Electronics Meet Animal Brains

Electronics meet Animal brains
Introduction:
Until recently, neurobiologists have used computers for simulation, data collection and data analysis, but not to interactdirectly with nerve tissue in live, behavinganimals.Although digital computers andnerve tissue both use voltage waveforms to transmitand process information, engineers and neurobiologistshave yet to cohesively link the electronic signalling of digital computerswiththeelectronicsignalingofnervetissueinfreelybehavinganimals.
Recentadvancement inmicroelectromechanical 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 reidentifiable cells with specific, known neural functions. The key components of such a brain-computer system include neural probes, analogelectronics, and a miniature microcomputer.
Researchers developing neural probes such as submicronMEMS probes, microclamps, microprobe arrays, and similar structures can now penetrateand make electrical contact with nerve cells without causing significant or long-term damage to probes or cells. Researchers developing analog electronics such as low-power amplifiers and analog-todigital converters can now integrate these devices with microcontrollers on a single lowpower CMOS die. Further, researchers developing embedded computer systems can now incorporate all the core circuitryof 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.
Chapter 2. Working architecture 2.1. Introduction: Before moving to real implications of BCI and its application let us first discuss the three
types of BCI. These types are decided on the basis of the technique used for the interface.
Each of these techniques has some advantages as well as some disadvantages. The three types
of BCI are as follows with there features:
2.2. Invasive BCI:
Invasive BCI are directly implanted into the grey matter of the brain during neurosurgery.
They produce the highest quality signals of BCI devices . Invasive BCIs has targeted
repairing damaged sight and providing new functionality to paralyzed people. But these BCIs
are prone to building up of scar-tissue which causes the signal to become weaker and even
lost as body reacts to a foreign object in the brain.
fig.2.2.1: Jens Naumann, a man with acquired blindness, being interviewed about his vision
BCI on CBS's The Early Show
In vision science, direct brain implants have been used to treat non-congenital i.e. acquired
blindness. One of the first scientists to come up with a working brain interface to restore sight
as private researcher, William Dobelle. Dobelles first prototype was implanted into Jerry, a
man blinded in adulthood, in1978. A single-array BCI containing 68 electrodes was
implanted onto Division of Computer Science and Engineering, SOE, CUSAT 3 Brai
Computer Int
Jerrys visual cortex and succeeded in producing phosphenes, the sensation of seeing light.
The system included TV cameras mounted on glasses to send signals to the implant. Initially
the implant allowed Jerry to see shades of grey in a limited field of vision and at a low
frame-rate also requiring him to be hooked up to a two-ton mainframe. Shrinking electronics
10
and faster computers made his artificial eye more portable and allowed him to perform simple tasks unassisted. In 2002, Jens Naumann, also blinded in adulthood, became the first in a series of 16 paying patients to receive Dobelles second generation implant, marking one of the earliest commercial uses of BCIs. The second generation device used a more sophisticated implant enabling better mapping of phosphenes into coherent vision. Phosphenes are spread out across the visual field in what researchers call the starry-night effect. Immediately after his implant, Jens was able to use imperfectly restored vision to drive slowly around the parking area of the research institute. BCIs focusing on motor Neuroprosthetics aim to either restore movement in paralyzed individuals or provide devices to assist them, such as interfaces with computers or robot arms. Researchers at Emory University in Atlanta led by Philip Kennedy and Roy Bakay were first to install a brain implant in a human that produced signals of high enough quality to stimulate movement. Their patient, Johnny Ray, suffered from locked-in syndrome after suffering a brain-stem stroke. Rays implant was installed in 1998 and he lived long enough to start working with the implant, eventually learning to control a computer cursor. Tetraplegic Matt Nagle became the first person to control an artificial hand using a BCI in 2005 as part of the nine-month human trail of cyber kinetics Neurotechnologys Braingate chip-implant. Implanted in Nagles right precentral gyrus(area of the motor cortex for arm movement), the 96 electrode Braingate implant allowed Nagle to control a robotic arm by thinking about moving his hand as well as a computer cursor, lights and TV. Division of Computer Science and Engineering, SOE, CUSAT 4 Brain Computer Interface
11
2.3. Partially Invasive BCI: Partially invasive BCI devices are implanted inside the skull but rest outside the brain rather than amidst the grey matter. They produce better resolution signals than noninvasive BCIs where the bone tissue of the cranium deflects and deforms signals and have a lower risk of forming scar-tissue in the brain than fully-invasive BCIs. Electrocorticography(ECoG) uses the same technology as non-invasive
electroencephalography, but the electrodes are embedded in a thin plastic pad that is placed above the cortex, beneath the dura mater. ECoG technologies were first traled in humans in 2004 by Eric Leuthardt and Daniel Moran from Washington University in St Louis. In a later trial, the researchers enabled a teenage boy to play Space Invaders using his ECoG implant. This research indicates that it is difficult to produce kinematic BCI devices with more than one dimension of control using ECoG. Light Reactive Imaging BCI devices are still in the realm of theory. These would involve implanting laser inside the skull. The laser would be trained on a single neuron and the neurons reflectance measured by a separate sensor. When neuron fires, The laser light pattern and wavelengths it reflects would change slightly. This would allow researchers to monitor single neurons but require less contact with tissue and reduce the risk of scartissue build up. 2.4. Non-Invasive BCI : As well as invasive experiments, there have also been experiments in humans using noninvasive neuroimaging technologies as interfaces. Signals recorded in this way have been used to power muscle implants and restore partial movement in an experimental volunteer. Although they are easy to wear, non-invasive implants produce poor signal resolution because the skull dampens signals, dispersing and blurring the electromagnetic waves created by the neurons. Although the waves can still be detected it is more difficult to determine the area of the brain that created them or the actions of individual neurons. Division of Computer Science and Engineering, SOE, CUSAT 5 Brain Computer Interface
