospital, London, UK
Robert Chen
Affiliation:
Toronto Western Hospital, Ontario, Canada
Simon Boniface
Affiliation:
Addenbrooke's Hospital, Cambridge
Ulf Ziemann
Affiliation:
Johann Wolfgang Goethe-Universität Frankfurt
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Summary

Introduction

Functional recovery or compensation following nervous system injury may be facilitated by plasticity within the central nervous system. For example, activation of the visual cortex that occurs during Braille reading in the early blind (under 14 years of age) is of functional importance (Cohen et al., 1997) and there is convincing evidence that plasticity can play an adaptive role following deafferentation (Pascual-Leone & Torres, 1993). Whether this kind of functional reorganization occurs in the motor system is less clear.

In the motor system, the skilled use of our muscles requires the integrative actions of sensory feedback and descending motor commands, which result in appropriate activation of motoneurones through activation of spinal interneurons, i.e. sensorimotor integration (Baldissera et al., 1981).The corticospinal system, the vital component of volitional movement, controls spinal motoneuronal activity through interneuronally mediated pathways (Lundberg & Voorhoeve, 1962; Pierrot-Deseilligny, 1996; Alstermark et al., 1999), and through their direct monosynaptic contacts with spinal motoneurons (Jankowska et al., 1975). The alterations in the control of the corticospinal system have received the greatest attention in TMS studies of plasticity in humans.

The importance of tonic sensory input in regulating cortical excitability and cortical body part representation in the motor cortex was initially shown in animal studies wherein peripheral nerve injury triggers a massive reorganization in the rat (Sanes et al., 1990).

Type
Chapter
Information
Plasticity in the Human Nervous System
Investigations with Transcranial Magnetic Stimulation
, pp. 204 - 230
Publisher: Cambridge University Press
Print publication year: 2003

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References

Ackermann, H., Thomas, C., Guschlbauer, B. & Dichgans, J. (1992). Neurophysiological evaluation of sensorimotor functions of the leg: comparison of evoked potentials following electrical and mechanical stimulation, long latency muscle responses, and transcranial magnetic stimulation. J. Neurophysiol., 239: 218–222Google ScholarPubMed
Alstermark, B., Isa, T., Ohki, Y. & Saito, Y. (1999). Disynaptic pyramidal excitation in forelimb motoneurons mediated via C(3)–C(4) propriospinal neurons in the Macaca fuscata. J. Neurophysiol., 82: 3580–3585CrossRefGoogle Scholar
Angel, M. J., Guertin, P., Jimenez, I. & McCrea, D. A. (1996). Group I afferents evoke disynaptic EPSPs in cat hindlimb motoneurones during fictive locomotion. J. Physiol. (Lond.), 494: 851–861CrossRefGoogle Scholar
Baldissera, F., Hultborn, H. & Illert, M. (1981). Integration in spinal neuronal systems. In Handbook of Physiology – The Nervous System, ed. J. M. Brookhart & V. B. Mountcastle, pp. 509–595. Bethesda: Williams and Wilkins
Barbeau, H., Norman, K., Fung, J., Visintin, M. & Ladouceur, M. (1998). Does neurorehabilitation play a role in the recovery of walking in neurological populations? In Neuronal Mechanisms for Generating Locomotor Activity, ed. O. Kien, R. M. Harris-Warrick, L. M. Jordan, H. Hultborn & N. Kudo, Ann. N. Y. Acad. Sci., 16: 377–392
