Invasive and non-invasive methods to elicit sensoriy feedback: a computational approach

Upper limb neuroprostheses are innovative interfaces that combine two properties, the possibility to be controlled by the subject and the possibility to deliver sensations to the subject related to the external environment or to the interaction with objects. Actually these devices can be controlled by processing electromyographic signal extracted from muscular activity of the arm. To deliver sensations, different techniques can be used. One of the most explored and promising techniques is the neural electrical stimulation: electrical stimuli are directly delivered to the residual nerves of the forearm to restore tactile sensation similar to the natural ones. Because of the high invasiveness of this technique, it can be useful to study it by means of computational models to evaluate the interaction between the nerve and electrode, to estimate optimal stimulation parameters and to design novel interfaces. Another technique to restore sensory feedback, is the Focused Ultrasound Stimulation applied to the Central Nervous System. Also the study of this technique in simulation environment is important because of its possibility to damage tissues related to the high power intensity delivered. The aim of this Ph.D. thesis is to study and discuss these techniques in simulation environment. A review study on the main modeling and computational frameworks adopted to investigate peripheral nerve stimulation is performed. Mathematical models of neural cells with a detailed description of ion channels and numerical simulations using finite element methods (FEM) to describe the dynamics of electrical stimulation by implanted electrodes in peripheral nerves are treated. Different cell models with different ion channels present in neurons are evaluated to provide a guideline on multiscale numerical simulations of electrical nerve fibers stimulation. The interaction between electrode stimulation and nerve fibers is studied to evaluate the ability to activate fibers. DS-FILE intraneural electrode is considered in the FEM simulation to study its interaction with nerve fibers. The results can be very useful for the advancement of more realistic tactile sensations in amputee subjects from two point of view: the efficacy of the stimulation, that is related to the activation of axons subjected to the electrical stimulation, and the safety of the stimulation, related from a first consideration to the current intensity and waveform used. Therefore, the results of three type of waveform, that are the more safe as reported in literature, are analyzed and compared. The research aims to study, by means of a FEM-Neuron computational model, the axon fibers activation by means of the intraneural stimulation using different types of stimulus waveforms. The obtained results show that, using a biphasic charge unbalanced stimulus, the threshold to activate all the fibers considered in a location near an active site of the electrode is lower than the threshold found using biphasic charge balanced stimuli. This is an important result because the stimulation is equally efficient using low current amplitude. The three different types of stimulation waveforms (i.e. biphasic charge balanced stimulus with inter-pulse delay, biphasic charge balanced stimulus without inter-pulse delay, biphasic charge unbalanced stimulus with inter-pulse delay) are also considered in three different nerve fascicles, i.e. two sensory and one motor fascicle at ten distances from the electrode in the fascicles. The efficacy of the stimulation, expressed as the percentage of activation of the fibers, and the safety, in terms of current intensity and used waveform, are studied in the previously described different conditions and the results are compared. The obtained results show that: i. stimulating a sensory fascicle with implanted active sites can activate a fascicle close to it, but not all the fascicles belonging to the same nerve. In fact, in the nerve considered in the study, a motor fascicle cannot be activated due to the values of the electrical potential which are too low to activate the fibers; ii. the current intensity necessary to activate fibers increases according to the distance from the source of the stimulus; iii. by using a biphasic charge unbalanced stimulus, the threshold to activate the fibers is lower than using the other tested waveforms. It is an important result because the stimulation is efficient but safer since current intensity is lower than the one used for the other two waveforms. Another important aspect to be evaluated is the computational time to find the solution of the FEM-Neuron simulations. Often, a high computational simulation time is also related to the complexity of the model geometry; therefore using a geometrical simplified model can be an important aspect to be analyzed. The aim is to deepen, the possibility of approximating a realistic 3D human median nerve model, based on anatomical imaging to a simplified model using hybrid FEM-Neuron approach. So the simplified model is built approximating inner fascicles shape to simple geometrical shapes, i.e. ellipses. The results obtained allow concluding that the percentage of activation ranges at different distances from the active site obtained by the two model are comparable. The hybrid FEM-Neuron computational models can be also used to study fibers activation in human median nerve with the aims of evaluating differences in activation obtained by using ds-FILE and cuff electrodes and comparing simulation results with experimental evidence in a human amputee. The obtained results show that: i) fiber activation into the fascicles increases with the electrical charge, starting from the fascicles closer to the active site; ii) current amplitude necessary to activate fibers using the cuff electrode is higher than for the ds-FILE; iii) comparing the results of simulation with the experimental ones, it can be assumed that the increase of the intensity sensation in the amputee subject corresponds, in the simulation framework, to an increase of number of fibers activated in one or more fascicles. The simulation study on transcranial Focused Ultrasound Stimulation (tFUS) technique aims at evaluating, by the means of a computational model, the maximum pressure and the average acoustic intensity generated by a pulsed tFUS stimulation waveform, whose duty cycle (DC) is modulated in the range from 100% to 40%. The main goal is to investigate the efficacy and the safety, respectively in terms of pressure and intensity, of the stimulus waveform when the DC is decreased. Moreover, the Full Width at Half Maximum (FWHM) intensity at the focus is observed. The obtained results showed that the amount of average acoustic intensity decreased with the DC and the maximum pressure remains constant. Therefore, low value of DC permits to effectively and safely extend the stimulation duration. Moreover, the FWHM did not vary during DC modulation; hence, the spatial resolution of the focus remained unchanged. These results suggest that tFUS can be adopted to safely stimulate the somatosensory cortex, properly modulating the stimulus duration, in order to elicit different sensations in the human hand.