On the way to large-scale and high-resolution brain-chip interfacing

Brain-chip-interfaces (BCHIs) are hybrid entities where chips and nerve cells establish a close physical interaction allowing the transfer of information in one or both directions. Typical examples are represented by multi-site-recording chips interfaced to cultured neurons, cultured/acute brain slices, or implanted “in vivo”. This paper provides an overview on recent achievements in our laboratory in the field of BCHIs leading to enhancement of signals transmission from nerve cells to chip or from chip to nerve cells with an emphasis on in vivo interfacing, either in terms of signal-to-noise ratio or of spatiotemporal resolution. Oxide-insulated chips featuring large-scale and high-resolution arrays of stimulation and recording elements are presented as a promising technology for high spatiotemporal resolution interfacing, as recently demonstrated by recordings obtained from hippocampal slices and brain cortex in implanted animals. Finally, we report on an automated tool for processing and analysis of acquired signals by BCHIs

Trends and challenges in neuroengineering: toward "Intelligent" neuroprostheses through brain-"brain inspired systems" communication

Future technologies aiming at restoring and enhancing organs function will intimately rely on near-physiological and energy-efficient communication between living and artificial biomimetic systems. Interfacing brain-inspired devices with the real brain is at the forefront of such emerging field, with the term "neurobiohybrids" indicating all those systems where such interaction is established. We argue that achieving a "high-level" communication and functional synergy between natural and artificial neuronal networks in vivo, will allow the development of a heterogeneous world of neurobiohybrids, which will include "living robots" but will also embrace “intelligent” neuroprostheses for augmentation of brain function. The societal and economical impact of intelligent neuroprostheses is likely to be potentially strong, as they will offer novel therapeutic perspectives for a number of diseases, and going beyond classical pharmaceutical schemes. However, they will unavoidably raise fundamental ethical questions on the intermingling between man and machine and more specifically, on how deeply it should be allowed that brain processing is affected by implanted "intelligent" artificial systems. Following this perspective, we provide the reader with insights on ongoing developments and trends in the field of neurobiohybrids. We address the topic also from a "community building" perspective, showing through a quantitative bibliographic analysis, how scientists working on the engineering of brain-inspired devices and brain-machine interfaces are increasing their interactions. We foresee that such trend preludes to a formidable technological and scientific revolution in brain-machine communication and to the opening of new avenues for restoring or even augmenting brain function for therapeutic purposes

On Real-Time AER 2-D Convolutions Hardware for Neuromorphic Spike-Based Cortical Processing

In this paper, a chip that performs real-time image convolutions with programmable kernels of arbitrary shape is presented. The chip is a first experimental prototype of reduced size to validate the implemented circuits and system level techniques. The convolution processing is based on the address–event-representation (AER) technique, which is a spike-based biologically inspired image and video representation technique that favors communication bandwidth for pixels with more information. As a first test prototype, a pixel array of 16x16 has been implemented with programmable kernel size of up to 16x16. The chip has been fabricated in a standard 0.35- m complimentary metal–oxide–semiconductor (CMOS) process. The technique also allows to process larger size images by assembling 2-D arrays of such chips. Pixel operation exploits low-power mixed analog–digital circuit techniques. Because of the low currents involved (down to nanoamperes or even picoamperes), an important amount of pixel area is devoted to mismatch calibration. The rest of the chip uses digital circuit techniques, both synchronous and asynchronous. The fabricated chip has been thoroughly tested, both at the pixel level and at the system level. Specific computer interfaces have been developed for generating AER streams from conventional computers and feeding them as inputs to the convolution chip, and for grabbing AER streams coming out of the convolution chip and storing and analyzing them on computers. Extensive experimental results are provided. At the end of this paper, we provide discussions and results on scaling up the approach for larger pixel arrays and multilayer cortical AER systems.Commission of the European Communities IST-2001-34124 (CAVIAR)Commission of the European Communities 216777 (NABAB)Ministerio de Educación y Ciencia TIC-2000-0406-P4Ministerio de Educación y Ciencia TIC-2003-08164-C03-01Ministerio de Educación y Ciencia TEC2006-11730-C03-01Junta de Andalucía TIC-141

Roadmap on semiconductor-cell biointerfaces.

