ReGAIT: A new rehabilitation approach of locomotion for incomplete spinal cord injury patients by integrating neural interfaces, lower-limb powered robotic systems and transcutaneous spinal current stimulation strategies

SUBPROJECT 1: Development of a self-tuned Neural-Machine Interface for closed-loop control of lower-limb exoskeletons (PID2021-124111OB-C31)

  • Principal Investigators: José M. Azorín & Eduardo Iáñez
  • Center: Miguel Hernández University of Elche, Spain

SUBPROJECT 2: Design of transcutaneous spinal current stimulation strategies for rehabilitation of gait

  • Principal Investigators: Hatice Kumru
  • Center: Guttmann Institute, Spain

SUBPROJECT 3: Development of a novel strategy to analyze the effect on gait biomechanics when combining lower-limb powered exoskeletons controlled by Neural-Machine Interfaces and transcutaneous spinal current stimulation in incomplete spinal cord injured patients

  • Principal Investigators: Angel M. Gil-Agudo & Mónica Alcobendas Maestro
  • Center: Hospital for Paraplegics, Spain

 

Abstract

Spinal Cord Injury (SCI) is one of the major motor disorders due to damage in the human nervous system leading to physical impairment in Western society. These conditions will in general disrupt sensory and motor pathways that in turn lead to permanent pathological gait, resulting in impaired independent ambulation. Subsequent restoration of motor function is often variable and incomplete. Usually, therapists try to recover some residual ability for movement when possible, acting over the distal physical level, trying to influence the neural system through mechanisms of neural plasticity (BOTTOM-UP approach). Traditional therapies to improve functional ambulation for patients in the sub-acute phase (3-11 weeks post-injury) use overground training and require designed preparatory exercises, observation by a physical therapist, direct manipulation of the limbs during gait over a regular surface, followed by supervised walking. This kind of physical rehabilitation is both physically burdensome and time-consuming for the therapists. With recent advances in robotic technologies, lower-limb robotic exoskeletons have emerged as aids for over-ground, bipedal ambulation for individuals with motor limitations. However, there have been many discussions over the clinical relevance of exoskeletons, being still elusive the specific benefits of long-term use of exoskeletons in gait training.

This project proposes a new approach to produce enhanced neuroplasticity changes during rehabilitation of locomotion in incomplete thoracic SCI patients by associating and synchronizing the use of lower-limb powered robotic systems with neural activity voluntarily generated by patients and with stimulation of the spinal cord. The neural activity will be detected by means of a Neural-Machine Interface (NMI) composed by a Brain-Machine Interface (BMI) based on electroencephalography (EEG) and a Spinal cord Machine Interface (SMI) based on electrospinography (ESG). On the other hand, different transcutaneous spinal current stimulation (tSCS) strategies for rehabilitation of gait will be explored to induce neuroplasticity, selecting the most effective to be synchronized with the lower-limb exoskeleton commanded by the NMI. Thus, the project will combine a TOP-DOWN rehabilitation approach, i.e. association of neural activity voluntarily generated by the patient with the afferent feedback provided by an exoskeleton, and a BOTTOM-UP approach based on transcutaneous spinal current stimulation. It is expected that this new rehabilitation intervention improves brain plasticity, which is believed to be the responsible for functional improvements. To evaluate the performance progress of the gait rehabilitation, new metrics will be defined based on biomechanical analysis techniques. These metrics will allow us to have an objective knowledge of the gait and of the biomechanical and physiological mechanisms of the recovery achieved. The new rehabilitation approach will be evaluated with incomplete SCI patients in two hospitals focused on research and clinical therapies in SCI people: National Hospital for Paraplegics (HNP: Hospital Nacional de Parapléjicos, Toledo, Spain) and Guttmann Institute (IG: Institut Guttmann, Barcelona, Spain), which are members of the consortium of this project.

