Cortical Spinal Stimulation in Nonhuman Primates

Tyler Maxeld
Eberhard Fetz Research Group
December 13, 2013
Abstract
Millions of Americans experience inhibited motor function due to neural damage
caused by stroke and spinal cord injuries. The Fetz Laboratory has developed meth-
ods to stimulate neurons based on current neural activity at other sites. They use
recurrent brain computer interfaces to record neural activity at one location and use
the information to logically dictate stimulation at another location. This has been
shown to be useful in strengthening neural connections and has been hypothesized to
be helpful for patients who have experienced neural damage that results in a decrease
in motor function. However a limiting factor for correlation to humans is the longevity
of electrodes and the delity of the signal recorded. My project focuses on monitoring
cortical electrodes, post implant, and characterizing the electrochemical changes. I am
adjunctly working on creating a spinal cord electrode array for use with the Neurochip
series.
1
Contents
1 Background and Signicance 3
1.1 Signicance . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3
1.2 Innovation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3
1.2.1 Preliminary Data . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4
1.3 Impact . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6
1.3.1 Consequences of success . . . . . . . . . . . . . . . . . . . . . . . . . 6
1.3.2 Ethical and Social Issues . . . . . . . . . . . . . . . . . . . . . . . . . 6
1.3.3 Economic Issues . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7
1.4 Legal and Regulatory Issues . . . . . . . . . . . . . . . . . . . . . . . . . . . 7
2 Plan of Work 8
2.1 Specic Phases of Project . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8
2.1.1 Phase I . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8
2.1.2 Phase II . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8
2.1.3 Phase III . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8
2.2 Design Strategy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9
2.2.1 Phase I . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9
2.2.2 Phase II . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11
2.2.3 Phase III . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13
2.3 Key Personel . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14
2.4 Equipment, Facilities and Resources . . . . . . . . . . . . . . . . . . . . . . 14
3 Appendix 14
3.1 Gantt Chart . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14
3.2 Request for Proposal . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14
3.3 Concept Sheet . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14
2
1 Background and Signicance
1.1 Signicance
Over 2.9 million Americans suer from debilitating eects due to a stroke or traumatic
brain or spinal injury.[1] After such injuries, many patients lose the ability to control part
of their body because the neurons in the brain that initiate movement and those respon-
sible for actual muscle contraction are either no longer connected, or diminished in their
connectivity. The Neurochip (NC) is a recurrent brain computer interface (r-BCI) that
allows for real-time recording and stimulation of neural cells and is small enough to be
encased in a housing attached to the monkeys head. This self contained design allows for
it to be used during free behavior, that is while the monkey is not restrained and connected
to an external computer.
This technology provides a valuable tool for the reorganization of neural connections af-
ter a traumatic brain injury. However, the translatability into humans is limited by the
longevity of such a device and the delity of the signals recorded. Over time, the signals
recorded from monkeys degrade, eventually reaching the point that the signal is no longer
able to be reliably detected. The mechanism of this signal degradation is the focal point
for several research projects. If any chronic neuroprosthetic device is to be implemented
in humans, the lifetime of the implant would need to be at least ve to ten years.
1.2 Innovation
Currently, there are no cures for paralysis and the focus is on helping the patient adapt
to daily life in order to live as independently as possible. The science of neuroprosthetics
uses the idea that a signal can be recorded from the brain and used to control a prosthetic
limb. Other BCIs use neural mapping to try to decode what the brain is intending to
do.[9] In a study done by Tan, H. G. et al. they used the neural mapping of patients to
relay control signals to a bionic prosthetic. This approach is costly, time consuming, and
has thus far been ineective as a means for mass application. It relies on the ability to
accurately record ring patterns of the brain on a large scale and an understanding of what
the pattern actually means in regards to movement. This also requires calibration of the
neuroprosthetic to each individual patient.[9] It also demands substantial computational
power in order to map and decode brain activity in real time. In contrast, the NC is
a low-power, low-computation, real time device that records volitional neural activity in
localized regions. This bypasses the need to decode the overall activity of the brain in
regards to imagined movement.
