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Lower urinary tract dysfunction, such as incontinence or urinary retention, is one of the leading consequences of neurological diseases. This significantly impacts the quality of life for those affected, with implications extending not only to humans but also to clinical veterinary care. Having motor and sensory fibers, the pudendal nerve is an optimal candidate for neuromodulation therapies using bidirectional intraneural prostheses, paving the way towards the restoration of a more physiological urination cycle: bladder state can be detected from recorded neural signals, then an electrical current can be injected to the nerve based on the real-time need of the bladder. To develop such prostheses and investigate this novel approach, animal studies are still required since the morphology of the target nerve is fundamental to optimizing the prosthesis design. This study aims to describe the porcine pudendal nerve as a model for neuromodulation studies aiming at restoring lower urinary tract dysfunction. Five male farm pigs were involved in the study. First, a surgical procedure to access the porcine pudendal nerve without muscle resection was developed. Then, an intraneural interface was implanted to confirm the presence of fibers innervating the external urethral sphincter by measuring its electromyographic activity. Finally, the morphophysiology of the porcine pudendal nerve at the level of surgical exposure was described by using histological and immunohistochemical characterization. This analysis confirmed the fasciculate nature of the nerve and the presence of mixed fibers with a spatial and functional organization. These achievements pave the way for further pudendal neuromodulation studies by using a clinically relevant animal model with the potential for translating the findings into clinical applications.

Tinnitus is a clinical condition where a sound is perceived without an external sound source. Homeostatic plasticity (HSP), serving to increase neural activity as compensation for the reduced input to the auditory pathway after hearing loss, has been proposed as a mechanism underlying tinnitus. In support, animal models of tinnitus show evidence of increased neural activity after hearing loss, including increased spontaneous and sound-driven firing rate, as well as increased neural noise throughout the auditory processing pathway. Bridging these findings to human tinnitus, however, has proven to be challenging. Here we implement hearing loss-induced HSP in a Wilson-Cowan Cortical Model of the auditory cortex to predict how homeostatic principles operating at the microscale translate to the meso- to macroscale accessible through human neuroimaging. We observed HSP-induced response changes in the model that were previously proposed as neural signatures of tinnitus, but that have also been reported as correlates of hearing loss and hyperacusis. As expected, HSP increased spontaneous and sound-driven responsiveness in hearing-loss affected frequency channels of the model. We furthermore observed evidence of increased neural noise and the appearance of spatiotemporal modulations in neural activity, which we discuss in light of recent human neuroimaging findings. Our computational model makes quantitative predictions that require experimental validation, and may thereby serve as the basis of future human studies of hearing loss, tinnitus, and hyperacusis.

The usage of multi-physics simulation tools is steadily increasing in the field of electrochemistry. While this is a great opportunity for closing the gap between analytical electrochemists used to simple 1D models and experimentalists, there are possible pitfalls that must be avoided. In this work, we raise awareness on numerical artifacts that can mislead the interpretation of cyclic voltammetry experiments through simulations of geometries with different number of spatial dimensions. In particular, we show that one-dimensional simulations can suffer from substantial errors when models go beyond charge neutrality assumption. We exemplify such situations using simple electrolyte/electrode structures with 1D, 2D and 3D geometries. We then show the occurrence of artifacts related to the geometry of the simulation domain on the simulation of cyclic voltammetric curves as those typically performed to characterize conjugated polymer/electrolyte blends. All the models are implemented using COMSOL Multiphysics and are accompanied by a detailed description of their implementation. However, geometrical artifacts identified in this work also apply to other simulation approaches.