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NeuroMeddle

Development of Stable Long Term Brain Implants
Funder: French National Research Agency (ANR)Project code: ANR-15-CE19-0006
Funder Contribution: 874,781 EUR
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Description

Dysfunctions of the central nervous system are a major economic and social issue. Neural prostheses and brain-computer interfaces offer promising perspectives to restore motor functions and communication capabilities in patients suffering from severe paralysis. These approaches require the implantation of arrays of microelectrodes offering the possibility to record brain activity with stability on the long term. However, to date, the fabrication of brain implants housing a large number of microelectrodes and offering a stable connection with the neural tissue on the long term remains impaired by two major limitations. The first one stems from the electrode material itself when the size of the electrodes becomes small. Noble metals such as Platinum or Iridium have been used for decades to make macroscopic electrodes, which are now used in routine for neural recording and stimulation in several clinical applications such as cochlear implants, deep brain stimulation for Parkinson disease, and also the pre-surgical functional evaluation of epilepsy. However, thanks to the development of microfabrication technologies, the past decades have seen the development of new types of implants housing tens or even hundreds of microelectrodes on the micrometer scale. Yet, when the size of the electrodes diminishes, two problems arise: The intrinsic (thermal) noise level of the electrodes increase, and their safe charge injection limits decrease, which prevents delivering sufficient currents to activate neural networks without inducing lesions due to electrochemical reactions at the electrode/tissue interface. In this context, the first goal of the NeuroMeddle project will be to consider new types of materials based on the electrodeposition of pure or doped PEDOT/PSS to develop electrodes with improved performance and stable on the long term. A second main problem of existing brain implants (for instance like the Utah array) is the instability over days and even the loss of neural signals along time after a few weeks or months. This is especially the case for action potential signals, either of single or multiple units. This instability is mostly due to the combined effect of the movements of the brain and the inadequacy of the rigidity of implant materials versus the soft properties of the brain tissue. For this reason, an important line of research worldwide is the development of flexible implants matching the geometry and the mechanical properties of the brain, while still compatible with intracortical recordings. In this quest, an important open challenge remains to find strategies to insert flexible microelectrodes so that they meddle into the brain to create intimate and stable connections with individual neurons on the long term. Hence, the second goal of the NeuroMeddle project will be to develop implants offering such conformational stability, based on transient rigidification of flexible electrodes using biodegradable embedding materials (PEG, PLA, Chitosan, Silk fibroin) for the time of implantation. We will particularly focus on silk fibroin, which offers high rigidity and is not yet used in Europe for this type of application, while well mastered by one of the NeuroMeddle partner. The new electrode materials based on PEDOT/PSS, as well as biodegradable materials will first be tested in vivo in the rat. In a second step, we will consider another model closer to the human brain in order to face similar problems of stability of implants. We will use a paradigm for cortical recordings underlying vocalization in the awake mini pig, which allows to test the stability of long term recordings of unit and multiunit signals using the new conformational implants developed in the project.

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