Journals:

    • Hernandez-Navarro, A., Ros-Alsina, A., Yurtseven, M., Wright, M., Kumru, H. (2025) Non-invasive cerebral and spinal cord stimulation for motor and gait recovery in incomplete spinal cord injury: systematic review and meta-analysis. J NeuroEngineering Rehabil 22, 53 (2025). https://doi.org/10.1186/s12984-025-01557-4
    • Soriano-Segura, P., Ortiz, M., Iáñez, E., & Azorín, J. M. (2024). Design of a brain-machine interface for reducing false activations of a lower-limb exoskeleton based on error related potential. Computer Methods and Programs in Biomedicine, 255, 108332. https://doi.org/10.1016/j.cmpb.2024.108332
    • Herrera-Valenzuela D, Sinovas-Alonso I, de-los-Reyes-Guzmán A, Gil-Agudo A, del-Ama AJ. Improvement of the gait deviation index for spinal cord injury to broaden its applicability: the reduced gait deviation index for spinal cord injury (rSCI-GDI). Front Bioeng Biotechnol. 2024;12. https://doi.org/10.3389/fbioe.2024.1431596
    • Blanco-Coloma L, García-González L, Sinovas-Alonso I, Torio-Álvarez S, Martos-Hernández P, González-Expósito S, Gil-Agudo A, Herrera-Valenzuela D. Validation of inertial measurement units based on waveform similarity assessment against a photogrammetry system for gait kinematic analysis. Front Bioeng Biotechnol. 2024;12. https://doi.org/10.3389/fbioe.2024.1449698
    • Ferrero, L., Soriano-Segura, P., Navarro, J., Jones, O., Ortiz, M., Iáñez, E., Azorín, J.M., Contreras-Vidal, J.L. (2024). Brain–machine interface based on deep learning to control asynchronously a lower-limb robotic exoskeleton: a case-of-study. Journal of NeuroEngineering and Rehabilitation, 21(1), 48. https://doi.org/10.1186/s12984-024-01342-9
    • Hatice Kumru; Aina Ros-Alsina; Loreto García Alén; Joan Vidal; Yury Gerasimenko; Agusti Hernandez; Mark Wrigth (2024) International Journal of Molecular Sciences, IP. 5.6: » Improvement in Motor and Walking Capacity During Multisegmental Transcutaneous Spinal Stimulation in Individuals with Incomplete Spinal Cord Injury. International Journal of Molecular Sciences 2024-04-19. https://doi.org/10.3390/ijms25084480
    • Juan, J. V., Martínez, R., Iáñez, E., Ortiz, M., Tornero, J., & Azorín, J. M. (2024). Exploring EEG-based motor imagery decoding: a dual approach using spatial features and spectro-spatial Deep Learning model IFNet. Frontiers in Neuroinformatics, 18, 1345425. https://doi.org/10.3389/fninf.2024.1345425
    • Sinovas-Alonso I, Herrera-Valenzuela D, de-los-Reyes-Guzmán A, Cano-de-la-Cuerda R, del-Ama AJ, Gil-Agudo Á. Construct Validity of the Gait Deviation Index for People With Incomplete Spinal Cord Injury (GDI-SCI). Neurorehabil Neural Repair. 2023;37(10):705-715. https://doi.org/10.1177/15459683231206747
    • Ferrero, L., Quiles, V., Ortiz, M., Iáñez, E., Gil-Agudo, Á., & Azorín, J. M. (2023). Brain-computer interface enhanced by virtual reality training for controlling a lower limb exoskeleton. Iscience, 26(5). https://doi.org/10.1016/j.isci.2023.106675
    • Kumru H, García-Alén L, Ros-Alsina A, Albu S, Valles M, Vidal J. (2023) Transcutaneous Spinal Cord Stimulation Improves Respiratory Muscle Strength and Function in Subjects with Cervical Spinal Cord Injury: Original Research. Biomedicines. 2023;11(8):2121. Published 2023 Jul 27. https://doi.org/10.3390/biomedicines11082121
    • Kumru H, Castillo-Escario Y, Jane R, Vidal J, García-Alén L. (2023) Effect of Transcutaneous Cervical Spinal Cord Stimulation on Trunk Function in Subjects with Cervical Spinal Cord Injury. J Spine Res Surg. 2023;5(4). Published 2023 December. https://doi.org/10.26502/fjsrs0067

