Cochlear Implant for the Deaf

Introduction to Neural Prosthesis

Sung June Kim

Neural Prosthetic Engineering 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.

Neural Prosthetic Engineering 2 Successful Areas of Neural Prosthesis

• (Bionic Ear) • Hearing: Cochlear Implant • Vision: Retinal Implant • Parkinson’s Disease: DBS (Deep Brain Stimulation)

Neural Prosthetic Engineering 3 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.

Neural Prosthetic Engineering 4 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.

http://www.cochlearamericas.com/

Neural Prosthetic Engineering 5 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.

External Unit

Neural Prosthetic Engineering 6 Speech Processor, An example of External Unit

7 www. bionicear.com, www.medel.com, www.cochlear.com Neural Prosthetic Engineering What are needed in NP? (2)

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

External Unit Internal Unit

Neural Prosthetic Engineering 8 Example of the Internal Unit

10 mm

Neural Prosthetic Engineering 9 Nurobiosys Corp., Korea What are needed in NP? (3)

• 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.

External Unit Internal Unit

Neural Prosthetic Engineering 10 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.

External Unit Internal Unit

Neural Prosthetic Engineering 11 System example: Cochlear Implant

③ Data & Power Transmission Microphone Internal Coil External ④ Signal Coil Demodulation Implantable Current Stimulator

① Sound Signal ⑥ Auditory Cortex

② RF Modulation ⑤ Stimulation Inserted Pulse train Electrode array

Wearable Speech Processor Neural Prosthetic Engineering 12 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

Neural Prosthetic Engineering 13 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.

Neural Prosthetic Engineering 14 Neural prosthetic Milestones

1961: 1st motor 1952: Hodgkin- 1977: Bone-anchored prosthesis for foot hearing aid made Huxley theory of drop in hemiplegics action potential available in Europe 1957: 1st cochlear implant developed 1973-74: organized clinical trials of the 1979: 1st 1934: Electronic 1958: Internal 1st wearable cochlear auditory hearing aid developed pacemaker implant begin brainstem developed implant 1930 1940 1950 1960 1970

1971: 1945: Invention 1956 Nobel Prize 1961: Silicon Microprocessor of transistor of Physics awarded chips first appear invented (Intel, to Shockley, (TI, J. Kilby) 4004) Bardeen and Brattain 1963: CMOS 1977: VLSI invented developed(Modular 1959: MOSFET (Fairchild, design by Mead invented (BL, Wanlass) and Conway) D.Khang) Engineering/Computer Milestones 15 Finn, Warren E., and Peter G. LoPresti, eds. Handbook of neuroprosthetic methods. CRC Press, 2002. Neural prosthetic Milestones

1980: 1st successful 1995: 1997: 2000: 1986-95: FES allows FDA approval 1-channel cochlear paraplegics to stand - Human trials of visual - FDA authorizes implant in a child cortex prosthesis of DBS on Optobionics to begin - German group begin thalamus for human trials of Subretinal implant Parkinson’s Artificial Silicon 1981: Peripheral nerve Disease Retina (ASR) bridge implanted into st 1996: Optic nerve - FDA approval of 1 spinal cord of rat 1988: MIT-Harvard, prosthesis middle-ear implant Johns Hopkins begin development - FAD approval of research on begins in Belgium auditory brainstem epiretinal implant implant

1980 1985 1990 1995 2000

1981: IBM PC, STM invented 2000: Deep Brain Stimulation (ACTIVA) develped to treat 1985: MS Windows Parkinson’s disease developed

1980: silicon 1989: Intel 486 1998: Google microelectrode for processor extracellular recording begun Engineering/Computer Milestones 16 Finn, Warren E., and Peter G. LoPresti, eds. Handbook of neuroprosthetic methods. CRC Press, 2002. Neural prosthetic Milestones

2005-2009: 2004: 1500 channel subretinal Human- photodiode array by implanted BCI German group 2005: Optogenetic 2013: FDA approval of system for 2007: clinical trials of Secondsight Argus II 2002-2004: 16-channel mammalian 60-channel Argus II epiretinal prosthesis retinal prosthesis Argus I neuron begin developed

2000 2005 2010 2015

2008: 2010: 2012: 2014: 2003: completion iPhone 3G iPhone 4 iPhone 5 iPhone 6 of the Human Genome Project

2001: 2006: 1st Tesla all- st 1 dual-core 2004: electric vehicle processor (IBM) Facebook launched Engineering/Computer Milestones 17 Neural Prosthetic Engineering

• 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.

