introduction to neural prosthesis -...

Neural Prosthetic Engineering

Introduction to Neural Prosthesis

Sung June Kim

1


Neural Prosthesis

• A device that connects directly with the nervous system to replace or supplement sensory or motor function.

• A device that improves the quality of life of a neurologically impaired individual so much that he/she is willing to put up with the surgery, gadgetry, etc.

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Successful Areas of Neural Prosthesis

• (Bionic Ear)

• Hearing: Cochlear Implant

• Vision: Retinal Implant

• Parkinson’s Disease: DBS (Deep Brain Stimulation)

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Why these three?

• Success in Cochlear Implant

• The other two were inspired by its (the CI’s) success.

• The Cochlear and Retinal implants are sensory prosthetics, using electrical stimulation of neurons.

• The DBS deals with motion disability yet uses CI like neuronal stimulation.

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Why was CI so successful?

• Spatially isolated space was available for the electrode array. The electrode array was still electrically connected to the target neurons.

• Timely development of the transistor based microelectronics technologies that made the electronics small (wearable, implantable) but powerful.

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http://www.cochlearamericas.com/


What are needed in NP? (1)

• External unit is needed if there is a signal to process.

• Speech is the signal to process in Cochlear Implant

• Image is the signal to process in Retinal Implant

• There is no external signal to process in DBS.

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External Unit


Speech Processor, An example of External Unit

www. bionicear.com, www.medel.com, www.cochlear.com7



• Internal Unit (Implantable Unit)

• This unit generates electrical signals, and apply them to the array of electrodes that stimulate target neurons.

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External Unit Internal Unit


Example of the Internal Unit

Nurobiosys Corp., Korea9

10 mm



• Communication (Connection) between the two.

• If the connection is wired, it is called “percutaneous connection”,

• Percutaneous connection is simplest, best with signal to noise ratio, but there is risk for infection.

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What are needed in NP? (4)• Thus modern NP uses wireless communication

(telemetry).

• The telemetry requires extra circuit to transmit and receive signals from the external unit to the internal one.

• There are forward telemetry and reverse telemetry.

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System example: Cochlear Implant

Wearable

Speech

Processor

Microphone

External

Coil

Internal

Coil

Implantable Current

Stimulator

Inserted

Electrode array

① Sound Signal

② RF Modulation

③ Data & Power

Transmission

⑤ Stimulation

Pulse train

④ Signal

Demodulation

⑥ Auditory Cortex

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Problems addressed

• Cell loss is the common problem.

• Cells that act as transducers (sensors) for hearing and vision– Hair cells in cochlea in hearing impairment

– Photoreceptor cells in retina for vision impairment

• Cells that are essential in controlled movement:– Substantia Nigra cells in Parkinson’s disease

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Possible solutions

• Stem cells: IPSC (Induced Pluripotent Stem Cells) are the typical approach

• However, these are not proven safe for clinical applications yet.

• Currently Neural Prosthesis is the only working solution: An array of electrodes are inserted to electrically stimulate surviving neighbor neuron cells to substitute or replace the lost functions.

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Neural prosthetic Milestones

1930 1940 1950 1960 1970

1934: Electronic hearing aid developed

1945: Invention of transistor

1956 Nobel Prize of Physics awarded to Shockley, Bardeen and Brattain

1952: Hodgkin-Huxley theory of action potential

1957: 1st cochlear implant developed

1958: Internal pacemaker developed

1959: MOSFET invented (BL,D.Khang)

1961: 1st motor prosthesis for foot drop in hemiplegics

1961: Silicon chips first appear(TI, J. Kilby)

1963: CMOS invented (Fairchild, Wanlass)

1977: Bone-anchored hearing aid made available in Europe

1977: VLSI developed(Modular design by Mead and Conway)

1973-74: organized clinical trials of the 1st wearable cochlear implant begin

1971: Microprocessor invented (Intel, 4004)

1979: 1st

auditory brainstem implant

Engineering/Computer MilestonesFinn, Warren E., and Peter G. LoPresti, eds. Handbook of neuroprosthetic methods. CRC Press, 2002.

