When Spinal Neuromodulation Meets Sensorimotor Rehabilitation: Lessons Learned From Animal Models to Regain Manual Dexterity After a Spinal Cord Injury

Electrical neuromodulation has strongly hit the foundations of spinal cord injury and repair. Clinical and experimental studies have demonstrated the ability to neuromodulate and engage spinal cord circuits to recover volitional motor functions lost after the injury. Although the science and technology behind electrical neuromodulation has attracted much of the attention, it cannot be obviated that electrical stimulation must be applied concomitantly to sensorimotor rehabilitation, and one would be very difficult to understand without the other, as both need to be finely tuned to efficiently execute movements. The present review explores the difficulties faced by experimental and clinical neuroscientists when attempting to neuromodulate and rehabilitate manual dexterity in spinal cord injured subjects. From a translational point of view, we will describe the major rehabilitation interventions employed in animal research to promote recovery of forelimb motor function. On the other hand, we will outline some of the state-of-the-art findings when applying electrical neuromodulation to the spinal cord in animal models and human patients, highlighting how evidences from lumbar stimulation are paving the path to cervical neuromodulation

Onset detection to study muscle activity in reaching and grasping movements in rats

© 2019 IEEE. Personal use of this material is permitted. Permission from IEEE must be obtained for all other uses, in any current or future media, including reprinting/republishing this material for advertising or promotional purposes, creating new collective works, for resale or redistribution to servers or lists, or reuse of any copyrighted component of this work in other works.© 2019 IEEE. Personal use of this material is permitted. Permission from IEEE must be obtained for all other uses, in any current or future media, including reprinting/republishing this material for advertising or promotional purposes, creating new collective works, for resale or redistribution to servers or lists, or reuse of any copyrighted component of this work in other works.EMG signals reflect the neuromuscular activation patterns related to the execution of a certain movement or task. In this work, we focus on reaching and grasping (R&G) movements in rats. Our objective is to develop an automatic algorithm to detect the onsets and offsets of muscle activity and use it to study muscle latencies in R&G maneuvers. We had a dataset of intramuscular EMG signals containing 51 R&G attempts from 2 different animals. Simultaneous video recordings were used for segmentation and comparison. We developed an automatic onset/offset detector based on the ratio of local maxima of Teager-Kaiser Energy (TKE). Then, we applied it to compute muscle latencies and other features related to the muscle activation pattern during R&G cycles. The automatic onsets that we found were consistent with visual inspection and video labels. Despite the variability between attempts and animals, the two rats shared a sequential pattern of muscle activations. Statistical tests confirmed the differences between the latencies of the studied muscles during R&G tasks. This work provides an automatic tool to detect EMG onsets and offsets and conducts a preliminary characterization of muscle activation during R&G movements in rats. This kind of approaches and data processing algorithms can facilitate the studies on upper limb motor control and motor impairment after spinal cord injury or stroke.Postprint (published version

Cervical Electrical Neuromodulation Effectively Enhances Hand Motor Output in Healthy Subjects by Engaging a Use-Dependent Intervention

Altres ajuts: Fundació La Marató de TV3 2017 (201713.31) to G.G.-A.; Premi Beca "Mike Lane" 2019-Castellers de la Vila de Gràcia to H.K.; and National Institutes of Health Grant 1R01 NS102920-01A1 to Y.G.Electrical enabling motor control (eEmc) through transcutaneous spinal cord stimulation is a non-invasive method that can modify the functional state of the sensory-motor system. We hypothesize that eEmc delivery, together with hand training, improves hand function in healthy subjects more than either intervention alone by inducing plastic changes at spinal and cortical levels. Ten voluntary participants were included in the following three interventions: (i) hand grip training, (ii) eEmc, and (iii) eEmc with hand training. Functional evaluation included the box and blocks test (BBT) and hand grip maximum voluntary contraction (MVC), spinal and cortical motor evoked potential (sMEP and cMEP), and resting motor thresholds (RMT), short interval intracortical inhibition (SICI), and F wave in the abductor pollicis brevis muscle. eEmc combined with hand training retained MVC and increased F wave amplitude and persistency, reduced cortical RMT and facilitated cMEP amplitude. In contrast, eEmc alone only increased F wave amplitude, whereas hand training alone reduced MVC and increased cortical RMT and SICI. In conclusion, eEmc combined with hand grip training enhanced hand motor output and induced plastic changes at spinal and cortical level in healthy subjects when compared to either intervention alone. These data suggest that electrical neuromodulation changes spinal and, perhaps, supraspinal networks to a more malleable state, while a concomitant use-dependent mechanism drives these networks to a higher functional state

Cervical electrical neuromodulation effectively enhances hand motor output in healthy subjects by engaging a use-dependent intervention

Electrical enabling motor control (eEmc) through transcutaneous spinal cord stimulation is a non-invasive method that can modify the functional state of the sensory-motor system. We hypothesize that eEmc delivery, together with hand training, improves hand function in healthy subjects more than either intervention alone by inducing plastic changes at spinal and cortical levels. Ten voluntary participants were included in the following three interventions: (i) hand grip training, (ii) eEmc, and (iii) eEmc with hand training. Functional evaluation included the box and blocks test (BBT) and hand grip maximum voluntary contraction (MVC), spinal and cortical motor evoked potential (sMEP and cMEP), and resting motor thresholds (RMT), short interval intracortical inhibition (SICI), and F wave in the abductor pollicis brevis muscle. eEmc combined with hand training retained MVC and increased F wave amplitude and persistency, reduced cortical RMT and facilitated cMEP amplitude. In contrast, eEmc alone only increased F wave amplitude, whereas hand training alone reduced MVC and increased cortical RMT and SICI. In conclusion, eEmc combined with hand grip training enhanced hand motor output and induced plastic changes at spinal and cortical level in healthy subjects when compared to either intervention alone. These data suggest that electrical neuromodulation changes spinal and, perhaps, supraspinal networks to a more malleable state, while a concomitant use-dependent mechanism drives these networks to a higher functional state