International and national conferences:

  • Juan, J.V., Martínez, R., Iáñez, E., Ortiz, M., Tornero, J., Azorín, J.M. (2025, February). Mitigating Catastrophic Forgetting in Pedaling Motor Imagery Decodification Using Continuous Progressive Neural Network. In International Conference on NeuroRehabilitation (ICNR 2024), Converging Clinical and Engineering Research on Neurorehabilitation V – Volume I, pp. 89-93. November 5-8, 2024, La Granja de San Ildefonso, Spain
  • C. Polo-Hortigüela, J.V. Juan, M. Ortiz, E. Iáñez, J.M. Azorín. (2024). Análisis de señales EEG en movimientos de flexión plantar y dorsal mediante el empleo de un exoesqueleto de bajo coste parala caracterización de la acción motora. Congreso anual de la sociedad española de ingeniería biomédica (CASEIB 2024), pp: 381-384, November 13- 15, 2024, Sevilla, Spain.
  • D. I. Gracia, J. A. Flores-Yepes, J. M. Cano, Ortiz, M., & J. M. Azorín. (2024). Optimización de parámetros para el filtrado de artefactos cardíacos en señales electroespinográficas no invasivas: un caso de estudio. Congreso anual de la sociedad española de ingeniería biomédica (CASEIB 2024), pp: 201-204, November 13- 15, 2024, Sevilla, Spain.
  • Gracia, D. I., Polo-Hortigüela, C., Iáñez, E., Ortiz, M., & Azorín, J. M. (2024, November). A Novel Technique for Removing Electrocardiography Artifacts from Electroespinography Signals by Preserving Low Frequencies. In International Conference on NeuroRehabilitation (ICNR 2024), Converging Clinical and Engineering Research on Neurorehabilitation V – Volume II, pp. 698-702. November 5-8, 2024, La Granja de San Ildefonso, Spain
  • Polo-Hortigüela, C., Gracia, D. I., Quiles, V., Ortiz, M., Iáñez, E., & Azorín, J. M. (2024, November). Design and Construction of a Low-Cost Ankle Exoskeleton for Neurorehabilitation System. In International Conference on NeuroRehabilitation (ICNR 2024), Converging Clinical and Engineering Research on Neurorehabilitation V – Volume II, pp. 703-707. November 5-8, 2024, La Granja de San Ildefonso, Spain
  • Soriano-Segura, P., García-Villalón, J., Ortiz, M., Iáñez, E., Bayón-Calatayud, M., & Azorín, J. M. (2024, November). Comparing Generic and Personalized Models for Detecting Error Potentials During Gait Initiation of a Lower-Limb Exoskeleton. In International Conference on NeuroRehabilitation (ICNR 2024), Converging Clinical and Engineering Research on Neurorehabilitation V – Volume II, pp. 680-683. November 5-8, 2024, La Granja de San Ildefonso, Spain
  • García-Villalón, J., Soriano-Segura, P., Ortiz, M., Iáñez, E., Azorín, J. M. (2024, November). Decoding motor imagery of starting walk with a lower-limb exoskeleton by using EEGnet and TSNE. Neuroscience 2024. October 5-9, 2024, Chicago, EEUU.
  • Gracia, D. I., Polo-Hortigüela, C., Bayón-Calatayud, M., Iáñez, E., Ortiz, M., & Azorín, J. M. (2024, October). A Case Study for Removing Cardiac Artifacts from Non-Invasive Electrospinography Signals. In 2024 IEEE International Conference on Metrology for eXtended Reality, Artificial Intelligence and Neural Engineering (MetroXRAINE), pp. 1147-1152. October 21-23, 2024, St. Albans, London, UK.
  • Polo-Hortigüela, C., Gracia, D. I., Soriano-Segura, P., Ortiz, M., Iáñez, E., Cavaliere-Ballesta, C., & Azorín, J. M. (2024, October). Motor Imagery Analysis of EEG Signals Using a Low-Cost Ankle Exoskeleton. In 2024 IEEE International Conference on Metrology for eXtended Reality, Artificial Intelligence and Neural Engineering (MetroXRAINE), pp. 1135-1140. October 21-23, 2024, St. Albans, London, UK.
