B.

E (7thsem) SEMINAR REPORT

DEPARTMENT OF ELECTRONICS AND COMMUNICATION ENGINEERING

SSM COLLEGE OF ENGINEERING

DIVAR PARIHASPORA PATTAN

APRIL - 2020
 Stimulation of PNS using Electroceuticals

A SEMINAR REPORT

submitted to

SSM COLLEGE OF ENGINEERING

by

MALIK SHEEZA

in partial fulfillment for the award of the degree

of

BACHELOR OF ENGINEERING
in

ELECTRONICS AND COMMUNICATION ENGINEERING

DEPARTMENT OF ELECTRONICS AND COMMUNICATION ENGINEERING

SSM COLLEGE OF ENGINEERING

DIVAR PARIHASPORA PATTAN.

APRIL - 2020
 Acknowledgement

At the very beginning, I would like to express my deepest gratitude to almighty Allah for giving
me the strength and the composure to complete and prepare this report within the scheduled
time.

During the period of my seminar topic research, I have received generous help from many
quarters, which I like to put on record here with deep gratitude and great pleasure.

First and foremost, I am grateful to my supervisor, Mrs. Shahida Kawoosa, faculty from the
department of ECE.She allowed me to encroach upon her precious time freely right from the
very beginning of this research work till its completion.

My gratitude goes to Mr. Majid sir as his encouragement and suggestions provided me
necessary insight into the research topic. I have no hesitation to say that, without his constant
support and valuable advice from time-to-time, I would probably fail to complete the work in
an appropriate manner.

My special gratitude goes to Mr. Manzoor sir, HOD (ECE) for his modern outlook and
meticulous supervision.
 SSM COLLEGE OF ENGINEERING

DIVAR PARIHASPORA, PATTAN.

CERTIFICATE

This is to certify that the seminar report entitled “ Stimulation of PNS using Electroceutical”

is a paper presented by MALIK SHEEZA bearing enrollment number 6292 in partial fulfillment

for the award of Degree of Bachelor of Engineering in Electronics and Communication Engineering

Name of the seminar coordinator

Designation

ER. MANZOOR AHMAD MIR

H.O.D (Department of E&C)

 ABSTRACT

KEYWORDS: amputation, artificial limb, prostheses and implants, neuroprosthesis, peripheral

nervous system, neural conduction, electromyography, electric stimulation, electrodes, extremities

ABSTRACT: The field of prosthetics has been evolving and advancing over the past decade, as

patients with missing extremities are expecting to control their prostheses in as normal a way as

possible. Scientists have attempted to satisfy this expectation by designing a connection between the

nervous system of the patient and the prosthetic limb, creating the field of neuroprosthetics. In this

paper, we broadly review the techniques used to bridge the patient’s peripheral nervous system to a

prosthetic limb. First, we describe the electrical methods including myoelectric systems, surgical

innovations and the role of nerve electrodes. We then describe non-electrical methods used alone or in

combination with electrical methods. Design concerns from an engineering point of view are explored,

and novel improvements to obtain a more stable interface are described. Finally, a critique of the

methods with respect to their long-term impacts is provided. In this review, nerve electrodes are found

to be one of the most promising interfaces in the future for intuitive user control. Clinical trials with

larger patient populations, and for longer periods of time for certain interfaces, will help to evaluate the

clinical application of nerve electrodes.

 CONTENTS

Title

Page

ACKNOWLEDGEMENTS…………………………………………………………………….. i
ABSTRACT..…………………………………………………………………………………. ii
LIST OF TABLES …………………………………………………………………………….. iii
LIST OF FIGURES …………………………………………………………………………… iv
ABBREVIATIONS ……………………………………………………………………………. v
NOMENCLATURE …………………………………………………………………………... vi