Transcutaneous Electrical Neuromodulation of the Cervical Spinal Cord Depends Both on the Stimulation Intensity and the Degree of Voluntary Activity for Training. A Pilot Study

Electrical enabling motor control (eEmc) through transcutaneous spinal cord stimulation offers promise in improving hand function. However, it is still unknown which stimulus intensity or which muscle force level could be better for this improvement. Nine healthy individuals received the following interventions: (i) eEmc intensities at 80%, 90% and 110% of abductor pollicis brevis motor threshold combined with hand training consisting in 100% handgrip strength; (ii) hand training consisting in 100% and 50% of maximal handgrip strength combined with 90% eEmc intensity. The evaluations included box and blocks test (BBT), maximal voluntary contraction (MVC), F wave persistency, F/M ratio, spinal and cortical motor evoked potentials (MEP), recruitment curves of spinal MEP and cortical MEP and short-interval intracortical inhibition. The results showed that: (i) 90% eEmc intensity increased BBT, MVC, F wave persistency, F/M ratio and cortical MEP recruitment curve; 110% eEmc intensity increased BBT, F wave persistency and cortical MEP and recruitment curve of cortical MEP; (ii) 100% handgrip strength training significantly modulated MVC, F wave persistency, F/M wave and cortical MEP recruitment curve in comparison to 50% handgrip strength. In conclusion, eEmc intensity and muscle strength during training both influence the results for neuromodulation at the cervical level

Tomar la palabra (II). Intertextualidad e intermedialidad como herramientas pedagógicas para la enseñanza de la literatura y otros discursos

Este proyecto explora las relaciones entre obras literarias y literatura y otras artes (música, pintura, fotografía, cine, etc.) como medio para desarrollar la competencia lectora y expresiva y estimular el disfrute literario en ámbito universitario

CIBERER : Spanish national network for research on rare diseases: A highly productive collaborative initiative

Altres ajuts: Instituto de Salud Carlos III (ISCIII); Ministerio de Ciencia e Innovación.CIBER (Center for Biomedical Network Research; Centro de Investigación Biomédica En Red) is a public national consortium created in 2006 under the umbrella of the Spanish National Institute of Health Carlos III (ISCIII). This innovative research structure comprises 11 different specific areas dedicated to the main public health priorities in the National Health System. CIBERER, the thematic area of CIBER focused on rare diseases (RDs) currently consists of 75 research groups belonging to universities, research centers, and hospitals of the entire country. CIBERER's mission is to be a center prioritizing and favoring collaboration and cooperation between biomedical and clinical research groups, with special emphasis on the aspects of genetic, molecular, biochemical, and cellular research of RDs. This research is the basis for providing new tools for the diagnosis and therapy of low-prevalence diseases, in line with the International Rare Diseases Research Consortium (IRDiRC) objectives, thus favoring translational research between the scientific environment of the laboratory and the clinical setting of health centers. In this article, we intend to review CIBERER's 15-year journey and summarize the main results obtained in terms of internationalization, scientific production, contributions toward the discovery of new therapies and novel genes associated to diseases, cooperation with patients' associations and many other topics related to RD research

Efectos del transplante de glía envolvente del bulbo olfatorio en un modelo de lesión fotoquímica de la médula espinal de la rata

En la presente Tesis doctoral se ha caraterizado un modelo de lesión fotoquímica de la médula espinal de la rata, basado en la aplicación tópica del agente fotoactivo rosa de bengala. En los diferentes grupos experimentales estudiados, se ha constatado que a mayor tiempo de fotoactivación del colorante, mayor es la lesión producida en los animales, que desemboca en un pérdida progresiva de las capacidades neurológicas y funcionales de éstos (Trabajo 1). Asimismo, las lesiones fotoquímicas realizadas producen cambios en la reactividad glial y neuronal similares a los producidos tras una lesión traumática de la médula espinal (Trabajo 2). Con el objetivo de avanzar an la búsqueda y mejora de una terapia promotora de la recuperación funcional de la médula espinal dañada, se han evaluado los efectos del transplante de glía envolvente del bulbo olfatorio en animales con una lesión fotoquímica. En los estudios a corto plazo, se ha evidenciado el papel neuroprotector ejercido por el transplante glial, ya que los animales con transplante presentaron una menor cavidad necrótica, atribuible a una menor reactividad astrocitaria, que los animales del grupo control (Trabajo 3). También se han estudiado los efectos de una lesión en diferentes segmentos espinales, y se ha evidenciado que la lesiones en los segmentos lumbares afectan severamente las funciones motoras, en comparación a las producidas en los segmentos torácicos de la médula espinal (Trabajo 4). Con el fin de evaluar la influencia del transplante en la recuperación funcional de los animales a largo plazo, se escogió el modelo de lesión fotoquímica en el segmento torácico. Los resultados obtenidos muestran que los animales con el transplante celular presentaron mayor preservación de parénquima medular, así como una mejor respuesta neurológica y funcional que los animales sin transplante (Trabajo 5). Además, en comparación con el transplante de células de Schwann, el transplante de glía envolvente redujo la reactividad glial y promovió una mejor respuesta electrofisiológica (Trabajo 6).Por último, se ha estudiado la influencia del método de transplante celular en los efectos ejercidos por este en la médula espinal, observándose que el transplante por medio de una inyección, a baja presión y de forma continua es similar al transplante en forma de pulsos de aire repetidos (Trabajo 7)