Lecture 9

Neural Devices and

Systems
Neurons and the Brain

microelectrode

Recording site

neurons
 Interfacing with the
Nervous System
Interfacing with Neurons
- Microelectrodes
- Electrical, neurochemical
- Microdrive mechanisms

Interfacing with Brain

Tissue Slices
- Microelectrode arrays
- Electrical/optical recording

Recording and Stimulating

Whole Brain Neural microsystem with neural
- Microelectrode arrays tissue and the microsystem.
- Electrical and chemical recording;
Stimulation
- VLSI circuitry, Wireless telemetry
 Neural Interfaces

Direct Interfacing Brain slices Neuronal culture

to the brain
Brain/neural Prosthesis. In-vitro culture In-vitro culture of
In-vivo implantation of of slices brain cells
the electrodes.

• Applications of interfacing microelectrodes to neurons

- studying the effect of different chemicals/ neuro-trophic factors
- study of axon growth and regeneration

• Applications of interfacing microelectrodes to

brain
- large scale neurophysiological studies of mechanisms, diseases
- emerging fields like brain computer interface
Interfacing
with Neurons
 Microfabrication to
immobilize neurons
Micro-fabricated pickets (green)
with a neuron (orange) trapped
in the middle.
P. Fromherz, “Semiconductor chips with ion channels, nerve cells and brain slices”,
Neural Engineering, 2003, Conference Proceedings, First International IEEE EMBS
Conference
pp. 1, 20-22 March 2003.

Neurons cultured on cell adhesive

molecules immobilized on micro-
stamped surface.
L. Griscom, P. Degenaar, B. LePioufle, E. Tamiya, H. Fujita. (2002). “Techniques for
patterning and guidance of primary culture neurons on micro-electrode arrays.” Sensors and
Actuators B: Chemical, vol. 83, no. 1-3, pp. 15-21, 15 March 2002.
 Neural Cultures on
Microelectrode Arrays (MEA)
Rat Hippocampal Neurons in culture in a
4x4 matrix, with 80 micron squares and 4
micron wide lines of poly-lysine
From Wyart, et al., Journal of Neuroscience
Methods, 117 (2002) 123-131

Neurons culture on MEA.

http://soma.npa.uiuc.edu/labs/wheeler
 Neurons in Microfabricated
Structures
Primary neurons after 48 hours
with sprouting dendrites and
axons (and debris) in
microfluidic channel.
L. Griscom, P. Degenaar, M. Denoual, F. Mori, “Culturing of neurons in microfluidic
arrays”, Microtechnologies in Medicine & Biology 2nd Annual International IEEE-EMB
Special Topic Conference , 2-4 May 2002, pp. 160 - 163.

Micromachined array of
neurowells partially loaded with
neurons. Parylene neurocage
(inset)
http://www.its.caltech.edu/~pinelab/new_pinelab_page/current-
research/current_research.html
 Dielectrophoretic trapping of
neurons on microelectrodes
Planar electrode for
Dielectrophoretic
trapping of neurons

Neurons moving towards the

electrodes during DEP
positioning
• Prasad, S, Yang, M, Zhang, X, Ozkan, C, and Ozkan, M. 2003.
Electric Field Assisted Patterning of Neural Networks to Study Brain Functions, J of Biomedical Microdevices, J. of BMMD, 5:2, 125-137
 Dielectrophoretic Attraction of
Neurons on to the Sensors

(A) Random deposition of neurons on electrodes before the application of

AC fields, (B) Patterned arraying of neurons on electrode edges on applying
an AC field of 8Vpp at 4.6 MHz due to positive dielectrophoresis.
S. Prasad, M. Ozkan et al, UCR
 Neuron Silicon Interface

Neuron interfaced with silicon can be stimulated using

microelectrodes fabricated on silicon and signals can be
recorded from the neurons using transistors.

Fromherz, P. (2003). Semiconductor chips with ion channels, nerve cells and brain
slices. Neural Engineering, 2003. Conference Proceedings. First International IEEE
EMBS Conference on.
 Hydrogel scaffold for guided
3D cell growth and migration

Biochemical channels syntesized in agarose hydrogels were

characterized with a fluorescein-tagged GRGDS peptide.