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1980 1985 1990 1995 2000

1980: 1st successful 1-channel cochlear implant in a child

1981: IBM PC,STM invented

1986-95: FES allows paraplegics to stand

1981: Peripheral nerve bridge implanted into spinal cord of rat

1980: silicon microelectrode for extracellular recording begun

1995: - Human trials of visual cortex prosthesis - German group begin Subretinal implant

2000: - FDA authorizes Optobionics to begin human trials of Artificial Silicon Retina (ASR)

- FDA approval of 1st

middle-ear implant- FAD approval of auditory brainstem implant

1996: Optic nerve prosthesis development begins in Belgium

Engineering/Computer Milestones

1985: MS Windows developed

1988: MIT-Harvard, Johns Hopkins begin research on epiretinal implant

1989: Intel 486 processor

1997: FDA approval of DBS on thalamus for Parkinson’s Disease

2000: Deep Brain Stimulation (ACTIVA) develped to treat Parkinson’s disease

1998: Google

Finn, Warren E., and Peter G. LoPresti, eds. Handbook of neuroprosthetic methods. CRC Press, 2002.16


2000 2005 2010 2015

2008: iPhone 3G

Engineering/Computer Milestones

2010: iPhone 4

2012: iPhone 5

2014: iPhone 6

2013: FDA approval of Secondsight Argus II epiretinal prosthesis

2002-2004: 16-channel retinal prosthesis Argus I developed

2007: clinical trials of 60-channel Argus II begin

2005-2009: 1500 channel subretinal photodiode array by German group

2003: completion of the Human Genome Project

2005: Optogenetic system for mammalian neuron

2001: 1st dual-core processor (IBM)

2006: 1st Tesla all-electric vehicle

2004: Human-implanted BCI

2004: Facebook launched

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• Biomedical Engineering.

• A Biomedical engineer is one who challenges many problem

in the modern heath care system.

• Neural Engineering

• Artificial Organs (Devices for replacement or augmentation

of bodily functions)

• Can join professional societies such as IEEE EMBS

(Engineering in Medicine and Biology Society). They hold

annual meeting called EMBC (Engineering in Medicine and

Biology Conference).

• BMES (Biomedical Engineering Society) is another major

biomedical engineering society.

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IEEE EMBS

• IEEE Engineering in Medicine and Biology society• The IEEE is the largest international professional organization in the world

and accommodates 37 different societies and councils under its umbrella structure.

• The EMBS represents the foremost international organization serving the

need of more than 8000 biomedical engineering members around the world.

• publications:

• Transaction on Biomedical Engineering(TBME: a monthly journal)

• Transactions on Biomedical Circuits and Systems

• Transaction on Rehabilitation Engineering

• Transaction of Information Technology in Biomedicine(two quarterly journals))

• IEEE Engineering in Medicine and Biology magazine(a bimonthly magazine)

19http://www.ieee.org/embs

Conferences and Meetings we can travel to

• Institute of Electrical and Electronic Engineers(IEEE) Engineering in Medicine and

Biology Society(EMBS) Conference

• IEEE EMBS Neural Engineering Conference

• Biomedical Engineering Society(BMES) Meeting

• Neural Interfaces Conference

• Biomedical Circuits and Systems(BioCAS) Conference

• Conference on Implantable Auditory Prostheses(CIAP)

• European Symposium on Paediatric Cochlear Implantation(ESPCI)

• Asia Pacific Symposium on Cochlear Implant and Related Sciences(APSCI)

• American Cochlear Implant Alliance CI Symposium

• The Eye and The Chip Meeting

• Annual Meetings of Association for Research in Vision and Ophthalmology (ARVO)

• International Neuromodulation Society(INS) World Congress

• Society for Neuroscience(SFN) Conference

• World Society for Stereotactic Functional Neurosurgery(WSSFN)

• International Federation for Medical & Biological Engineering(IFMBE)

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Journals we can publish our research in

• Includes, but not limited to,

• Journal of Neural Engineering

• Journal of Neuroscience Methods

• Medical & Biological Engineering &

Computing

• Biomedical Instrumentation and

Technology

• Journal of Clinical Engineering

• Computer Methods and Programs

in Biomedicine

• Neural Computation

• Science

• Nature

• Small

• Optics Express

• Otology and Neurotology

• Journal of Neuromodulation

• Sensors and Materials

• Sensors & Actuators

• Computational and Mathematical

Methods in Medicine

• ACS Nano 21

• Biosensors and Bioelectronics

• Investigative Ophthalmology &

Visual Science

• Clinical & Experimental

Otorhinolaryngol

• Optics Letters

• Biotechnology and Bioengineering

• Neuromodulation

• Nanotechnolgy

• Optics Communications

• NeuroImage

• Invest Ophthalmol Vision Science

• Tissue Engineering

• Bioelectromagnetics

• Sensors

• Journal of Materials Science:

Materials in Medicine

• Journal of Biomedicine and

Biotechnology

• Biochimica et Biophysica Acta

• Medical Engineering & Physics

• And more.

