Initiating extension of the lower limbs in subjects with complete spinal cord injury by epidural lumbar cord stimulation
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Abstract
We provide evidence that the human spinal cord is able to respond to external afferent input and to generate a sustained extension of the lower extremities when isolated from brain control. The present study demonstrates that sustained, nonpatterned electrical stimulation of the lumbosacral cord—applied at a frequency in the range of 5–15 Hz and a strength above the thresholds for twitches in the thigh and leg muscles—can initiate and retain lower-limb extension in paraplegic subjects with a long history of complete spinal cord injury. We hypothesize that the induced extension is due to tonic input applied by the epidural stimulation to primary sensory afferents. The induced volleys elicit muscle twitches (posterior root muscle-reflex responses) at short and constant latency times and coactivate the configuration of the lumbosacral interneuronal network, presumably via collaterals of the primary sensory neurons and their connectivity with this network. We speculate that the volleys induced externally to the lumbosacral network at a frequency of 5–15 Hz initiate and retain an “extension pattern generator” organization. Once established, this organization would recruit a larger population of motor units in the hip and ankle extensor muscles as compared to the flexors, resulting in an extension movement of the lower limbs. In the electromyograms of the lower-limb muscle groups, such activity is reflected as a characteristic spatiotemporal pattern of compound motor-unit potentials.
Keywords
Spinal cord injury Spinal cord stimulation Lower limb extensionAbbreviations
- C
Cervical
- CMUP
Compound motor-unit potential
- EMG
Potential
- CNS
Central nervous system
- EMG
Electromyography, electromyographic
- H
Hamstring
- L
Lumbar
- MLR
Mesencephalic locomotor region
- PARA
Paraspinal muscles
- Q
Quadriceps
- S
Sacral
- SCI
Spinal cord injury, spinal cord-injured
- SCS
Spinal cord stimulation
- T
Thoracic
- TA
Tibialis anterior
- TS
Triceps surae
Notes
Acknowledgements
Special thanks are due to Ms. Auer, Ms. Preinfalk, and Ms. Alesch for their excellent technical support. This study was supported by the Austrian Science Fund (FWF), research project P15469; the Austrian Ministry of Transport, Innovation and Technology; and a grant from the Kent Waldrep National Paralysis Foundation in Addison, Texas, USA.
References
- Barolat G, Singh-Sahni K, Staas WE et al. (1995) Epidural spinal cord stimulation in the management of spasms in spinal cord injury. A prospective study. Stereotact Funct Neurosurg 64:153–164PubMedGoogle Scholar
- Beric A (1988) Stability of lumbosacral somatosensory evoked potentials in a long-term follow-up. Muscle Nerve 11:621–626PubMedGoogle Scholar
- Bizzi E, Giszter SF, Loeb E, Mussa-Ivaldi FA, Saltiel P (1995) Modular organization of motor behavior in the frog’s spinal cord. Trends Neurosci 18:442–446CrossRefPubMedGoogle Scholar
- Brooke JD, McIlroy WE (1985) Locomotor limb synergism through short latency afferent links. Electroencephalogr Clin Neurophysiol 60:39–45CrossRefPubMedGoogle Scholar
- Brown TG (1911) The intrinsic factors in the act of progression in the mammal. Proc R Soc B 84:308–319Google Scholar
- Coburn B (1985) A theoretical study of epidural electrical stimulation of the spinal cord. II. Effects on long myelinated fibers. IEEE Trans Biomed Eng 32:978–986PubMedGoogle Scholar
- De Leon RD, Hodgson JA, Roy RR, Edgerton VR (1998) Full weight bearing hind limb standing following stand training in the adult spinal cat. J Neurophysiol 80:83–91PubMedGoogle Scholar
- Dietz V, Wirz M, Colombo G, Curt A (1997) Locomotor capacity and recovery of spinal cord function in paraplegic patients: a clinical and electrophysiological evaluation. Electroencephalogr Clin Neurophysiol 109:140–153CrossRefGoogle Scholar