CHAPTER 1: INTRODUCTION

1.1 IMPLANT SYSTEM OVERVIEW 3

1.2 Simulation Using Computational Fluid Dynamics 5
CHAPTER 2: Important Electrode Requirements
2.1  Electrodes

2.2
2.1 Diesel Combustion Model 25
...........................................................................................................................................
……………………………………………………………………………………………
……………………………………………………………………………………………
REFERENCE 50
LIST OF PUBLICATIONS 55
 CHAPTER 1

INTRODUCTION

Future medicine will be revolutionized by implantable ‘electroceuticals’ that target neural pathways for
therapeutic intervention, as opposed to prevalent pharmacological approaches .Stimulation of the peripheral
nervous system (PNS) has shown great promise for the treatment of a range of conditions including:
neurological, auto inflammatory, autoimmune, cardiovascular diseases, and diabetes. For instance, vagus
nerve stimulation is effective for the treatment of epilepsy, rheumatoid arthritis, inflammatory bowel
disease, and diabetes, sacral and pudendal nerve stimulation can facilitate bladder control, and ethmoid
nerve stimulation can be used to treat dry eye disease. Aggressive miniaturization of neuro stimulators to
millimeter (mm) dimensions is essential for avoiding invasive surgery, and the associated post-surgery
trauma and infection. This necessitates wireless powering to eliminate bulky batteries and wired interfaces.
While body-powered prosthetics remain popular today, they are designed with a functional intent and do not
confer intuitive control. The lack of intuitive control prompted the development of neuroprosthetic
interfaces, which brought the potential of natural use of the artificial limbs by the user’s own nervous
system. As the name implies, these interfaces aim to communicate with the user’s nervous system.
Communication within the nervous system is primarily through the rate and pattern of action potentials, and
it is the number or spacing of these action potentials per unit time that code information. Thus, information
can be introduced into the nervous system by inducing action potentials, or these action potentials can be
read to obtain information from the nervous system.
The specific methods to interface to the peripheral nerves include myoelectric systems and nerve electrodes.
Muscle electrodes are the fundamental elements of myoelectric systems, and can be divided into two
categories based on their invasiveness: surface electrodes that are placed on the skin, and implanted
electrodes that are applied directly to the muscles. Implanted electrodes can be further subdivided into two
types: epimysial electrodes which are sutured onto the surface of a muscle, and intramuscular electrodes
which pierce the epimysium. Nerve electrodes can be classified as extraneural or intraneural according to
their location with respect to the epineurium . Intraneural electrodes that penetrate the epineurium but not the
nerve fascicles are called inter-fascicular electrodes. Electrodes that penetrate both the nerve and the
fascicles are called intra-fascicular electrodes. Specific electrodes that are designed to be placed transversely
at the cut end of a transected nerve are named regenerative electrodes. An important characteristic of the
nerve electrodes is that they pose a direct interface to the PNS, whereas myoelectric systems are primarily
connected to the muscles leading to an indirect interface with the PNS.
 1.1 Prosthetics Control

A closed-loop control around the user is characterized by a bidirectional communication between the

user and the prosthetic system (fig 1).

Fig 1Block scheme of the PNS-based control of a prosthetic system

The control of the prosthesis benefits from information coming from the efferent pathway, translating
neural or muscular commands. In a PNS-based control of a prosthetic hand the subject intention of
movement can be extracted from muscular or neural signals through EMG and ENG interfaces,
respectively. Muscular commands can be acquired in invasive or non-invasive ways using epymisial or
superficial electrodes, respectively. Instead, the extraction of neural signal always requires the use of an
invasive technique to implant neural interfaces around (cuff electrodes) or inside the nerve (intraneural
electrodes).

On the other hand, the afferent pathway is used for returning to the user the information on the
interaction between prosthesis and environment (tactile perception, proprioception, pain, and
temperature) .  Three different afferent pathways were proposed, based on:

(i) visual or auditory feedback signals

(ii) somatic sensory signals, i.e., tactile, proprioception, vibration; Somatic sensory signals
can be generated through non-invasive or invasive interfacing techniques such as:
vibrotactile, electrotactile, mechanotactile, targeted sensory reinnervation (TSR) and
neural stimulation.