12
fig.2.4.1: Recordings of brainwaves produced by an electroencephalogram Electroencephalography(EEG) is the most studied potential non-invasive interface, mainly due to its fine temporal resolutions, ease of use, portability and low set-up cost. But as well as the technology's susceptibility to noise, another substantial barrier to using EEG as a brain-computer interface is the extensive training required before users can work the technology. For example, in experiments beginning in the mid-1990s, Niels Birbaumer of the University of Tbingen in Germany used EEG recordings of slow cortical potential to give paralysed patients limited control over a computer cursor.(Birbaumer had earlier trained epileptics to prevent impending fits by controlling this low voltage wave.) The experiment saw ten patients trained to move a computer cursor by controlling their brainwaves. The process was slow, requiring more than an hour for patients to write 100 characters with the cursor, while training often took many months. Another research parameter is the type of waves measured. Birbaumer's later research with Jonathan Wolpaw at New York State University has focused on developing technology that would allow users to choose the brain signals they found easiest to operate a BCI, including mu and beta waves. A further parameter is the method of feedback used and this is shown in studies of P300 signals. Patterns of P300 waves are generated involuntarily (stimulus-feedback) when people see something they recognise and may allow BCIs to decode categories of thoughts without training patients first. By contrast, the biofeedback methods described above require learning to control brainwaves so the resulting brain activity can be detected. In 2000, for example, research by Jessica Bayliss at the University of Rochester showed that volunteers wearing virtual reality helmets could Division of Computer Science and Engineering, SOE, CUSAT 6 Brain Computer Interface
13
control elements in a virtual world using their P300 EEG readings, including turning lights on and off and bringing a mock-up car to a stop. In 1999, researchers at Case Western Reserve University led by Hunter Peckham, used 64-electrode EEG skullcap to return limited hand movements to quadriplegic Jim Jatich. As Jatich concentrated on simple but opposite concepts like up and down, his beta-rhythm EEG output was analysed using software to identify patterns in the noise. A basic pattern was identified and used to control a switch: Above average activity was set to on, below average off. As well as enabling Jatich to control a computer cursor the signals were also used to drive the nerve controllers embedded in his hands, restoring some movement. Electronic neural-networks have been deployed which shift the learning phase from the user to the computer. Experiments by scientists at the Fraunhofer Society in 2004 using neural networks led to noticeable improvements within 30 minutes of training. Experiments by Edurado Miranda aim to use EEG recordings of mental activity associated with music to allow the disabled to express themselves musically through an encephalophone. Magnetoencephalography (MEG) and functional magnetic resonance imaging (fMRI) have both been used successfully as non-invasive BCIs. In a widely reported experiment, fMRI allowed two users being scanned to play Pong in real-time by altering their haemodynamic response or brain blood flow through biofeedback techniques. fMRI measurements of haemodynamic responses in real time have also been used to control robot arms with a seven second delay between thought and movement. 2.5. Animal BCI research: fig.2.5.1: Rats implanted with BCIs in Theodore Berger's experiments Division of Computer Science and Engineering, SOE, CUSAT 7 Brain Computer Interface
14
Several laboratories have managed to record signals from monkey and rat cerebral cortexes in order to operate BCIs to carry out movement. Monkeys have navigated computer cursors on screen and commanded robotic arms to perform simple tasks simply by thinking about the task and without any motor output. Other research on cats has decoded visual signals. 2.5.1. Early work Studies that developed algorithms to reconstruct movements from motor cortex neurons, which control movement, date back to the 1970s. Work by groups led by Schmidt, Fetz and Baker in the 1970s established that monkeys could quickly learn to voluntarily control the firing rate of individual neurons in the primary motor cortex after closed-loop operant conditioning, a training method using punishment and rewards. In the 1980s, Apostolos Georgopoulos at Johns Hopkins University found a mathematical relationship between the electrical responses of single motor-cortex neurons in rhesus macaque monkeys and the direction that monkeys moved their arms (based on a cosine function). He also found that dispersed groups of neurons in different areas of the brain collectively controlled motor commands but was only able to record the firings of neurons in one area at a time because of technical limitations imposed by his equipment. There has been rapid development in BCIs since the mid-1990s. Several groups have been able to capture complex brain motor centre signals using recordings from neural ensembles (groups of neurons) and use these to control external devices, including research groups led by Richard Andersen, John Donoghue, Phillip Kennedy, Miguel Nicolelis, and Andrew Schwartz. 2.5.2. Prominent research successes Phillip Kennedy and colleagues built the first intracortical brain-computer interface by implanting neurotrophic-cone electrodes into monkeys. Division of Computer Science and Engineering, SOE, CUSAT 8 Brain Computer Interface
15
fig.2.5.2: Garrett Stanley's recordings of cat vision using a BCI implanted in the lateral geniculate nucleus (top row: original image; bottom row: recording) In 1999, researchers led by Garrett Stanley at Harvard University decoded neuronal firings to reproduce images seen by cats. The team used an array of electrodes embedded in the thalamus (which integrates all of the brains sensory input) of sharp-eyed cats. Researchers targeted 177 brain cells in the thalamus lateral geniculate nucleus area, which decodes signals from the retina. The cats were shown eight short movies, and their neuron firings were recorded. Using mathematical filters, the researchers decoded the signals to generate movies of what the cats saw and were able to reconstruct recognisable scenes and moving objects. Miguel Nicolelis has been a prominent proponent of using multiple electrodes spread over a greater area of the brain to obtain neuronal signals to drive a BCI. Such neural ensembles are said to reduce the variability in output produced by single electrodes, which could make it difficult to operate a BCI. After conducting initial studies in rats during the 1990s, Nicolelis and his colleagues developed BCIs that decoded brain activity in owl monkeys and used the devices to reproduce monkey movements in robotic arms. Monkeys have advanced reaching and grasping abilities and good hand manipulation skills, making them ideal test subjects for this kind of work. By 2000, the group succeeded in building a BCI that reproduced owl monkey movements while the monkey operated a joystick or reached for food.The BCI operated in real time and could also control a separate robot remotely over Internet protocol. But the monkeys could not see the arm moving and did not receive any feedback, a so-called open-loop BCI. Division of Computer Science and Engineering, SOE, CUSAT 9 Brain Computer Interface