Furthermore, other approaches focus on using BCIs to control bionic limbs. While this
is useful for patients who have lost a limb, it is not particularly benecial to those who
suer from paralysis unless they opt for limb replacement. Otherwise, state of the art
3
treatment has been focused on functional electrical stimulation (FES) of muscles. This
technique relies on external electrodes to deliver a stimulus to contract muscles. Current
FES systems are in place as methods of exercise and muscle rehabilitation.[6] Due to lim-
itations on amount of stimulus without causing tissue damage, they require the user to
manually switch electrodes in order to target dierent muscle groups. These systems are
also not very specic for the muscle group they target, which can cause other, nearby groups
to contract.[6] And because the electrode is stimulating motor neurons from outside of the
body and not upstream of the motor neurons, full use of the muscle group is not obtained
and the motor units are stimulated in the reverse order of the natural pathway.[6] This
means that ne control of movement can not be obtained because the large, power-stroke
motor units are activated at lower electrical threshold than the small, ne control units.
Lastly, most studies mentioned have been short-term, bypassing the problems associated
with electrode and signal delity decay. The NC is an alternative in that it allows for
long-term studies to be accomplished during free behavior. Without the NC3 and its
predecessors, recording and stimulation of neurons is done while the monkey is seated
into a special chair with many wire leads connecting to an external computer. This con-
strains movement signicantly and does not allow for data collection during free behavior.
The Neurochip sits in a special housing on the top of the monkeys head and allows for
autonomous, real time data collection and stimulation of neurons during days of free, un-
restricted behavior in non-human primates (NHP).[4]
By studying the electrochemical changes in the electrodes over time, in relation to stimu-
lation events, I will be able to characterize the degradation prole of the electrodes as well
as gain an understanding of some of the biological and mechanical reasons for the changes.
1.2.1 Preliminary Data
The Fetz Laboratory has shown that monkeys are able to volitionally control single neuron
ring rates in order to control wrist exion.[7] The NC works by recording the ring pattern
of individual cells, or groups of cells, and making logic decisions based on the frequency of
ring. The cells being recorded are able to be volitionally controlled by the monkey. Those
logic decisions dictate how, where and if stimulation will occur.[4]
As of now, the Fetz Laboratory has focused on the intra-brain applications of the NC2
and NC3 as well as brain muscle control. For intra-brain interactions, it has been shown
that a single recording channel of the NC2 can be used to deliver stimuli at another site
when the recording neuron res action potentials above a certain frequency. This articial
connection between recording site and stimulation site causes the natural neural pathway
between the two to be strengthened, even days after stimulation has ceased.[5] This eect,
known as Hebbian plasticity, has been theorized to be useful for victims of stroke and could
aid in the strengthening of synaptic connections.
4
Figure 1: a, The schematic shows a non-human primate with a peripheral nerve block.
Activity of the cortical cell is converted into FES b, In this example, the paralyzed wrist
extensors are controlled by FES. Extensor (red shading) and centre (grey shading) wrist
torque targets were randomly presented on a computer monitor before the monkey. Mon-
keys learned to control cell ring rate in order to control muscle stimulation. Propor-
tionality of muscle stimulation was determined by how far above threshold the amplitude
was. Here pps indicates pulses per second. c, Histograms of cell rates while acquiring
targets, both extensor and centre. Shading indicates the period the target was held and
the horizontal line is the baseline cell rate.[7]
Work has also been done showing that Macaca nemestrina monkeys can be trained to
control the activity of neurons in the motor cortex in order to directly control stimulation
of muscles in the arm, restoring goal-directed movement in an arm that has been paralyzed
(Figure 1).[7] Furthermore, it is not necessary for the neurons being recorded to have been
previously associated with the specic movement desired. In fact, if the neuron was previ-
ously associated with another movement, such as exion of the ankle, operant conditioning
will allow the cell to be used for controlling arm muscles.[7]
5
1.3 Impact
1.3.1 Consequences of success
If my project is successful, it will have great impact, helping to bridge the gap between
electrical implants and the human body. It will yield new information and designs that
will lead to the advancement in the technologies that will one day allow those who suer
from paralysis due to a failed neural pathway to regain control of their currently useless
limb. After surgical implantation, the electrode would be used for both stimulation and
recording. The degradation rate of the stimulus channels, in relation to the magnitude
of the evoked responses would be determined to test for longevity. Because the improved
electrode array will be able to work with the Neurochip, it will allow for more long term
data collection of neural responses to rBCIs. Also, because multiple operations on the same
site causes damage and thus limit the number of times those operations can be done on a
single monkey, my contribution to the design will increase the duration that the electrodes
can be used for testing. Furthermore, when looking ahead at possible applications of
rBCIs in humans with neural damage, one would expect the electrodes to last upwards of
a decade. My research and design focused on the creation of a long-lasting electrode array
will bring the medical industry one step closer toward this realization. Future iterations of
this design will serve to improve the electrodes specicity, number of neural connections
and longevity while maintaining the exibility necessary for functionality.