- Dietz V, Muller R, Colombo G (2002) Locomotor activity in spinal man: significance of afferent input from joint and load receptors. Brain 125:2626–2634CrossRefPubMedGoogle Scholar
- Dimitrijevic MR (1994) Motor control in chronic spinal cord injury patients. Scand J Rehabil Med (Suppl) 30:53–62Google Scholar
- Dimitrijevic MR (1998) Chronic spinal cord stimulation for spasticity. In: Gindelberg PL, Tasker RR (eds) Textbook for stereotactic and functional neurosurgery. McGraw-Hill, New York, pp 1267–1273Google Scholar
- Dimitrijevic MR (2001) What does the human brain tell to the spinal cord to generate and control standing and walking? World Congress on Neuroinformatics, Vienna 2001. Abstracts 53–54. ISBN 3–901608–20–6Google Scholar
- Dimitrijevic MR, Nathan PW (1967) Studies of spasticity in man. 1. Some features of spasticity. Brain 90:1–30PubMedGoogle Scholar
- Dimitrijevic MR, Faganel J, Gregoric M, Nathan M, Trontelj JK (1972) Habituation: effects of regular and stochastic stimulation. J Neurol Neurosurg Psychiatry 35:234–242PubMedGoogle Scholar
- Dimitrijevic MR, Faganel J, Sharkey PC, Sherwood AM (1980) Study of sensation and muscle twitch responses to spinal cord stimulation. Int Rehabil Med 2:76–81PubMedGoogle Scholar
- Dimitrijevic MR, Prevec TS, Sherwood AM (1983) Somatosensory perception and cortical evoked potentials in established paraplegia. J Neurol Sci 60:253–265CrossRefPubMedGoogle Scholar
- Dimitrijevic MR, Gerasimenko Y, Pinter MM (1998a) Effect of reduced afferent input on lumbar CPG in spinal cord injury subjects. Soc Neurosci Abstr 24:654.23Google Scholar
- Dimitrijevic MR, Gerasimenko Y, Pinter MM (1998b) Evidence for a spinal central pattern generator in humans. In: Kien O, Harris-Warrick RM, Jordan L, Hultborn H, Kudo N (eds) Neuronal mechanism for generating locomotor activity. Ann NY Acad Sci 860:360–376PubMedGoogle Scholar
- Dimitrijevic MR, Minassian K, Murg M et al. (2001) Study of locomotor capabilities induced by spinal cord stimulation (SCS) of the human lumbar cord isolated from the brain control by post traumatic spinal cord injury. Soc Neurosci 27:935.6Google Scholar
- Dobkin BH, Harkema S, Requejo P, Edgerton VR (1995) Modulation of locomotor-like EMG activity in subjects with complete and incomplete spinal cord injury. J Neurol Rehabil 9(4):183–190PubMedGoogle Scholar
- Gerasimenko Y, McKay B, Sherwood A, Dimitrijevic MR (1996) Stepping movements in paraplegic patients induced by spinal cord stimulation. Soc Neurosci Abstr 22:1372Google Scholar
- Giszter SF, Mussa-Ivaldi FA, Bizzi E (1993) Convergent force fields organized in the frog’s spinal cord. J Neurosci 13(2):467–491PubMedGoogle Scholar
- Grillner S, Zangger P (1979) On the central generation of locomotion in the low spinal cat. Exp Brain Res 34:241–261PubMedGoogle Scholar
- Gurfinkel VS, Levik YuS, Kazennikov OV, Selionov VA (1998) Locomotor-like movements evoked by leg muscle vibration in humans. Eur J Neurosci 10:1608–1612CrossRefPubMedGoogle Scholar
- Guru K, Mailis A, Ashby P, Vanderlinden G (1987) Postsynaptic potentials in motoneurons caused by spinal cord stimulation in humans. Electroencephalogr Clin Neurophysiol 66:275–280Google Scholar
- Harkema SJ (2001) Neural plasticity after human spinal cord injury: application of locomotor training to the rehabilitation of walking. Prog Clin Neurosci 7(5):455–468Google Scholar
- Harkema SJ, Hurley SL, Patel UK et al. (1997) Human lumbosacral spinal cord interprets loading during stepping. J Neurophysiol 77:797–811PubMedGoogle Scholar
- He J, Barolat G, Holsheimer J, Struijk JJ (1994) Perception treshold and electrode position for spinal cord stimulation. Pain 59:55–63Google Scholar