Hydrogel can be used as 3D scaffold to

immobilize cells like neurons.
Primary rat dorsal root ganglia cells plated on 3D patterned GRGDS
oligopeptide modified agarose gels. Images a) Optical microscopy
b) Confocal fluorescent microscopy.
Interfacing
with In Vitro
Brain Slices
Interfacing with Brain slice
Brain slice study is useful in brain
disease (epilepsy) research, drug
delivery and computing (models
of hippocampus) application
Integrated microelectrode array
and chamber
P. A. Passeraub, A. C. Almeida, N. V. Thakor,
"Design, microfabrication and characterization of a
microfluidic chamber for the perfusion of brain tissue
slices," Biomedical Microdevices, vol. 5, pp. 147-155,
June, 2003.
 Microelectrodes for
in vitro brain slices
Scanning electron
microscope image of TiN
microelectrode fabricated
by plasma etching process.
For brain slice study.
U. Egert, B. Schlosshauer, S. Fennrich, W. Nisch, M. Fejtl,
T. Knott, T. Müller, H. Hämmerle, “A novel organotypic
long-term culture of the rat hippocampus on substrate-
integrated multielectrode array”, Brain Research Protocols,
vol. 2, no. 4, pp. 229-242, June 1998.

Microelectrode array Microelectrode with

brain slice culture. Steps for fabrication of the electrodes
 Microelectrodes
Microfabricated Pt-tip electrodes by
anisotropic etching of silicon and Platinum
deposition.
Pt-tip microelectrode with large open surface.
Inset: Pt electrode with small open area.
P. Thiébaud, C. Beuret, N. F. de Rooij, M. Koudelka-Hep, “Microfabrication of Pt-tip
microelectrodes”, Sensors and Actuators B 70, 2000, no. 1-3,pp. 51-56, 1 November 2000

Sequences for fabrication

of the microelectrodes
Microelectrodes Fabrication process for the silicon electrodes

Passivation of SiO2

Patterning

Multipoint record able Au evaporation

penetrating probes with

on-chip signal processing
circuitry. Silicon wire Lift off
electrodes grown with
selective VLS (vapor-
liquid-solid) growth VLS growth

process and IC process.

T. Kawano, Y. Kato, M. Futagawa, H. Takao, K. Sawada, M. Ishida, “Fabrication and properties of ultrasmall Si wire arrays with circuits by vapor-liquid-solid growth”,
Sensors and Actuators A 3302, pp. 709-715, 2002.
 Microfluidic Chamber for
brain slice perfusion

Picture of a micro-fabricated flat perfusion chamber

Photo resist Pillars in microfluidic chamber
with integrated 6x6 microelectrodes

Fluidic perfusion and drug delivery

through the chamber View of microfluidic chamber from top and side

P. A. Passeraub, A. C. Almeida, N. V. Thakor, "Design, microfabrication and characterization of a microfluidic chamber for the perfusion of brain tissue slices," Biomedical Microdevices, vol. 5,
pp. 147-155, June, 2003.
 Neurochemical Sensor:
Microelectrode

Figure 1. (a) Design of a carbon fiber electrode for neurotransmitter, NO, measurements. The
membranes Nafion and the polymers mPD and Resorcinol provide selectivity against ascorbate,
nitrites and other confounding chemicals. b) Calibration (upper right) and sensitivity/selectivity
test of the NO electrode. (bottom right)
J. K. Park, A. Bandyopadhyay
 Screen-printed C electrode arrays

Screen printed carbon neurotransmitter sensor arrays

George et al. used the screen printing of carbon ink to develop a grid of microsensors
for the sensing of neurotransmitters.
 Neurochemical Sensor:
Photolithographic Fabrication

200 µm
Fig. 2. Left:
Schematic of the
16-electrode sensor
array (2-x-2
(mm)2. Right:
Close-up of a
single site. The
sensor site was
200-x-200 (µm)2.
The connecting
wire was 50-µm
wide.

M. Naware, A. Rege, P. George

 Carbon Sensor Arrays on Glass

Fig: Electrode Pattern. The sensor array consists of 36 sensing sites

arranged in a 6-x-6 format. The figure on the right is a close up of the
central part of the grid which has the actual electrode points at the ends
of the individual traces. The large contacts are designed to interface
with flat cable ribbon.
Interfacing
with Brain
 Neural Microelectrodes

Flat array of micro Pyramidal shaped

electrode for in- microelectrode for
vivo application in-vivo application Simple, triple and multiple
shank electrode for in-vivo
application
 Cortical Recording/Stimulation

G. Kovacs, Integrated circuits lab, Stanford Univ.

Center for Neural comm. Tech., Univ. of Michigan,
Ann Arbor.
Implantable probe with
integrated VLSI
potentiostat and
electrochemical sensors.
P. A. Passeraub, A. C. Almeida, N. V. Thakor, "Design,
microfabrication and characterization of a microfluidic chamber for the
perfusion of brain tissue slices," Biomedical Microdevices, vol. 5, pp.
147-155, June, 2003.

