A biomimetic electrical stimulation strategy to induce asynchronous stochastic neural activity.

OBJECTIVE: Electrical stimulation is an effective method for artificially modulating the activity of the nervous system. However, current stimulation paradigms fail to reproduce the stochastic and asynchronous properties of natural neural activity. Here, we introduce a novel biomimetic stimulation (BioS) strategy that overcomes these limitations. APPROACH: We hypothesized that high-frequency amplitude-modulated bursts of stimulation could induce asynchronous neural firings by distributing recruitment over the duration of a burst, without sacrificing the ability to precisely control neural activity. We tested this hypothesis using computer simulations and ex vivo experiments. MAIN RESULTS: We found that BioS bursts induce asynchronous, stochastic, yet controllable, neural activity. We established that varying the amplitude, duration, and repetition frequency of a BioS burst enables graded modulation of the number of recruited fibers, their firing rate, and the synchronicity of their responses. SIGNIFICANCE: These results demonstrate an unprecedented level of control over artificially induced neural activity, enabling the design of next-generation BioS paradigms with potentially profound consequences for the field of neurostimulation.

A microfabricated nerve-on-a-chip platform for rapid assessment of neural conduction in explanted peripheral nerve fibers.

Peripheral nerves are anisotropic and heterogeneous neural tissues. Their complex physiology restricts realistic in vitro models, and high resolution and selective probing of axonal activity. Here, we present a nerve-on-a-chip platform that enables rapid extracellular recording and axonal tracking of action potentials collected from tens of myelinated fibers. The platform consists of microfabricated stimulation and recording microchannel electrode arrays. First, we identify conduction velocities of action potentials traveling through the microchannel and propose a robust data-sorting algorithm using velocity selective recording. We optimize channel geometry and electrode spacing to enhance the algorithm reliability. Second, we demonstrate selective heat-induced neuro-inhibition of peripheral nerve activity upon local illumination of a conjugated polymer (P3HT) blended with a fullerene derivative (PCBM) coated on the floor of the microchannel. We demonstrate the nerve-on-a-chip platform is a versatile tool to optimize the design of implantable peripheral nerve interfaces and test selective neuromodulation techniques ex vivo.