Midterm Project #1:

ME 5358 Biomaterials

Integrating Prosthesis with Amputees’ Nervous System

in Order to Provide Somatosensory Feedback: A Review

Instructor:

Dr. Jenny Qiu

By:

Matthew Mills

October 4, 2018
Abstract

Providing amputees with somatosensory feedback from prosthetic devices not only makes the
prosthetic device easier to use, but also connects the user with the world around them. Providing
an amputee with the feedback involves trans-disciplinary research in engineering, psychology and
physiology. Methods of collecting sensory data, transmitting data, and interfacing with the nervous
system all need to be created while considering how the implant will work, how the materials used
will interact with the surround biological tissue, and how the brain will be able to collect and
interpret the date. Research in the last ten years has been conducted to determine the most effective
reinnervation interface location, including the peripheral nerve, the median nerve, the dorsal root
ganglia, or directly to the brain. For nerve interfaces, research has been conducted to determine
the optimal invasive level of implants to achieve a natural, yet highly discriminatory neurological
signal. These methods include Targeted Sensory Reinnervation, Regenerative Electrodes, Extra-
Fascicular Electrodes, and Intra-Fascicular Electrodes. Research is also being performed on the
effectiveness of completely non-invasive procedures and the use of biological cell infused lattice
structure nerve cuffs for reinnervation materials. Research will be analyzed and compared based
on the methods for transmitting somatosensory signals and how/where signals are received by the
amputee’s nervous system. The types of materials used for signal electrodes will also be discussed.

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1. Introduction
1.1. Purpose: The purpose of this review is to evaluate the current state of research in regards
to restoring amputees tactile sensing capabilities. Because this problem is trans-
disciplinary in nature, research from both engineering and medical sources will be
considered in this review. The scope will cover both design and interface of implant
devices, but will limit the sensing characteristic to tactile, or touch, sensing and how those
signals are created, transmitted, and received by the host body. This review will not
consider auditory or optical sensing.
1.2. Importance: Research in this area is important because, when an individual loses a limb,
they also lose touch with the world around them. Historically, amputees have lived with a
significantly reduced quality of life due to the lack of sophistication of prosthesis.
Transmission of tactile data, including pressure or temperature, will improve amputees’
ability to connect with the physical world around them. Studies have shown that only
approximately 50-60% [1] of amputees utilize prosthetics on a daily basis. This is due, in
part, to difficulties associated with operating a prosthetic limb including the ease of control
over the device. Even though the more advanced modern prosthetics have dexterity which
nearly matches the human hand, performing basic function without tactile feedback is very
difficult. Tactile feedback from a prosthetic device will not only reconnect the user with
the world, but also allow better control and functionality.
1.3. Methods of Comparison: Research will be analyzed and compared based on the methods
for transmitting somatosensory signals and how/where signals are received by the
amputee’s nervous system. The types of materials used for signal electrodes will also be
discussed.
2. Locations for Reinnervation
2.1. What is Reinnervation: Reinnervation is the restoration of tactile sensing to some part
of the body. Somatosensory (specific sensing) signals originate in the human body and
travel through the nervous system to be interpreted by the brain. Amputees, specifically
upper-limb amputees, have severed the nerve connections to the fingers due to the loss of
the arm. The prosthetic device, while restoring motor function does not provide tactile
feedback. Reinnervation applied to amputees seeks to integrate the prosthetic device in

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 order to provide somatosensory feedback to the amputee’s nervous system. This can be
done through various types of interfaces.
2.2. Reinnervation through the Peripheral Nerve [2]: Interface with this nerve poses a
reduced risk when compared to implants that interface directly to the brain with regard to
the surgery involved. Also, the brain is better able to understand the neural coding
originating from the peripheral nerve than neural coding that is being delivered directly to
the brain. This is partially due to the little-understood parallel nature of the body’s
processes involved with transporting signals through the nervous system. Delivering the
sensory signals to the peripheral nerve better mimics the body’s natural system for
transporting and processing somatosensory signals.
2.3. Reinnervation through the Median Nerve [3]: The median nerve shares the same
benefits of the peripheral nerve; it reduces the risks associated with more invasive implant
surgeries while providing a natural method for transmitting somatosensory data to the
brain. However, the median nerve is a larger nerve cluster and innervates more areas of
the arm. Because of this, greater levels of somatosensory discrimination can be achieved
through an interface at this location. However, interfacing with this nerve poses greater
risk of activating efferent (motor) fibers and causing a motor response. This method is less
invasive than direct to brain reinnervation and more invasive than reinnervation through
the peripheral nerve.
2.4. Reinnervation through the Dorsal Root Ganglia [2]: The dorsal rood ganglia is located
near the spinal cord and electrode arrays can be directly implanted at this location. Similar
to reinnervation through the peripheral nerve, this method similarly matches the body’s
natural somatosensory response because tactile information is transferred through the one
of three dorsal roots creating a more natural biological response. Additionally, interfacing
directly to this portion of the nervous system is advantageous due to the reduced risk of
activating efferent fibers and causing an involuntary motor response. However, due to its
close proximity to the spinal cord, the implant surgery necessary for interfacing with the
dorsal root ganglia is more invasive and dangerous than previously mentioned nerve
interface methods.
2.5. Reinnervation Directly to the Brain [4]: Brain-Machine interfaces (BMI’s) allow users
to control robotic devices, including prosthetic hands, by decoding brain signals and

