Refining Stereotaxic Neurosurgery Techniques and Welfare Assessment for Long-Term Intracerebroventricular Device Implantation in Rodents.

Stereotaxic surgeries enable precise access to specific brain regions, being of particular interest for chronic intracerebroventricular drug delivery. However, the challenge of long-term studies at this level is to allow the implantation of drug storage devices and their correct intrathecal connection while guaranteeing animal welfare during the entire study period. In this study, we propose an optimized method for safe intrathecal device implantation, focusing on preoperative, intraoperative, and postoperative procedures, following the 3Rs principle and animal welfare regulations. Our optimized protocol introduces three main refinements. Firstly, we modify the dimensions of the implantable devices, notably diminishing the device-to-mouse weight ratio. Secondly, we use a combination of cyanoacrylate tissue adhesive and UV light-curing resin, which decreases surgery time, improves healing, and notably minimizes cannula detachment or adverse effects. Thirdly, we develop a customized welfare assessment scoresheet to accurately monitor animal well-being during long-term implantations. Taken together, these refinements positively impacted animal welfare by minimizing the negative effects on body weight, surgery-related complications, and anxiety-like behaviors. Overall, the proposed refinements have the potential to reduce animal use, enhance experimental data quality, and improve reproducibility. Additionally, these improvements can be extended to other neurosurgical techniques, thereby advancing neuroscience research, and benefiting the scientific community.

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.

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.

Estimulación no invasiva cerebral y medular para la recuperación motora y funcional tras una lesión medular / Non-invasive brain and spinal cord stimulation for motor and functional recovery after a spinal cord injury

INTRODUCCIÓN: La lesión medular es un evento traumático o no traumático que causa una alteración de la función sensorial, motora o autonómica y, en última instancia, afecta a las características físicas, psicológicas y el bienestar social de la persona que lo sufre. El abordaje integral de la lesión medular requiere muchos recursos de salud y puede representar una considerable carga financiera para los pacientes, sus familias y la comunidad. OBJETIVO: Revisar la bibliografía publicada sobre el uso de la estimulación cerebral no invasiva, incluida la estimulación magnética transcraneal repetitiva (EMTr), la estimulación de corriente continua directa transcraneal (tDCS), así como la estimulación medular no invasiva transcutánea (tcSCS), como estrategias terapéuticas para mejorar la funcionalidad de los pacientes con lesión medular. Los estudios se agruparon bien como de estimulación no invasiva cerebral, bien como de estimulación medular no invasiva. DESARROLLO: Se identificaron 32 estudios: 21 de estimulación cerebral (14 en EMTr y 7 en tDCS) y 11 de estimulación medular (tcSCS). Todos los estudios se realizaron en pacientes adultos que sufrieron una lesión medular. A pesar de la variabilidad significativa en los protocolos de tratamiento, las características de los pacientes y la evaluación clínica, los cambios observados se describieron en casi todos los estudios sin producir efectos secundarios con mejoría motora o funcional. CONCLUSIÓN: La estimulación cerebral no invasiva, así como la estimulación medular, son técnicas prometedoras para la rehabilitación de pacientes con lesión medular debido a su novedad, su efectividad y mínimos efectos secundarios

INTRODUCTION: Spinal cord injury is a traumatic or non-traumatic event that causes an alteration of sensory, motor or autonomic functioning and ultimately affects the physical, psychological and social well-being of the person who suffers it. A comprehensive approach to spinal cord injury requires many health resources and can place a considerable financial burden on patients, their families and the community. AIM: To review the literature published to date on the use of non-invasive brain stimulation, including repetitive transcranial magnetic stimulation (rTMS), transcranial direct current stimulation (tDCS), and transcutaneous non-invasive spinal cord stimulation (tcSCS), as therapeutic strategies to improve the functionality of patients with spinal cord injury. The studies were grouped as addressing either non-invasive brain stimulation or non-invasive spinal cord stimulation. DEVELOPMENT: Altogether 32 studies were identified: 21 involving brain stimulation (14 in rTMS and 7 in tDCS) and 11 with spinal cord stimulation (tcSCS). All the studies were conducted in adult patients who had undergone a spinal cord injury. Despite significant variability in treatment protocols, patient characteristics and clinical assessment, the changes observed were reported in almost all the studies without producing any side effects and with motor or functional improvement. CONCLUSION: Non-invasive brain stimulation, as well as spinal cord stimulation, are promising techniques for the rehabilitation of patients with spinal cord injury due to their novelty, effectiveness and minimal side effects

Onset Detection to Study Muscle Activity in Reaching and Grasping Movements in Rats.

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.