2011.09.14.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 1 Development of Complex Curricula for Molecular Bionics and InfobionicsPrograms within a consortial* framework** Consortium leader PETER PAZMANY CATHOLIC UNIVERSITY Consortium members SEMMELWEIS UNIVERSITY, DIALOG CAMPUS PUBLISHER The Project has been realized with the support of the European Union and has been co-financed by the European Social Fund *** **Molekuláris Bionikaés InfobionikaSzakok tananyagának komplex fejlesztése konzorciumi keretben ***A projekt az Európai Unió támogatásával, az Európai Szociális Alap társfinanszírozásával valósul meg. PETER PAZMANY CATHOLIC UNIVERSITY SEMMELWEIS UNIVERSITY sote_logo.jpg dk_fejlec.gif INFOBLOKK 2011.09.14. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 2 Peter Pazmany Catholic University Faculty of Information Technology NEURAL INTERFACES AND IMPLANTS RETINAL IMPLANTS www.itk.ppke.hu (Neurális interfészek és implantátumok) (Retina implantátumok) Ákos Kusnyerik, Bálint Péter Kerekes and György Karmos LECTURE9 NEURAL INTERFACES AND PROSTHESES:RETINAL IMPLANTS 2011.09.14. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 3 www.itk.ppke.hu CONTENTS • Aims • Biological basics– The structure of the eye – The structure of the retina – The visual pathway – Retinal degenerations • Basic research areas on visual prostheses • Visual implants– Retinal implants – Cortical implants – Other solutions NEURAL INTERFACES AND PROSTHESES:RETINAL IMPLANTS WORLD’S ARTIFICIAL VISION CENTERS 4 2011.09.14. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 www.itk.ppke.hu MerabetLB, RizzoJF, Pascual-LeoneA, FernandezE. NeuralEng. 4 (2007) NEURAL INTERFACES AND PROSTHESES:RETINAL IMPLANTS 2011.09.14. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 5 www.itk.ppke.hu AIMS Theobjectiveistoevaluatethesafetyandutilityofthedifferentartificialretinaimplantsinprovidingvisualfunctiontoblindsubjectswithseveretoprofoundretinitispigmentosa. Theoutcomeofclinicaltrialrevealsthepossibilitiesoftheretinalimplanttoimprovethesituationofpatientswithhereditaryretinalblindnesscausedbydegenerationsoftheouterretina.Furtheraimsaretostudyimportantinformationonsafetyandefficacyofsub-retinalimplants. Patientssufferingfromhereditaryretinaldegenerationreceivearetinalimplanttorestoresight. http://www.clinicaltrials.gov NEURAL INTERFACES AND PROSTHESES:RETINAL IMPLANTS 2011.09.14. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 6 www.itk.ppke.hu BIOLOGICAL BASICS • The structure of the eye • The structure of the retina • The visual pathway • Retinal degenerations NEURAL INTERFACES AND PROSTHESES:RETINAL IMPLANTS 2011.09.14. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 7 www.itk.ppke.hu THE STRUCTURE OF THE EYE retinaszov eye LAYERS OF THE VERTEBRATE RETINA (1.) From innermost to outermost include: • Inner limiting membrane–Müllercellfootplates • Nerve fiber layer–essentially the axons of the ganglion cell nuclei • Ganglion cell layer–layer that contains nuclei of ganglion cells, the axons of which become the optic nerve fibers for messages • Inner plexiformlayer–contains the synapse between the bipolar cell axons and the dendrites of the ganglion and amacrinecells. • Inner nuclear layer–contains the nuclei and surrounding cell bodies (perikarya) of thebipolar cells. 2011.09.14. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 8 NEURAL INTERFACES AND PROSTHESES:RETINAL IMPLANTS www.itk.ppke.hu LAYERS OF THE VERTEBRATE RETINA (2.) • Outer plexiformlayer–projections of rods and cones ending in the rod spherule and cone pedicle, respectively. These make synapses with dendrites of bipolar cells.In themacular region, this is known as theFiber layer of Henle • Outer nuclear layer • External limiting membrane–layer that separates the inner segment portions of the photoreceptors from their cell nucleus • Photoreceptor layer–rods/cones • Retinal pigment epithelium 2011.09.14. