Neural Stimulation Hardware for the Selective Intrafascicular Modulation of the Vagus Nerve.

The neural stimulation of the vagus nerve is able to modulate various functions of the parasympathetic response in different organs. The stimulation of the vagus nerve is a promising approach to treating inflammatory diseases, obesity, diabetes, heart failure, and hypertension. The complexity of the vagus nerve requires highly selective stimulation, allowing the modulation of target-specific organs without side effects. Here, we address this issue by adapting a neural stimulator and developing an intraneural electrode for the particular modulation of the vagus nerve. The neurostimulator parameters such as amplitude, pulse width, and pulse shape were modulated. Single-, and multi-channel stimulation was performed at different amplitudes. For the first time, a polyimide thin-film neural electrode was designed for the specific stimulation of the vagus nerve. In vivo experiments were performed in the adult minipig to validate to elicit electrically evoked action potentials and to modulate physiological functions, validating the spatial selectivity of intraneural stimulation. Electrochemical tests of the electrode and the neurostimulator showed that the stimulation hardware was working correctly. Stimulating the porcine vagus nerve resulted in spatially selective modulation of the vagus nerve. ECAP belonging to alpha and beta fibers could be distinguished during single- and multi-channel stimulation. We have shown that the here presented system is able to activate the vagus nerve and can therefore modulate the heart rate, diastolic pressure, and systolic pressure. The here presented system may be used to restore the cardiac loop after denervation by implementing biomimetic stimulation patterns. Presented methods may be used to develop intraneural electrodes adapted for various applications.

Decoding bladder state from pudendal intraneural signals in pigs.

Neuroprosthetic devices used for the treatment of lower urinary tract dysfunction, such as incontinence or urinary retention, apply a pre-set continuous, open-loop stimulation paradigm, which can cause voiding dysfunctions due to neural adaptation. In the literature, conditional, closed-loop stimulation paradigms have been shown to increase bladder capacity and voiding efficacy compared to continuous stimulation. Current limitations to the implementation of the closed-loop stimulation paradigm include the lack of robust and real-time decoding strategies for the bladder fullness state. We recorded intraneural pudendal nerve signals in five anesthetized pigs. Three bladder-filling states, corresponding to empty, full, and micturition, were decoded using the Random Forest classifier. The decoding algorithm showed a mean balanced accuracy above 86.67% among the three classes for all five animals. Our approach could represent an important step toward the implementation of an adaptive real-time closed-loop stimulation protocol for pudendal nerve modulation, paving the way for the design of an assisted-as-needed neuroprosthesis.