This roadmap outlines the role semiconductor-based materials play in understanding the complex biophysical dynamics at multiple length scales, as well as the design and implementation of next-generation electronic, optoelectronic, and mechanical devices for biointerfaces. The roadmap emphasizes the advantages of semiconductor building blocks in interfacing, monitoring, and manipulating the activity of biological components, and discusses the possibility of using active semiconductor-cell interfaces for discovering new signaling processes in the biological world

Biointegrated and wirelessly powered implantable brain devices: a review

Implantable neural interfacing devices have added significantly to neural engineering by introducing the low-frequency oscillations of small populations of neurons known as local field potential as well as high-frequency action potentials of individual neurons. Regardless of the astounding progression as of late, conventional neural modulating system is still incapable to achieve the desired chronic in vivo implantation. The real constraint emerges from mechanical and physical diffierences between implants and brain tissue that initiates an inflammatory reaction and glial scar formation that reduces the recording and stimulation quality. Furthermore, traditional strategies consisting of rigid and tethered neural devices cause substantial tissue damage and impede the natural behaviour of an animal, thus hindering chronic in vivo measurements. Therefore, enabling fully implantable neural devices, requires biocompatibility, wireless power/data capability, biointegration using thin and flexible electronics, and chronic recording properties. This paper reviews biocompatibility and design approaches for developing biointegrated and wirelessly powered implantable neural devices in animals aimed at long-term neural interfacing and outlines current challenges toward developing the next generation of implantable neural devices

A novel Three-Dimensional Micro-Electrode Array for in-vitro electrophysiological applications

Microelectrode arrays (MEAs) represent a powerful and popular tool to study in vitro neuronal networks and acute brain slices. The research standard for MEAs is planar or 2D-MEAs, which have been in existence for over 30 years and used for extracellular recording and stimulation from cultured neuronal cells and tissue slices. However, planar MEAs suffer from rapid data attenuation in the z-direction when stimulating/recording from 3D in-vitro neuronal cultures or brain slices. The existing proposed 3D in-vitro neuronal models allow to record the electrophysiological activity of the 3D network only from the bottom layer (i.e. the one directly coupled to the planar MEAs). Thus, to further develop and optimize such 3D neuronal network systems and to study and understand how the 3D neuronal network dynamics changes in different layers of the 3D structure, new three-dimensional microelectrodes arrays (3D-MEAs) are required. Early attempts in this field resulted in interesting integrated approaches toward protruding or spiked 3D-MEAs. Although these first prototypes could be successfully employed with brain slices, the limited heights of the electrodes (up to max 70 \u3bcm) and the peculiar shape of the recording areas made them not an ideal solution for 3D neuronal cultures. Moreover, a convenient and versatile method for the fabrication of multilevel 3D microelectrode arrays has yet to be obtained, due to the usually complicated and expensive designs and a lack of a full compatibility with standard MEAs both in terms of materials and recording area dimensions. To overcome the afore-mentioned challenges, in this work, I present the design, microfabrication, and characterization of a new 3D-MEA composed of pillar-shaped gold 3D structures with heights of more than 100 \u3bcm that can be used, in principle, on every kind of MEA, both custom-made and commercial. I successfully demonstrate the capability and ability of such 3D-MEA to record electrophysiological spontaneous activity from 3D engineered in-vitro neuronal networks and both 4-AP-induced epileptiform-like and electrically-evoked activity from mouse acute brain slices. I also demonstrate how the developed 3D-MEA allows better recording and stimulating conditions while interfacing with acute brain slices as compared to planar electrode arrays and previously reported 3D MEA technologies

Multiplexed, High Density Electrophysiology with Nanofabricated Neural Probes

Extracellular electrode arrays can reveal the neuronal network correlates of behavior with single-cell, single-spike, and sub-millisecond resolution. However, implantable electrodes are inherently invasive, and efforts to scale up the number and density of recording sites must compromise on device size in order to connect the electrodes. Here, we report on silicon-based neural probes employing nanofabricated, high-density electrical leads. Furthermore, we address the challenge of reading out multichannel data with an application-specific integrated circuit (ASIC) performing signal amplification, band-pass filtering, and multiplexing functions. We demonstrate high spatial resolution extracellular measurements with a fully integrated, low noise 64-channel system weighing just 330 mg. The on-chip multiplexers make possible recordings with substantially fewer external wires than the number of input channels. By combining nanofabricated probes with ASICs we have implemented a system for performing large-scale, high-density electrophysiology in small, freely behaving animals that is both minimally invasive and highly scalable