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 9 NEURAL INTERFACES AND PROSTHESES:RETINAL IMPLANTS www.itk.ppke.hu NEURAL INTERFACES AND PROSTHESES:RETINAL IMPLANTS 2011.09.14.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 10 www.itk.ppke.hu THE STRUCTURE OF THE RETINA R,rod; C,cone, FMB,flatmidgetbipolarcell;IMB,invaginatingmidgetbipolarcell; H,horizontalcell; IDB,invaginatingdiffusebipolarcell; RB,rodbipolarcell; I,interplexiformcell; A,amacrinecell; G,ganglioncell; MG,midgetganglioncell. http://www.scholarpedia.org/article/Retina ret NEURAL INTERFACES AND PROSTHESES:RETINAL IMPLANTS Fovea: responsibleforsharpcentralvision Blind spot: wheretheopticnerveescapestheeyeball(nocones,norods) Macula dense with cones and rods Thediagramshowstherelativeacuityofthelefthumaneye(horizontalsection)indegreesfromthefovea. http://en.wikipedia.org/wiki/Retinal_prosthesis TÁMOP –4.1.2-08/2/A/KMR-2009-0006 2011.09.14.. www.itk.ppke.hu 724px-AcuityHumanEye 11 2011.09.14.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 12 NEURAL INTERFACES AND PROSTHESES:RETINAL IMPLANTS THE „NUMBERS” RELATED WITH THE EYE The eye: 10 cm3, axial length: 24 mm, Vitreous humour: 4-6,5 ml, 98% H2O Retina: thickness 150-500 µm ~ 126 million photoreceptors ~ 1,2 million ganglion delegates the information to the cortex 120 M rod –6.5 M cone –1 M fiber(big convergence) Photoreceptor : ganglion cell = 1:100 Fovea information processing capability: ~ 0.6 Mb/s www.itk.ppke.hu NEURAL INTERFACES AND PROSTHESES:RETINAL IMPLANTS THE SPECTRAL SENSITIVENESS OF THE CONETYPES 2011.09.14.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 www.itk.ppke.hu 13 Dowling:"The Retina: an approachable part of the brain." HUP1987 NEURAL INTERFACES AND PROSTHESES:RETINAL IMPLANTS PHOTORECEPTORS REACTION AND ITS PROPAGATION www.itk.ppke.hu 2011.09.14.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 300px-Retina_figure_4 http://www.scholarpedia.org/article/Retina 14 Intracellularresponsesfromreceptor,horizontal,bipolar, amacrine,andganglioncellsofmudpuppyretina.Distal retinalneurons(receptor,horizontal,andbipolarcells) respondtoilluminationwithsustainedgradedpotentials; proximalretinalneuronsshowbothsustainedandtransient potentialsandactionpotentials.Receptor,bipolar,and ganglioncellsresponddifferentlytocenter(spot)and surround(annular)illumination.Horizontalandamacrine cellsusuallyrespondsimilarlytospotandannular illumination;here,responsestoasmallannulus(250?m) areshownthatstimulateboththecenterandsurroundofthe receptivefield.Thebipolarcellillustratedisacenter- hyperpolarizingcell,theamacrinecellshownisatransient amacrinecell,andtheganglioncellisanoff-centercell. Arrowsindicateinageneralwayhowtheresponsesare synapticallygenerated. NEURAL INTERFACES AND PROSTHESES:RETINAL PROSTHESES ON-AND OFF-BIPOLAR CELLS a) Idealizedresponsesandreceptivefieldmapsforon-center(top)andoff-center(bottom)contrast-sensitiveganglioncells.Thedrawingsontheleftrepresenthypotheticalresponsestoaspotoflightpresentedinthecenterofthereceptivefield,inthesurroundofthereceptivefield,orinboththecenterandsurroundregionsofthereceptivefield.A+symbolonthereceptivefieldmapindicatesanincreaseinthefiringrateofthecell,thatis,excitation;a–symbolindicatesadecreaseinthefiringrate,thatis,inhibition. b) Idealizedresponsesandareceptivefieldmapforadirection-sensitiveganglioncell.Suchcellsrespondwithaburstofimpulsesatboththeonsetandtheterminationofaspotoflightpresentedanywhereinthecell’sreceptivefield.Thisresponseisindicatedby+symbolsalloverthemap.Movementofaspotoflightthroughthereceptivefieldinthepreferreddirection(opencircle)elicitsfiringfromthecellthatlastsforaslongasthespotiswithinthefield.Movementofaspotoflightintheopposite(null)direction(opensquare)causesinhibitionofthecell’smaintainedactivityforaslongasthespotiswithinthereceptivefield. 2011.09.14.