High density comb

shaped metal
microelectrode.
U. H. Balbale, J. E. Huggins, S. L. BeMent, S. P. Levine,
“Multi-channel analysis of human event-related cortical
potentials for the development of a direct brain interface”, vol.
1, pp 13-16, 1999.
 Ceramic - based In Vivo Implantation
Multisite Electrode and Recording

A. 200µm
B. C.
200 µm
Courtesy K. Moxon
200 µm

Multisite recording from barrel cortex

 Cortical Microelectrodes
Implantable Silicon
micromachined electrodes
to stimulate the cortex.

PJ Rousche , RA Norman, “Chronic intracortical microstimulation

(ICMS) of cat sensory cortex using Uthan intracortical electrode array”,
Rehabilitation Engineering, IEEE Transactions, vol 7, pp. 56-68

High density
electrode array for
recording.
(http://www.eecs.umich.edu/~wise/R
esearch/Overview/Wise_Research.pd
f)
 Neural Probe for Drug
Delivery
Micromachined drug
delivery probe with
channels for drug
delivery and electrodes
for stimulating

Cross section of drug delivery channel

J. Chen, K.D. Wise, JF Hetke, Jr SCB (1997a), “A multichannel neural probe for selective chemical delivery at the cellular level”, Biomedical Engineering IEEE Transactions, pp 760-769.
 MEMS Probe
Microelectrode Actuator
A

SEM of gear assembly –

rotational to linear motion.
(Sandia Labs, NM)

J. Muthuswamy (ASU) and M. Okandan (Sandia)

SEM of an output gear

 MEMS Microprobe for
Brain Tissue Penetration
Successful penetration cortex
with dura pierced microprobe

100 µ 120 µ 140 µ

2.5 m 2.5 m
2.5 m
1 2
10 msec 1
1
0.0 0.0 0.0

-2.5 -2.5 -2.5

microprobe 300 µ
-5.0 V -5.0 -5.0
Integrated
VLSI Circuits
and Systems
Neurochemical Measurement
• For electrical recording -> you need an amplifier…
takes mV signal -> makes it bigger => amplifiers
are used in electrical recording…from
microelectrode amplifiers to EEG amplifiers

• For chemical recording -> you need an

electrochemical sensor/amplifier called a
potentiostat -> Potentiostat is a circuit that applies
a voltage to the electrode to drive
oxidation/reduction (redox) reaction -> redox
reaction gives an estimate of the chemical
activity/concentration => Potentiostat and
chemical electrodes are used for neurotransmitter
measurements
 Neural Chips &
Very Large Scale Integrated (VLSI) Circuit
Potentiostat

VLSI Potentiostat

Hippocampal
slice chamber

Nitric oxide (NO)

sensor array for
electrochemical neural From K. Murari, G
recording Cauwenberghs, N.
Thakor
 VLSI Potentiostat for
Neurotransmitter Sensing

Envisioned implantable probe with

integrated VLSI potentiostat and
electrochemical sensor

Setup showing the potentiostat chip acquiring

8 channel real time neurotransmitter
measurements with sensor array.

K. Murari, M. Stanacevic, G. Cauwenberghs, N. Thakor, “Wide-Range, Picoampere-sensitivity Multichannel VLSI potentiostat for
Neurotransmitter sensing” IEEE/Eng Med Biol Soc, San Fransisco, 2004, in press.
 Neurochemical Sensing and
VLSI Potentiostat Interface

Block diagram of integrated track and hold potentiostat.

Chip micrograph of the 16 channel

integrated track and hold potentiostat.
200 µ
m

M. Naware, A. Rege, R. Genov, M. Stanacevic, Cauwenberghs, N. Thakor,

“Integrated Multi-electrode Fluidic Nitric-oxide sensor and VLSI Potentiostat array”, IEEE Symposium on Circuits and Systems, Canada, 23-26 May 2004.
 Power Harvesting and
Telemetry in Implanted devices

Wireless power harvesting and

telemetry chip, operates without
batteries.
RF power harvesting through
inductive coupling for power
gathering. Also used to send data
back to base station creating
two-way link.

