Introduction to Neural Prosthesis

Transcription

1 Introduction to Neural Prosthesis Sung June Kim Neural Prosthetic Engineering 1

2 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

3 Successful Areas of Neural Prosthesis (Bionic Ear) Hearing: Cochlear Implant Vision: Retinal Implant Parkinson s Disease: DBS (Deep Brain Stimulation) Neural Prosthetic Engineering 3

4 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

5 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. Neural Prosthetic Engineering 5

6 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

7 Speech Processor, An example of External Unit www. bionicear.com, Neural Prosthetic Engineering 7

8 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

9 Example of the Internal Unit 10 mm Neural Prosthetic Engineering 9 Nurobiosys Corp., Korea

10 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

11 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

12 System example: Cochlear Implant 1 Sound Signal Microphone External Coil 3 Data & Power Transmission Internal Coil 4 Signal Demodulation Implantable Current Stimulator 6 Auditory Cortex 2 RF Modulation 5 Stimulation Pulse train Inserted Electrode array Wearable Speech Processor Neural Prosthetic Engineering 12

13 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

14 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

15 Neural prosthetic Milestones 1934: Electronic hearing aid developed 1952: Hodgkin- Huxley theory of action potential 1957: 1 st cochlear implant developed 1961: 1 st motor prosthesis for foot drop in hemiplegics 1958: Internal pacemaker developed : organized clinical trials of the 1 st wearable cochlear implant begin 1977: Bone-anchored hearing aid made available in Europe 1979: 1 st auditory brainstem implant : Invention of transistor 1956 Nobel Prize of Physics awarded to Shockley, Bardeen and Brattain 1961: Silicon chips first appear (TI, J. Kilby) 1971: Microprocessor invented (Intel, 4004) 1959: MOSFET invented (BL, D.Khang) 1963: CMOS invented (Fairchild, Wanlass) Engineering/Computer Milestones Finn, Warren E., and Peter G. LoPresti, eds. Handbook of neuroprosthetic methods. CRC Press, : VLSI developed(modular design by Mead and Conway) 15

16 Neural prosthetic Milestones 1980: 1 st successful 1-channel cochlear implant in a child 1981: Peripheral nerve bridge implanted into spinal cord of rat : FES allows paraplegics to stand 1988: MIT-Harvard, Johns Hopkins begin research on epiretinal implant 1995: - Human trials of visual cortex prosthesis - German group begin Subretinal implant 1996: Optic nerve prosthesis development begins in Belgium 1997: FDA approval of DBS on thalamus for Parkinson s Disease 2000: - FDA authorizes Optobionics to begin human trials of Artificial Silicon Retina (ASR) - FDA approval of 1 st middle-ear implant - FAD approval of auditory brainstem implant : IBM PC, STM invented 1980: silicon microelectrode for extracellular recording begun 1985: MS Windows developed 1989: Intel 486 processor 1998: Google 2000: Deep Brain Stimulation (ACTIVA) develped to treat Parkinson s disease Engineering/Computer Milestones Finn, Warren E., and Peter G. LoPresti, eds. Handbook of neuroprosthetic methods. CRC Press,

17 Neural prosthetic Milestones 2004: Humanimplanted BCI : 16-channel retinal prosthesis Argus I developed 2005: Optogenetic system for mammalian neuron : 1500 channel subretinal photodiode array by German group 2007: clinical trials of 60-channel Argus II begin 2013: FDA approval of Secondsight Argus II epiretinal prosthesis : completion of the Human Genome Project 2008: iphone 3G 2010: iphone : iphone : iphone : 1 st dual-core processor (IBM) 2004: Facebook launched 2006: 1 st Tesla allelectric vehicle Engineering/Computer Milestones 17

18 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

19 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

20 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

21 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 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. 21

22 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

23 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 ,

24 Number of channels = Number of electrode sites (Illustration from Dorman and Wilson, 2004) 24

25 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

26 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

27 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) William House (ENT Surgeon) Eyries (ENT surgeon) House/3M single channel device 27

28 History of the Cochlear Implant Development of a Mutichannel Device ( s) 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. Rod Saunders (First multichannel CI patient) and 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

29 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

30 Recent Advances Bilateral electrical stimulation Combined electric and acoustic stimulation (EAS) for patients with residual, low-frequency hearing 30

31 Retinal Implant: Visual Prosthesis 31

32 Anatomy of an Eye 32/31

33 Retinal Structure Responsible for Vision 33

34 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 RP AMD 34/31

35 Retinal Prosthesis (Artificial Retina) Retinal prosthesis: Replace the function of degenerated photoreceptors Light Neural Signal By electrical stimulation of retinal cells Microelectrodes array implanted into retina Retina Optic Nerve LGN Visual Cortex Second Sight 35

36 Visual restoration: Other therapies 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) 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

37 Visual restoration: Electrical stimulation Retina Optic Nerve Prosthesis Optic Nerve LGN (Lateral Geniculate Nucleus) Cortical Prosthesis Visual Cortex 37

38 Principle of Artificial Retina Device

39 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 40

41 USC-SecondSight FDA Approval Argus II 60-Channel Epi-retinal 41

42 An Artificial Vision Patient

43 How many pixels are required? 8 x 8 32 x x 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

44 Deep Brain Stimulator 44

45 History of Deep Brain Stimulation A.D 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 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. Electric Ray 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

46 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 FDA approved DBS of the thalamus for PD and essential tremor 2002 FDA approved DBS STN and GPi for symptoms of PD 46

47 Deep Brain Stimulation- PD Medtronic Inc. Activa Tremor Control Therapy 47

48 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 48

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

50 Deep Brain Stimulation--Pain Medtronic Inc. Activa Tremor Control Therapy 50

51 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) 51