#72: ¿Existen los Generadores Centrales de Patrones (CPG) de la marcha en humanos?

En el episodio de hoy, tratamos de responder a la pregunta que formulamos, sobre todo matizando la autonomía o no de esos CPGs en la médula humana. Revisamos los principales autores y estudios sobre el tema y ahondamos en la evidencia más actual sobre el sistema de interneuronas que conforman los CPGs y las implicaciones para la neurorrehabilitación (estimulación epidural y terapia intensiva). Referencias del episodio: 1. Angeli, C. A., Edgerton, V. R., Gerasimenko, Y. P., & Harkema, S. J. (2014). Altering spinal cord excitability enables voluntary movements after chronic complete paralysis in humans. Brain : a journal of neurology, 137(Pt 5), 1394–1409. https://doi.org/10.1093/brain/awu038 (https://pubmed.ncbi.nlm.nih.gov/24713270/). 2. Barkan, C. L., & Zornik, E. (2019). Feedback to the future: motor neuron contributions to central pattern generator function. The Journal of experimental biology, 222(Pt 16), jeb193318. https://doi.org/10.1242/jeb.193318 (https://pmc.ncbi.nlm.nih.gov/articles/PMC6739810/). 3. Brown, T. G. (1911). The Intrinsic Factors in the Act of Progression in the Mammal. Proceedings of the Royal Society of London. Series B, Containing Papers of a Biological Character, 84(572), 308–319. http://www.jstor.org/stable/80647 (https://www.jstor.org/stable/80647). 4. Cherni, Y., Begon, M., Chababe, H., & Moissenet, F. (2017). Use of electromyography to optimize Lokomat® settings for subject-specific gait rehabilitation in post-stroke hemiparetic patients: A proof-of-concept study. Neurophysiologie clinique = Clinical neurophysiology, 47(4), 293–299. https://doi.org/10.1016/j.neucli.2017.01.008 (https://pubmed.ncbi.nlm.nih.gov/28318816/). 5. Courtine, G., Gerasimenko, Y., van den Brand, R., Yew, A., Musienko, P., Zhong, H., Song, B., Ao, Y., Ichiyama, R. M., Lavrov, I., Roy, R. R., Sofroniew, M. V., & Edgerton, V. R. (2009). Transformation of nonfunctional spinal circuits into functional states after the loss of brain input. Nature neuroscience, 12(10), 1333–1342. https://doi.org/10.1038/nn.2401 (https://pubmed.ncbi.nlm.nih.gov/19767747/). 6. Dietz V. (2010). Behavior of spinal neurons deprived of supraspinal input. Nature reviews. Neurology, 6(3), 167–174. https://doi.org/10.1038/nrneurol.2009.227 (https://pubmed.ncbi.nlm.nih.gov/20101254/). 7. Dimitrijevic, M. R., Gerasimenko, Y., & Pinter, M. M. (1998). Evidence for a spinal central pattern generator in humans. Annals of the New York Academy of Sciences, 860, 360–376. https://doi.org/10.1111/j.1749-6632.1998.tb09062.x (https://pubmed.ncbi.nlm.nih.gov/9928325/). 8. Dzeladini, F., van den Kieboom, J., & Ijspeert, A. (2014). The contribution of a central pattern generator in a reflex-based neuromuscular model. Frontiers in human neuroscience, 8, 371. https://doi.org/10.3389/fnhum.2014.00371 (https://pmc.ncbi.nlm.nih.gov/articles/PMC4071613/). 9. Gizzi, L., Nielsen, J. F., Felici, F., Moreno, J. C., Pons, J. L., & Farina, D. (2012). Motor modules in robot-aided walking. Journal of neuroengineering and rehabilitation, 9, 76. https://doi.org/10.1186/1743-0003-9-76 (https://pubmed.ncbi.nlm.nih.gov/23043818/). 