16
fig.2.5.3: Diagram of the BCI developed by Miguel Nicolelis and collegues for use on Rhesus monkeys. Later experiments by Nicolelis using rhesus monkeys, succeeded in closing the feedback loop and reproduced monkey reaching and grasping movements in a robot arm. With their deeply cleft and furrowed brains, rhesus monkeys are considered to be better models for human neurophysiology than owl monkeys. The monkeys were trained to reach and grasp objects on a computer screen by manipulating a joystick while corresponding movements by a robot arm were hidden. The monkeys were later shown the robot directly and learned to control it by viewing its movements. The BCI used velocity predictions to control reaching movements and simultaneously predicted hand gripping force. Other labs that develop BCIs and algorithms that decode neuron signals include John Donoghue from Brown University, Andrew Schwartz from the University of Pittsburgh and Richard Andersen from Caltech. These researchers were able to produce working BCIs even though they recorded signals from far fewer
2.INTEGRATING SILICON AND NEUROBIOLOGY:Neurons and neuronal networksdecide, remember, modulate, and control an animals every sensation, thought, movement, and act. The intimatedetails of this network, including the dynamic properties of individualneurons and neuron populations, give a nervous system the power to control a wide array of behavioralfunctions. The goal of understanding these details motivatesmany workers in modern neurobiology.
17
To makesignificant progress, these neurobiologists need methods for recording the activity of single neurons or neuron assemblies, for long timescales, at highfidelity, in animals that can interact freely with theirsensory world and express normal behavioural responses.
3 .Conventional techniques :-
Neurobiologists examine the activities of brain cells tied to sensory inputs, integrative processes, and motor outputs to understand the neural basisBy enabling better study of animal behaviors neural basis, implantablecomputers may revolutionize field biology and eventually lead to neuralprosthetics, hardware-based human-computer interfaces, and artificialsystems that incorporate biological intelligence principles.
Chris Diorio
Jaideep
Mavoori
University of Washington 70 Computer 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 tissue1: 3.1 :-intracellular micropipettes:-to impale or patchclampsingle cells for interrogation of the cells internal workings, and 3.2:-extracellular wires or micromachined probes:-for interrogating multisite patterns of extracellular 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
18
system.2 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 animals normal 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 brains neural signaling while the animal roams freely in its natural environment. 4. Salient objectives:-
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, semiconductor electronics, embedded systems, biocompatible materials, and electronic packaging finally allow neuroscientists and engineers to begin packaging entire neurobiology experiments intohardware and firmware that occupy less space thana human fingernail. Researchers call these bioembedded systems neurochips. Scientists from the University of Washington, Caltech, and Case Western Reserve University have teamed to build these miniaturized implantable experimental setups to explore the neural basis of behavior.3 This research effort has developed or is in the process of developing the following: miniaturized silicon MEMS probes for recording from the insides of nerve cells; biocompatible coatings that protect these probes from protein fouling; a stand-alone implantable microcomputer that records from and stimulates neurons, sensory pathways, or motor control pathways in an intact animal, using intracellular probes, extracellular probes, or wire electrodes; neurophysiological preparations and techniques for implanting microchips and wire
19
electrodes or MEMS probes into or onto animals in a way that does not damage the probes or tissue; firmwarethat performs real-time biology experiments with implanted computers, using analytical models of the underlying biology;and software to study and interpret the experimental results, eventually leading to reverseengineered 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.
5.DESIGNER NEUROCHIPS:-
Like their benchtop experimental counterparts,neurochips use amplifiers to boost lowvoltage biological signals, analog-to-digital converters (ADCs) to digitize these signals, microcomputers to process the signals, onboard memory to store the signals, digital-to-
Figure 1.Neurochip functional block diagram. Solid lines show required components, dashed lines show some optional components analog converters (DACs) to stimulate nerves, and software to control theoverall experiment. Figure 1 shows a neurochips basic elements. The key requirements are that the neurochip be small and lightweight enough to fit inside or onto the animal,
20
have adequate signal fidelity for interacting with the millivolt-level signals characteristic of nerve tissue, and have sufficient processing power to perform experiments of real scientific value.
The basic components of a neurochip are commerciallyavailable today. They include instrumentationamplifiers, ADCs/DACs, reconfigurable microcomputers, and highdensity memory. For January 2003 71Currentlywe are implanting neurochips in two types of animals to study their neuronal behavior. Fig. 2(a) gives a functional overview of the neurochip The neural signal
from a chronically implanted microwire electrode is buffered, bandpass
filtered 500 Hz5 kHz by a four-pole multiple feedback Butterworth filter
and amplifi 1500 (Fig. 2(b)). This signal passes to one input of a
Programmabl System-on-a-Chip (PSoC CY8C27443 from Cypress
Semiconductor). This chip incorporates a configurab array of analog
modules which are used to implement a variable gain amplifier that allows
additional amplification of (148), followed by an 8-bit deltasigma ADC sampling
at 11.7 ksps (details of the internal PSoC settings required to implement
these modules can be obtained by contacting the first author). Additionally,
the PSoC includes an 8-bit microprocessor core which runs a spike
discrimination algorithm
The algorithm, which identifies action potentials based on a threshold