(iii) feedback signals intrinsic to the prosthesis control system, which use information of the
sensors embedded in the prosthesis for automatically adjusting the grasping force.
Vibrotactile and electrotactile sensory substitutions stimulate the skin with mechanical vibrations or
local electrical currents. The reduced power consumption and the fast response to the stimulus are the
main advantages of the electrotactile technique with respect to the vibrotactile one. Mechanotactile
feedback consists of providing a pressure or a force normal to the skin by means of a pusher. In Antfolk
et al. (2013a), it has been suggested that the amputees' ability to detect pressure stimulation exceeds
their ability to discriminate vibrotactile stimulation, thus supporting the choice of mechanotactile
stimulation to vibrotactile one. Furthermore, mechanical feedback is more accepted than electrotactile
feedback by myolelectric prostheses users since in the electrotactile modality it is difficult to isolate and
elicit a specific sensation for a specific task.

In the TSR, the skin near or over a targeted muscle (a big muscle spared by the lesion, often
the pectoralis major) is reinnervated with afferent fibers of the remaining hand nerves: when the skin is
touched, it provides the amputee with a sense of the missing part .The feedback is returned in a
physiologically correct manner by means of tactors positioned on the residual limb. Although promising,
this technique is younger than the previously described feedback methods and more invasive, thus being
limited to few cases of very proximal amputation.

An alternative to the aforementioned techniques is the sensory feedback directly provided on the afferent
pathway through neural electrodes, thus exploiting the natural pathways of communication between the
hand and the peripheral nervous system (PNS). For this strategy, the great challenge is to recover the
bidirectional communication with the PNS in amputees through the surgical implantation of neural
electrodes in the upper-limb peripheral nerves. Studies on long-term amputees indicated that central
pathways associated with amputated peripheral nerves retain at least some sensory and motor
function .This supports the possibility of performing a natural control of the prosthesis and of returning a
natural sensory feedback to the amputee in a closed loop control by means of implantable peripheral
interfaces.
 1.1 Myoelectric systems

The most frequent way to interface to the PNS is to utilize the innervation of remaining muscle groups after an
amputation. Originally, these muscle groups are not created to control the required action, rather they are
aimed at executing different motor tasks. Accordingly, the user of a myoelectric prosthesis needs to relearn to
perform certain actions through repetitive exercises, which usually takes many months. The simplest method is
to apply surface electrodes made of biocompatible metals on patient’s skin. The action potentials generated by
the underlying muscles are recorded by these electrodes, and these recorded signals are detected, decomposed,
and processed by various different methodologies such as external software, for the prosthesis to perform an
action. Thus, control of the prosthetic limb is dependent on the activation of residual muscles. This non-
invasive, uncomplicated method has certain drawbacks, such as the requirement of daily placement and
calibration, the need for maintenance of the skin condition, movement artifacts, recording from unintended
muscles, and low signal-to-noise ratio .If the residual muscle mass of the extremity is inadequate, this method
is unfavorable.
An alternative approach to record impulses and stimulate muscles is to utilize implantable muscle electrodes.
Although invasive, this method provides increased spatial resolution and increased signal-to-noise ratio. It also
eliminates the need for daily placement and issues with skin conditions. There are two approaches for
implantable muscle electrodes: securing the electrode to the epimysium or implanting it intramuscularly. The
less invasive one, the epimysial electrode (Fig. 1), can be sutured to the epimysium close to the motor
endplate. The optimal place can be estimated via stimulation of the muscle intraoperatively . One of the
common designs consists of a platinum-iridium disc with silicone elastomer backing.