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 300px-Retina_figure_5 http://www.scholarpedia.org/article/Retina 15 www.itk.ppke.hu NEURAL INTERFACES AND PROSTHESES:RETINAL PROSTHESES* GENERATION OF THE ON AND OFF REACTION www.itk.ppke.hu 2011.09.14.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 16 NEURAL INTERFACES AND PROSTHESES:RETINAL PROSTHESES* 2011.09.14.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 17 www.itk.ppke.hu THE VISUAL PATHWAY: eye -> retina -> optic nerve -> LGN (6 layer) -> visual cortices -> higher order cortices VISUAL PROCESSING: visual convergence/ divergence, visual paths crossings, objects placement on retina, LGN, and visual cortex wikipedia.org 2011.09.14.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 18 NEURAL INTERFACES AND PROSTHESES:RETINAL PROSTHESES www.itk.ppke.hu CONVERGENCEAND DIVERGENCEINTHEVISUAL PATHWAY H.F. Kreyand H. Brauer(1988) NEURAL INTERFACES AND PROSTHESES:RETINAL PROSTHESES 2011.09.14.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 19 www.itk.ppke.hu RETINAL DEGENERATIONS Age-related macula degeneration (AMD), Retinitis pigmentosa(RP), Choroidereamia … RESEARCH AREAS FOR TREATING RETINAL DISORDERS: -genetically modified cells -medicinal replacement of the dead cells cell transplantation, -stem-cell research -retinal implants NEURAL INTERFACES AND PROSTHESES:RETINAL PROSTHESES* www.itk.ppke.hu 2011.09.14.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 20 NEURAL INTERFACES AND PROSTHESES:RETINAL PROSTHESES www.itk.ppke.hu 2011.09.14.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 RP CHANGE OF VISION IN AMD-AND RP DISEASE 21 NEURAL INTERFACES AND PROSTHESES:RETINAL PROSTHESES ARTIFICIAL SIGHT: IMPACT ON BLINDNESS “Blindness is feared more than cancer” Worldwide, many 100,000’stotally blind from photoreceptor loss and loss of optic nerve function maybe helped by a low resolution device Millions of patients profoundly impaired by these diseases may be helped by a higher resolution device The Problem what needs to be solved: 1.5 million people related with the most inheritable blindness clinical picture-the retinitis pigmentosa-worldwide; In developed world nearly 700.000 people diagnosed AMD yearly; In Germany more than 100.000 blind people live ; and the number is growing with thousands a year. The most frequent degenerate retinal disease: -Retinitis pigmentosa(RP) (10%) and -Age-related Macular-Degeneration (15%) (ARMD) www.itk.ppke.hu 2011.09.14.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 22 NEURAL INTERFACES AND PROSTHESES:RETINAL PROSTHESES SPATIAL LIMITS: RETINAL REWIRING byRobert Marc • Ultra-structural evidence from donor RP/AMD retinas: –Extensive rewiring of inner retinal cells –Neuriteprocesses spread over long distances (~300µm) –Glial cells migrate into choroid • Injected electrical current may spread through www.itk.ppke.hu 2011.09.14.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 23 Progress in Retinal and Eye Research (2003)22:5, 607-655 NEURAL INTERFACES AND PROSTHESES:RETINAL PROSTHESES SPATIAL LIMITS: IMPLICATIONS OF RETINAL REWIRING • Stimulating degenerated retina may be like writing on tissue paper with a fountain pen: –Charge diffusion over distances up to 1o –Phospheneslikely to be blurry (Gaussian blobs), not sharp –Minor effect if electrodes are widely spaced (>= 2o) –Phosphenesfrom closely spaced electrodes may overlap/fuse Retinal prosthetic vision may be pretty blurry… TÁMOP –4.1.2-08/2/A/KMR-2009-0006 2011.09.14.. www.itk.ppke.hu 24 G. Dagnelie, Lions Vision Research & Rehabilitation JHU, 2004 NEURAL INTERFACES AND PROSTHESES:RETINAL PROSTHESES www.itk.ppke.hu 2011.09.14.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 TEMPORAL LIMITS: PERSISTENCE • Single electrode, acute testing: –Flicker fusion occurs at 25-40 Hz • Multi-electrodeimplant testing: –Rapid changes are hard to detect –Flicker fusion at lower frequency? Maybe prosthetic vision will be not just blurry, but also streaky… 25 G. Dagnelie, Lions Vision Research & Rehabilitation JHU, 2004 NEURAL INTERFACES AND PROSTHESES:RETINAL PROSTHESES 2011.09.14.