Brasil-Neto, J., Valls-Sole, J., Pascual-Leone, A.. (1993). Rapid modulation of human cortical motor output following ischaemic nerve block. Brain, 116, 511–525CrossRefGoogle Scholar
Brouwer, B. & Hopkins-Rosseel, D. H. (1997). Motor cortical mapping of proximal upper extremity muscles following spinal cord injury. Spinal Cord, 35: 205–212CrossRefGoogle ScholarPubMed
Capaday, C., Richardson, M. P., Rothewll, J. C. & Brooks, D. J. (2000). Long-term changes of GABAergic function in the sensorimotor cortex of amputees: a combined magnetic stimulation and 11C-flumazenil PET study. Exp. Brain Res., 133: 552–556CrossRefGoogle ScholarPubMed
Cariga, P., Cately, M., Mathias, C. J., Savic, G., Frankel, H. L. & Ellaway, P. H. (2002). Organisation of the sympathetic skin response in spinal cord injury. J. Neurol. Neurosurg. Psychiatry, 72: 356–360CrossRefGoogle ScholarPubMed
Chang, C-W. & Lien, I-N. (1991). Estimate of motor conduction in human spinal cord: slowed conduction in spinal cord injury. Muscle Nerve, 14: 990–996CrossRefGoogle ScholarPubMed
Cheliout-Heraut, F., Loubert, G., Masri-Zada, T., Aubrun, F. & Pasteyer, J. (1998). Evaluation of early motor and sensory evoked potentials in cervical spinal cord injury. Neurophysiol. Clin., 39–55CrossRefGoogle ScholarPubMed
Chen, R., Corwell, B., Yaseen, Z., Hallett, M. & Cohen, L. G. (1998). Mechanisms of cortical reorganization in lower-limb amputees. J. Neurosci., 18: 3443–3450CrossRefGoogle ScholarPubMed
Chen, R., Lozano, A. M. & Ashby, P. (1999). Mechanism of the silent period following transcranial magnetic stimulation. Evidence from epidural recordings. Exp. Brain Res., 128: 539–542CrossRefGoogle ScholarPubMed
Clarke, C. E., Modarres-Sadeghi, H., Twomey, J. A. & Burt, A. A. (1994). Prognostic value of cortical magnetic stimulation in spinal cord injury. Paraplegia, 32: 554–560Google ScholarPubMed
Cohen, L. G., Bandinelli, S., Findley, T. W. & Hallet, M. (1991a). Motor reorganization after upper limb amputation in man: a study with focal magnetic stimulation. Brain, 114: 615–627CrossRefGoogle Scholar
Cohen, L. G., Roth, B. J., Wassermann, E.. (1991b). Magnetic stimulation of the human cerebral cortex, an indicator of reorganization in motor pathways in certain pathological conditions. J. Clin. Neurophysiol., 8: 65CrossRefGoogle Scholar
Cohen, L. G., Topka, H., Cole, R. A. & Hallet, M. (1991c). Leg paresthesias induced by magnetic brain stimulation in subjects with thoracic spinal cord injury. Neurology, 41: 1283–1288CrossRefGoogle Scholar
Cohen, L. G., Celnik, P., Pascual-Leone, A.. (1997). Functional relevance of cross-modal plasticity in the blind. Nature, 389: 180–183CrossRefGoogle Scholar
Curt, A., Weinhardt, C. & Dietz, V. (1996). Significance of sympathetic skin responses in assessment of autonomic failure in subjects with spinal cord injury. J. Auton. Nerv. Syst., 61: 175–180CrossRefGoogle Scholar
Davey, N. J., Romaiguère, P., Maskill, D. W. & Ellaway, P. H. (1994). Suppression of voluntary motor activity revealed using transcranial magnetic stimulation of the motor cortex in man. J. Physiol., 477: 223–235CrossRefGoogle ScholarPubMed
Davey, N. J., Smith, H. C., Wells, E., Maskill, D. W., Ellaway, P. H. & Frankel, H. L. (1998). Responses of thenar muscles to transcranial magnetic stimulation of the motor cortex in patients with incomplete spinal cord injury. J. Neurol. Neurosurg. Psychiatry, 65: 80–87CrossRefGoogle ScholarPubMed
Davey, N. J., Smith, H. C., Savic, G., Maskill, D. W., Ellaway, P. H. & Frankel, H. L. (1999). Comparison of input-output patterns in the corticospinal system of normal subjects and incomplete spinal cord injured patients. Exp. Brain Res., 127: 382–390CrossRefGoogle ScholarPubMed
