9/14/2011. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 1 Development of Complex Curricula for Molecular Bionics and Infobionics Programs within a consortial* framework** Consortium leader PETER PAZMANY CATHOLIC UNIVERSITY Consortium members SEMMELWEIS UNIVERSITY, DIALOG CAMPUS PUBLISHER The Project has been realised with the support of the European Union and has been co-financed by the European Social Fund *** **Molekuláris bionika és Infobionika Szakok 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 Peter Pazmany Catholic University Faculty of Information Technology www.itk.ppke.hu (Neurális interfészek és protézisek ) LECTURE 1 INTRODUCTION (Bevezetés) GYÖRGY KARMOS NEURALINTERFACESAND PROSTHESES NEURALINTERFACESAND PROSTHESESINTRODUCTION 9/14/2011 TÁMOP –4.1.2-08/2/A/KMR-2009-0006 3 AIMS OF THE COURSE: In this course the students will become familiar with the new developments of neural engineering in the field of neuroprostheticdevices that can restore lost neural functions. These devices require direct interfaces with the peripheral and central nervous system. Some of these devices are already routinely used in the clinical practice like the cochlear prostheses for restoring hearing, others are still in the developmental or experimental phase. The lectures will give summary of the recent results in the divergent fields of neural interfaces and prostheses. Both engineering and medical aspects of the field will be shortly covered in the lectures. www.itk.ppke.hu NEURALINTERFACESAND PROSTHESESINTRODUCTION 9/14/2011 TÁMOP –4.1.2-08/2/A/KMR-2009-0006 4 DEFINITIONS Neuroprostheticsis a discipline related toneuroscience andbiomedical engineering, its main activity is the development and application of neuralprostheses. Neural prostheses are a series of devices that can substitute a motor, sensory or cognitive modality that might have been damaged as a result of an injury or a disease. Neural interface is a connection between the living tissue and a man-made device, in most case a bioelectrode. Electrode-tissue connectionis formed by the electrode, i. e. an electron conductor and an electrolyte i. e. an ionic conductor. Ideal electrode does not exist: electrodes cannot have ideal signal transmission characteristics. Living tissue is a chemically aggressive medium for electrodes: there is always a chemical reaction between the electrode and the tissue. www.itk.ppke.hu NEURALINTERFACESAND PROSTHESESINTRODUCTION 9/14/2011 TÁMOP –4.1.2-08/2/A/KMR-2009-0006 5 DEFINITIONS(CONT.) Recording electrodes detect bioelectric signals in the peripheral or central nervous system at single cell, local population or macropotentiallevel. Stimulating electrodes elicit excitation electrically in neural or muscle tissue by charge injection. Brain-computer interface (BCI) is a system that includes a means for measuring neural signals from the brain, a method/algorithm for decoding these signals and a technique for using this decoding to control a behavior or action. Biocompatibility:Implantable medical device do not elicit any undesirable local or systemic effects in the human body Biostability:implanted material should be stable and must be able to withstand attack from a harsh ionic body environment. www.itk.ppke.hu NEURALINTERFACESAND PROSTHESESINTRODUCTION 9/14/2011 TÁMOP –4.1.2-08/2/A/KMR-2009-0006 6 Neuroprostheticsis integrating different fields of medical and engineering disciplines. New discoveries in neuroproscheticsare always the result of close collaboration of experts in most different areas of research. Related areas: Neuroscience dechiphersthe neural codes in sensory systems reveals central representation of motor control commands. Understanding bioelectric signals needs complex signal analysis techniques to isolate action potentials of single neruons, to extract useful parameters from field potentials and EEG type activity. Material science is essential to supply materials suitable for encapsulation of pacemakers, to find better biocompatible electrode materials by developing new conducting polymers. Electrochemistry reveals complex processes at the electrode tissue interface. www.itk.ppke.hu NEURALINTERFACESAND PROSTHESESINTRODUCTION 9/14/2011 TÁMOP –4.1.2-08/2/A/KMR-2009-0006 7 Engineering sciences developed the electrode arrays recently successfully used in human subjects. Micromaschiningof micromechanical systems (MEMS) technology opened new vistas in sensor as well as actuator technology. Miniaturization of electrical circuits, large scale integrated circuits made possible production of implantable devices like hearing prostheses. Mathematical and computer sciences were essential in developing complex signal analysis methods and all the prostheses contain microprocessors with special purpose software. These were only examples. Neuroprostheticsis a rather