Fig.1. Epimysial electrode

Myoelectric control :
One of the first solutions of myoelectric control is the on-off control: when the EMG signals exceed a
threshold, a certain prosthesis function is activated (Scott and Parker, 1988). This simple and intuitive
control modality requires many sites to extract the EMG signal, one for each function to control. This
condition is often prohibitive in proximal amputees and hugely restricts the number of functions to
select. One way to overcome this drawback is to have different activation thresholds, but this solution
(called Double-Command Control) affects the simplicity of use (Battyeet et al., 1955) and limits its
application. As an alternative, the Agonist/Antagonist Control can be used. It consists of using a couple
of electrodes on agonist-antagonist muscle pairs (Popov, 1965). The contraction of one muscle is
associated to the motion of opening with constant speed, while the contraction of the other muscle
controls the closure; simultaneous muscle pair contraction (co-contraction) allows switching from one
function to another. Setting an intermediate threshold of the muscle contraction it is possible to obtain a
two-speed motion (i.e., Two-Speed Control) of the prosthesis (slow and fast) to accommodate fine
movements.

Proportional control (Fougner et al., 2012) permits to vary force and speed proportionally to the
amplitude of the recorded EMG signal. Hence, the voltage command for the motors is taken as
proportional to the contraction intensity. Measuring EMG signals from agonist/antagonist muscles is a
common procedure in proportional control and co-contraction of the muscle pair is used to select the
degree of freedom to control.

The main limitation of agonist/antagonist control consists of the limited number of independently
controllable DoFs (far from the multifunctional control of the human hand). Anyway, thanks to its
simplicity and robustness, it results to be the most adopted control option for myoelectric prostheses in
commercially available systems as well as in clinical applications (Jiang and Farina, 2014).

Two additional techniques have been developed in the framework of myoelectric control, i.e. the
Targeted Muscle Reinnervation (TMR) (Hijjawi et al., 2006) and the recent nerve transfer in brachial
plexus injury (Aszmann et al., 2015). In the TMR Hijjawi et al. (2006), the remaining arm nerves are
reallocated to residual chest or upper-arm muscles that are no longer biomechanically functional due to
the amputation. Once re-innervated, these muscles serve as biological amplifiers of motor commands
from the transferred arm nerves and provide physiologically appropriate EMG signals for the arm
control. This procedure is especially applied to subjects with very proximal amputation, which usually
control the motors of the prosthetic arm through switches actuated with residual shoulder movement or
myoelectric signals acquired from muscles of the chest and back. With respect to these control
techniques, TMR presents several advantages, such as improvements in function (measured both
objectively and subjectively), ease of use, simultaneous control of more than one DoF, fast and seamless
motion (Miller et al., 2008).
 CHAPTER 2

Important Electrode Requirements

Overall electrode usability for neuroprostheses depends on multiple electrode properties. Electrode-
tissue interaction is an major group of properties. Important properties in this group are the mechanical
mismatch between the tissue and electrode and coating possibilities to influence the immunological
reaction of the tissue.Signal transmission is another class, which is influenced by electrode properties
such as impedance and the location of the electrode.  Two important requirements were selected for
electrode comparison. First, it is important to which extent the electrode can be used chronically in vivo.
This means that the electrode should be able to extract meaningful signals over a long time span. The
electrode should inflict little chronic physiological or histological damage due to movement with respect
to the surrounding tissue because this can influence the long term performance. Likewise, an
inflammatory reaction caused by the electrode material should influence recording or stimulation as
little as possible. Second, maximization of the number of interfaces between electrode and nerve fiber is
desired, both for distinguishing different sensory sensations at different areas of the limb and for
controlling different parts of the prosthesis. However, placing a large amount of electrodes might be
undesirable and therefore a high spatial resolution to limit the amount of electrodes is preferred.
  Electrodes

The peripheral nerve electrodes can be divided into three categories, surface electrodes (Cuff
electrodes), penetrating electrodes (LIFE, TIME and USEA) and regenerative electrodes.