Cochlea’s Operating Principle

Cochlear implant electrically stimulates neural cells to compensate for the problem of lost or damaged hair cells.

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Cochlear's operating principles

Cochlear Implant for the Deaf

Normal Deafened

B. Wilson & M. Dorman (IEEE Sensors Journal, 2008)

Figures fromB. S. Wilson and M. F. Dorman, "Interfacing Sensors With the Nervous System: Lessons From the Development and Success of the Cochlear Implant," Sensors Journal, IEEE, vol. 8, pp. 131-147, 2008.

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(Illustration from Dorman and Wilson, 2004)

Number of channels = Number of electrode sites

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Initially it was seen to be impossible.

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The basic premise was: There is no way to replace even crudely the exquisite structure and function of the cochlea

Amazing Outcome• The CI is the most successful neural prosthesis to date

• Cumulative CI users: approximately 120,000 persons

• Open-set speech recognition scores (in quiet): about 90 %

Percent correct scores for 55 CI users

B. Wilson & M. Dorman (IEEE Sensors Journal, 2008)

Cumulative number of implants across years

B. Wilson & M. Dorman (Hearing Research, 2008)

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History of the Cochlear Implant• Pioneers

– Andre Djourno and Charles Eyries (in Paris, 1957)

• Eyries implants Djourno's induction coils in two patients

• Alternating current transmitted to the coil produces perception of sound

• Early Developments in the Western Hemisphere

– William House, John Doyle, James Doyle (Los Angeles, 1960)

• Effect electrical stimulation during stapes surgery

• Implant 3 patients with a single gold electrode

– F, Blair Simmons (Stanford University, 1964)

• Develops a six-electrode system using a percutaneous plug ( Ineraid)

– William House (Los Angeles, 1969)

• Implants first hardwire five-electrode system in 3 patients

– Robert Michelson (San Francisco, 1970)

• Implant 3 patients using a gold two-electrode system ( Advanced Bionics)

– William House (Los Angeles, 1972)

• First wearable cochlear implant device using a centering coil and magnet

• House/3M single channel cochlear implant (approved by the FDA in 1984)

Djourno

(Physiologist)

Eyries(ENT surgeon)

William House

(ENT Surgeon)

House/3M

single channel device

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History of the Cochlear Implant• Development of a Mutichannel Device (1970-80s)

– Single channel device Very Poor speech understanding

– Competition

• Michelson, Merzenich, Robert Schindler (UCSF) Advanced Bionics Corp.

• Hochmair (Vienna, Austria) Med-El GmbH.

• Graeme Clark (The University of Melbourne in Australia)

– Research supported by public donation (commenced 1967)

– First Multichannel Cochlear Implant Patient (1978) Cochlear Ltd.

• FDA Approved Multichannel CI Manufacturers

– Cochlear (Australia) – 1985

– Advanced Bionics (Austria) – 1996

– Med-El (Austria) – 2001 (1994 – European release)

• Lasker~DeBakey Clinical Medical Research Award (2013)

– Graeme M. Clark, Ingeborg Hochmair and Blake S. Wilson

• For the development of the modern cochlear implant - a device that bestows hearing to individuals with profound deafness.

Rod Saunders (First multi-

channel CI patient) and

Graeme Clark

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Areas of Improvement

• Wide range of outcomes

• Speech reception in noise

• Sound localization• Reception of signals

more complex than speech, e.g., symphonic music

• High effort in listening for the great majority of patients

• High Cost

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Recent Advances

• Bilateral electrical stimulation

• Combined electric and acoustic stimulation (EAS) for patients with residual, low-frequency hearing

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Retinal Implant:

Visual Prosthesis

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Anatomy of an Eye

32/31

Retinal Structure Responsible for Vision

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Blindness due to Retinal Degeneration

• Retinal Degeneration occupies 30% of Adult Blindness

– Loss of Photoreceptor cells of retina

– RP (Retinitis Pigmentosa): 1/4000 (normal people)

– AMD (Age-related Macular Degeneration): 1/20(>65 years old)

– >2,000 people get blind every year in Korea

– >2 mil. RP & AMD patients in U.S.A

• Visual Function is so important

– It is needless to say…

– Legally, 24% (monocular) or 100% (binocular blindness) of whole-body disability

34/31RP AMD

Retinal prosthesis:

Replace the function of degenerated photoreceptors Light → Neural Signal

By electrical stimulation of retinal cells Microelectrodes array implanted into retina

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Retinal Prosthesis (Artificial Retina)