new discipline. It has been grown at a tremendous rate in the last decade. Some products are successfully applied in everyday practice like cochlear implants. Others are in experimental or clinical trial phase. In the course we intend to give a survey of divergent areas of neuroprosthetics. www.itk.ppke.hu NEURALINTERFACESAND PROSTHESESINTRODUCTION 9/14/2011 TÁMOP –4.1.2-08/2/A/KMR-2009-0006 8 LECTURES OF THE COURSE: 1. Introduction 2. Physiologicalbasisof electricalstimulation 3. Functionalelectricalstimulation 4. Stereotaxictechnique, electrodeimplantation 5. Deep brainstimulation 6. Transcranialmagneticstimulation 7. Cochlearfunctin, implantablehearingaids 8. Cochlearprocesses 9. Retinalprostheses 10. Physiologicalbasisof brain-computerinterface 11. ProsthesesworkingonEEG and singlecellprinciple 12. Perspectivesof brain-machineinterface www.itk.ppke.hu NEURALINTERFACESAND PROSTHESESINTRODUCTION 9/14/2011 TÁMOP –4.1.2-08/2/A/KMR-2009-0006 9 HISTORICAL MILESTONES IN NEUROBIOLOGY OF ELECTRICAL STIMULATION AND NEUROPROSTHETICS Since the dispute of Galvani and Volta on „animal electricity” at the end of XVIII. century, the close link between nervous processes and electricity became generally known. Perhaps Aldini, the nephew and assistant of Galvani, was the first who demonstrated for the public in cadavers that electrical stimulation induce muscle twitches. LuigiGalvani(1737-1798)AlessandroVolta(1745-1827)GiovanniAldini(1762-1834) www.itk.ppke.hu NEURALINTERFACESAND PROSTHESESINTRODUCTION 9/14/2011 TÁMOP –4.1.2-08/2/A/KMR-2009-0006 10 In the XIX. century series of famous neurophysiologists revealed at the available technical level the basic neural processes by electrical stimulation in acute animal experiments. Matteucciwith his experiments he proved unequivocally, that the living organism can truly generate electric signals,Du Bois-Reymondcan be regarded as the founder of the experimental electrophysiology,Helmholtz was the first who measured the nerve conduction velocity in frog nerve. CarloMateucci(1811-1868)EmilduBois-Reymond(1818-1896)HermannL. F. von Helmholtz(1820-1894) www.itk.ppke.hu NEURALINTERFACESAND PROSTHESESINTRODUCTION 9/14/2011 TÁMOP –4.1.2-08/2/A/KMR-2009-0006 11 In the second part of the XIX. century already great diversity of devices and techniques were used in the general practice to carry out single or repetitive electrical stimulations through the skin to alleviate pain and cure different diseases. These can be regarded as early antecedents of the present transdermal electrical nerve stimulation (TENS) and functional electrical stimulation (FES). The pioneering work of first mapping the neocortex by electrical stimulation in dogs was carried out in the 1870sby two German scientists Fritsch and Hitzig. Their work was continued by Ferrier, who systematically studied the cortical areas of dogs and monkeys and inspired modern neurosurgery. Eduard Hitzig(1838-1907)Gustav Fritsch(1838-1927)David Ferrier(1843-1924) www.itk.ppke.hu NEURALINTERFACESAND PROSTHESESINTRODUCTION 9/14/2011 TÁMOP –4.1.2-08/2/A/KMR-2009-0006 12 Richard Catonwas the first who recorded bioelectric signals from the exposed cerebral cortex of cats, monkeys and rabbits in 1875. Independent of his findings, in the next decade others also demonstrated brain electrical potential changes in different species (Danyilevszkij, Beck, von Marxow). Human electroencephalogramwas first recorded by the Jena psychiatrist Hans Berger. He discovered and named the first brain rhythms: the alpha activity appears in a relaxed, but alert state, when the eyes are closed. It disappears and are repleaced by faster beta rhythm at eye opening or when counting or other mental activities are performed. EEG is one of the brain electrical signal used in brain-computer interface. Richard CatonHans Berger (1842-1926)(1873-1941) www.itk.ppke.hu NEURALINTERFACESAND PROSTHESESINTRODUCTION 9/14/2011 TÁMOP –4.1.2-08/2/A/KMR-2009-0006 13 In the first half of XX. century Nobel prices were given to electrophysiologistsfor the discoveries in neural membrane processes and nerve conduction (Nernst, Adrian and Sherrington, Erlanger and Gasser), developing new recording techniques (Einthoven). In 1908the British physiologist and surgeonSir Victor A. H. Horsley(1857-1916) and his colleague Robert Clarke invented the stereotaxic method that made possible mapping of the subcortical structures inanimalsand later on opened the way for neurosurgical implantation of electrodes in humans that led to the success story of deep brain stimulation. Victor Horsley(1857-1916) and hisstereotaxicframe www.itk.ppke.hu NEURALINTERFACESAND PROSTHESESINTRODUCTION 9/14/2011 TÁMOP –4.1.2-08/2/A/KMR-2009-0006 14 Development in neurosurgical techniques resulted in the use of intraoperativelectrical stimulation to map cortical functions and