1.3.2 Ethical and Social Issues
Whenever using an animal model there are inherent ethical issues. For my research I will
be using Macaca nemestrina monkeys to test the electrochemical properties of cortical elec-
trodes. However, my research is relevant to the research that is being conducted by Brian
Mogen that uses these electrodes to study the eects of RBCIs in the monkeys. That is, no
monkey will be used solely for the purposes of my research. Furthermore, all tests done on
the primates will be reviewed by the appropriate animal care committee before being con-
ducted. This will insure that no unethical treatment is taking place. Non-human primates
are an important tool for the eld of neural research as human testing rightly follows much
more stringent protocols. In order to advance the eld it is necessary to use non-human
primate models. This research has and will continue to provide valuable information that
can be applied for the treatment of serious human conditions such as paralysis and stroke.
On another note, the Fetz Laboratory is showing that the connections between locations
in the brain can be strengthened and rerouted. This is important because the clinical
application of this technology will be to focus on rehabilitating those with motor impair-
ments due to a traumatic brain injury. A stroke in the motor cortex would no longer be
the severe impairment it is today. The research toward this goal is made easier by having
subjects that are able to be used for longer, saving time that is currently wasted training
each monkey before any experiments can be done. It also reduces the total number of
6
monkeys that will need to be used from experiment to experiment.
1.3.3 Economic Issues
Currently, surgical implantation of devices is expensive. However the NC and the elec-
trodes that are used with it are not overly complicated. The NC does not rely on massive
computation power or advanced processors to function. Instead, stimulation is controlled
by logic gates and recordings are processed using onboard functionality. Since no device
like this exists on the market as of yet, it is dicult to foresee the economic feasibility
of implementing this technology in patients. However, if this technology does reach the
clinic, there would be doctors and surgeons who are specialized in using this technology to
treat their patients. This would open up a new market. There are currently just under 3
million Americans living with some form of paralysis due to stroke or spinal cord injury.[1]
These patients are looking for a solution and this research promotes the realization of that
solution.
1.4 Legal and Regulatory Issues
When dealing with implants that connect to neural tissue there is always the risk of severe
damage. If this technology were to be implemented on humans, it would be vital that the
patients give consent to the procedures with full disclosure of the statistical risks they are
undertaking, weighted against the potential benets. Clearly, the technology is not yet
developed for clinical use.
It has yet to be determined if the FDA will approve such devices for purposes not related
to medical rehabilitation. Yet in the coming decades of neural engineering advancements
and progress in the eld of BCIs, I foresee this becoming an issue that will need to be
addressed. The research we are conducting is with the idea of helping those who have
had traumatic neural damage that decreases their motor functionality, a clear need for the
regulatory obstacles.
The University of Washington IACUC requires that I take several courses before being
allowed to work with monkeys. In particular, I participated in University of Washington
Animal Use Laws and Regulations training, had an Animal Use Medical screening, peti-
tioned to be added to the IACUC approved protocol, took animal handling and behavior
courses, as well as courses that taught me proper aseptic surgical procedure.
The Washington National Primate Research Center is overseen by the UW IACUC, and
the Oce of Laboratory Animal Welfare (OLAW). The standards of safety, animal use,
housing, and experimentation developed by the UW IACUC comply and in some cases
exceed the standards set by OLAW. This ensures that, upon OLAW inspection, we will be
certied again. Without this certication, NIH and NSF funding would be impossible to
7
renew.
2 Plan of Work
Over the next year, I will focus on
2.1 Specic Phases of Project
2.1.1 Phase I
My rst goal will be to study the both the biological and electrical factors that are leading
to the rapid degradation and subsequent ineectiveness of the current electrode design.