  • Sempere, J.M., Gracia, D.I., Azorín, J.M., Úbeda, A., Iáñez, E. (2024, September). Optimización del registro en tiempo real de sensor de fuerza. XLV Jornadas de Automática, September 4-6, 2024. Málaga, Spain
  • Soriano-Segura, P., García-Villalón, J., Ortiz, M., Martínez, E. I., & Azorín, J. M. (2024). Protocolo para detectar el ErrP durante la marcha con exoesqueleto. XLV Jornadas de Automática, September 4-6, 2024. Málaga, Spain
  • Villalón, J. G., García, M. O., Segura, P. S., Martínez, E. I., & Poveda, J. M. A. (2024). Análisis de la influencia de EEGNET en una BMI basada en máquina de estados para el control de un exoesqueleto de miembro inferior. In Actas del Simposio de Robótica, Bioingeniería y Visión por Computador, pp. 185-190, May 29-31 2024, Badajoz, Spain
  • Laura Ferrero,Soriano Segura, P.,Jacobo Navarro,Oscar Jones,Ortiz Garcia, M.,Iañez E,Azorín, J.M.,José Contreras-Vidal (2023, November). Optimizing Motor Imagery Training for Lower-Limb Exoskeleton Control Through BCI. In Proceedings of XII Congreso Iberoamericano de Tecnologías de Apoyo a la Discapacidad (IBERDISCAP 2023), pp: 232-237, November 20-22, 2023, Sao Paulo, Brasil.
  • Soriano Segura, P.,Laura Ferrero,Ortiz Garcia, M.,Iañez E,Azorín, J.M. (2023, November). Protocol for evaluating error related potentials in a lower-limb exoskeleton commanded by a brain-machine interface. In Proceedings of XII Congreso Iberoamericano de Tecnologías de Apoyo a la Discapacidad (IBERDISCAP 2023). IBERDISCAP 2023, pp: 232-237, November 20-22, 2023, Sao Paulo, Brasil.
  • P. Soriano-Segura, L. Ferrero, D. I. Gracia, M. Ortiz, E. Iáñez and J. M. Azorín, «Analysis of Different Stimulus for Evoking the ErrP Potential in a MI-BMI for Starting the Gait with a Lower-Limb Exoskeleton,» 2023 IEEE International Conference on Systems, Man, and Cybernetics (SMC), Honolulu, Oahu, HI, USA, 2023, pp. 3653-3658, doi: 10.1109/SMC53992.2023.10393944.
  • Soriano-Segura, P., Ferrero, L., Gracia, D. I., Ortiz, M., Iáñez, E., & Azorín, J. M. (2023, October). Analysis of Different Stimulus for Evoking the ErrP Potential in a MI-BMI for Starting the Gait with a Lower-Limb Exoskeleton. In 2023 IEEE International Conference on Systems, Man, and Cybernetics (SMC), pp. 1124-1128. October 1-4, 2023, Oahu, Hawaii.
  • Soriano-Segura, P., Gracia, D.I, Ferrero, L., Iáñez, E., Ortiz, M., Azorín, J.M. (2023). Study of the variability of single trial error potential in relation to P300 and N500. XLIV Jornadas de Automática, 116-120. https://doi.org/10.17979/spudc.9788497498609.116
  • L. Ferrero et al., «Transfer Learning with CNN Models for Brain-Machine Interfaces to command lower-limb exoskeletons: A Solution for Limited Data,» 2023 45th Annual International Conference of the IEEE Engineering in Medicine & Biology Society (EMBC), Sydney, Australia, 2023, pp. 1-4, doi: 10.1109/EMBC40787.2023.10340008.
  • P. Soriano-Segura, L. Ferrero, M. Ortiz, E. Iáñez and J. M. Azorín, «Analysis of Error Potentials generated by a lower limb exoskeleton feedback in a BMI for gait control,» 2023 45th Annual International Conference of the IEEE Engineering in Medicine & Biology Society (EMBC), Sydney, Australia, 2023, pp. 1-4, doi: 10.1109/EMBC40787.2023.10340275.