21
crossing and two adjustable timeamplitude windows,is detailed in Section
4.1. On detecting a spike, the microprocessor can initiate a stimulation
control algorithm which instructs a stimulator to deliver precisely timed
stimuli
Fig. 1. (a) Components of the implant. All parts are enclosed in a titanium casing and mounted on the head. (b) Photograph of a neurochip circuit board. Actual size: 1.2 cm5.4 cm
22
Fig: Architecture of our implantable neurochip.
5. Experiments and results
5.1. Neural recording
Fig. 4(a) shows a typical sample of rawdata recorded from a microwire in the
arm area of the primary motor cortex (M1) while the animal moved freely
about his home cage.Again of 12,000 was used for this recording. The
background noise level (6_V rms) is comparable to recordings from the
same electrode with a conventional amplifier system (MCP-Plus, Alpha-
Omega Engineering). Several action potentials can be seen to rise clearly
above the background noise. In order to extract these discrete action
potential events from the continuous data, we use a spike discrimination
algorithm based on
23
Fig. 5. (a) Sample of multi-unit spike activity recorded by the neurochip
b) Operation of the timeamplitude window discriminator.Waveforms crossing the trigger level
24
Fig. 5. (a) Sample torque, rectifiedEMG from extensor carpradialis muscle and spike data obtained while the monkey performed a trained task
(b) Inter-spike interval histogram. The absence of intervals less than 2ms and a consistent spike
25
a threshold crossing and two timeamplitude windows (Fig.
5(b)). The spike discriminator is triggered whenever the digitized sample
crosses the user-defined threshold (shown as a dashed horizontal line). In
Fig. 5(b), successive spike waveforms have been overlaid and aligned to this
trigger crossing. Each spike event is accepted if the waveform subsequently
passes through two windows (shown as gray boxes). The vertical extent of
each of these windows, as well as the time latency following the trigger
event can be individually adjusted by the user and relayed to the neurochip
via the IR link. In Fig. 5(b), these windows have been chosen to discriminate
the larger action potentials in this record. These waveforms are shown in
black, while the spikes that were excluded by this algorithm are shown in
gray. In general, we find that two discrimination windows suffice to isolate
large single-units from our data records, although the program could be
extended to include additional windows or a more sophisticated spike sorter,
within limits of the computational capabilities of the microprocessor.
Because the spike discrimination algorithm runs in real time, accepted spike
26
events can be relayed immediately via IR for remote recording with
simultaneous behavioral data. Fig. 5 shows results from an experiment in
which the monkey, seated in a recording booth, performed a trained task that
involved controlling a cursor with torques generated about the wrist. The
neurochip was configured to emit an IR pulse for every detected spike. A
remote computer equipped with an IR receiver recorded the pulses along
with the wrist torque as measured by a force transducer attached to the
manipulandum.Because the neurochip is optically isolated from the
recording system, additional physiological signals (in this case
electromyograms) can be collected simultaneously with conventional rack
amplifiers without ground loop interference. The spike activity shows a clear
correlation to the muscle activity. The absence of short inter-spike intervals
(Fig. 5(b)) suggests that in this case the neurochip discriminated action
potentials from a single neuron with a refractory period. Raw spike
waveforms were subsequently uploaded from the neurochip to verify the
quality of discrimination (Fig. 5(b),
6. Taming a fighting bull