Christian Sauer, Milutin Stanacevic, Gert Cauwenberghs and Nitish Thakor,“Power harvesting and telemetry in CMOS Implanted devices”
 Neural
Microdrive
Mechanisms
 Micro-actuators in
Neurophysiology
Coronal section of adult rat
Rt—Reticular brain showing 4 microelectrodes
thalamus positioned (5-7 mm deep) in the
reticular thalamic nuclei at
different depths. The size of the
microdrive chip is expected to be
approximately 4 mmx 7mm.

microelectrodes

Upper
layer VI
pyramid
The schematic of two microelectrodes RT
superimposed over a biocytin tracing of
intrathalamic axonal arborizations. (Biocytin VPM
tracing from Bourassa et al., 1995).
200µm
Overview of the design
Photograph of completed microdrive before
implant
 Motor Drive
• Excellent design by Cham[13]
– Design similar to Fee[12]
– Piezoelectric actuators used instead of
DC motors
– Chamber (hollow plastic cylinder) exist
for protection of the electrode assembly
– One end of electrodes attached to brass
brushings by set screws, other end to
the motor assembly
– Guide tubes are 500um apart
– Vertical positioner adjusts the position of
motor
– Pt-Ir microwires are sharperned and
glass coated at the tip
– Actuators are operated with a saw tooth
voltage signal.
– final implant weighted 40g and
implanted in rat.
Schematic of the design
Motor and loading of electrode
 Electro-static microactuator
Principle
(1) d
Rotational motion
y
(2) V y-drive
x
(3) A
Link-
arms
B

Support x-drive
spring
SEM of gear assembly –
rotational to linear motion.
Left Right
(Sandia Labs, NM)
bank 1 bank 1

Shuttle Spring anchor

Right
Left
bank 2
bank 2

Ground SEM of an output gear

Plane
 MEMS Microprobe for
Brain Tissue Penetration
Successful penetration cortex
with dura pierced microprobe

100 µ 120 µ 140 µ

2.5 m 2.5 m
2.5 m
1 2
10 msec 1
1
0.0 0.0 0.0

-2.5 -2.5 -2.5

microprobe 300 µ
-5.0 V -5.0 -5.0
Result
 Result

• Impedance of the wires was between 100-150KOhms at 1Khz.

• Out of 20 channels on the microwire array 3 channels gave very good
recordings
• Normally only 1/5th of total number of channels are good(14).
• 3-D scatter plot (below) shows that spikes were recorded from 3 neurons
Neurochemical
Measurements
 Electrochemical Sensor

• Suitable for detection of neurotransmitters, chemical Gold Connector

agents (e.g. NO)
Copper Wire
• A: 100M ascorbate, B: 20M dopamine, C: 100M
nitrite, D: NO added in step increments of 2M. Glass micropipette

8
Non-conducting
Calibration with NO Epoxy
6
Current (nA)

Carbon fiber
4
D
2 A A B C C mPD/ R polymer
Nafion
0 Carbon fiber
150 250 350 450
Time (sec)
Screen Printed Sensor Array
(a)

(d)
(c)

60 µm (b)

30 µm

0 µm
1 mm

4 mm

Screen-printed Carbon microsensor array. Top: A 4 inch quartz wafer after

screen printing has been completed, bottom: image of diced carbon electrodes
before packaging, left: profilometer scan of one row of the carbon electrode
showing a height of 60µm, and right: SEM picture of single carbon electrode site.
 Integrated Instrumentation

Carbon fiber Microsensor

VLSI potentiostat
 Stand Alone Chem-Bio System
Neurotransmitter Electrodes

Gold contacts
Bond wires
Chip with telemetry
circuitry

Telemetry link
for power/ data

Only four bond shown for clarity

Inductor coil not shown for clarity
 Implantable Devices:
Prosthetics and
Functional Stimulation
 IMPLANTABLE DEVICES
• Device surgically placed in the body and left there.
• Issues
• Biocompatibility
• Power source
• Safety – leakage current etc.
• Risks from environment EM fields – MRI, airport X-Ray
• Why ?
• Many conditions require continuous monitering and the
action taken depends on that. Implantable devices can
achive this without loss of mobility.
 IMPLANTABLE CARDIAC
DEVICES

• Recall last lecture’s implantable cardiac assist devices

–
• defibrillators, pacemakers, cardioverters etc.
 IMPLANTABLE NEURAL
DEVICES
MEDTRONIC DEEPBRAIN STIMULATOR FOR PARKINSONS
DISEASE

www.medtronic.com
www.cyberonic.com
DEEP BRAIN STIMULATION
• Components
• Implantable
• Neurostimulators: A pacemaker-like device that
contains a battery and microelectronic circuitry for
controlled electrical pulse generation. Implanted
near the clavicle.
• DBSTM Electrodes: Four thin, insulated, coiled
wires bundled within polyurethane insulation. Each
wire ends in a 1.5 mm electrode, resulting in four
electrodes at the tip of the lead. DBS Leads are
implanted bilaterally in the brain

• Extension: The subcutaneous connection between

the above.
DEEP BRAIN STIMULATION
• Components
• For patient use
• Therapy controller: A patient places the compact,
handheld therapy controller over the neurostimulator
and presses buttons to turn the neurostimulator ON
and OFF.