Davis, K. D., Kiss, Z. H. T., Luo, L., Tasker, R. R., Lozano, A. M. & Dostrovsky, J. O. (1998). Phantom sensations generated by thalamic microstimulation. Nature, 391: 385–387CrossRefGoogle ScholarPubMed
Dettmers, C., Liepert, J., Adler, T.. (1999). Abnormal motor cortex organization contralateral to early upper limb amputation in humans. Neurosci. Lett., 263: 41–44CrossRefGoogle ScholarPubMed
Dietz, V., Wirz, M., Curt, A. & Columbo, G. (1998). Locomotor pattern in paraplegic patients: training effects and recovery of spinal cord function. Spinal Cord, 36: 380–390CrossRefGoogle ScholarPubMed
Dimitrijevic, M. R., Dimitrijevic, M. M., Faganel, J. & Sherwood, A. M. (1984). Suprasegmentally induced motor unit activity in paralyzed muscles of subjects with established spinal cord injury. Ann. Neurol., 16: 216–221CrossRefGoogle Scholar
Dimitrijevic, M. R., Hsu, C. Y. & McKay, W. B. (1992a). Neurophysiological assessment of spinal cord and head injury. J. Neurotrauma, 9: 293–300Google Scholar
Dimitrijevic, M. R., Kofler, M., McKay, W. B., Sherwood, A. M., Linden, C. & Lissens, M. A. (1992b). Early and late lower limb motor evoked potentials elicited by transcranial magneticmotor cortexstimulation. Electroencephalogr. Clin. Neurophysiol., 85: 365–373CrossRefGoogle Scholar
Edgerton, V. R., Leon, R. D. & Harkema, S. J. (2001). Retraining the injured spinal cord. J. Physiol., 533: 15–22CrossRefGoogle ScholarPubMed
Eidelberg, E., Walden, J. G. & Nguyen, L. H. (1981). Locomotor control in macacque monkeys. Brain, 104: 647–663CrossRefGoogle Scholar
Fuhr, P., Cohen, L. G., Dang, N.. (1992). Physiological analysis of motor reorganization following lower limb amputation. Electroencephalogr. Clin. Neurophysiol., 85: 53–60CrossRefGoogle ScholarPubMed
Ghosh, S. & Porter, R. (1988). Corticocortical synaptic influences on morphologically identified pyramidal neurones in the motor cortex of the monkey. J. Physiol., 400: 617–629CrossRefGoogle ScholarPubMed
Gianutsos, J., Eberstein, A., Ma, D., Holland, T. & Goodgold, J. (1987). A noninvasive technique to assess completeness of spinal cord lesions in humans. Exp. Neurol., 98: 34–40CrossRefGoogle ScholarPubMed
Giraux, P., Sirigu, A., Schneider, B. & Dubernard, J. M. (2001). Cortical reorganization in motor cortex after graft of both hands. Nat. Neurosci., 4: 691–692CrossRefGoogle ScholarPubMed
Gossard, J. P., Brownstone, R. M., Barajon, I. & Hultborn, H. (1994). Transmission in a locomotor-related group Ib pathway from hindlimb extensor muscles in the cat. Exp. Brain Res., 98: 213–228CrossRefGoogle Scholar
Green, J. B., Sora, E., Bialy, Y., Ricamato, A. & Thatcher, R. W. (1998). Cortical sensorimotor reorganization after spinal cord injury. Neurology, 50: 1115–1121CrossRefGoogle Scholar
Guertin, P., Angel, M. J., Perreault, M-C. & McCrea, D. A. (1995). Ankle extensor group I afferents excite extensors throught the hindlimb during fictive locomotion in the cat. J. Physiol., 487: 197–209CrossRefGoogle Scholar
Hall, E. J., Flament, D., Fraser, C. & Lemon, R. N. (1990). Non-invasive brain stimulation reveals reorganised cortical outputs in amputees. Neurosci. Lett., 116: 379–386CrossRefGoogle Scholar
Hallett, M. (2000). Transcranial magnetic stimulation and the human brain. Nature, 406: 147–150CrossRefGoogle ScholarPubMed
