# Magnetoelectric Nanoparticles for Wireless Peripheral Nerve Stimulation: A Computational Study
## 4 Discussion
Bipolar stimulation shows a greater influence on the distance between the MENPs and the fiber as the growth of the amplification demanded to excite the nervous tissue is greater than with monopolar stimulation. When considering larger distances from the MENPs, the required potential gain over the surface of the agglomerates approximately doubled when moving from perpendicular to parallel orientation. This trend is less pronounced when the agglomerates are attached to the fiber. The use of monopolar or bipolar stimulation controls the stimulating signal, which can be inhibitory or excitatory, and, therefore, commands the spiking activity of the neural fibers and their firing time [34]. This study allowed us to estimate the current injected into the intracellular space, as defined by [30; 31]. To excite an action potential, a minimum value of 47 nA is estimated to be injected into the neural fiber when the stimulation is punctually localized in the node of Ranvier, irrespective of the distance, and the stimulus is a one-period sinusoid. As the concentration of MENPs increases, the stimulation becomes less localized, leading to a variation in the equivalent current injected along the length of the fiber. The non-linear summation [26] of the currents injected into the fibers' intracellular space (Figure 6b) influences the behavior of the neural tissue and potentially triggers an action potential. The set of currents influences the recruitment volume, resulting in a wider stimulation at the increase in MENPs' concentration, as visible in Figure 5. Therefore, the stimulating system can be calibrated and characterized in relation to the injected current. This estimate is consistent with the method based on the use of the activating function, defined as the second derivative of the external potential measured along the fiber of interest, which is widely used in the literature to characterize and calibrate the effect of nerve fiber stimulation [24; 35; 36]. In this study, the interaction between MENPs and the surrounding nervous tissue was extensively characterized. Specific configurations were analyzed, incorporating simplifications and assumptions regarding the placement, concentration and orientation of MENPs. These findings are heavily influenced by the positioning of the MENPs, which were assumed to be near a Ranvier's node of a neural fiber. The results suggest a first quantitative analysis that supports in vitro experiments by providing effective information for the design of experimental studies. Considering the great variability in the interaction between the MENPs and the surrounding nervous tissue, future research will address possible strategies to optimize this approach. Different morphological structures, different signals delivered to MENPs, a more specific characterization of the environment close to neural membrane and, more in general, of the nerve models, would allow researchers to fit and explain the experimental behavior and then exploit the potential of MENP-based electric stimulation. As discussed in the literature [6; 11], the magnetoelectric effect is strongly influenced by the structure of the interface, the materials and the frequency of the external fields used to trigger the ME effect. Considering these parameters, it is possible to strongly vary the ME coefficient [18; 37; 38] and thus better tune and optimize the electric output of the MENPs to the values needed to activate the nerve fibers. However, the characterization of the MENPs was beyond the scope of this study. The results of this work not only confirm previous experimental studies utilizing MENPs for neural tissue stimulation [7; 12; 13; 14], but also lay the ground for more optimized and targeted future experimental in vitro and in vivo research.