• For clinician use

• Physician Programmer: The clinician uses the
Physician Programmer to adjust the stimulation
parameters noninvasively via telemetry.
 IMPLANTABLE SPINAL
STIMULATOR
SpF® IMPLANTABLE SPINAL FUSION STIMULATOR SYSTEM

• direct current stimulation improving the rate of

successful post-operative spinal fusions.

Details at http://www.spineuniverse.com/displayarticle.php/article2096.html
 COCHLEAR IMPLANT
NUCLEUS® 3 COCHLEAR IMPLANT SYSTEM
1. Sound is picked up by a directional
microphone.
2. Sound is sent from the microphone to
the speech processor.
3. The speech processor analyzes and
digitizes the sound into coded signals.
4. Coded signals are sent to the
transmitter via radio frequency.
5. The transmitter sends the code across the skin to the internal implant.
6. The internal implant converts the code to electrical signals.
7. The signals are sent to the electrodes to stimulate the remaining nerve
fibers.
8. The signals are recognized as sounds by the brain, producing a
hearing sensation.
Details at http://www.cochlear.com/
RETINAL IMPLANT
A SILICON RETINA FOR
RESTORING VISION

LIGHT → VIDEO CAMERA →

FOCUSSED ONTO SILICON VLSI
CHIP → LIGHT CONVERTED TO
ELECTRICAL SIGNALS →
TRANSFERRED ONTO OPTIC
NERVE.

Details at http://www.2-sight.com
 IMPLANTED PILL: BION

• TELEMETRICALLY
CONTROLLED.
• CAPABLE OF SEVERAL
FUBCTIONS
• SELECTIVE FUNCTIONAL
STIMULATION
• DIAGNOSTIC READOUTS FROM WITHIN THE BODY

Details at http://www.advancedbionics.com/products/bion.html
Brain-Machine
Interface
BRAIN COMPUTER INTERFACE
• Brain talks to a computer !!!!
• a computer can learn what the brain is doing or going to do.
• brain can accept the command from computer.

• Goals
• To provide a way for people with damaged sensory/motor
functions to use their brain to control artificial devices and
restore lost capabilities.
• To train and control the animal to behave according to
human's command.
CASE STUDY: QUADRUPLEGIC
COMMUNICATOR
THE PROBLEM

• Quadriplegics are limited in their motion and require

some device to help them communicate with the
world.
• Our device caters to those people who cannot move
their body from and including the neck downwards.
They cannot even speak or move their head about
their neck.
• The device will take inputs from such people and
convert them to text which will be output on the
computer screen.
CASE STUDY: QUADRUPLEGIC
COMMUNICATOR
THE QUEST FOR INPUTS
• Blinking of the Eyes • Eyeball tracking
It is very possible to tap This is very complicated to
this input except for stray implement and very costly to
signals due to regular
blinking. realize. Also, a lot of stray
signals will be introduced by
mere distractions.
• Sip and Puff
Though the quadriplegic
cannot move his head, he • EOG Inputs
can blow into or suck from
a pipe kept very near his Mr. Murphy whispered in my
mouth. This input is more ear -- “Delicate signals should
reliable. never be relied on”.

CHOICE: Sip & Puff and Blinking

 CASE STUDY: QUADRUPLEGIC
COMMUNICATOR
THE CONTRADICTION
Five Inputs in all.
1. Right Eye Closed 2. Left Eye Closed 3. Both Eyes Closed
4. Sipping action 5. Puffing Action

Minimum Forty input characters in all.

a) 26 alphabets b) 10 digits c) misc. characters (del etc)

A contradiction !!!

SOLUTION
Generate an on-screen keyboard and use inputs to navigate the on-screen
keyboard. Thus, a grid of characters was formed and the following navigational
controls were assigned.