© Second Sight

Retina

Optic Nerve

LGN

Visual Cortex

Drug Delivery Drug reservoir and needle

Limited duration time

Stem Cell Differentiation

Retinal progenitor cells by• Embryonic stem cell (ESC)

• Induced pluripotent stem cell (iPSC)

Optogenetics Channel Rhodopsin

Light-gated ion cannel

Neural activity controlled by light

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Visual restoration: Other therapies

http://www.rpip.tohoku.ac.jp/seeds/profile/104/lang:en/

J Bennicelli et al., Stem cells set their sights on retinitis pigmentosa, 2013

Deisseroth group

http://en.wikipedia.org/wiki/File:ChR2scheme.png

http://en.wikipedia.org/wiki/File:ChR2scheme.png

Visual restoration: Electrical stimulation

Retina

Optic Nerve

LGN (Lateral

Geniculate Nucleus)

Visual CortexCortical Prosthesis

Optic Nerve Prosthesis

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Principle of Artificial Retina Device

1

2

3

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Current Technologies

• “Argus II,” SecondSight, USA

– FDA-approved

– 60 channels (6x10) with a camera

– Titanium package

– Clinical trials

• Alpha-IMS, Zrenner Group, Germany

– 1,600 photodiode array

– No external camera

– Clinical trials

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http://www.gizmag.com/argus-ii-retinal-implant-european-approval/18758/picture/135057/

http://www.gizmag.com/argus-ii-retinal-implant-european-approval/18758/picture/135057/

USC-SecondSight

• 2013.2. FDA Approval

• Argus II 60-Channel Epi-retinal

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An Artificial Vision Patient

100 pixel image (10 x 10)

• 625 pixel image (25 x 25) : enable mobility

• 1024 pixel image (32 x 32) : partially useful vision

• 10,000 electrodes (100 x 100) : ambitious goal

320 x 320 32 x 32 8 x 8

How many pixels are required ?

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Deep Brain Stimulator

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• A.D. 46 - Ancient medicine Scribonius Largus suggested applying the live ray to the head of a patient suffering from a headache. This remedy was later used for hemorrhoids, gout, depression, and epilepsy.

• 18c – Electric fish were used for pain control

• 1870 - G. Fritsch and E. Hitzig bodily movements by electrical currents on cerebral tissue (motor cortex) possibility that neurological disorders affecting volitional movement could be treated with electrical stimulation.

• 1960s - Cardiac pacemaker was introduced Technological advances made possible the implantation of a comparable device for the focal stimulation of brain.

• 1960 Hassler et al., stimulation of the ventrolateral thalamus for tremor

• 1973 Hosobuuchi et al., for pain

Electric Ray

Advertisement for electrical stimulation

in the Boston Globe from 1882

History of Deep Brain Stimulation

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History of Deep Brain Stimulation• 1983~1990 – Recordings in the basal ganglia of both normal

and MPTP-treated monkeys helped to define the operational

principles of basal ganglia-thalamocortical loops, and showed

for the first time pronounced over-activity in a part of the

basal ganglia called the sub thalamic nucleus (STN)

• 1990 – Lesions of STN in monkeys were shown to completely

and permanently reverse the effects of MPTP

• 1993 – The first report from Benabid’s clinic of the use of

DBS in the STN to treat Parkinson’s Disease. Benabid’s

group had first used DBS in the thalamus, which is now the

standard approach in PD patients

• 1997 - FDA approved DBS of the thalamus for PD and

essential tremor

• 2002 – FDA approved DBS STN and GPi for symptoms of PD

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Medtronic Inc. Activa® Tremor Control Therapy

Deep Brain Stimulation- PD

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Neurological Movement Disorder

Cause of Disease

Loss of inhibitory neuron in the deep brain

structure that is responsible for motor

function(substantia nigra) causes Excessive

activity in adjacent neural network

Types and Symptoms

• Parkinson’s Disease

Tremor at rest state

lower shaking frequency-

Ceases during purposeful movement

• Essential Tremor

Tremor during movement

Higher shaking frequency

• Dyskinesia

Power Impairment of voluntary movement

• Dystonia

Disordered tonicity of muscles

substantia nigra

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Deep Brain Stimulation-Dystonia

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Deep Brain Stimulation--Pain

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Widening DBS applications

• Parkison’s disease, Essential Tremor• Dyskinesia, Dystonia,• Awakening from Vegetative State

• Depression, Obsesive Compulsive Disorder (OCD), Tourette’s Syndrome

• Chronic pain, Anorexia, Dementia (in the future)

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