# Magnetoelectric Nanoparticles for Wireless Peripheral Nerve Stimulation: A Computational Study
## 4 Discussion  
As the demand for safe, effective, and targeted electrical stimulation in the field of neuroprostheses continues to rise, along with highly selective and minimally invasive neural interfaces, researchers actively seek and propose innovative methods, strategies, and materials to meet these needs [33]. In this context, MENPs could play a significant role. This study aims to characterize the use of MENPs for the electrical stimulation of the peripheral nervous system through a computational assessment of the interaction of MENPs with the nervous system dynamics. The modeling starts from the electrical behavior of the core-shell CoFe\({}_{2}\)O\({}_{4}\)-BaTiO\({}_{3}\) nanoparticles. The computational approach used here allowed us to investigate the influence of the parameters that most affect the electric potential distribution generated by the MENPs in the nervous tissue, such as the MENPs-fiber distance, the MENPS concentration, and orientation. The different electric potential and distribution estimated were translated into a detailed assessment of the electric response of motor neural fibers. All the analyses performed assumed that the MENPs were positioned near a Ranvier's node of a single neural fiber. As expected, the electric potential distribution due to the presence of MENPs appears to be localized around them [25], and the extent to which that distribution can stimulate the nerve tissue is strictly related to the MENPs' concentration. Indeed, the influence of the MENPs increases with an increasing size of the agglomerates, as visible from the electric potential along the neural fiber (Figure 4). The same trend can be observed for the recruitment capability (Figure 5 and Table 2). The volume of the excited tissue increases with the increasing size of the MENPs for similar magnification factors. The ability to excite the fibers becomes broader as the MENPs become larger, up to the possibility of activating an entire nerve fascicle. Larger agglomerates mean a higher probability of stimulating the neural fibers and a higher ability to recruit than less targeted stimulation. As the recruitment ability of the MENPs increases, their efficiency improves, while their selectivity decreases significantly, i.e., individual MENPs show selectivity in the nanometer range, which increases to the micrometer range in agglomerates. For single MENPs and small agglomerates, selectivity is high, but recruitment is lower, as the placement of the MENPs along the neural fiber plays a significant contribution. Consequently, a trade-off between the selectivity and resolution of MENPs is evidenced by our simulations. When activated with a uniform magnetic field, the dipoles originating from the magnetoelectric effect align in the same direction, namely, that of the external magnetic field. This makes it possible to control the orientation of the MENPs by specifying the orientation of the external magnetic field exerted. In this study, the influence of two different orientations on the nervous  
Figure 6: Comparison of injected current \(I^{int}\) along the neural fiber for different MENPs’ configurations. (**a**) Single MENP at distance 1R with perpendicular orientation; (**b**) 500 \(\upmu\)m MENPs cluster at distance 1R perpendicularly oriented. tissue around the MENPs was analyzed. The results show how the two different MENPs' alignments affect the external potential sensed by the fiber length differently and how controlling the MENPs' orientation enables the control of the stimulation of the fibers. More specifically, the orientation of the MENPs influences both the electrical potential perceived along the fiber length, which can be equated to monopolar (in case of perpendicular orientation) or bipolar stimulation (in case of parallel orientation) (Figure 4), and the amplification of the external potential distribution needed for fibers' activation (Table 2).