1. Right Eye Closed = Move Right 2. Left Eye Closed = Move Left
3. Puff = Move Down 4. Sip = Delete 5. Both Eye Closed = Select
 CASE STUDY: QUADRUPLEGIC
COMMUNICATOR

Right Eye

Parallel Port Interface Connector

Blink Sensor
Comparator
(IR sensor)
Screen
Electronic Circuitry

Left Eye
Blink Sensor Comparator
(IR sensor)
CPU

Sip
Sip and Puff Comparator
Pressure Sensor
Puff
CASE STUDY: QUADRUPLEGIC
COMMUNICATOR
CASE STUDY: QUADRUPLEGIC
COMMUNICATOR
Brain-Computer
Brain-Machine
Interface
J.R. Wolpaw et al. 2002

BCI (BMI) bypasses the brain’s normal pathways of peripheral nerves and muscles
Motivation for BCI/BMI Research
rebuilding instead of repairing

In USA, more than 200,000 patients

live with the motor sequelae
(consequences) of serious injury.
There are two ways to help them
restore some motor function:
• Repair the damaged nerve axons
• Build neuroprosthetic device

Not a natural way, but a imitation Nicolelis, 2001

Coarse(mm)

http://ida.first.fhg.de/projects/bci/bbci_official/
EEG based BCI (Brain Computer Interface)

• non-invasive
• promising for some therapies
• time-consuming
• not suitable for precise control
Mussa-Ivaldi & Miller, 2003
Neuron Spike based BMI (Brain Machine Interface)

• high speed real time control

• precise control of movement
• invasive
• high risk for clinical application

Nicolelis, 2001
 Trends in BCI/BMI research

 From binary decision to 3-D control

 From open-loop to close-loop control
 From laboratory test to clinical trial
Trend 1 : From binary decision to 3-D control

ECoG based BCI Video

Donchin, 1988, 2000 Leuthardt et al.,2004

 2D/3D movement control Donoghue et al, 2002,
Schwartz et al.,2002

2D movement control 3D movement control

Question: Is it possible to make it on human subject?

www.cybekinetics.com …. John Donoghue (Neurosci) at Brown University
Trend 2: From open-loop to close-loop

half of the story…

• Brain to Action
• Sensation to Brain

Question: Is it possible to realize a two-way BCI/BMI?

Trend 3: From laboratory test to clinical trial
 Acute ensemble recordings
 Subthalamic nucleus and
thalamic motor areas
 11 awake patients
 During deep brain stimulator
surgery
 32 platinum-iridium microwire
array
 Visual feedback hand-gripping
force task.
 Offline analysis

Parag G. Patil et al (Duke BMI group) , Neurosurgery 55(1), July 2004

FDA approval for brain implant

Cyberkinetics Inc. Neural Signals Inc.

 from trend to opportunity:
Possible directions of current BCI research
• Toward clinical applications: make a
tradeoff between invasiveness and
performance

• Toward two-way BCI/BMI: combine

movement control and sensory feedback
together for a complete story
Our current BCI research

• Brain2Brain Communication
Project
Toward two-way BCI/BMI

• ECoG based gamma BCI project

Toward clinical trials
(collaborating with Dr. Nathan Crone)
Brain to Brain Communication Project

• To extend BCI/BMI to a prototype of

brain-to-brain communication
• To improve the communication speed of
current BCI/BMIs
• To expand the understanding of input
and output channels of brain

we are exploring the possibility of establishing a

direct brain-to-brain communication channel,
which may be a pilot work of two-way prosthesis of
the brain function.
Rat navigation guided by remote
control
Chapin et al., Nature, 2002
 Forward training
 Left and Right cueing
Robotic rat remotely guided by human brain
Human intentions of remote control (carried on EEG signal) are sent
wirelessly to a receiver and stimulator implanted in the rat brain. The scene
will be that you remotely control a rat's motion by your brain directly.
Motion Tracking Device

CCD camera

SCREEN

EEG Amplifier

X-Y coordinates of rat

Maze

Stimulus Command
 Subsystems of the project
• Human EEG recording
– Electrodes (where, how many, holding cap)
– Amplifier (IBT or BioSemi, USB interface)
– Recording software (Labview)
• BCI software
– Visual feedback and stimulation (with rat motion on the screen)
– Command translation from EEG
– BCI paradigm for real time control (SSVEP or Motor imagining)
• Wireless micro-stimulator
– Transmitter and receiver pair (Bluetooth)
– Microprocessor to produce bipolar stimulation (TTL pulse train)
• Rat model
– Animal use/care protocol;
– Electrode implantation
– MFB reinforcement training
• Video motion tracking
– Rat motion tracking (to plot the route)
– Derivation of movement direction for proper MFB stimulation
– Real time target display for visual feedback of human
Wireless micro-stimulator
6