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 transmitting them wirelessly to the device. This is achieved through brain surface
electroencephalograms (ECoGs) implanted directly onto the brain and powered by 400
mW of external wirelessly transmitted power. This means that an amputee could control
the prosthesis through thought rather than through muscle flexure. The somatosensory
feedback signals would be able to be delivered directly to the brain. However, as
previously mentioned, the amount of risk involved with performing the surgery to implant
this device is high whereas the PSM is able to deliver somatosensory feedback without
any invasive surgery or implants. While the risk associated with this method may cause
average amputees to implement alternative reinnervation methods, reinnervation directly
to the brain is not without merit. This method could greatly improve individuals with
severely debilitating injuries who have permeant paralysis.
3. Methods of Reinnervation
3.1. Targeted Sensory Reinnervation (TSR) [2]: This reinnervation method does not have a
direct electrical connection to the amputee’s residual nerve. The residual nerves are
instead rerouted to another region of the amputee’s body, typically the chest, where, when
stimulated, elicit a tactile response which the brain interprets to exist where the amputee’s
hand/finger used to exist. This method would create a region on the subject’s body where
a device would interact the reinnervated area. This device would receive tactile data from
the prosthetic fingertip and activate respective nerves in the reinnervated region where the
brain would interpret as originating in the fingertip. This interface method is advantageous
because it does not involve permanently implanting any devices inside the human body,
it has long term stability, and the sensations are more natural. However, because the device
is not implanted and can be removed, it would require calibration whenever it is reattached
to the reinnervated area.
3.2. Regenerative Electrodes (RGE) [2]: This method of reinnervation utilizes a fine mesh
that is implanted close to the severed nerve. As the nerves regenerate, they grow through
the mesh and can then be selectively stimulated. This method has the potential to achieve
a high level of resolution. However, nerve regeneration requires time and several months
can pass before this method becomes a viable source of somatosensory signals. Also,
nerves can degenerate over time which would lead to a reduction in available signals.

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3.3. Extra-Fascicular Electrodes (EFE) [2]: This method utilizes an implant directly onto
the nerve. The implant does not penetrate the protective sheath of the nerve, but rather
encircles the nerve providing numerous distinct contact locations around its
circumference. This general nerve-interface method is referred to as a cuff electrode. Due
to the cuff electrode implementation, this method causes less damage than nerve-interface
methods that penetrate the protective sheath of the nerve. However, this method is
perceived by the brain as highly unnatural and often evokes paresthesia. Also, electrical
signals from the cuff can be picked up by nearby efferent fibers creating an involuntary
motor response.
3.4. Intra-Fascicular Electrodes (IFE) [2]: This method employs electrodes inserted into the
protective layer of the nerve so that the stimulation is applied directly to the residual nerve.
As expected, this method tends to have a better contact with the nerve fibers than the EFE
method due to the electrode penetration. Due to this contact, IFE methods require lower
operating currents to activate nerve fibers which in turn allows for greater discrimination
between activation sites and greater resolution of the neurological response. Although it
has not yet been physically demonstrated, it has been theorized that, if small enough
electrodes are inserted, individual nerve fibers could be activated resulting in a more
natural biological response. However, this method often leads to long term nerve damage
due to the relative movement of nerve and the electrodes. Also, similar to the EFE method
but to a lesser extent due to the lower operating currents, electrical signals can be picked
up by nearby efferent fibers creating an involuntary motor response.
3.5. Phantom Sensation Mapping (PSM) [5][6]: This method focuses on the methodology
for transmitting tactile data from the sensory input location to the area of the body which
will interpret the sensory data. Although not technically a reinnervation method, PSM
aims to allow amputees to experience the same somatosensory feedback as invasive
methods without permanent implants or nerve relocation surgery. Amputees frequently
experience some level of phantom sensation after amputation surgery resulting from
interaction with some portion of the residual limb. This means that when an individual
with an amputation is touched in a specific location on the residual limb, the individual
experiences the sensation of being touched on the missing limb. For each amputee this
sensation is unique and he/she may have limited discrimination between phantom digits.