27
delgado showed that stimulation of the motor cortex could elicit specific
physical reactions, such as movement of the limbs. One patient clenched his fist when stimulated, even when he tried to resist. I guess, doctor, that your electricity is stronger than my will, the patient commented. Another subject,
turning his head from side to side in response to stimulation, insisted he was doing so voluntarily, explaining, I am looking for my slippers. By
stimulating different regions of the limbic system, which regulates emotion,
Delgado could also induce fear, rage, lust, hilarity, garrulousness and other
reactions, some of them startling in their intensity. In one experiment,
Delgado and two collaborators at Harvard University stimulated the
temporal lobe of a 21-year-old epileptic woman while she was calmly
playing a guitar; in response, she flew into a rage and smashed her guitar against a wall, narrowly missing a researchers head. Delgados most famous experiment took place in 1963 at a bull-breeding
ranch in Cordoba, Spain. After inserting stimoreceivers into the brains of several fi ghting bulls, he stood in a bullring with one bull at a time and, by pressing buttons on a handheld transmitter, controlled each animals
28
actions. In one in stance, captured in a dramatic photograph, Delgado forced
stimulating its caudate nucleus. The New York Times published a frontpage story on the event, calling it the most spectacular demonstration ever
performed of the deliberate modification of animal behavior through external control of the brain. Other articles hailed Delgados transformation
of an aggressive beast into a real-life version of Ferdinand the bull, the gentle hero of a popular childrens story. In terms of scientific significance
Fig(a): FIGHTING BULL with a stimoceiver in its brain
29
Fig(b): stopped and turned in response to a radio signal from Delgado
6.Wiring a sea slug :-
(1) (2) Figure A. Monitoring a giant sea slug. (1) Tritodiomedeashown with its prey, an orangeseapen, in the backgroundis typically 20 cm in length, has a readily accessible brain with large and well-characterized neurons, and is extraordinarily tolerant of surgical insult. (2) Artists conception of a neural recording setup implanted inside Tritonia. 1 cm
30
Beneath a research vessel anchored in the Puget Sound, two scientists clad in scuba gear hover over the bright orange sea slug shown in Figure A. From the outside, this slug looks like any other. But this particular slug has a battery-powered microcomputer implanted in its brain and minuscule silicon needles communicating with its neurons.
The microcomputer faithfully performs a biology experiment as the animal goes about its normal behavior. Meanwhile, the scientists videotape the slugs feeding, fleeing, and social behaviorswhile measuring water currents and geomagnetic fields. Later, these scientists will study the environmental measurements and electronic recordings in an attempt to decode how the slugs brain patterns correlate with behavior. The anticipated outcome: groundbreakingfindings in behavioral neurobiology. Monitoring a moths flight controls:-
7.
In a small, dark zoology lab, a giant moth performs an aerial ballet as it feeds from a robotically controlled artificial flower, unaware that the flowers movements are programmed to test the moths flight dynamics. The ultra-high-speed infrared video recorder tapes the moths every movement. But the special part of this experiment is neither the flower nor the videotaping. It is the tiny battery-powered microcomputer attached to the moths thorax that records electrical signals from the flight muscles and sense organs and stores this data in onboard memory. Suddenly, the moth appears to struggle to keep up with the flower. But the flowers movements havent changed. Rather,
(1) (2) Figure B. Tracking a moths movements. (1) Manducasexta is typically 4 cm in length with a wingspan of about 12 cm; at 2.5 gm, it is one of the largest flying insects. It can
31
carry loads up to a gram and fly at speeds up to 30 miles per hour, flapping its wings 25 times a second. (2) Artists conception of a neurochip attached to Manducas thorax theonboard microcomputer has begun stimulating the nerves that enervate the moths wing muscles, adjusting the wing-stroke phase in subtle ways that will let scientists measure the impulse response of the moths flight-control loops. These experiments and others like them will soon be played out in biology laboratories across the country, if the multidisciplinary team of computer engineers and zoologists that is developing these implantable computers has its way.
Neuroscience Application Examples
Tritoniadiomedea MEMS probe tip,amplifier Brain MicrocontrollerA/D,cacheMemoryBattery Visceral Tether cavity Real rhododendrons Computercontrolled artificial flower
Figure C. High-speed infrared video captures Manduca hovering and sipping nectar from a moving flower. Visually guided flight control lets the animal compensate for rapid changes in wind direction and the flowers swaying movements.
72 Computer example, a Programmable System-on-a-Chip from Cypress MicroSystems integrates a microprocessor, variable-gain amplifiers, an ADC, a memory controller,
32
and a DAC into a single integrated circuit.
