Until recently, neurobiologists have used computers for simulation, data collection, and data analysis, but not to interact directly with nerve tissue in live, behaving animals. Although digital computers and nerve tissue both use voltage waveforms to transmit and process information, engineers and neurobiologists have yet to cohesively link the electronic signaling of digital computers with the electronic signaling of nerve tissue in freely behaving animals.
Recent advances in micro electromechanical systems (MEMS), CMOS electronics, and embedded computer systems will finally let us link computer circuitry to neural cells in live animals and, in particular, to reidenifiable cells with specific, known neural functions. The key components of such a brain-computer system include neural probes, analog electronics, and a miniature microcomputer. Researchers developing neural probes such as sub- micron MEMS probes, microclamps, microprobe arrays, and similar structures can now penetrate and make electrical contact with nerve cells with out causing significant or long-term damage to probes or cells.
Researchers developing analog electronics such as low-power amplifiers and analog-to-digital converters can now integrate these devices with micro- controllers on a single low-power CMOS die. Further, researchers developing embedded computer systems can now incorporate all the core circuitry of a modern computer on a single silicon chip that can run on miniscule power from a tiny watch battery. In short, engineers have all the pieces they need to build truly autonomous implantable computer systems.
Until now, high signal-to-noise recording as well as digital processing of real-time neuronal signals have been possible only in constrained laboratory experiments. By combining MEMS probes with analog electronics and modern CMOS computing into self-contained, implantable microsystems, implantable computers will free neuroscientists from the lab bench.
INTEGRATING SILICON AND NEUROBIOLOGY
Neurons and neuronal networks decide, remember, modulate, and control an animalâ„¢s every sensation, thought, movement, and act. The intimate details of this network, including the dynamic properties of individual neurons and neuron populations, give a nervous system the power to control a wide array of behavioral functions.
The goal of understanding these details motivates many workers in modern neurobiology. To make significant progress, these neurobiologists need methods for recording the activity of single neurons or neuron assemblies, for long timescales, at high fidelity, in animals that can interact freely with their sensory world and express normal behavioral responses.
Neurobiologists examine the activities of brain cells tied to sensory inputs, integrative processes, and motor outputs to understand the neural basis of animal behavior and intelligence. They also probe the components of neuronal control circuitry to understand the plasticity and dynamics of control. They want to know more about neuronal dynamics and networks, about synaptic interactions between neurons, and about the inextricable links between environmental stimuli and neuronal signaling, behavior, and control.
To explore the details of this biological circuitry, neurobiologists use two classes of electrodes to record and stimulate electrical signals in tissue
Â¢ intracellular micropipettes to impale or patch- clamp single cells for interrogation of the cellâ„¢s internal workings, and
Â¢ extracellular wires or micromachined probes for interrogating multisite patterns of extra- cellular neural signaling or electrical activity in muscles.
Neurobiologists use amplifiers and signal generators to stimulate and record to and from neurons through these electrodes, and signal-processing systems to analyze the results. They have used these techniques for decades to accumulate a wealth of understanding about the nervous system. Unfortunately, to date, most of these experiments have been performed on slices of brain tissue or on restrained and immobilized animals, primarily because the electronic instruments required to run the experiments occupy the better part of a lab bench.
This situation leaves neurobiologists with a nagging question: Are they measuring the animalâ„¢s nor mal brain signals or something far different? Further, neurobiologists want to understand how animal brains respond and react to environmental stimuli. The only way to truly answer these questions is to measure a brainâ„¢s neural signaling while the animal roams freely in its natural environment.
The solution to these problems lies in making the test equipment so small that a scientist can implant it into or onto the animal, using materials and implantation techniques that hurt neither computer nor animal. Recent developments in MEMS, semi conductor electronics, embedded systems, bio compatible materials, and electronic packaging finally allow neuroscientists and engineers to begin packaging entire neurobiology experiments into hardware and firmware that occupy less space than a human fingernail.
Researchers call these bioembedded systems neurochips. Scientists from the University of Washing-ton, Caltech, and Case Western Reserve University have teamed to build these miniaturized implantable experimental setups to explore the neural basis of behavior.
This research effort has developed or is in the process of developing the following:
Â¢ miniaturized silicon MEMS probes for recording from the insides of nerve cells;
Â¢ biocompatible coatings that protect these probes from protein fouling;
Â¢ a stand-alone implantable microcomputer that records from and stimulates neurons, sensory pathways, or motor control pathways in an intact animal, using intracellular probes, extra- cellular probes, or wire electrodes;
Â¢ neurophysiological preparations and techniques for implanting microchips and wire electrodes or MEMS probes into or onto animals in a way that does not damage the probes or tissue;
Â¢ firmware that performs real-time biology experiments with implanted computers, using analytical models of the underlying biology; and
Â¢ software to study and interpret the experimental results, eventually leading to reverse- engineered studies of animal behavior.
As the Neuroscience Application Examples sidebar shows, the first neurochip experiments use sea slugs and moths in artificial environments, but broad interest has already arisen for using implantable computers in many other animals.
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