  • Hatice Kumru, Aina Ros Alsina, M. Wright, Loreto Garcia, Joan Vidal. «N°50 – To Improve Gait Function during Multilevel Transcutaneous Spinal Cord Stimulation Following Incomplete Motor Spinal Cord Injury». Clinical Neurophysiology, vol. 150, junio de 2023, pp. e87-88. https://doi.org/10.1016/j.clinph.2023.03.059.
  • Hatice Kumru. Improving Transcutaneous Spinal Cord Stimulation paradigms in health and/or tSCS for the recovery of different motor function following spinal cord injury individuals. Institut Guttmann (Barcelona, Spain). 45th Annual International Conference of the IEEE Engineering in Medicine and Biology Society, 24-27 julio 2023, Sydney (Australia). Invited speaker.
  • Hatice Kumru, Yolanda Castillo, Loreto García-Alen, Eloy Opisso Neurofisiología en Neurorehabilitación. 3ª Jornada científica sobre electrodiagnóstico neurológico (SELECNE), 6 marzo 2024
  • Hatice Kumru. “Nuevos campos de la Neurofisiología Clínica y técnicas en desarrollo”. LX Reunión Anual de la Sociedad Española de Neurofisiología Clínica (SENFC), 3 octubre 2024, Barcelona (Spain). Session moderator.
  • Agustín Hernández y Hatice Kumru. Póster en ICNR 2024: “Changes in spasticity and medullar reflexes after tSCS application”. ICNR 2024, 5 noviembre 2024, Segovia (Spain).
  • Hatice Kumru. “Transcutaneous spinal cord stimulation (scTS) en lesión medular”. XXXIV Congreso de la Sociedad Valenciana de Medicina Física y Rehabilitación (SVMEFR), 1 marzo 2025, Valencia (Spain).
  • Hatice Kumru «Advancing neurorehabilitation: new frontiers in spinal cord injury and stroke treatments, cellular therapy, andneuromodulation”. International Congres son Neurorehabilitation and Neural Repair, 15 mayo 2025, Maastricht (Netherland). Symposium moderationw with James Guest, José Pones and Xabier Urra.
  • Hatice Kumru. “Structure and connextivity informed stimulation of the nervous system: how the micro level may guide macro level stimulation interventions”. Reunión conjunta de la Red Española de Estimulación Cerebral y de la Asociación Española de Estimulación Cerebral. Jornadas de estimulación cerebral 2025: Brain stimulation meeting 2025: where are we going? 26 mayo 2025, Sevilla (Spain). Session moderator with Guillermo Sánchez-Garrido, Miguel Ángel García-Cabezas, Lorena Chanes and Juha Silvanto.
  • Hatice Kumru. “Restoring Function After SCI: The Emerging Potential of Transcutaneous SC” in the session “From Research to Reality: Advances in Spinal Cord Stimulation for Improved Outcomes”. Reunión conjunta de la Red Española de Estimulación Cerebral y de la Asociación Española de Estimulación Cerebral. Jornadas de estimulación cerebral 2025: Brain stimulation meeting 2025: where are we going? 26 mayo 2025, Sevilla (Spain).
  • Hatice Kumru. “Avances en el tratamiento del dolor neuropático: el papel de la neuromodulación y neuroestimulación”. Congreso Nacional de Paraplejia, 12 de junio 2025, A Coruña (Spain).

 

more details…

 

  • Research Centers: Universidad Miguel Hernández de Elche, Institut Guttmann, Hospital Nacional de Parapléjicos
  • Duration: September 1, 2022 - August 31, 2025 (extended to Agust 31, 2026)
  • Financial Entity: MCIN/AEI/10.13039/501100011033 and by ERDF A way of making Europe
  • Coordinators and UMH principal Investigators: Jose M. Azorin, Eduardo Iáñez