First-generation neurochips integrate one ormore ICs, passive elements such as capacitors, batteries, and I/O pads on small micro-PCBs. The prototype neurochip shown in Figure 2 used packaged ICs and button cells, and occupied a 1 cm 3 cm printedcircuit board. The production version, due out of processing in early 2003, uses dieonboard technology and thin-film batteries, and is ADC CPU Amplifier DAC Amplifier Memory Accelerometer Infrared LED for synchronizing with video camera Nerve + muscle signals +_ Upload/ Downloadlink toexternalcomputer
. Figure 2.Prototype neurochips. (a, b) Afirst-generation neurochip comprising differential amplifiers and batteries on a micro-PCB attached to theManduca moths thorax. The animals exoskeleton provides a simple attach point without
33
biocompatibility issues. Manually implanted bipolarrecording electrodes connect to
recording sites.
(c) A tethered inflight recording from the thoracic flight musculature. (d) A second-
generation neurochip prototype records from two nerve or muscle fiber sites, storing
the signals in onboard non-volatile memory. (a) (b) (c) (d) smaller than 1 square centimeter. Future-generation neurochips will integrate all the
electronicsonto a single silicon chip, and will likely be smaller than 10 mm on a side. 7.Probes:-
Figure 3.Micromachined silicon probes, flexible interconnect structures, and
34
sea slug surgery. (a) Released, flexible silicon devices ready for implantation; (b) a sharp microelectrode on a flexible polyamide support; (c) the implantation procedure places the needle on the exposed brain of a sea slug and the silicon base with the external wires tucks under the slugs skin; and (d) the postsurgery sea slug with implanted device can move freely in the water tank
Building the probes that let a neurochip eavesdrop on the electrical signaling in a nerve bundle, group of neurons, or single neuron presents a daunting task. Benchtopexperiments on constrained animals typically use metallic needles often made ofstainless steel or tungstento communicate with nerve bundles, micromachinedsilicon probes to record from groups of neurons,4 or glass capillaries filled with a conductive ionic solution to penetrate and record from the inside of individual neurons.
In unconstrained animals, flexible metallic needles, attached to the animal with surgical superglue, and micromachined silicon probes still work. However, replicating the performance of glass capillaries in flying, swimming, wigglinganimals is a different story entirely.
Several centimeters long and quite fragile, the glasscapillaries that neurobiologists use to probe the insides of nerve cells typically have tip diameters smaller than 0.3 microns. They impale neurons even more fragile than the probes themselves. Neurobiologists use micromanipulators to painstakinglyand precisely drive single probes into single neurons. Fortunately, MEMS technology offers a possible alternative to these glass capillaries. As
Figure 3 shows, University of Washington researchers are developing silicon MEMS probes and flexible interconnect structures to mimic the performance of glass capillaries in an implanted preparation.5 Researchers have already recorded intracellular signals with early prototypes, and development is ongoing.
35
8. Glyme
Researchers seek to implant both probes and neurochips inside an animals brain. Unfortunately, an animals immune system rapidly and indiscriminately encapsulates all foreign bodies with proteins, without regard for the research value of implanted probes and neurochips.
The adsorbed proteins not only attenuate the recorded electricalsignals, but can also jeopardize the animals survival by causing abnormal tissue growth.
Figure 4. A fluorescence microscope image of a patterned 1,500 m 1,500 m protein-resistant plasma polymerized tetraglyme (pp4G) pad on a silicon-dioxide substrate, with additional 200 micron 200 micron gold pads on and around the PP4G pad, after incubation in a solution containing fluorescently labeled
36
proteins.
The silicon-dioxide and gold areas adsorb protein and appear light,while the pp4Gcoated areas resist protein adsorption and appear dark
Researchers at the University of Washingtons Center for Engineered Biomaterials have developed plasma-deposited ether-terminated oligoethylene glycol coatings that inhibit protein fouling, as
Figure 4 shows.6 Preliminary research indicates thatthese glyme coatings can reduce the protein fouling of probes and neurochips to levels acceptable for week-long experiments.
9. The power struggle:-
Neurochips can derive power from onboard batteries, external radiofrequency sources, a wire January 2003 73 . . 74 Computertether, or the nerve tissue itself. The ultimate decision on the power source depends on the nature of the experiments and the animals environment. Batteries are attractive because they avoid the antennas and charge pumps required to capture RF energy, operate in all environments, do not restrict the animals movement the way a tether does, and provide much more power than tapping nerve cellsfor energy.
Batteries have a weight disadvantage, but thinfilmtechnologies using LiCoO2/LiPON/Li and Ni/KOH/Zn promise flexible rechargeable batteries with peak current densities
37
greater than 12 mA per square centimeterfor short-duration experiments, and lifetimes measured in days or longer at low-current densities.7,8 Batteries are ideal for the two sample preparations shown in the Neuroscience Application Examples sidebar.