The current design uses a exible polymer, parylene, with platinum micro wires traced on
the surface. At the end of each micro wire is a circular platinum electrode or either 300m
or 500m, depending on the intended function (gure 2). A second exible polymer layer
is then placed on top of the rst layer to prevent electrical short circuiting. On this second
layer are small circular holes that correspond to the locations and sizes of the 18 electrodes.
The exibility of this electrode design is necessary for two reasons. First, the electrode array
is intended to be surgically implanted and wrapped around the dura of the monkeys spinal
cord. This involves making a dorsal incision and removing the dorsal spinous processes
of the target vertebrae.[8] The electrode must then be fed around the spinal cord and
securely connected. Second, during free behavior, the spinal cord moves vertically within
the vertebrae so it is needed that the design be robust to this expected, continued motion. I
will use the information that I gather during this phase to determine the leading biochemical
and electrical causes of the electrodes degradation.
2.1.2 Phase II
During this phase, I will use the information gathered during phase I to design workarounds
for the leading causes of electrode failure. As phase I is not yet completed it is dicult
to tell what phase II will entail. However, I can foresee this phase being focused either
on spatial design of the electrode surface, or surface coating of the electrode with certain
chemical buers or biochemical signaling molecules. This phase will also involve in vitro
testing of the electrode array designs, where designs will be tested for their feasibility of
manufacturing and longevity.
2.1.3 Phase III
Phase III will focus on the in vivo testing of the newly designed spinal electrode array
in non-human primates. This will involve the surgical implantation of a select few design
iterations into monkeys that have not previously had this surgery performed. After the
8
Figure 2: The current designs of the spinal stimulating electrode that will work adjunct
with the Neurochip. One of each design will be implanted into the monkey to test which
parylene shape is best suited for anchoring. On the right is the plug that will allow for
the electrode to be attached to leads connected to the neurochip or a large, xed controller
of recording and stimulation. The circles along the bottom of each are the electrodes I will
be testing.
recovery time, similar testing to phase I will be done on the electrodes in order to quantify
the eect of our design modications.
2.2 Design Strategy
2.2.1 Phase I
A monkey was implanted with a cortical array of 30 epidural and 30 intracortical electrodes.
Each epidural electrode is paired with an intracortical electrode such that the epidural lies
directly above the intracortical. Over several months a sub-population of these electrodes
were used by doctoral candidate, Brian Mogen, to stimulate and record. I will perform
electrochemical analysis of the dierent electrode channels, looking for dierences between
the channels used for stimulation and recording. I will also take measurements on stimulus
9
channels directly before and directly after stimulation cycles. Because there are specic
histological reactions that take place directly after surgery, resulting in changes in the elec-
trochemical interface between the electrode and the tissue, no measurements were taken
until 2 weeks after surgery.
In order to test the electrodes, I use two techniques, the rst is known as complex impedance
spectroscopy (CI). In this technique, a sinusoidal input voltage with an amplitude of 5 mV
is ranged from 50 Hz to 2 kHz, sampled at 12 points per decade frequency. Measurements
are made using a CH Instruments CHI750D Electrochemical Workstation. This provides
data on the impedance prole across multiple frequencies, which will change depending on
changes in the electrode and surrounding tissue. I measured the complex impedance of
each stimulating electrode each day that the monkey was brought in for electrical condi-
tioning.
To factor in the amount of stimulation a particular electrode has been used for, data
will be kept that monitors the number of stimulation events per electrode as well as du-
ration and current intensity of each stimulus. One of the potential problems that could
be leading to the electrode failure is the fact that large voltages are required to drive the
amount of current needed to activate the targeted neurons.
Another consideration for the cause of electrode degradation is the bodys response to
electrical stimulation. To monitor the compounds present on the surface of the electrode,
I will use the technique cyclic voltammery. In this procedure, voltage is ramped at a lin-
ear rate of 0.05 V/s between -0.6 and 0.8 V and the resulting current is measured. This
produces a current vs. voltage curve similar to the one shown in gure 4. Any chemical ox-
idation or reduction within this voltage range will have a unique current vs. voltage curve
and by searching for compounds that match the particular curves we acquire from our tests,
we can determine which molecules are present at the surface of the electrode as well as their
concentration. I will use this information to test the hypothesis that protein absorption on
the surface of the electrodes is responsible for changes in impedance. CV data will be taken
on each electrode prior to the start of stimulation conditioning experiments, as well as after.