1. Cuff Electrode
The cuff electrode is a surface electrode which is wrapped around the nerve (Fig 2a). It measures
differences in electrical potential at the outside of the nerve during the propagation of action potentials.
There are multiple variants of the cuff electrode. The split ring electrode is a flat ring which has been
split at one side such that it can be placed around the nerve (Xue et al., 2015). Naples et al. developed
an electrode consisting of conductive segments embedded within a self-curling sheath of bio compatible
insulation which gives it a “self-sizing” property (Naples et al., 1988). The other variant is the flat
interface nerve electrode (FINE) which flattens the nerve to achieve a greater proximity to the fascicles
(Tyler and Durand, 2003) (Fig 2b). The FINE is interesting because it gives rise to multiple methods to
increase the spatial resolution (Yoo and Durand, 2005; Wodlinger and Durand, 2009).

Fig 2a: cutoff electrode Fig 2b: FIN electrode

1a.Longevity

Cuff electrodes are relatively non-invasive (compared to the penetrating electrodes discussed in the
following sections), which positively influences their longevity. It is seen that a large numbers of cuff
electrodes chronically implanted on human peripheral nerves can be stable and work up to 10.4 years
(duration of study) (Christie et al., 2017).

FINEs do have an acute effect on nerve functionality as a consequence of mechanical pressure, via
changes in nerve myelination and axon density. It is seem however, that the nerves can recover over
time and the electrodes have no further chronic physiological effects (Tyler and Durand, 2003). The
nerve can be reshaped significantly without long term physiological or histological damage up to 3
months after implantation .

1b. Spatial Resolution

As the cuff does not penetrate the epineurium, it is difficult to achieve highly selective recording from
individual fascicles. However, the spatial resolution can be increased by using FINE, which reshapes the
nerve and results in the electrodes having a closer proximity to the fascicles.

In addition, the data from multiple electrodes near the nerve can be used to estimate the origin of the
signal using various signal processing techniques, like spatial filtering (Wodlinger and Durand, 2009).
More recently, a Bayesian Source Filter for signal Extraction (BSFE) algorithm based on spatial filtering
was developed (Tang et al., 2014). High selectivity and stability can be achieved through an extraneural
interface, which can provide sensory feedback to amputees.

2.  Longitudinal Intrafascicular Electrode (LIFE)

The longitudinal intrafascicular electrode is a flexible, insulated wire with a small deinsulated region.
The wire is surgically inserted into the nerve with a round needle until it reaches a fascicle. It is inserted
along the fascicle and then pinched out of the nerve again. The wire is pulled through the insertion until
the deinsulated region lays adjacent to the nerve fibers .This is illustrated in Fig 2c.

Fig 2c: LIFE electrode

LIFEs consist of 25–50 μm diameter Pt or Pt-Ir wires insulated with Teflon or metalized Kevlar fibers,
mostly insulated with medical-grade silicone. The recording sites are areas of 0.5–1.5 mm long which
are left uninsulated .Tensile strength and flexibility is best in the multistranded Kevlar LIFEs, which is
important for in situ long-term recording. A more recent version of LIFEs is the thin-film LIFEs
(tfLIFE), based on a thin micropatterned polyimide substrate. These consist of a highly flexible substrate
filament, which can host eight contact sites.

2a Longevity

The first Pt-Ir LIFEs are quite stiff, which results in a relative motion of the electrode within the fascicle.
This in turn resulted in a gradual drift of the recorded nerve fiber population and a reduction in signal
quality (Goodall et al., 1991). Navarro et al. showed that tfLIFEs functional decline due to surgical
implantation and mechanical damage was slight and reversible after 3 months. Moreover, histological
evaluation in a rat model after several months showed a mild inflammatory reaction and no evidence of
nerve degeneration (Navarro et al., 2007).

2b. Spatial Resolution

Even though tfLIFEs electrodes contain 8 individual contact sites, it is still difficult to selectively
stimulate or record from individual fascicles with tfLIFE. The electrodes are only in close proximity to
part of the fascicles, because of the longitudinal montage of LIFE (Kundu et al., 2014a).