localize epileptic focus. The founder of modern neurosurgery was Cushing and his student Penfield carried out at that time revolutionary studies by electrical stimulation of the neocortex in awake patients during surgery. Stimulating the temporal lobes (the lower parts of the brain on each side) he could elicit meaningful, integrated responses such as memory, including sound, movement, and color. Harvey W. Cushing(1869-1939)Wilder G. Penfield(1891-1976), www.itk.ppke.hu NEURALINTERFACESAND PROSTHESESINTRODUCTION 9/14/2011 TÁMOP –4.1.2-08/2/A/KMR-2009-0006 15 Walter Rudolf Hess was awarded with the Nobel Prize in Physiology or Medicine in 1949 for mapping the areas of the brain involved in the control of internal organs. Hess was the first who implanted stimulating electrodes into the depth of the brain of cats. He carried out chronic experiments stimulating the diencephalon of the animals. He could induce complex behavioral responses like feeding and rage with concomitant autonomic reactions. James Olds also stimulating the hypothalamus in rats demonstrated the „selfstimulation” phenomenon in the 1950s. Walter Rudolf Hess (1881-1973)James Olds(1922-1976) www.itk.ppke.hu NEURALINTERFACESAND PROSTHESESINTRODUCTION 9/14/2011 TÁMOP –4.1.2-08/2/A/KMR-2009-0006 16 The Nobel Prize in Physiology in 1963 was awarded jointly to John Carew Eccles, Alan Lloyd Hodgkin and Andrew Fielding Huxley"for their discoveries concerning the ionic mechanisms involved in excitation and inhibition in the peripheral and central portions of the nerve cell membrane". The membrane properties described by Hodgkin and Huxley serve as basic knowledge for stimulations of nerves and brain structures. Eccleswas pioneer of single unit recording that is more and more important in central neuroprostheses. Alan L. HodgkinAndrew F. HuxleyJohn C. Eccles (1914-1998)(1917-)(1903-1997) www.itk.ppke.hu NEURALINTERFACESAND PROSTHESESINTRODUCTION 9/14/2011 TÁMOP –4.1.2-08/2/A/KMR-2009-0006 17 HISTORICALLANDMARKSINTHE DEVELOPMENTOF COCHLEARIMPLANTS The first clinical cochlear electrode was implanted in 1957 by Djournoand Eyries. The recipient got a single channel device.It helped with lipreadingby providing the rhythm of the speech. In 1970, Robin Michelson, M.D. reported preliminary results of cochlear implantation in three deaf adults implanted with gold wire electrodes. In 1964, Blair Simmons atStanford University implanted some recipients with a six-channel device. In 1961 Dr William House (an otologist), John Doyle (a neurosurgeon) and James Doyle (an electrical engineer) commenced work on a single-channel device. In 1972, a speech processor was developed to interface with the House 3M single-electrode implant and was the first to be commercially marketed. www.itk.ppke.hu NEURALINTERFACESAND PROSTHESESINTRODUCTION 9/14/2011 TÁMOP –4.1.2-08/2/A/KMR-2009-0006 18 HISTORICALLANDMARKSINTHE DEVELOPMENTOF COCHLEARIMPLANTS2 In 1978 Australian prototype bionic ear was implanted into the first patient. In1984 theFDAformallyapprovedtheHouse 3M device. In1984 inAustralia Clark and colleagues developeda multi-channel cochlear implant"NucleusMulti-channelCochlearImplant„ withF0/F21985 F0/F1/F2strategy. In1985 the Nucleus developedthe„wearable speech processor”(WSP)strategy. In1989 Ingeborgand Erwin Hochmairfounded MED-EL, producer of hearing implants, in Austria. In 1990 the FDA lowered the approved age for implantation to two years. In2005 thefirsttotallyimplantablecochlearimplant, inAustralia. www.itk.ppke.hu NEURALINTERFACESAND PROSTHESESINTRODUCTION 9/14/2011 TÁMOP –4.1.2-08/2/A/KMR-2009-0006 19 REFERENCES Yeomans, J.S.: Principlesof BrainStimulation,Oxford Univ. Press, Oxford, 1990. Finn, W.E., LoPresti, P.G. (eds.): Handbookof NeuroprostheticMethods, (BiomedicalEngineeringSeries), CRCPress, 2003. Zhou, D.D., Greenbaum, E. (eds.): ImplantableNeuralProstheses2, Techniquesand EngineeringApproaches, Springer, 2010. Brazier, MAB, The historical development of neurophysiology. In Handbook of PhysiologyVol.1.Field,J., H.W Magoun, VEHall, Eds. American Physiological Society, Washington, DC, 1-59. Finger, S.: Originsof Neuroscience, A Historyof ExplorationsintoBrainFunction, Oxford Univ. Press, New York, 1994. http://www.utdallas.edu/~loizou/cimplants/tutorial/tutorial.htm http://biomed.brown.edu/Courses/BI108/BI108_2001_Groups/Cochlear_Implants/References.htm#History of Cochlear Implants http://nobelprize.org/nobel_prizes/medicine/nerve_signaling.html www.itk.ppke.hu NEURALINTERFACESAND PROSTHESESINTRODUCTION 9/14/2011 TÁMOP –4.1.2-08/2/A/KMR-2009-0006 20 REVIEW QUESTIONS: • What is neuroprosthetics? • Who was the first to map the neocortex by electrical stimulation? • What is the brain-computer interface? • Who got Nobel Price for brain electrical stimulation? • What is selfstimulationand who described it? www.itk.ppke.hu