18 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)

19 http://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)

20 Journals we can publish our research in

• Includes, but not limited to, • Biosensors and Bioelectronics • Journal of Neural Engineering • Investigative Ophthalmology & Visual Science • Journal of Neuroscience Methods • Clinical & Experimental • Medical & Biological Engineering & Otorhinolaryngol Computing • Optics Letters • Biomedical Instrumentation and Technology • Biotechnology and Bioengineering • Journal of Clinical Engineering • Neuromodulation • Computer Methods and Programs • Nanotechnolgy in Biomedicine • Optics Communications • Neural Computation • NeuroImage • Science • Invest Ophthalmol Vision Science • Nature • Tissue Engineering • Small • Bioelectromagnetics • Optics Express • Sensors • Otology and Neurotology • Journal of Materials Science: • Journal of Neuromodulation Materials in Medicine • Sensors and Materials • Journal of Biomedicine and Biotechnology • Sensors & Actuators • Biochimica et Biophysica Acta • Computational and Mathematical Methods in Medicine • Medical Engineering & Physics

• ACS Nano • And more. 21 Cochlea’s Operating Principle

Cochlear's operating principles

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

22 Cochlear Implant for the Deaf

Normal Deafened

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

Figures from B. 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.

23 Number of channels = Number of electrode sites

(Illustration from Dorman and Wilson, 2004)

24 Initially it was seen to be impossible.

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

25 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 %

Cumulative number of implants across years Percent correct scores for 55 CI users

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

B. Wilson & M. Dorman (Hearing Research, 2008) 26 History of the Cochlear Implant

• Pioneers – Andre Djourno and Charles Eyries (in Paris, 1957) • Eyries implants Djourno's induction coils in two patients Djourno Eyries • Alternating current transmitted to the coil produces perception of sound (Physiologist) (ENT surgeon) • 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 – William House (Los Angeles, 1969) (ENT Surgeon) • Implants first hardwire five-electrode system in 3 patients – Robert Michelson (San Francisco, 1970) House/3M • Implant 3 patients using a gold two-electrode system ( Advanced Bionics) single channel device – 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)

27 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) Rod Saunders (First multi- – Research supported by public donation (commenced 1967) channel CI patient) and – First Multichannel Cochlear Implant Patient (1978)  Cochlear Ltd. Graeme Clark

• 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.

28 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

29 Recent Advances

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

30 Retinal Implant: Visual Prosthesis

31 Anatomy of an Eye

32/31 Retinal Structure Responsible for Vision

33 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

AMD RP 34/31 Retinal Prosthesis (Artificial Retina)

Retinal prosthesis: Retina  Replace the function of degenerated photoreceptors  Light → Neural Signal Optic Nerve  By electrical stimulation of retinal cells  Microelectrodes array implanted into retina LGN

Visual Cortex

 Drug Delivery  Drug reservoir and needle  Limited duration time

http://www.rpip.tohoku.ac.jp/seeds/profile/104/lang:en/  Stem Cell  Differentiation  Retinal progenitor cells by • Embryonic stem cell (ESC) • Induced pluripotent stem cell (iPSC)

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

 Optogenetics  Channel Rhodopsin  Light-gated ion cannel  Neural activity controlled by light

Deisseroth group 36 Visual restoration: Electrical stimulation

Retina

Optic Nerve Prosthesis Optic Nerve

LGN (Lateral Geniculate Nucleus)

Cortical Prosthesis Visual Cortex

37 Principle of Artificial Retina Device

3 1

2 38 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

39 40 USC-SecondSight

• 2013.2. FDA Approval • Argus II 60-Channel Epi-retinal

41 An Artificial Vision Patient How many pixels are required ?

8 x 8 32 x 32 320 x 320

. 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

43 Deep Brain Stimulator

44 History of Deep Brain Stimulation • 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) Electric Ray  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 Advertisement for electrical stimulation in the Boston Globe from 1882 45 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

46 Deep Brain Stimulation- PD

Medtronic Inc. Activa® Tremor Control Therapy 47 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 substantia nigra • 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 48 Deep Brain Stimulation-Dystonia

Medtronic Inc. Activa® Tremor Control Therapy 49 Deep Brain Stimulation--Pain

Medtronic Inc. Activa® Tremor Control Therapy 50 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)