3.  Transverse Intrafascicular Multichannel Electrode (TIME)

The transverse intrafascicular multichannel electrode (TIME) is developed by Boretius et al. in the
international 'TIME-project', funded by the European Union (Boretius et al., 2010). It is designed to be
transversally inserted in the nerve. As stated by its developers, it “pursues the objectives of (1) achieving
a good contact with nerve fibers, (2) addressing several fascicles over the nerve cross-section to obtain
reasonable spatial selectivity and (3) minimizing the mismatch of technical material and nerve tissue.”
The TIME-electrode consists of a thin, strip-like polyimide substrate with platinum electrode sites. The
substrate is folded to align several electrodes and the folded substrate is threaded transversely through
the nerve between the fascicles (Figures 1C, 4). TIME electrodes have already been used in sensory
stimulation of the ulnar and median nerve as feedback for the control of a prosthetic hand (Raspopovic
et al., 2014).

Fig 2d: Schematic view of the implementation of the double folded TIME electrode through three fascicles.

3a. Longevity

Since one thin device may suffice to interface several groups of nerve fibers, surgical implantation
damage is minimized. This may avoid potential nerve damage.

3b. Spatial Resolution

As the TIME is oriented transversely in the nerve, its contact sites lay in close proximity to multiple
fibers belonging to different fascicles across the nerve, which should allow for more specific recording
and stimulation of individual fascicles than LIFE. Although the TIME was designed for both selective
stimulation of and recording from peripheral nerve fascicles, all studies using the TIME have focused on
its stimulation characteristics.
REFERENCES
[1] Abraham, J., F.V. Bracco, and R.D. Reitz (1985) Comparison of Omputed
and Measured Premixed Charge Engine Combustion. Combustion and Flame, Vol. 60,
309 –
322.

[2] Affes,
H., N. Trigui., D. Smith, and V. Griaznov (1998) Shape Optimization of
IC Engine Ports and Chambers. SAE Paper No.980127.

[3] Anderson, J.D. (1995) Computational Fluid Dynamics. McGraw Hill, Singapore
1995.

[4] Arcoumanis, C., A.F. Bicen, and J.H. Whitelaw (1993) Measurments in a Motored
Four Stroke Reciprocating Model Engine. Journal of Fluids Engineering, Vol.104.

[5] Arcoumanis, C., J.H. Whitelaw, W. Hentschel, K.P. Schindler (1994) Flow and
Combustion in a Transparent 1.9 Litre Direct Injection Diesel Engine. Proc. Instn. Mech.
Engrs., Vol. 208.

[6] Arcoumanis, C., Z. Hu, and J.H. Whitelaw (1993) Steady Flow
Characterization of Tumble-Generating Four – Valve Cylinder Heads. Proc.Instn. Mech.
Engrs. Vol 207.

[7] Babu,S.S., P.I. Haneef, P.A. Lakshminarayanan, P. Deshpande, N. Bhalla, P.

Sagar, and J. Sekar (2005) Two Methods for Improving Torque of a Diesel Engine in
the Low Speed Range. SAE Paper No. 2005-26-001.

[8] Balajimopoulos, A, D.N. Assani, D.L. Floweers, S.M. Aceves, and P. Hessel (2005)
A Fully Coupled Computational Fluid Dynamics and Multi-Zone Model with
Detailed Chemical Kinetics for the Simulation of Premixed Charge Compression
Ignition. IMechE. J. Engine Research, Vol. 6, No. 5.

H., C. Hasse, and N. Peters (2000) Computational Fluid Dynamics Modeling

[9] Barths,
of Non-Premixed Combustion in Direct Injection Diesel Engines. Proceedings of the
IMechE Volume 1, Journal of Engine Research.

Baulch, D.L., D.D. Drysdall, D.G. Horne, and A.C. Lloyd (1973)
[10] Evaluated
Kinetic Data for High Temperature Reactions. Butterworth.

[11] Beard, O. C and M. Miche (2003) Improved Modeling of DI Diesel Engines Using
Sub Grid Description of Spray and Combustion. SAE Paper No. 2003-01-0008