The typical hawkmoth flight time is less than 60 seconds. The 12 mA provided by a 200 mg, one-square-centimeter battery easily powers a neurochip for this experiments duration. The sea slug trolling methodically along theseafloor lies at the opposite end of the spectrum, needing only a few milliamps of current to power a neurochip for a week. The slug can easily accommodate a large battery in its visceral cavity, allowing extended untethered experiments.
10.Out of memory?:-
Once implanted, an embedded neurochip must read its experimental procedure from memory, run the experiment, acquire the neural spike trains, thenstore the results in memory. As with all computer systems, memory size is an issue for neurochips.Fortunately, the electrical spike trains generated by nerve tissue have a stereotyped shape as shown in Figure 2c, suggesting that neurochips should compress the neural waveforms before storing them in memory. Compressing the signals has two advantages.
10.1:-First, it effectively increases the onboard storage capacity.
10.2:- Second, it decreases the frequency ofmemory writes, reducing power consumption. Even simple compression algorithms such as runlengthencoding can achieve better than 10 to 1 compression ratios on neural signals. Custom algorithms that apply vector quantization, run-length encoding, and Huffman encoding to different parts of the neural waveform can achieve up to 1,000 to 1 compression ratios.9 Given the limited computing power of an implantable microcomputer, simpler is better when it comes to compression, but even simple RLE offers huge power and memory-size benefits.
38
11.A STIMULATING WORLD:-
Passive neurochips that do nothing more than record will provide neurobiologists with a wealth of data. But even now, with the first neurochipsbarely in production, neurobiologists are already calling for designs that stimulate nerve tissue as well as record from it.
Active neurochips will allow stimulus- response experiments that test models of how nervous systems control behavior, such as how sensory inputs inform motor-circuit loops and the logic or model behind the response. Indeed, the neurochip projects long-term goal isto develop a hardware and software environment in which a neurobiologist conceives a stimulus-response experiment, encodes that experiment in software,downloads the experiment to an implanted neurochip, and recovers the data when the experimentconcludes.
Figure 5 shows a model of integrative biology in which neurochips play a key part. With advances in integrated circuit processing will come ever more capable and power-efficient embedded computers. The simple neurochips of today will become the complex embedded systems of tomorrow, when embeddingin this ultimate sense will mean computer electronics embedded in nerve tissue.
39
Figure 5.Integrative biology using neurochips. A neurochip can splice into neuromuscular pathways to unravel the internal biological circuitry. Neurochips armed with recording and stimulation channels will help neurobiologists understand the complex interactions among the moths various neural control systems.
12.Neurochip Technology Forecast:-
Even as the first miniature neurochips record neuronal action potentials,researchers at the University of Washington are testing stimulus paradigms to evoke controlled muscular extension and contraction. Rather than driving the muscles directly using high-resolution voltage stimulus waveforms generated by digital synthesis and a digital-toanalogconverter, they tried stimulating nerve bundles instead, using simple digital waveforms directly. They derived pulse-width modulated signals directly from logic gates, and drove these waveforms into the nerve bundles that enervate the muscles.
Early results show great promise, not only because the technique actually worked, but because a microcontroller can easily generate digital pulses, and the drive currents needed
40
for nerve stimulation are up to 100 times smaller than those needed to drive muscle tissue directly. This power savings will allow functional stimulation by miniature neurochips.1
Next on the research agenda: statistical machine learning. Researchers already plan to use smart algorithms, smart software, and smart chips to interact dynamically with nerve tissue.
They suspect that machine learning can help them study the cause-and-effect relationships involved in the behavior of sensory motor circuits. Beyond that, they wont speculate, but the applications of this neurochip research to robotics, medical prosthetics, and a host of other applications seem obvious.
13: conclusion
We have designed and built an implantable neurochip forlong-term
recording and stimulation experiments in primates. Our system is lightweight
and compact and could be adapted for smaller animals. The neurochip
operates autonomously in conjunction with chronically implanted cortical
electrodes. An onboard spike discriminator isolates action potentials from a
single neuron, and the neurochip can store both raw waveform data and
binned spike rates. The stimulator is capable of delivering biphasic, constantcurrent stimuli sufficient to elicit an overt motor response. The neurochips
power consumption is low, allowing continuous operation on a single