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 26 www.itk.ppke.hu BASIC RESEARCH AREAS ON VISUAL IMPLANTS: • Cortical stimulation (N. Cottaris, Detroit) •Implants visual simulation (G. Dagnelie, Baltimore) •Electronic impulses distribution (S. Fried, Boston) •Dynamics of retina degeneration (R. Marc, Salt Lake City) •Optimal impulse pattern making (R. Wilke,Tübingen) •Picture coding (R. Eckmiller, Bonn) •Chronic electrical stimulations effect in tissue (J. Weiland, Baltimore) G. Dagnelie, Lions Vision Research & Rehabilitation JHU, 2004 NEURAL INTERFACES AND PROSTHESES:RETINAL PROSTHESES* 2011.09.14.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 27 www.itk.ppke.hu VISUAL IMPLANTS • Retinal prostheses• Epiretinal • Subretinal • Cortical implants • Optic nerve • Other solutions impl NEURAL INTERFACES AND PROSTHESES:RETINAL PROSTHESES 2011.09.14.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 28 www.itk.ppke.hu VISUAL IMPLANTS epiretinal, subretinalsolutions, comparison of retinal implants Preclinical researches: MIT Visual Prosthesis (S. Kelly Cambridge, USA) The Australian Visual Prosthesis (G. Suaning, Sydney, Australia) Cortical Prosthesis Project (V.Towle, Chicago , USA) The C-Sight Project (Q. Ren, Beijing, China) The Seoul Visual Prosthesis (Hum Chung, S-Korea) The Suprachoriodal-approach (Y.Terasawa, Japan) Boston Retinal Implant Project (J.Rizzo, Wyatt,Boston,USA) High Res. Photovoltaic Prosthesis (D. Palanker, Stanford, USA) Clinicalsurveys(clinicaltrials.gov) NEURAL INTERFACES AND PROSTHESES:RETINAL PROSTHESES 2011.09.14.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 29 www.itk.ppke.hu VISUAL IMPLANTS Epiretinal –Second Sight ARGUS Trials (M Humayun), USA –The EpiretTrial (P Walter, Mokwa, Schanze), Aachen, Giessen, Germany. Subretinal –Retina Implant Pilot Study (E Zrenner), TübingenGermany. –Under registration: Boston Retina Implant (J. Rizzo) Boston, USA IMI-IRIS Trial –GisbertRichard (Hamburg, Germany) 2011.09.14.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 30 NEURAL INTERFACES AND PROSTHESES:RETINAL PROSTHESES VISUAL IMPLANTS Epiretinal SECOND SIGHT ARGUS TRIALSUSA Extra-ocular processing; only electrode array inside eye: Based on proven cochlear implant technology –Six patients implanted with 4x4array –External camera and image processor –Psychophysics in progress –Today: 60 electrodes on a single chip Website: http://www.2-sight.com www.itk.ppke.hu artificial retina project ARGUS • Leader: M. Humayun, LA, CA,USA • Argus I –2002-2004: 6 patient: –16 pixel –Result: light seeing, moving recognized, eating devices were recognized • Argus II –from 2005l: 36 patient implanted –60 pixel –Result: lines, lights, visual feeling BBC's InsideOut London 2011.09.14.. NEURAL INTERFACES AND PROSTHESES:RETINAL PROSTHESES TÁMOP –4.1.2-08/2/A/KMR-2009-0006 www.itk.ppke.hu 8841_200208105335 2011.09.14.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 32 NEURAL INTERFACES AND PROSTHESES:RETINAL PROSTHESES Epiretinal –THE EPIRETTRIAL(P Walter, Mokwa, Schanze), Aachen, Giessen, Germany. Wiewtheattachmentsonthelinksbelow http://www.egms.de/static/de/meetings/ri2009/09ri20.shtml http://www.egms.de/static/de/meetings/ri2009/09ri09.shtml www.itk.ppke.hu epiret 2011.09.14.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 33 NEURAL INTERFACES AND PROSTHESES:RETINAL PROSTHESES THE EPIRETTRIAL 2003-2006 EPIRET3 prototype designed and fabricated. EPIRET3 is a completely intraocular retinal stimulator with integrated electronics and inductive links for data and energy transfer, data handling, and pulse generation. 