From phase 1, I will be able to deliver a written report of my ndings that includes
possible causes of impedance changes. This will include the degradation prole of the plat-
inum electrodes in the form of electrode impedance since time of rst stimulation event.
In the report I will discuss the outcomes of each of my tests. I will discuss whether there is
biological degradation happening prior to rst stimulation, whether biological compounds
are contributing to the changes, and whether amount of stimulation is directly causing
impedance changes.
During this period, I will also be developing a suitable spinal electrode array design.
10
Figure 3: A cross section of a vertebra. The dura matter is separated from the spinal cord
by the subaracnoid space. This distance contributes to the necessarily high current used
to stimulate spinal neuron ring.[3]
The previous design is no longer producible. A complication with the equipment in the
lab that was producing the paralyene arrays resulted in an indenite delay in fabrication.
Therefore, the next generation of spinal array will be produced within our own lab.
The new design uses a ribbon cable layout of platinum-iridium micro wires, whose insulation
has been stripped in specic locations using a laser. The laser etching process will be
characterized during this phase in order to determine the correct intensity and number
of sweeps needed to remove the insulation and not damage the wire. Also, the physical
arrangement of the wires needs to be maintained after handling during surgery. The small
size of the wires and the method of connection needs to be taken into consideration in
order to develop a mechanically stable and surgically manipulatable electrode. In order to
test the eectiveness of the design, a trial surgery will be preformed on a monkey that is
scheduled to be euthanized.
2.2.2 Phase II
As mentioned, this phase will focus on applying the data collected during phase I in the
hopes of creating a longer lasting electrode array. By the end of the previous phase, I will
have data regarding the normal decay proles of the electrodes with respect to time and
number of stimulating events. I will also have data regarding the biochemical reactions
happening at the surface of the electrode and how those may be aecting the degradation.
I plan on using this collected data to rst brainstorm what I think are the major contribut-
ing factors to the electrode failure.
At this point, I will further think about the potential design changes that can be made
11
Figure 4: An example output from cyclic voltammery. This is the typical current-voltage
curve for ferricyanide/ferrocyanide.[2]
that will mitigate the largest contributors to degradation. I will redesign the cortical elec-
trode array with these changes in mind. This may involve learning how to fabricate the
components of the new design, including but not limited to learning SolidWorks, applying
biolms, or applying chemical coats to the electrode surface.
I will then test each of these design changes individually in vitro, possibly using culture
models of neurons. To test the eectiveness of my new designs ability to counteract the
biochemical aects that may have been found to contribute to degradation, I will use com-
plex impedance spectroscopy. This will be done by placing the old and new electrodes in
various concentration solutions of the compound in question and nding the degradation
prole over time, similar to how this was done in vivo in phase I. The goal is to create an
electrode that will be usable for both recording and stimulation for many months to years,
without deterioration. Based on my ndings about the eectiveness of my design changes,
I will either continue with the design change, continue with multiple design changes in
combination, or look to implement other options for design change. If I choose to continue
with multiple modications in combination, I may need to test the eectiveness of the com-
bination design using the same methods I used for testing each design change individually
From this phase, I should be able to deliver an electrode that has been shown, in vitro,
to resist degradation due to the contributing factors found in phase I. I will also be able
to deliver data regarding the in vitro testing of the electrode and how the new design
compares, in regards to longevity, to the old one. There is the potential that none of
12
my design modications will show statistically substantial eects on longevity of the elec-
trode. In this situation, I would go back to brainstorming and consulting with experts on
electrode design. I would consider implementing methods that I had previously rejected
and also try to think of potential modications that I had not thought of earlier. This
may involve online research into what other scientists have done and using whatever other
resources I have at my disposal, including but not limited to: faculty, peers, and textbooks.
I will also deliver a nal design of the new generation of spinal electrodes. These will
be implanted in the spine of a monkey between the C5 and T1 vertebrae, through which
stimulation and recording of specic neurons will be done. Over the course of about three
months, these electrodes will be used for research of doctoral candidate Brian Mogen. I
will use these electrodes to study the bodys reaction and the muscle responses evoked by
neural stimulation. In order to test whether there is a biological response to the implanted
electrode that is causing the rapid deterioration, some electrodes will be staggered in their
use as a stimulator. For example, several of the electrodes will be used for both recording
and stimulation as soon as the monkey has recovered and is ready for experiments. How-
ever, at this time, many others will be used only for recording. Recording causes negligible
current ow and has been shown to not cause problems with electrode longevity in the
past.