­2

­4

­6
­140 ­120 ­100 ­80 ­60 ­40 ­20 0
Rat model
• Medial Forebrain Bundle
3.0-4.8 mm posterior to bregma,
0.7-1.6 mm lateral, 8.3-8.4 mm
below the skull surface
• Wisker Barrel Field
3.0 mm posterior, 5.5mm lateral,
0.5mm below the cortex surface

PlasticsOne electrode
Implanting surgery
Shanbao Tong Ph.D and Homayoun Mozaffari, M.D.
Video Motion Tracking
Human EEG recording and BCI software
Key points of technique
• Speed compatibility between rat motion
and human mind control
• Position accuracy of micro-electrode
implantation
• Efficiency of wireless micro-stimulator
How to speed up EEG translation?
SSVEP solution

fL
fR

make fL and fR as apart as possible

How to speed up EEG translation?
Motor Related Potential solution

lateralized readiness potential (LRP).

Motor imagery
Signal processing methods
(Time-Frequency domain)

• FFT
• Subband entropy
• Bandpass filtering + AR modeling
(use reflective coefficient ki instead of ai
because k vectors are orthogonal to each
other )
ECoG based gamma BCI project

• ECoG has higher spatial resolution than EEG

• Broader bandwidth than EEG (0–200 Hz versus 0–40
Hz. So gamma BCI is possible)
• Higher amplitude (50–100 µV maximum versus 10–20 µV)
• Far less vulnerability to artifacts such as EMG
• Likely to have greater long-term stability and
might be safer than single-neuron recording
ECoG based gamma BCI
 BCI is becoming a big wave

140
127
120
100
80
60 SCI paper
48
40
20
2 4
0
1985- 1991- 1996- 2001-
1990 1995 2000 2004
What is Neurorobotics?

The ability create a

direct interface
between the brain
and an external
device in real-time
 Neurorobotics: Neural Control of External Device

1. rat initially trained

to press a bar to
retrieve a water
reward using a 4. controller
robot
robot arm (a-f) arm switched
so that command
controller
signal controls
robot arm (j)
2. neural signals
from single
neurons
recorded (g)
3. neural signals combined into a command
signal to control robot arm (h-i)
Chapin JK Moxon KA et al. Nature Neuroscience 2(7), 1999
Role of Neurorobotics in Spinal Injury

A spinal injury is also a brain

injury
Neurons located throughout the brain send their axons
downs the spinal cord.

The injury can damage and sever these axons.

Cells in the brain will atrophy and some will die.

Role of Neurorobotics in Spinal Injury

Neuronal
Population
A spinal injury is Recordings

also a brain injury

Neurons located throughout the
brain send their axons downs the spinal
Sensory
spinal cord. prosthesis
prosthesis
controllor
The injury can damage and sever
these axons.

Cells in the brain will atrophy and

some will die.
FES
Role of Neurorobotics in Spinal Injury
A spinal injury is
also a brain injury
Neurons located throughout the
brain send their axons downs the
spinal cord.
The injury can damage and sever
these axons.
Cells in the brain will atrophy and
some will die.
Neurorobotics can be used as
a method for assessing
brain function in the
absence of normal
sensorimotor function
3. Quantitatively measure the loss of
passive sensory input and motor
output
4. Use neurorobotics to address the
‘functional’ capacity of the
surviving brain circuits
 Outline

Part 1 Hardware Development

• Electrodes
• VLSI and Telemetry

Part 2 Neural Recordings

• Before and After Spinal Injury

Part 3 Neurorobotic Interface

• Algorithms for neurorobotic control
• Before and After Spinal Injury
Neurorobotics: Hardware Development:
Electrodes
 Thin Film Multisite Electrode Designs

• Wise, K.D., Angell, J.B., Starr, A., An integrated-circuit approach to

extracellular microelectrodes, IEEE Trans. Biomed., Eng., 17(3), 1970

• Blum, N.A., Carkhuff, B.G., Charles, H.K., Edwards, R.L., Meyer,

R.A., Multisite microprobes for neural recordings, IEEE Trans. on
Biomedical Engineering, 38(1), 68, 1991

• Prohaska, O.J. Thin-film multiple electrode proes; Possibilities and

limitations, IEEE Trans. Biomed. Eng. 33, 223, 1986

• Eichman, H., Kuperstein, M., Extracellular neural recording with

multichannel microelectrodes, J. Electrophysiol. Tech., 13, 189, 1986

• Maynard, E.M., Nordhausen, C.T., Normann, R.A., The Utah

intracortical electrode array: a recording structure for potential brain-
computer interfaces, Electroencephalogr. Clin. Neurophysiol., 102, 228,
1997.
Multisite Electrode Designs