Hayes, K. C., Allatt, R. D., Wolfe, D. L., Kasai, T. & Hsieh, J. (1992). Reinforcement of subliminal flexion reflexes by transcranial magnetic stimulation of motor cortex in subjects with spinal cord injury. Electroencephalogr. Clin. Neurophysiol., 85: 102–109CrossRefGoogle ScholarPubMed
Hess, G. & Donoghue, J. P. (1994). Long-term potentiation of horizontal connections provides a mechanism to reorganize cortical maps. J. Neurophysiol., 71: 2543–2547CrossRefGoogle Scholar
Hess, G. & Donoghue, J. P. (1996). Long-term depression of horizontal connections in rat motor cortex. Eur. J. Neurosci., 8: 658–665CrossRefGoogle ScholarPubMed
Hu-Xin, Q., Stepniewaska, I. & Kaas, J. H. (2000). Reorganization of primary motor cortex in adult macaque monkeys with long-standing amputations. J. Neurophysiol., 84: 2133–2147Google Scholar
Jacobs, K. & Donoghue, J. (1991). Reshaping the cortical map by unmasking latent intracortical connections. Science, 251: 944–947CrossRefGoogle ScholarPubMed
Jankowska, E., Padel, Y. & Tanaka, R. (1975). Projections of pyramidal tract cells to alpha-motoneurons innervating hindlimb muscles in the monkey. J. Physiol., 249: 637–667CrossRefGoogle Scholar
Kaneko, K., Kawai, S., Fuchigami, Y., Morita, H. & Ofuji, A. (1996). The effect of current direction induced by transcranial magnetic stimulation on the corticospinal excitability in human brain. Electroencephalogr. Clin. Neurophysiol., 101: 478–482Google ScholarPubMed
Kew, J. J. M., Ridding, M. C., Rothwell, J. C.. (1994). Reorganization of cortical blood flow and transcranial magnetic stimulation maps in human subjects after upper limb amputation. J. Neurophysiol., 72: 2517–2524CrossRefGoogle ScholarPubMed
Kujirai, T., Caramia, M. D., Rothwell, J. C.. (1993). Corticocortical inhibition in human motor cortex. J. Physiol., 471: 501–519CrossRefGoogle ScholarPubMed
Leach, M. J., Marden, C. M. & Miller, A. A. (1986). Pharmacological studies on lamotrigine, a novel potential antiepileptic drug: II. Neurochemical studies on the mechanism of action. Epilepsia, 27: 490–497CrossRefGoogle ScholarPubMed
Levy, W. J., Amassian, V. E., Traad, M. & Cadwell, J. (1990). Focal magnetic coil stimulation reveals motor cortical system reorganized in humans after traumatic quadriplegia. Brain Res., 510: 130–134CrossRefGoogle ScholarPubMed
Leyton, A. S. F. & Sherrington, C. S. (1917). Observations on the excitable cortex of the chimpanzee, orangutan, and gorilla. Quart. J. Exp. Physiol., 11: 135–222CrossRefGoogle Scholar
Liepert, J., Tegenthoff, M. & Malin, J. P. (1995). Changes of cortical motor area size during immobilization. Electroencephalogr. Clin. Neurophysiol., 97: 382–386CrossRefGoogle ScholarPubMed
Liepert, J., Bauder, H., Wolfgang, H. R., Miltner, W. H., Taub, E. & Weiller, C. (2000). Treatment-induced cortical reorganization after stroke in humans. Stroke, 31: 1210–1216CrossRefGoogle ScholarPubMed
Lissens, M. A. & Vanderstraeten, G. G. (1996). Motor evoked potentials of the respiratory muscles in tetraplegic subjects. Spinal Cord, 34: 673–678CrossRefGoogle Scholar
Lundberg, A. & Voorhoeve, P. (1962). Effects from the pyramidal tract on spinal reflex arcs. Acta Physiol. Scand., 56: 201–219CrossRefGoogle ScholarPubMed
McCrea, D. A. (2001). Spinal circuitry of sensorimotor control of locomotion. J. Physiol., 533: 41–50CrossRefGoogle ScholarPubMed
McCrea, D. A., Shefchyk, S. J., Stephens, M. J. & Pearson, K. G. (1995). Disynaptic group I excitation of synergist ankle extensor motorneurones during fictive locomotion in the cat. J. Physiol., 487: 527–539CrossRefGoogle Scholar
