Selective electrical and optical neuromodulation of the central nervous system with conformable microfabricated implants

Neuroprosthetic systems are designed to interface with the nervous system, for the replacement or restoration of damaged functions in the motor and/or sensory systems. In order to have an efficient communication with the nervous tissue leading to optimized clinical outcomes, achieving neural stimulation with high selectivity is essential. This thesis aims at finding technological routes to enable spatial, structural and cell-type selective surface neuromodulation using electrical and optogenetic stimulation and to validate them in in vivo models. Thin and conformable electrode arrays enable close contact with the target tissue, thereby leading to minimal distances with the target neurons and maximal spatial selectivity. Flexible polymer technologies based on polyimide (PI) are used to design thin (< 10 ÎŒm thick) electrode arrays with small feature size (< 100 ÎŒm), resulting in miniaturized conformable arrays for surface stimulation. PEDOT conducting polymer coatings are used on the miniaturized electrical stimulation sites (100 ÎŒm diameter) to improve their charge injection properties. This implant is used for auditory brainstem stimulation in a rat model, and is shown to generate robust activation of the auditory system. Analysis of the multiunit recordings obtained from the inferior colliculus (IC), an auditory structure of the midbrain, led to the identification of different phases in the responses, with various frequency tuning properties. The stimulation configuration is shown to influence the tonotopic organisation of the frequency-tuned responses. Bipolar stimulation with small interelectrode distances (400 ÎŒm) is shown to generate responses that are more frequency-selective than with larger interelectrode distances (800 ÎŒm). The orientation of the electrode pair and the waveformof stimulation current are also shown to influence the response properties. An updated design of the clinical auditory brainstem implant(ABI) is then proposed, integrating higher electrode density and guidelines for a more tissue-conformal format. The main steps in the road towards improvement of ABI outcomes are then discussed, with proposed changes in the stimulation protocol and electrode array in parallel. Another approach to cell-specific neuromodulation is the implementation of optogenetics. This requires not only genetic engineering of the neurons but also the manufacturing of implantable light-emitting devices. Here, we introduce a fabrication process for the integration of thin (50 ÎŒm) LEDs into a polyimide-based device. A proof-of-concept in vivo study shows that stimulation of the spinal cord of a mouse model generates robust EMG responses in both legs over the course of several weeks. The walking integrity is confirmed, showing the absence of functional damages to the spinal cord. These results show that the presented LED array can provide a way of stimulating key elements of the locomotor neural circuitry, potentially leading to a greater understanding of the role of each neuronal subtypes in the spinal cord. Through the applications of ABI and spinal cord stimulation, this thesis thus highlights the importance and potential use of specifically tailored technologies enabling selective surface stimulation of the nervous system.

Related material