• Wise, K.D., Angell, J.B., Starr, A., An

Design Consideration
integrated-circuit approach to extracellular
microelectrodes, IEEE Trans. Biomed., Eng., 17(3), • Precise inter-site distances
1970
• Blum, N.A., Carkhuff, B.G., Charles,
H.K., Edwards, R.L., Meyer, R.A., Multisite • Easily modifiable inter-site distances
microprobes for neural recordings, IEEE Trans. on
Biomedical Engineering, 38(1), 68, 1991
• Chronic recordings
• Prohaska, O.J. Thin-film multiple electrode
proes; Possibilities and limitations, IEEE Trans. Biomed.
Eng. 33, 223, 1986 • Ability to reach deep structures
• Eichman, H., Kuperstein, M., Extracellular
neural recording with multichannel microelectrodes,
J. Electrophysiol. Tech., 13, 189, 1986
• Maynard, E.M., Nordhausen, C.T.,
Normann, R.A., The Utah intracortical electrode
array: a recording structure for potential brain-
computer interfaces, Electroencephalogr. Clin.
Neurophysiol., 102, 228, 1997.
Multisite Electrode Designs

• Wise, K.D., Angell, J.B., Starr, A., An

Design Consideration
integrated-circuit approach to extracellular
microelectrodes, IEEE Trans. Biomed., Eng., 17(3), • Precise inter-site distances
1970
• Blum, N.A., Carkhuff, B.G., Charles,
H.K., Edwards, R.L., Meyer, R.A., Multisite • Easily modifiable inter-site distances
microprobes for neural recordings, IEEE Trans. on
Biomedical Engineering, 38(1), 68, 1991
• Chronic recordings
• Prohaska, O.J. Thin-film multiple electrode
proes; Possibilities and limitations, IEEE Trans. Biomed.
Eng. 33, 223, 1986 • Ability to reach deep structures
• Eichman, H., Kuperstein, M., Extracellular
neural recording with multichannel microelectrodes,
J. Electrophysiol. Tech., 13, 189, 1986 • Multifunctional
• Maynard, E.M., Nordhausen, C.T., •Single neuron electrophysiology
Normann, R.A., The Utah intracortical electrode •Microstimulation
array: a recording structure for potential brain- •On-board electronics
computer interfaces, Electroencephalogr. Clin.
Neurophysiol., 102, 228, 1997. •Electrochemistry
 Design Ceramic Based Multisite Electrode (CBMSE)

bonding pads

conducting
lines

recording
sites

Moxon, Leiser, Gerhardt, Barbee, Chapin,IEEE Transaction on Biomedical Engineering, in press

Ion Beam Assisted Deposition of Alumina

Substrate

+ +
+
+
+ +
Mixed
+
+ +
Interface Zone
+
+
+ Coating

+
+ Interactive
+ Site +
+
+
Energetic Ions
Coating Atoms Substrate (s) Substrate Holder
Vacuum
Chamber

Energized
Ions
Evaporated
Alumina
Ion Source
Evaporator
Scanning
Electron
Micrographs
1.

A.
A.
B.
B.
C.
C.
2. 3.
Ceramic –based Multisite Electrode
In-vivo Implantation
 A. 24 hours Post Surgery B. 3 weeks Post Surgery

site1

site2

site3

site4
 Recordings from Single Cortical Barrel

Whisker C2 Cytochrome oxidase is an enzyme used in metabolism

 Recordings from Single Cortical Barrel

A. B. C.

200µm

200 µm

200 µm
 Neurorobotics: Part 1 Hardware Development:
VLSI Development

Input 1

OUT1
BIAS
Hybrid Circuit Neural Control Device

VDD
VSS

VSS
electrode subassembly PC Board
16 channel µ-probe

R1

variable
spacing

C1 VSS

C2 VDD

ground

OUT16
VDD
VSS

VDD
Input 16

ACG
Obeid, I. M., Morizio, J.C., Moxon, K.A., Nicolelis, M.A.L. Wolf, P.D. , IEEE Transaction on
Biomedical Engineering, 2002
 Hybrid Circuit Neural Control Device

Design Schematic Design Layout

Hybrid Circuit Neural Control Device
 Control of Rat Movement using CMBSE

left stimulus right stimulus

left turn right turn
MFB reward MFB reward

elevated platform
 Future Directions

• Combine single neuron recording with telemetry

system

• Improve biocompatibility: modify the surface with

nanostructured matrices to deliver bioactive
molecules that can reduce glial scarring

• Coat surface with a layer of carbon for simultaneous

electrochemistry and electrophysiological recording