McKiernan, B. J., Maracario, J. K., Karrer, J. H. & Cheney, P. D. (1998). Corticomotoneural (CM) postspike effects on shoulder, elbow, wrist, digit, and intrinsic hand muscles during a reach and prehension task in the monkey. J. Neurophysiol., 83: 99–115CrossRefGoogle Scholar
McNutly, P. A., Macefield, V. G., Taylor, J. L. & Hallet, M. (2002). Cortically evoked neural volleys to the human hand are increased during ischemic block of the forearm. J. Physiol., 538: 279–288Google Scholar
Mano, Y., Nakamuro, T., Tamura, R.. (1995). Central motor reorganization after anastomosis of the musculocutaneous and intercostal nerves following cervical root avulsion. Ann. Neurol., 38: 15–20CrossRefGoogle ScholarPubMed
Mills, K. R., Boniface, S. J. & Schubert, M. (1992). Magnetic brain stimulation with a double coil: the importance of coil orientation. Electroencephalogr. Clin. Neurophysiol., 85: 17–21CrossRefGoogle ScholarPubMed
Morita, H., Baumgarten, J., Petersen, N., Christensen, L. O. & Neilsen, J. (1999). Recruitment of extensor-carpi-radialis motor units by transcranial magnetic stimulation and radial-nerve stimulation in human subjects. Exp. Brain Res., 128: 557–562CrossRefGoogle ScholarPubMed
Pascual-Leone, A. & Torres, F. (1993). Plasticity of the sensorimotor cortex representation of the reading finger in Braille readers. Brain, 116: 39–52CrossRefGoogle ScholarPubMed
Pascual-Leone, A., Dang, N., Cohen, L. G., Brasil-Neto, J. P., Cammarota, A. & Hallett, M. (1995). Modulation of muscle responses evoked by transcranial magnetic stimulation during acquisition of new fine motor-skills. J. Neurophysiol., 74: 1037–1045CrossRefGoogle ScholarPubMed
Pascual-Leone, A., Peris, M., Tormos, J. M., Pascual, A. P. & Catala, M. D. (1996). Reorganization ofhuman corticalmotor output mapsfollowing traumatic forearmamputation. Neuroreport, 7: 2068–2070CrossRefGoogle Scholar
Pierrot-Deseilligny, E. (1996). Transmission of the cortical command for human voluntary movement through cervical propriospinal premotoneurons. Progr. Neurobiol., 48: 489–517CrossRefGoogle ScholarPubMed
Puri, B. K., Smith, H. C., Cox, I. J.. (1998). The human motor cortex following incomplete spinal cord injury: an investigation using proton magnetic resonance spectroscopy. J. Neurol. Neurosurg. Psychiatry, 65: 748–754CrossRefGoogle Scholar
Raineteau, O. & Schwab, M. E. (2001). Plasticity of motor systems after incomplete spinal cord injury. Nat. Rev. Neurosci., 2: 263–273CrossRefGoogle ScholarPubMed
Ridding, M. C. & Rothwell, J. C. (1997). Stimulus/response curves as a method of measuring motor cortical excitability in man. Electroencephalogr. Clin. Neurophysiol., 105: 340–344CrossRefGoogle ScholarPubMed
Roricht, S. & Meyer, B-U. (2000). Residual function in motor cortex contralateral to amputated hand. Neurology, 54: 984–987CrossRefGoogle ScholarPubMed
Roricht, S., Meyer, B. U., Niehaus, L. & Brandt, S. A. (1999). Long-term reorganization of motor cortex outputs after arm amputation. Neurology, 53: 106–111CrossRefGoogle ScholarPubMed
Roricht, S., Machetanz, J., Irlbacher, K., Niehaus, L., Biemer, E. & Meyer, B. U. (2001). Reorganization of human motor cortex after hand replantation. Ann. Neurol., 50: 240–249CrossRefGoogle ScholarPubMed
Rothwell, J. C. (1997). Techniques and mechanisms of action of transcranial stimulation of the human motor cortex. J. Neurosci. Methods, 74: 113–122CrossRefGoogle ScholarPubMed
Sanes, J. N. & Donoghue, J. P. (2000). Plasticity and primary motor cortex. Annu. Rev. Neurosci., 23: 393–415CrossRefGoogle ScholarPubMed