10. Gosgnach S. (2022). Synaptic connectivity amongst components of the locomotor central pattern generator. Frontiers in neural circuits, 16, 1076766. https://doi.org/10.3389/fncir.2022.1076766 (https://pmc.ncbi.nlm.nih.gov/articles/PMC9730330/). 11. Grillner, S. (1981). Control of Locomotion in Bipeds, Tetrapods, and Fish. Comprehensive Physiology, 1179-1236 (https://onlinelibrary.wiley.com/doi/10.1002/cphy.cp010226). 12. Guertin P. A. (2014). Preclinical evidence supporting the clinical development of central pattern generator-modulating therapies for chronic spinal cord-injured patients. Frontiers in human neuroscience, 8, 272. https://doi.org/10.3389/fnhum.2014.00272 (https://pubmed.ncbi.nlm.nih.gov/24910602/). 13. Harkema, S., Gerasimenko, Y., Hodes, J., Burdick, J., Angeli, C., Chen, Y., Ferreira, C., Willhite, A., Rejc, E., Grossman, R. G., & Edgerton, V. R. (2011). Effect of epidural stimulation of the lumbosacral spinal cord on voluntary movement, standing, and assisted stepping after motor complete paraplegia: a case study. Lancet (London, England), 377(9781), 1938–1947. https://doi.org/10.1016/S0140-6736(11)60547-3 (https://pubmed.ncbi.nlm.nih.gov/21601270/). 14. Kathe, C., Skinnider, M. A., Hutson, T. H., Regazzi, N., Gautier, M., Demesmaeker, R., Komi, S., Ceto, S., James, N. D., Cho, N., Baud, L., Galan, K., Matson, K. J. E., Rowald, A., Kim, K., Wang, R., Minassian, K., Prior, J. O., Asboth, L., Barraud, Q., … Courtine, G. (2022). The neurons that restore walking after paralysis. Nature, 611(7936), 540–547. https://doi.org/10.1038/s41586-022-05385-7 (https://pubmed.ncbi.nlm.nih.gov/36352232/). 15. Minassian, K., Jilge, B., Rattay, F., Pinter, M. M., Binder, H., Gerstenbrand, F., & Dimitrijevic, M. R. (2004). Stepping-like movements in humans with complete spinal cord injury induced by epidural stimulation of the lumbar cord: electromyographic study of compound muscle action potentials. Spinal cord, 42(7), 401–416. https://doi.org/10.1038/sj.sc.3101615 (https://pubmed.ncbi.nlm.nih.gov/15124000/). 16. Minassian, K., Persy, I., Rattay, F., Dimitrijevic, M. R., Hofer, C., & Kern, H. (2007). Posterior root-muscle reflexes elicited by transcutaneous stimulation of the human lumbosacral cord. Muscle & nerve, 35(3), 327–336. https://doi.org/10.1002/mus.20700 (https://pubmed.ncbi.nlm.nih.gov/17117411/). 17. Radhakrishna, M., Steuer, I., Prince, F., Roberts, M., Mongeon, D., Kia, M., Dyck, S., Matte, G., Vaillancourt, M., & Guertin, P. A. (2017). Double-Blind, Placebo-Controlled, Randomized Phase I/IIa Study (Safety and Efficacy) with Buspirone/Levodopa/Carbidopa (SpinalonTM) in Subjects with Complete AIS A or Motor-Complete AIS B Spinal Cord Injury. Current pharmaceutical design, 23(12), 1789–1804. https://doi.org/10.2174/1381612822666161227152200 (https://pubmed.ncbi.nlm.nih.gov/28025945/). 18. Reier, P. J., Howland, D. R., Mitchell, G., Wolpaw, J. R., Hoh, D., & Lane, M. A. (2017). Spinal cord injury: repair, plasticity and rehabilitation. eLS, 1-12 (https://onlinelibrary.wiley.com/doi/abs/10.1002/9780470015902.a0021403.pub2).