2.2.3 Phase III
This phase will focus on testing the deliverable from phase II, namely the newly designed
electrode arrays. In particular, the electrode array will be tested in non-human primates
in the same way I will be testing the current design during phase I. This will involve surgi-
cal implantation of the new electrode arrays, most likely multiple designs that each show
signicant potential for increased longevity. I will then conduct the same protocol as was
done for phase I to determine the degradation proles of the new designs. This will involve
using the techniques cyclic voltammography and complex impedance spectroscopy. For
information on how these tests will be conducted, see phase I.
The main deliverables from these new tests will be ecacy data regarding the theorized
increased longevity of my new design. This will include a report that will compare the
current design with the one I will help create from phase II. I will compare the complex
impedance spectroscopy data from phase I to that of phase III and use the inferences made
about the degradation proles to discuss the benets of the new design and how it relates
to the eld of neuroscience research and rBCIs.
Also similar to phase I is the fact that I do not foresee any signicant challenges in this
phase. At worst, I will nd that my design modications have no signicant eect on
electrode longevity. However, even that information is benecial as it provides valuable
13
information about what doesnt work, thus narrowing the list of possible changes that can
be made with the goal of increased electrode longevity.
2.3 Key Personel
This project will involve Eberhard Fetz, the primary investigator of the lab I will be working
in. His contribution and expertise has thus far increased my knowledge regarding rBCIs
tremendously. I hope to use him as a sounding board for ideas and as a resource when I
am stuck trying to solve problems in my design. I will also be working with Bioengineering
doctoral candidate Brian Mogen. His research has to do with the interaction of spinal
neurons and cortical brain cells when connected using rBCI technology. So far, he has
been an immense help in teaching me about dierent techniques used in the lab and I hope
to use him as my rst line of defense when I run into problems I can not solve on my own.
2.4 Equipment, Facilities and Resources
My work will be along side Brian Mogens work and I will be testing the electrode degra-
dation on the monkeys he will be using for his research. The project will take place at the
Washington National Primate Research Center (WNPRC), which houses all of the tools
I will need for evaluating the current electrode array design as well as future designs. If
all phases are completed, I will be using two separate monkeys for testing. However, I
am testing the degradation of electrodes, and those electrodes will already be in use for
Brian Mogens research. This means that no monkeys need be used for the sole purpose of
completing my research and design project. Any software needed is already in use within
the WNPRC and funds are provided by the National Science Foundation.
3 Appendix
3.1 Gantt Chart
3.2 Request for Proposal
3.3 Concept Sheet
14
This pioposal iesponus to a iequest fiom the Fetz Reseaich uioup. The Fetz
Reseaich uioup seeks to a solution to exploit the multiple stimulation channels of
Neuiochip S foi musculai contiol. The ueliveiable to be pioviueu is a spinal neuion
stimulation aiiay that is capable of the following: 1) it can stimulate the fiiing of
specific neuions in the spinal coiu. 2) It can stimulate spinal neuions with a vaiiety
of voltages S) Each neuion stimulation event coiiesponus to an output fiom the
NCS.
Tyler Maxfield 4/19/13 4:21 PM
Deleted: This pioposal iesponus to a
iequest fiom the Fetz Reseaich uioup. The
Fetz Reseaich uioup seeks to a solution to
exploit the multiple stimulation channels of
Neuiochip S. The ueliveiable to be pioviueu
is a musculai stimulation uevice that is
capable of the following: 1) it can tiiggei
contiaction in 4 oi moie muscle gioups. 2)
It can stimulate a muscle gioup to contiact
with vaiying uegiees of foice. S) Each
muscle gioup anu uesiieu foice coiiesponus
to uiffeient combination of output channels
fiom the NCS.