Sanes, J. N., Suner, S. & Donoghue, J. P. (1990). Dynamic organization of primary motor cortex output to target muscle in adult rats. I. Long-term patterns of reorganization following motor or mixed peripheral nerve lesion. Exp. Brain Res., 79: 479–491CrossRefGoogle Scholar
Schieber, M. H. (2001). Constraints on somatotropic organization in the primary motor cortex. J. Neurophysiol., 86: 2125–2143CrossRefGoogle Scholar
Schwenkreis, P., Witscher, K., Janssen, F.. (2000). Changes of cortical excitability in patients with upper limb amputation. Neurosci. Lett., 293: 143–146CrossRefGoogle ScholarPubMed
Schwenkreis, P., Witscher, K., Janssen, F.. (2001). Assessment of reorganization in the sensorimotor cortex after upper limb amputation. Clin. Neurophysiol., 112: 627–635CrossRefGoogle ScholarPubMed
Smith, H. C., Davey, N. J., Savic, G.. (2000a). Modulation of single motor unit discharges using magnetic stimulation of the motor cortex in incomplete spinal cord injury. J. Neurol. Neurosurg. Psychiatry, 68: 516–520CrossRefGoogle Scholar
Smith, H. C., Savic, G., Frankel, H. L.. (2000b). Corticospinal function studied over time following incomplete spinal cord injury. Spinal Cord, 38: 292–300CrossRefGoogle Scholar
Streletz, L. J., Belevich, J. K. S., Jones, S. M., Bhushan, A., Shah, S. H. & Herbison, G. J. (1995). Transcranial magnetic stimulation: cortical motor maps in acute spinal cord injury. Brain Topography, 7: 245–250CrossRefGoogle ScholarPubMed
Taylor, J. L., Allen, G. M., Butler, J. E. & Gandevia, S. C. (1997). Effect of contraction strength on responses in biceps brachii and adductor pollicis to transcranial magnetic stimulation. Exp. Res., 117: 472–478CrossRefGoogle ScholarPubMed
Tegenthoff, M. (1992). Clinical applications of transcranial magnetic stimulation in acute spinal cord injury. In Clinical Applications of Magnetic Transcranial Stimulation, ed. M. A. Lissens, pp. 33–44. Leuven: Uitgeverij, Peters
Topka, H., Cohen, L. G., Cole, R. A. & Hallet, M. (1991). Reorganization of corticospinal pathways following spinal cord injury. Neurology, 41: 1276–1283CrossRefGoogle ScholarPubMed
Wei, F., Li, P. & Zhuo, M. (1999). Loss of synaptic depression in mammalian anterior cingulate cortex after amputation. J. Neuorsci., 19: 9346–9354CrossRefGoogle ScholarPubMed
Whelan, P. J. & Pearson, K. G. (1997). Plasticity in reflex pathways controlling stepping in the cat. J. Neurophysiol., 78: 1643–1650CrossRefGoogle Scholar
Wirz, M., Colombo, G. & Dietz, V. (2002). Long term effects of locomotor training in spinal humans. J. Neurol. Neurosurg. Psychiatry, 71: 93–96CrossRefGoogle Scholar
Wolfe, D. L., Hayes, K. C., Potter, P. J. & Delaney, G. A. (1996). Conditioning lower limb H-reflexes by transcranial magnetic stimulation of motor cortex reveals preserved innervation in SCI subjects. J. Neurotrauma, 13: 281–291Google Scholar
Wolfe, D. L., Hayes, K. C., Hsieh, J. T. & Potter, P. J. (2001). Effects of 4-aminopyrridine on motor evoked potentials in patients with spinal cord injury: a double-blinded, placebo-controlled crossover trial. J. Neurotrauma, 18: 757–771CrossRefGoogle ScholarPubMed
Wolpaw, J. R. & Tennissen, A. M. (2001). Activity-dependent spinal cord plasticity in health and disease. Annu. Rev. Neurosci., 24: 807–843CrossRefGoogle ScholarPubMed
Ziemann, U., Hallett, M. & Cohen, L. G. (1998). Mechanisms of deafferentation-induced plasticity in human motor cortex. J. Neuroscience, 18: 7000–7007CrossRefGoogle ScholarPubMed

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