- Hultborn H (2001) State-dependent modulation of sensory feedback. J Physiol 533.1:5–13Google Scholar
- Hunter JP, Ashby P (1994) Segmental effects of epidural spinal cord stimulation in humans. J Physiol 474:407–419Google Scholar
- Iwahara T, Atsuta Y, Garcia-Rill E, Skinner RD (1991) Spinal cord stimulation induced locomotion in the adult cat. Brain Res Bull 28:99–105CrossRefGoogle Scholar
- Jankowska E (2001) Spinal interneuronal system: identification, multifunctional character and reconfigurations in mammals. J Physiol (Lond) 533(1):31–40Google Scholar
- Jilge B, Minassian K, Dimitrijevic MR (2001) Electrical stimulation of the human lumbar cord can elicit standing parallel extension of paralyzed lower limbs after spinal cord injury. World Congress on Neuroinformatics, Vienna 2001. Abstracts 63–64 (ISBN 3–901608–20–6)Google Scholar
- Jilge B, Minassian K, Rattay F, Dimitrijevic MR (2002) Tonic and rhythmical motor-unit activity of the cord induced by epidural stimulation can alter posterior roots muscle reflex responses. Proc IFESS 2002 Conference, Ljubljana, Slovenia 164–166Google Scholar
- Jordan LM, Pratt CA, Menzies JE (1979) Locomotion evoked by brain stem stimulation: occurrence without phasic segmental afferent input. Brain Res 177:204–207PubMedGoogle Scholar
- Kameyama T et al. (1996) Morphologic features of the normal human cadaveric spinal cord. Spine 21:1285–1290CrossRefPubMedGoogle Scholar
- Kazennikov OV, Shik ML, Yakovleva GV (1983) Stepping elicited by stimulation of the dorsolateral funiculus in the cat spinal cord. Bull Exp Biol Med 96(8):8–10Google Scholar
- Kuhn R (1950) Functional capacity of the isolated human spinal cord. Brain 1:1–51Google Scholar
- Lang J, Geisel U (1983) Lumbosacral part of the dural sac and the topography of its contents. Morphol Med 3:27–46 (in German)PubMedGoogle Scholar
- Lehmkuhl D, Dimitrijevic MR, Renoul E (1984) Electrophysiological characteristics of lumbosacral evoked potentials in subjects with established spinal cord injury. Electroencephalogr Clin Neurophysiol 59:142–155CrossRefPubMedGoogle Scholar
- Maccabee PJ, Lipitz ME, Desudchit T et al. (1996) A new method using neuromagnetic stimulation to measure conduction time within the cauda equina. Electroencephalogr Clin Neurophysiol 101:153–166CrossRefPubMedGoogle Scholar
- Macpherson JM, Deliagina TG, Orlovsky GN (1999) Control of body orientation and equilibrium in vertebrates. In: Stein PSG, Grillner S, Selverston AI, Stuart DG (eds) Neurons, networks and motor behavior. MIT Press, Cambridge, MA, pp 257–267Google Scholar
- Minassian K, Pinter MM, Murg M et al. (2001a) Effective spinal cord stimulation (SCS) train for evoking stepping locomotor movement of paralyzed human lower limbs due to SCI elicits a late response additionally to the early monosynaptic response. Soc Neurosci Abstr 27:935.12Google Scholar
- Minassian K, Rattay F, Dimitrijevic MR (2001b) Features of the reflex responses of the human lumbar cord isolated from the brain but during externally controlled locomotor activity. World Congress on Neuroinformatics, Vienna 2001. Abstracts 55–56 (ISBN 3–901608–20–6)Google Scholar
- Minassian K, Rattay F, Dimitrijevic MR (2001c) A computer simulation and electrophysiological methods to identify the primary stimulated spinal cord structures with epidural electrodes. World Congress on Neuroinformatics, Vienna 2001. Abstracts 64–65 (ISBN 3–901608–20–6)Google Scholar
- Minassian K, Jilge B, Rattay F et al. (2002) Effective spinal cord stimulation (SCS) for evoking stepping movement of paralyzed human lower limbs: study of posterior root muscle reflex responses. Proc IFESS 2002 Conference, Ljubljana, Slovenia 167–169Google Scholar
- Mori S (1987) Integration of posture and locomotion in acute decerebrate cats and in awake, freely moving cats. Prog Neurobiol 28:161–195PubMedGoogle Scholar