25 iridium oxide electrodes are mounted on a polyimide base. Minimally invasive implantation procedure. Animal experiments demonstrated the long term functionality and biocompatibility of the system. Cortical recordings and metabolic mapping of the visual cortex in implanted cats, local activations occurred within the visual cortex corresponding to the area of stimulation in the retina. 6 blind volunteers with Retinitis pigmentosa. http://www.egms.de/static/de/meetings/ri2009/09ri20.shtml www.itk.ppke.hu 2011.09.14.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 34 NEURAL INTERFACES AND PROSTHESES:RETINAL PROSTHESES THE EPIRETTRIAL The implant was inserted after enlargement of the corneal incision. The receiver module was inserted in the posterior chamber and transsclerallysutured. The stimulator module was placed on the retinal surface in the macula and retinal tacks were used for stable fixation. No intraoperative complications. Postoperatively, mild inflammatory responses were seen. At three time points stimulus thresholds were determined for selected electrodes and perception patterns were recorded in comparison to the stimulation patterns. In all patients the implant was fully functional after the implantation procedure. The phosphenepatterns corresponded to the stimulus patterns and stimulus thresholds on average were 15nC/cm2. Angiograms showed no vascular changes. In summary, the EPIRET3 system proved that a completely implantable retinal implant system without any transscleralconnections for data and energy can be fabricated and implanted. http://www.egms.de/static/de/meetings/ri2009/09ri20.shtml www.itk.ppke.hu www.itk.ppke.hu 2011.09.14.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 35 NEURAL INTERFACES AND PROSTHESES:RETINAL PROSTHESES* VISUAL IMPLANTS Subretinal –RETINA IMPLANT PILOT STUDY(E Zrenner), Tübingen Germany. Leader: E. Zrenner Tübingen Germany –from 2005: 11 patient implanted. –Resolution: 1520 pixel (40x38) –Result: lines, lights, visual feeling, more greytone, moving-, and some daily stuffs were recognized. LandoltC test (VA=20/1240 (logMAR1.79 A 2011.09.14.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 36 NEURAL INTERFACES AND PROSTHESES:RETINAL PROSTHESES VISUAL IMPLANTS Subretinal –BOSTON RETINA IMPLANT(J. Rizzo) Boston, USA Emphasis on extraoculartransmission and processing away from stimulation site: • Receiver coil on temporal sclera • Multi-chip implant • Hermetic packaging Interactive modell: http://www.bostonretinalimplant.org/chip.php http://www.bostonretinalimplant.org/implant2.html www.itk.ppke.hu 2011.09.14.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 37 NEURAL INTERFACES AND PROSTHESES:RETINAL PROSTHESES BOSTONRETINAIMPLANT Artist’sconceptionofthesecondgenerationimplantsystem.Theimageobtainedbyanexternalcameraistranslatedintoanelectromagneticsignaltransmittedwirelesslyfromtheexternalprimarydatacoilmountedonapairofglassestotheimplantedsecondarydatacoilattachedtotheoutsidewall(sclera)oftheeyesurroundingtheiris.Poweristransmittedsimilarly.Mostofthevolumeoftheimplantliesoutsidetheeye,withonlytheelectrodearraypenetratingthesclera.Right:Theelectrodearrayisplacedbeneaththeretinathroughascleralflapinthesterileregionoftheeyebehindtheconjunctiva. http://www.bostonretinalimplant.orghttp://www.rle.mit.edu/media/pr150/20.pdf www.itk.ppke.hu 2011.09.14.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 38 NEURAL INTERFACES AND PROSTHESES:RETINAL PROSTHESES VISUAL IMPLANTS IMI-IRIS Trial –GisbertRichard (Hamburg, Germany) Leader: GisbertRichard, Hamburg, Germany •First etap: in 2003: 45min20 patient •Second etap: in 2005: 4 patient •Third etap: from 2007 www.itk.ppke.hu 2011.09.14.