BIOENGINEERING SOLUTIONS TO REAL WORLD PROBLEMS



References: Fetz, Inst i t ut e f or Transl at i onal Heal t h Sc i enc es Washi ngt on Nat i onal Pri mat e Researc h Cent er
Igni t i on Award. Application. 2008; Chet T. Moritz, Di rec t c ont rol of paral ysed musc l es by c ort i c al neurons . Nature, 2008


Helping the Paralyzed Help Themselves
Clinical Need or Research Question
Millions of people suffer from debilitating affects after a stroke or traumatic
brain or spinal injury. After such injuries, many patients lose the ability to
control part of their body. Many are no longer able to perform basic functions
for themselves and thus must rely on specialized care, at a great cost to the
familys resources. Despite many technological advances in the healthcare
industry, few new developments have been made in helping those who lose the
ability to control their own body. The non-linear nature of the brain has posed a
great obstacle for extending our knowledge to clinical applications.

Bioengineering Solution or Approach
Implantable recurrent brain-computer interfaces (R-BCI) provide a promising
new approach to assisting those disabled from traumatic events. The R-BCI
continually records electrical activity of specific cells in the brain, and based on
those recordings can make decisions to stimulate the spinal cord, brain, or
muscle during free behavior. Using the paradigm of spinal cord stimulation, I
will design a spinal cord stimulator that will deliver precise stimulations that
will induce movement in a limb that has been paralyzed due to a peripheral
nerve block. This stimulator will receive signals from the R-BCI and deliver
impulses to the spinal cord, allowing the subject to regain control of the parlized
limb.

Current Status and Results
The Fetz Research Group has already demonstrated that non-human primates
are able to volitionally control the firing rates of motor cortex neurons and that
this control can be translated into directed movement. However, past
experiments have mostly focused on using this volitional control to stimulate
firing in other areas of the brain. This approach has been focused on
strengthening the inter-neuron connectivity within the brain, with the potential
for application in a person suffering from a stroke.

A thin-flexible cortical spinal stimulator has been developed by Brian Mogan,
who later found that the thin wires were unable to withstand the electrical
current needed to stimulate the neurons of the spinal cord. This led to the
degradation of the stimulators efficacy after about a month. The intended area
of stimulation is positioned ventrally on the spinal cord, making access to the
area difficult with a more robust system. A solution that incorporates flexibility
and robust current output needs to be designed in order to move forward with
this application.

Direct control of
paralysed muscles
by cortical neurons

Chet T. Moritz1, Steve I.
Perlmutter1 & Eberhard
E. Fetz1. Nature, 2008.


Personnel
Tyler Maxfield
Eberhard Fetz
Funding
NATIONAL
INSTITUTE OF
NEUROLOGICAL
DISORDERS AND
STROKE


April 26
th,
2013
Concept Sheet


References
[1] One degree of separation:paralysis and spinal cord injury in the united states. Web,
May 2013.
[2] Andrew Barron. Introduction to cyclic voltammetry measurements, June 2010.
[3] Caleb Bartlett. Understanding spinal cord injury: Part 1, June 2013.
[4] Eberhard E. Fetz. Reseach plan. April 2013.
[5] Jaideep Mavoori Jackson, Andrew and Eberhard E. Fetz. Long-term motor cortex
plasticity induced by an electronic neural implant. Nature, 444(7115):5660, 2006.
[6] C. Hofer M. Modlin D. Raschka-Hgler W. Mayr Kern, H. and H. Sthr. Denervated
muscles in humans: Limitations and problems of currently used functional electrical
stimulation training protocols.
[7] Steve I. Perlmutter Moritz, Chet T. and Eberhard E. Fetz. Direct control of paralysed
mus- cles by cortical neurons. Nature, 456(7222):63942, 2008.
[8] Yukio Nishimura, Steve I Perlmutter, and Eberhard E Fetz. Restoration of upper limb
movement via articial corticospinal and musculospinal connections in a monkey with
spinal cord injury. Frontiers in Neural Circuits, 7(57), 2013.
[9] K. H.; Shee C.Y.; Wang C.C.; Guan C.T.; Ang W.T. Tan, H. G.; Kong. Post-acute
stroke patients use brain-computer interface to activate electrical stimulation. Engineer-
ing in Medicine and Biology Society (EMBC), 2010 Annual International Conference
of the IEEE, pages 4234,4237, August 2010.
17
Figure 5: Gantt Chart showing the timeline of dierent stages of my proposed project.
18