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 Figure 1 [5] shows the average response of amputees with one of three amputation
locations.

Figure 1: (a) location of amputation (b) mapped phantom sensation drawn on the residual limb (c) location of phantom
sensation and level of somatosensory feedback sensitivity

PSM can be mapped for each amputee (shown in Figure 1(b)) and prosthetic devices can
be interfaced with the mapped location allowing the amputee to experience somatosensory
feedback from the device without invasive surgery or implants making it an excellent
alternative to other methods discussed. Due to the uniqueness of individuals, each
prosthetic would have to have customized sensory output locations and extensive mapping
would have to take place. However, this method may not be the best solution for all
amputees. Studies have found that the amputees are able to best distinguish between
phantom sensation digits and tactile sensitivity when the amount of post amputation
residual limb is greater. As shown in Figure 1, the location of amputation plays a role in
the level of discrimination between digits. The amount of limb removed during amputation
surgery is determined by the damage to the limb. The surgeon is unable improve the
patients’ ability to fully map phantom sensations through the process of the surgery.

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 Therefore, amputees with less residual limb after surgery may require invasive methods
for regaining tactile feedback.
4. Electro-Mechanical Methods for Transmitting Somatosensory Data to Non-Invasive
PSM Nodes
4.1. Types of Somatosensory Input [1][6][7]: The human hand can distinguish between a
number of somatosensory inputs including but not limited to touch, pressure, pressure and
buzz, pressure and vibration, pressure and numb, and tingling and pain with modulation
of current amplitude, pulse width, or frequency. In order to provide somatosensory data to
the brain which can be translated into distinct feedback types, research has been conducted
on how well different methods of sensory transmission when applied to PSM amputees’
residual limb. These inputs can be transmitted either through matched or mismatched
paradigm.
4.2. Matched Verse Mismatched Paradigm Feedback [1][6]: The somatosensory feedback
from prosthetic devices can be transmitted through either a matched or mismatched
paradigm. For matched paradigm, pressure input on the prosthetic fingertip is fed back to
the target points on the PSM residual limb as pressure. For mismatched paradigm, the
pressure input on the fingertip can be fed back to the target points as mechanical
vibrations. Studies characterizing amputees’ response to sensory data transmission was
compared to healthy, non-amputee, participant results. These studies found that utilization
of matched paradigm sensory transmission resulted in the highest level of input
discrimination. The participants that were able to fully mapped phantom sensations were
able to perform higher than the non-amputee participants. This means that this method of
matched paradigm sensor transmission to phantom sensation locations is a viable, non
invasive method for restoring tactile sensing for amputees. However, this method is
completely dependent on the amputee being able to fully map (establish locations on
residual limb for each digit) phantom sensations. The participants that were unable to fully
map performed much lower on sensory discrimination than healthy participants.
4.3. Object Slippage Study [7]: A study conducted by BioRobotics Institue in Italy aimed to
determine which somatosensory transmission method provided the best object slippage
feedback to individuals. This study involved ten healthy (non-amputee) individuals
interacting with a robotic hand with embedded force sensors. The robotic hand was

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 mounted to a table and was initially set up to be holding a 70 g box. The robotic hand was
also connected to sensors on the subjects’ forearms which activated the flexure of the
robotic digits. The participants were afforded sensory input in one of three ways: visual,
pressure and vibration. The visual feedback required the participant to watch the robotic
hand and react once the participant could see the object beginning to slip. This is the tactile
feedback method used by most amputees and is very cognitively taxing because it requires
constant focus on the object. The pressure and vibration feedback methods applied the
respective sensation to the participants’ forearm and, when the object began to slip,
reduced the pressure/vibration applied. Once the object began to slip, the participant could
save the object from falling, allow the object to fall, or over-compensate and crush the
object.

Figure 2: Success rates for each condition for three consecutive days with black dots representing the median, grey boxes
indicating 25th and 75th percentile and outliers marked with an x

Figure 2 shows the success rate percentage over the three days for each sensory
transmission type. Additionally, the reaction time decreased as the days progressed and
the crush rate, by the end of the study, was nearly zero for all categories. This demonstrates
that, over the course of the study, all participants adapted to each sensory transmission
method causing improved success rates towards the conclusion of the study. However, the
vibro-tactile feedback (vibration) yielded close to perfect results since the first day of
trials. Overall, the study proved two things: first, vibration sensory transmission is the
most effective method in terms of transmitting sensory data, and second, amputees can
adapt or be trained to associate a number of various transmission methods to tactile
sensing.