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 39 NEURAL INTERFACES AND PROSTHESES:RETINAL PROSTHESES VISUAL IMPLANTS THE RETINAL IMPLANT PROJECT (MIT) Mockupofthesecond-generationimplant.Allelectronicpartsarehermeticallysealedinatitaniumcasewith19feedthroughpinsconnectedtoanexternalflexcircuit.Thepoweranddatacoilsaresuturedtotheeyearoundtheiris(undertheconjunctiva)whiletheelectrodearrayisinsertedsubretinallyatthebackoftheeye.Thecaseissuturedtothesclerathroughthetwosuturetabsshown. www.itk.ppke.hu Left:Penetratingelectrodearray. Right:SEMimageofthe70µmtallSU8pillars. http://www.rle.mit.edu/media/pr150/20.pdf 2011.09.14.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 40 NEURAL INTERFACES AND PROSTHESES:RETINAL PROSTHESES www.itk.ppke.hu COMPARISON OF RETINAL IMPLANTS EPIRETINALAPPROACH: • Pros -Stimulating close to the photoreceptors so one can take advantage of native processing power in thalamus and cortex. -Surgical complications not necessarily as significant as cortical approach. • Cons- Requires functional optic nerve pathway. - May stimulate optic nerve fibers rather than cell bodies: this will greatly complicate visuotopicorganization. - Hard to imagine how saccadic eye motions will not cause very high sheer loads on implanted arrays(and eventual dislodging of array). - Difficult surgical access. - Difficult to adhere electrode array to retina. NEURAL INTERFACES AND PROSTHESES:RETINAL PROSTHESES COMPARISON OF RETINAL IMPLANTS SUBRETINALAPPROACH – Pros• Stimulating closest to the photoreceptors so one can take advantage of retinal, thalamic and cortical signal processing. • If bipolar cells can be directly stimulated, retinotopicorganization should be preserved. • Surgical complications not necessarily as significant as cortical approach. – Cons• Requires functional optic nerve pathway to convey signals to cortex. • Blockage of nutrients from choroid to remnant retina by the implant. • Very complex surgical access. • Can’t stimulate cells passively with microimplants (requires external power). www.itk.ppke.hu 2011.09.14.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 41 NEURAL INTERFACES AND PROSTHESES:RETINAL PROSTHESES COMPARISONOF RETINALIMPLANTS www.itk.ppke.hu 2011.09.14.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 42 NEURAL INTERFACES AND PROSTHESES:RETINAL PROSTHESES* Example of a profile of electrical excitation produced by light-sensitive areas of a subretinalimplant, activated by electrodes spaced 70 µmapart. (Bottom) If a regular three dimensional image (the face or optotype) is transformed into a two-dimensional excitation profile, the image would be represented by a two-dimensional array of 40 by 40 small excitation spots ( pixels), sized according to the width of the local electrical wave (see second column). When the light intensity is increased, each of the excitation spots enlarges and a more homogeneous picture emerges (see third column). A further increase in luminosity causes a merging of excitation spots, resulting in a blurred picture (see fourth column). www.itk.ppke.hu 2011.09.14.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 4040subret 43 THE PICTUREOF A 40X40ELECTRODERETINALIMPLANT NEURAL INTERFACES AND PROSTHESES:RETINAL PROSTHESES* 2011.09.14.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 44 www.itk.ppke.hu VISUAL IMPLANTS OtherSolutions: invitroand invivoexperiments NEURAL INTERFACES AND PROSTHESES:RETINAL PROSTHESES Other Solutions: In vitro: Successful subretinalstimulation of neural network of intact and degenerated retinas Threshold: 0.5 …. 1 nC Dynamic range: 0.5 to 10 nC Spatial resolution: 0.5°viewing angle In vivo: Epi/subretinalstimulation generates retinotopiccorrect cortical excitation Spatial resolution: 1°viewingangle www.itk.ppke.hu 2011.09.14.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 45 NEURAL INTERFACES AND PROSTHESES:RETINAL PROSTHESES DIRECTSTIMULATIONWITHELECTRODES www.itk.ppke.hu 2011.09.14.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 46 NEURAL INTERFACES AND PROSTHESES:RETINAL PROSTHESES CHIP DESIGN AnodicPulses: 0,5 -2,0 V (0,5 ms–5ms@ 0…20 Hz) -> nearlycharge-balanced 1500 pixel firingsimultaneously www.itk.ppke.hu 2011.09.14.