- Mori S, Kawahara K, Sakamoto T, Aoki M, Tomiyama T (1982) Setting and resetting of level of postural muscle tone in decerebrate cat by stimulation of brain stem. J Neurophysiol 48(3):737–748PubMedGoogle Scholar
- Murg M, Binder H, Dimitrijevic MR (2000) Epidural electrical stimulation of posterior structures of the human lumbar spinal cord. 1. Muscle twitches—a functional method to define the site of stimulation. Spinal Cord 38:394–402CrossRefPubMedGoogle Scholar
- Mushahwar VK, Collins DF, Prochazka A (2000) Spinal cord microstimulation generates functional limb movements in chronically implanted cats. Exp Neurol 163(2):422–429CrossRefPubMedGoogle Scholar
- Mushahwar VK, Gillard DM, Gauthier MJA, Prochazka A (2002) Intraspinal microstimulation generates locomotor-like and feedback-controlled movements. IEEE Trans Rehab Eng 10(1):68–81CrossRefGoogle Scholar
- Pearson KG, Collins DF (1993) Reversal of the influence of group Ib afferents from plantaris on activity in medial gastrocnemius muscle during locomotor activity. J Neurophysiol 70:1009–1017PubMedGoogle Scholar
- Pinter MM, Dimitrijevic MR, Dimitrijevic MM (1998) Effect of motor task on externally induced stepping movement in spinal cord subjects. Soc Neurosci Abstr 24:831.1Google Scholar
- Pinter MM, Gerstenbrand F, Dimitrijevic MR (2000) Epidural electrical stimulation of posterior structures of the human lumbosacral cord. 3. Control of spasticity. Spinal Cord 38:524–531CrossRefPubMedGoogle Scholar
- Pratt CA, Fung J, Macpherson JM (1994) Stance control in the chronic spinal cat. J Neurophysiol 71:1981–1985PubMedGoogle Scholar
- Rattay F, Minassian K, Dimitrijevic MR (2000) Epidural electrical stimulation of posterior structures of the human lumbosacral cord. 2. Quantitative analysis by computer modeling. Spinal Cord 38:473–489CrossRefPubMedGoogle Scholar
- Richardson RR, McLone DG (1978) Percutaneous epidural neurostimulation for paraplegic spasticity. Surg Neurol 9:153–155PubMedGoogle Scholar
- Riddoch G (1917) The reflex functions of the completely divided spinal cord in man compared with those associated with less severe lesions. Brain 40:264–402Google Scholar
- Roaf HE, Sherrington CS (1910) Further remarks on the spinal mammalian preparation. Q J Physiol 3:209–211Google Scholar
- Rosenfeld JE, McKay WB, Halter JA, Pollo F, Dimitrijevic MR (1995) Evidence of a pattern generator in paralyzed subjects with spinal cord injury during spinal cord stimulation. Soc Neurosci Abstr 21:688Google Scholar
- Sherwood AM, McKay WB, Dimitrijevic MR (1996) Motor control after spinal cord injury: assessment using surface EMG. Muscle Nerve 19:966–979CrossRefPubMedGoogle Scholar
- Shik ML (1997) Recognizing propriospinal and reticulospinal systems of initiation of stepping. Mot Control 1:310–313Google Scholar
- Shik ML, Orlovsky GN (1976) Neurophysiology of locomotor automatism. Physiol Rev 56:465–501PubMedGoogle Scholar
- Shik ML, Severin FV, Orlovsky GN (1966) Control of walking and running by means of electrical stimulation of the mid-brain. Biophysics 11:756–765Google Scholar
- Struijk JJ, Holsheimer J, Boom HB (1993) Excitation of dorsal root fibers in spinal cord stimulation: a theoretical study. IEEE Trans Biomed Eng 40:632–639CrossRefPubMedGoogle Scholar
- Tresch MC, Bizzi E (1999) Responses to spinal microstimulation in the chronically spinalized rat and their relationship to spinal systems activated by low threshold cutaneous stimulation. Exp Brain Res 129(3):401–416PubMedGoogle Scholar
- Troni W, Bianco C, Moja MC, Dotta M (1996) Improved methodology for lumbosacral nerve root stimulation. Muscle Nerve 19:595–604CrossRefPubMedGoogle Scholar
- Walsh FM (1919) On the genesis and physiological significance of spasticity and the disorders of motor innervation with a consideration of the functional relationship to the pyramidal tract. Brain 42:1–28Google Scholar