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5. Materials Used at the Innervation Interface
5.1. Michigan-Style Electrode (MSE) [8]: The majority of reinnervation techniques
discussed in this paper involve the use of electrodes. Electrodes have been developed in a
wide range of styles and utilize a wide range of materials. The MSE (pictured in Figure
3B below) is constructed using several microfabrication processes. The dielectric layer
consists of either a silicon oxide or a silicone nitride stack. In order to insulate the
electronics from the body, the dielectric probe is coated in an insulating polymer coating
such as Parylene-C or Epoxylite.

Figure 3: Four variations of electrode types [8]

5.2. Utah Electrode Array (UEA) [8]: The UEA (Figure 3C above) utilizes alternative
manufacturing techniques to the MSE due to the constructing materials. Instead of the
thin-film design of the MSE, the UEA utilizes a two-dimensional array of penetrating
electrode tines constructed of glass. The tips of the tines are sputtered with iridium oxide

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 (SIROF) and Parylene-C is applied through chemical vapor deposition in order to insulate
the device.
5.3. Regenerative Peripheral Nerve Interface (RPNI) [9]: A multi-university study
conducted by the University of Michigan and the University of Delaware involving
departments including engineering, health science, materials science, integrative
psychology and biomedical engineering sought to create a peripheral nerve interface using
cultured myoblasts, an undifferentiated embryonic cell which has the potential to form
into muscle fiber. The purpose was to create a biologically stable interface method that
would increase somatosensory signal amplification while preventing the formation of
neuroma, a type of tumor made of nerve cells which commonly occur at invasive
implant/nerve interface locations.

Figure 4: Schematic of a RPNI constructed using scaffold material (silicone mesh, acellular muscle or acellular muscle with
PEDOT conductive polymer) populated with myoblasts

The study resulted in several iterations including a scaffold structure constructed of either
silicone mesh, acellular muscle, or acellular muscle with PEDOT conductive polymer. The
myoblast cells diffused within the scaffold were grown from soleus muscle myoblasts from
isogenic female rats in a nutrient mixture and fetal bovine serum. During the course of the
study, the RPNI was implanted in 25 male F344 rats weighing between 300 and 400 grams.
While lightly sedated, stimulation of the plantar region of the foot elicited distinct EMG

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signals indicating that the nerve conduction utilizing the RPNI had high fidelity and
reproducibility. At the end of the trial period, between 59 and 111 days, all RPNIs were
clearly vascularized. The study concluded that myoblast RPNIs can detect physiologic
motor action potentials when interfaced with the peripheral nerve. Additionally, myoblast
RPNIs develop into mature muscle and are reinnervated, vascularized and prevent the
formation of neuroma.

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References
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Transradial Prosthetic Hands” IEEE Access 6 (2018): 6878-6899. Web of Science. Web. 1 Oct.
2018.
[2] Saal, Hannes P. et al. “Biomimetic Approaches to Bionic Touch Through a Peripheral Nerve
Interface” Neuropsychologia 79 (2015): 344-353. Web of Science. Web. 1 Oct. 2018.
[3] Martinez-Delgado, Ignacio, et al. “Fascicular Topography of the Human Median Nerve for
Neuroprosthetic Surgery” Frontiers in Neuroscience 10 (2016) 1-13. Web of Science. Web. 1 Oct.
2018.
[4] Matsushita, Kojiro, et al. “A Fully Implantable Wireless ECoG 128-Channel Recording Device
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[5] Chai, Guohong et al. “Characterization of Evoked Tactile Sensation in Forearm Amputees with
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[6] Antfolk, Christian, et al. “Artificial Redirection of Sensation from Prosthetic Fingers to the
Phantom Hand Map on Transradial Amputees: Vibrotactile Versus Mechanotactile Sensory
Feedback” IEEE Transactions on Neural Systems and Rehabilitation Engineering 21 (2013): 112-
120. Web of Science. Web. 1 Oct. 2018.
[7] Aboseria, Mohamed et al. “Discrete Vibro-Tactile Feedback Prevents Object Slippage in Hand
Prostheses More Intuitively Than Other Modalities” IEEE Transactions on Neural Systems and
Rehabilitation Engineering 26 (2018) 1577-1584. Web of Science. Web. 1 Oct. 2018.
[8] Jorfi, Mehdi, et al. “Progress Towards Biocompatible Intracortical Microelectrodes for Neural
Interfacing Applications” Journal of Neural Engineering 12 (2015). 1-88. Web of Science. Web.
3 Oct. 2018.
[9] Urbanchek, Melanie G. et al. “Development of a Regenerative Peripheral Nerve Interface for
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