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 47 2011.09.14.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 48 NEURAL INTERFACES AND PROSTHESES:RETINAL PROSTHESES* POWER-SUPPLY Afterthesecondpostop. weekitenablesfree movement www.itk.ppke.hu 2011.09.14.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 49 NEURAL INTERFACES AND PROSTHESES:RETINAL PROSTHESES EFFECT OF THE ELECTRIC FIELD Laboratory testing: electrode interaction negligible Electric field simulation: some edge effects with extended stimulation („picture frame“) -delicate patterns to be preferred -avoid black-on-white scenes A.Stett, M.Gerhardt, 2007 www.itk.ppke.hu 2011.09.14.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 50 NEURAL INTERFACES AND PROSTHESES:RETINAL PROSTHESES DETERMINING THE VISUAL SHARPNESS OF IMPLANTED PATIENTS, EFFECT OF THE RESOLUTION www.itk.ppke.hu felbont 2011.09.14.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 51 NEURAL INTERFACES AND PROSTHESES:RETINAL PROSTHESES* CORTICAL IMPLANTS: CONCEPT www.itk.ppke.hu 2011.09.14.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 52 NEURAL INTERFACES AND PROSTHESES:RETINAL PROSTHESES CORTICALIMPLANTS: Secondaryvisualcortex TheTwoStreamshypothesisisawidelyaccepted,butstillcontroversial,accountofvisualprocessing.Asvisualinformationexitstheoccipitallobe,itfollowstwomainchannels,or"streams". Theventraltravelstothetemporallobeandisinvolvedwithobjectidentification.Thedorsalstream(or,"wherepathway")terminatesintheparietallobeandprocessspatiallocations. www.itk.ppke.hu Ventral-dorsal_streams http://en.wikipedia.org/wiki/Two_Streams_hypothesis CONCEPT 2011.09.14.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 53 NEURAL INTERFACES AND PROSTHESES:RETINAL PROSTHESES Dobelle William Dobelle(† 2004) • Antiquated electrode technology, but it works, somewhat… • Sobelvision filtered input may not convey real form vision, but does provide crude localization Jerry reportedly had 68 electrodes, technically offering up to 68 pixels, but resulting in only some 20 effective pixels (phosphenes) at irregular positions and narrow field 16 pixels in a of view, like in tunnel vision. Dobelle,W.H., et al., 1976 www.itk.ppke.hu CORTICAL IMPLANTS: _606938_blind_man_300gra 2011.09.14.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 54 NEURAL INTERFACES AND PROSTHESES:RETINAL PROSTHESES CORTICAL IMPLANTS Dobelle Laboratories www.itk.ppke.hu NEURAL INTERFACES AND PROSTHESES:RETINAL PROSTHESES 2011.09.14.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 55 www.itk.ppke.hu Other solutions: Concept of the optic nerve stimulation 2011.09.14.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 56 NEURAL INTERFACES AND PROSTHESES:RETINAL PROSTHESES www.itk.ppke.hu OPTIC NERVE STIMULATION Claude Veraart • Emphasis on processing crude information: –4-8 electrodes in cuff around optic nerve –Light-dark, direction, and stimulus strength can be learned • Two RP patients implanted (1998/2004) Website: http://www.md.ucl.ac.be/gren/Projets/optivip.html 2011.09.14.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 57 NEURAL INTERFACES AND PROSTHESES:RETINAL PROSTHESES* www.itk.ppke.hu SANGHAIOPTICNERVEVISUALPROSTHESIS sanghai másolata 2011.09.14.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 58 NEURAL INTERFACES AND PROSTHESES:RETINAL PROSTHESES* www.itk.ppke.hu OTHER SOLUTIONS: BRAINPORT Neuroscientist Paul Bach-y-Rita hypothesized in the 1960sthat "we see with our brains not our eyes.” University of Pittsburgh Medical Center's UPMC EyeCenter http://www.nei.nih.gov/news/briefs/weihenmayer.asp NEURAL INTERFACES AND PROSTHESES:RETINAL PROSTHESES www.itk.ppke.hu 2011.09.14.