41
battery for up to 60 h.With battery changes, we have tracked an individual
cell continuously for up to 12 days. We havesuccessfully tested this implant
in vivo, collecting data while monkeys performed a trained task in a
recording booth and during fully free behavior.We are currently
investigating the consequences of chronic operation of the implant and the
ability of monkeys to incorporate the feedback connections into normal
motor behavior.
Reference:1. M.R. Enstrom et al., Abdominal Ruddering and the Control of Flight in Hawkmoth, to be published, 2003; www.sicb.org/meetings/2003/schedule/ abstractdetails.php3?id=758.Enabling neuroscientists to better understand the neural basis of behavior is reason enough to develop such devices. The long-term promisehinted at in the Neurochip Technology Forecast sidebaris much greater, however, perhaps leading one day to neural prosthetics, hardware-based human-computerinterfaces, and artificial systems that incorporateprinciples of biological intelligence. _ 1. T.G. Smith et al., eds., Voltage and Patch Clamping with Microelectrodes, Lippincott, Williams & Wilkins, 1995.
2. E.R. Kandel, J.H. Schwartz, and T.M. Jessell, Principles of Neuroscience, 4th ed., McGraw-Hill, 2000. 3. S. Combes, Bugs, Slugs, n Chips: Downloading
42
Biology, Northwest Science & Technology, Spring 2000, pp. 32-36. 4. M.D. Gingerich, J.A. Wiler, and K.D. Wise, Use of an Active Microelectrode Array for Stimulation and Recording in the Central Nervous System, Engineering in Medicine and Biology, 1999, Biomedical Eng. Soc., 1999, p. 471. 5. Y. Hanein et al., Towards MEMS Probes for Intracellular Neuronal Recording, Sensors Update, vol. 10, no. 1, 2002, pp. 1-29. 6. Y. Hanein et al., Micromachining of Nonfouling Coatings for Bio-MEMS Applications, Sensors and Actuators B: Chemical, vol. 81, no. 1, 2001, pp. 49-54. 7. J.B. Bates et al., Thin-Film Lithium and LithiumIon Batteries, Solid State Ionics, vol. 135, 2000, pp. 33-45.
8. L.G. Salmon, R.A. Barksdale, and B.R. Beachem, Development of Rechargeable Microbatteries for Autonomous MEMS Applications, Technical Digest, 1998, pp. 338-341.
9. M. Richardson, Data Compression of Neural Signaling in an Implantable Microchip, tech. report 0208-01, Dept. Computer Science, University of Washington, 2001.
Chris Dioriois an associate professor of computer

43
science at the University of Washington. His research interests lie at the interface of computing and biology. Diorio received a PhD in electrical engineering from the California Institute of Technology. Contact him at diorio@cs.washington.edu. JaideepMavooriis a PhD candidate in electrical engineering at the University of Washington. His research interests include biological intelligence usingbiocomputer interfaces. Mavoori received an MS in electrical engineering from Clemson University. Contact him at jaideep@washington.edu.
44

Electronics Meet Animal Brains

Enviado por

Dados do documento

Descrição original:

Título original

Direitos autorais

Formatos disponíveis

Compartilhar este documento

Compartilhar ou incorporar documento

Opções de compartilhamento

Você considera este documento útil?

Este conteúdo é inapropriado?

Direitos autorais:

Formatos disponíveis

Electronics Meet Animal Brains

Enviado por

Direitos autorais:

Formatos disponíveis

Electronics meet Animal brains