Peripheral neural interfaces have been successfully used in the recent past to restore sensory-motor functions in disabled subjects and for the neuromodulation of the autonomic nervous system. The optimization of these neural interfaces is crucial for ethical, clinical and economic reasons. In particular, hybrid models (HMs) constitute an effective framework to simulate direct nerve stimulation and optimize virtually every aspect of implantable electrode design: the type of electrode (for example, intrafascicular versus extrafascicular), their insertion position and the used stimulation routines. They are based on the combined use of finite element methods (to calculate the voltage distribution inside the nerve due to the electrical stimulation) and computational frameworks such as NEURON () to determine the effects of the electric field generated on the neural structures. They have already provided useful results for different applications, but the overall usability of this powerful approach is still limited by the intrinsic complexity of the procedure. Here, we illustrate a general, modular and expandable framework for the application of HMs to peripheral neural interfaces, in which the correct degree of approximation required to answer different kinds of research questions can be readily determined and implemented. The HM workflow is divided into the following tasks: identify and characterize the fiber subpopulations inside the fascicles of a given nerve section, determine different degrees of approximation for fascicular geometries, locate the fibers inside these geometries and parametrize electrode geometries and the geometry of the nerve-electrode interface. These tasks are examined in turn, and solutions to the most relevant issues regarding their implementation are described. Finally, some examples related to the simulation of common peripheral neural interfaces are provided.

Neural interfaces with implantable electrodes are used to modulate and restore function to the peripheral nervous system. Hybrid modeling described in this protocol is used to optimize each aspect of the implantable electrode design and operation.