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 59 ACKNOWLEDGEMENT University of Tuebingen, Tuebingen, Germany; Centre for Ophthalmology prof. E. Zrenner, prof. K. U. Bartz-Schmidt, R. Wilke, F. Gekeler, K. Porubska, Section Experimental MRI of the CNS, prof. W. Grodd, prof. U. Klose, M. Kroeger Retina Implant AG, Reutlingen, Germany U. Greppmaier, A. Hekmat, W. Wrobel Hungarian Bionic Vision Center, Budapest, Hungary SemmelweisUniversity, Dept. of Ophthalmology prof. I. Süveges, prof. J Németh, M. Resch, PázmányUniversity, Information Technology Faculty prof. T. Roska, K Karacs University of Regensburg, Regensburg, Germany Dept. of Ophthalmology prof. H. Sachs Name Developer Placeof stimulation Camera Resolution Web Second sight USC Epiretinal Yes 60 electrode http://www.2-sight.com Boston retina implant Harvard/MIT Epiretinal Yes 24 electrode http://www.bostonretinalimplant.org Epi-Ret Uni Bonn Epiretinal Yes 100 electrode http://www.nero.uni-bonn.de/projekte/ri/ri-index-en.htm Australian Vision Prosthesis Ausztrália Epiretinal Yes 100 electrode http://bionic.gsbme.unsw.edu.au JapanVisual Preosthesis Japán retinal Yes http://www.io.mei.titech.ac.jp/research/retina MPDA Tübingen Subretinal No 1500 diode http://www.retina-implant.de Optoelectronic Retinal Prothesis Stanford Subretinal Yes http://www.stanford.edu/~palanker/lab/retinalpros.html Artificial Silicon Retina Optobionics Subretinal No 3500 diode http://www.stanford.edu/~palanker/lab/retinalpros.html Optivip UC Leuven Opticnerve Yes 4-8 electrode http://www.gren.ucl.ac.be/Projets/optivip.html IntracorticalVisual Prosthesis IIT, Chicago Visual cortex Yes http://www.iit.edu/engineering/bme/faculty/highlights Utah Visual Neuroprosthesis Utah Visual cortex Yes 625 electrode http://www.bioen.utah.edu/cni/projects/blindness.htm CORTIVIS Alicante Visual cortex Yes 128 electrode http://cortivis.umh.es NEURAL INTERFACES AND PROSTHESES:RETINAL PROSTHESES www.itk.ppke.hu 2011.09.14.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 60 LINKS: NEURAL INTERFACES AND PROSTHESES:RETINAL PROSTHESES www.itk.ppke.hu 2011.09.14.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 61 REFERENCES Finn, W.E., LoPresti, P.G. (eds.): Handbook of NeuroprostheticMethods, (Biomedical Engineering Series), CRCPress, 2003. Horch, K.W., Dhillon, G.D.(eds.):Neuroprosthetics: Theory and Practice (Series on Bioengineering & Biomedical Engineering -Vol. 2), World Scientific Pub Co., 2004. Humayun, M.S., Weiland,J.D., Chadler, G. (eds.): Artificial sight:basic research, biomedical engineering, and clinical advances, Springer, 2007 Zhou D., GreenbaumE. (eds.), Implantable Neural Prostheses 1 –Devices and Applications, Springer, 2009. Zhou, D.D., Greenbaum, E. (eds.): Implantable Neural Prostheses 2, Techniques and Engineering Approaches, Springer, 2010. Dagnelie, G. (ed.): Visual Prosthetics:Physiology, Bioengineering and Rehabilitation, Springer, 2011 MerabetLB, Rizzo JF3rd, Pascual-Leone A, Fernandez E.: 'Who is the ideal candidate?': decisions and issues relating to visual neuroprosthesis development, patient testing and neuroplasticity,J. Neural. Eng. 2007, 4:S130-135. Dowling, J.: Current and future prospects for optoelectronic retinal prostheses, Eye2009,23:1999–2005 Chader, G., Weiland, J., Humayun, M.S.: Artificial vision: needs, functioning, and testing of a retinal electronic prosthesis, Progress in Brain Research, 2009,175: 317-332. NEURAL INTERFACES AND PROSTHESES:RETINAL PROSTHESES www.itk.ppke.hu 2011.09.14.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 62 REVIEWQUESTIONS •Describe the structure of the vertebrate retina. • Describe the photoreceptors and their functions. • What kind of information processing is done in the retina? • What are the characteristic degenerative diseases of the retina? • Which are the main types of the visual implants? • What are the characteristics of the epiretinalimplants? • What are the characteristics of the subretinalimplants? • What kinds of non-retinal implant were suggested as visual prostheses?