Epidural electrical stimulation (EES) of lumbosacral segments can restore a range of movements after spinal cord injury. However, the mechanisms and neural structures through which EES facilitates movement execution remain unclear. Here, we designed a computational model and performed in vivo experiments to investigate the type of fibers, neurons, and circuits recruited in response to EES. We first developed a realistic finite element computer model of rat lumbosacral segments to identify the currents generated by EES. To evaluate the impact of these currents on sensorimotor circuits, we coupled this model with an anatomically realistic axon-cable model of motoneurons, interneurons, and myelinated afferent fibers for antagonistic ankle muscles. Comparisons between computer simulations and experiments revealed the ability of the model to predict EES-evoked motor responses over multiple intensities and locations. Analysis of the recruited neural structures revealed the lack of direct influence of EES on motoneurons and interneurons. Simulations and pharmacological experiments demonstrated that EES engages spinal circuits trans-synaptically through the recruitment of myelinated afferent fibers. The model also predicted the capacity of spatially distinct EES to modulate side-specific limb movements and, to a lesser extent, extension versus flexion. These predictions were confirmed during standing and walking enabled by EES in spinal rats. These combined results provide a mechanistic framework for the design of spinal neuroprosthetic systems to improve standing and walking after neurological disorders.

This study investigated the hypothesis that the coupled contribution of all body segments to the whole-body response during both walking and managing unexpected perturbations is characterized by similar features which do not depend on the laterality (i.e., right versus left sides), but can be influenced by the direction (e.g., north, east, south, etc.) of the perturbation. The whole-body angular momentum was estimated as summation of segmental angular momenta, while 15 young adults managed ten unexpected unilateral perturbations during walking. Then, the Principal component analysis was used to extract primitive features describing intersegment coordination. Results showed that intersegment coupling was similar even though the reactive response to the perturbations elicited more consistent motor schemes across body segments than during walking, especially in the frontal plane. The direction of the perturbation significantly affected angular momentum regulation documenting the attitude of the central nervous system to interpret multiple sensory inputs in order to produce context-dependent reactive responses. With respect to the side, results highlighted anisotropic features of the elicited motor schemes that seemed to depend on subjects' dominance. Finally, results confirm that the coordination of upper and lower body segments is synergistically achieved strengthening the hypothesis that it may result from common neural pathways.

The vestibular organs are very important to generate reflexes critical for stabilizing gaze and body posture. Vestibular diseases significantly reduce the quality of life of people who are affected by them. Some research groups have recently started developing vestibular neuroprostheses to mitigate these symptoms. However, many scientific and technological issues need to be addressed to optimise their use in clinical trials. We developed a computational model able to mimic the response of human vestibular nerves and which can be exploited for "in-silico" testing of new strategies to design implantable vestibular prostheses. First, a digital model of the vestibular system was reconstructed from anatomical data. Monopolar stimulation was delivered at different positions and distances from ampullary nerves. The electrical potential induced by the injected current was computed through finite-element methods and drove extra-cellular stimulation of fibers in the vestibular, facial, and cochlear nerves. The electrical activity of vestibular nerves and the resulting eye movements elicited by different stimulation protocols were investigated. A set of electrode configurations was analyzed in terms of selectivity at increasing injected current. Electrode position along the nerve plays a major role in producing undesired activity in other nontargeted nerves, whereas distance from the fiber does not significantly affect selectivity. Indications are provided to minimize misalignment in nonoptimal electrode locations. Eye movements elicited by the different stimulation protocols are calculated and compared to experimental values, for the purpose of model validation.

BackgroundStudying the responses in human behaviour to external perturbations during daily motor tasks is of key importance for understanding mechanisms of balance control and for investigating the functional response of targeted subjects. Experimental platforms as far developed entail a low number of perturbations and, only in few cases, have been designed to measure variables used at run time to trigger events during a certain motor task.MethodsThis work introduces a new mechatronic device, named SENLY, that provides balance perturbations while subjects carry out daily motor tasks (e.g., walking, upright stance). SENLY mainly consists of two independently-controlled treadmills that destabilize balance by suddenly perturbing belts movements in the horizontal plane. It is also provided with force sensors, which can be used at run time to estimate the ground reaction forces and identify events along the gait cycle in order to trigger the platform perturbation. The paper also describes the customized procedures adopted to calibrate the platform and the first testing trials aimed at evaluating its performance.ResultsSENLY allows to measure both vertical ground reaction forces and their related location more precisely and more accurately than other platforms of the same size. Moreover, the platform kinematic and kinetic performance meets all required specifications, with a negligible influence of the instrumental noise.ConclusionA new perturbing platform able to reproduce different slipping paradigms while measuring GRFs at run time in order to enable the asynchronous triggering during the gait cycle was designed and developed. Calibration procedures and pilot tests show that SENLY allows to suitably estimate dynamical features of the load and to standardize experimental sessions, improving the efficacy of functional analysis.

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