Blue Brain

2009 - 2011

1.

INTRO

DUCTION
HumanbrainisthemostvaluablecreationofGod.Themaniscalledintelligentbecause ofthebrain.Thebraintranslatestheinformationdeliveredbytheimpulses,whichthenenables thepersontoreact.Butwelosstheknowledgeofabrainwhenthebodyisdestroyedafterthe deathofman.Thatknowledgemighthavebeenusedforthedevelopmentofthehumansociety. Whathappenifwecreateabrainanduploadthecontentsofnaturalbrainintoit?

1.1BlueBrain
BlueBrainisthenameoftheworldsrstvirtualbrain.Thatmeansamachinethatcan functionashumanbrain.Todayscientistsareinresearchtocreateanarticialbrainthatcan think,respond,takedecision,andkeepanythinginmemory.Themainaimistouploadhuman brainintomachinesothatmancanthink,takedecisionwithoutanyeffort.Afterthedeathofthe body,thevirtualbrainwillactastheman.So,evenafterthedeathofapersonwewillnotloose theknowledge,intelligence,personalities,feelingsandmemoriesofthatmanthatcanbeused forthedevelopmentofthehumansociety. Noonehaseverunderstoodthecomplexity ofhumanbrain.Itiscomplex than any circuitryintheworld.So,questionmayariseIsitreallypossibletocreateahuman

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brain?TheanswerisYes.Becausewhatevermanhascreatedtodayalwayshehasfollowed thenature.Whenmandoesnothaveadevicecalledcomputer,itwasabigquestionforall. Technologyisgrowingfasterthaneverything.IBMisnowinresearchtocreateavirtualbrain, calledBluebrain.Ifpossible,thiswouldbetherstvirtualbrainoftheworld.Within30 years,wewillbeabletoscanourselvesintothecomputers.Isthisthebeginningofeternallife?

1.2WhatisVirtualBrain?
Virtualbrainisanarticialbrain,whichisnotactuallythenaturalbrain,butcanactas thebrain.Itcanthinklikebrain,takedecisionsbasedonthepastexperience,andrespondasthe natural brain can.Itis possible byusing asupercomputer, witha hugeamount of storage capacity,processingpowerandaninterfacebetweenthehumanbrainandthisarticialone. Throughthisinterfacethedatastoredinthenaturalbraincanbeuploadedintothecomputer.So thebrainandtheknowledge,intelligenceofanyonecanbekeptandusedforever,evenafterthe deathoftheperson.

1.3WhyweneedVirtualBrain?
Todaywearedevelopedbecauseofourintelligence.Intelligenceistheinbornquality thatcannotbecreated.Somepeoplehavethisquality,sothattheycanthinkuptosuchanextent whereothercannotreach.Humansocietyisalwaysinneedofsuchintelligenceandsuchan intelligentbraintohavewith.Buttheintelligenceislostalongwiththebodyafterthedeath.The

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virtualbrainisasolutiontoit.Thebrainand

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intelligencewillbealiveevenafterthedeath.Weoftenfacedifficultiesinrememberingthings suchaspeoplesnames,theirbirthdays,andthespellingsofwords,propergrammar,important dates,history,factsetc...Inthebusylifeeveryonewantstoberelaxed.Cantweuseany machine to assistforall these? Virtual brain maybethe solution toit. What ifwe upload ourselvesintocomputer,weweresimplyawareofacomputer,ormaybe,whatifwelivedina computerasaprogram?

1.4Howitispossible?
First,itishelpfultodescribethebasicmannersinwhichapersonmaybeuploadedintoa computer.Raymond Kurzweil recentlyprovided aninteresting paperonthis topic.In it, he describesbothinvasiveandnoninvasivetechniques.Themostpromisingistheuseofverysmall robots, ornanobots.These robots willbesmall enough totravel throughout ourcirculatory systems. Traveling into the spine and brain, they will be able to monitor the activity and structureofourcentralnervoussystem. Theywillbeabletoprovideaninterfacewithcomputersthatisascloseasourmindcanbe whilewestillresideinourbiologicalform.Nanobotscouldalsocarefullyscanthestructureof ourbrain,providingacompletereadoutoftheconnectionsbetweeneachneuron.Theywould alsorecordthecurrentstateofthebrain.Thisinformation,whenenteredintoacomputer,could thencontinuetofunctionasus.Allthatisrequiredisacomputerwithlargeenoughstorage

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thatmakesupourconsciousselves?

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spaceandprocessingpower.Isthepatternandstateofneuronconnectionsinourbraintrulyall

Manypeoplebelievermlythosewepossesasoul,whilesomeverytechnicalpeoplebelieve thatquantumforcescontributetoourawareness.Butwehavetonowthinktechnically.Note, however,thatweneednotknowhowthebrainactuallyfunctions,totransferittoacomputer. We need only know the media and contents. The actual mystery of how we achieved consciousnessintherstplace,orhowwemaintainit,isaseparatediscussion.Reallythis conceptappearstobeverydifficultandcomplextous.Forthiswehavetorstknowhowthe humanbrainactuallyworks.

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2.

WORKING NATURAL BRAIN

OF

2.1GettingtoknowmoreaboutHumanBrain
The brain essentially serves as the bodys information processing centre. It receives signalsfromsensoryneurons(nervecellbodiesandtheiraxonsanddendrites)inthecentraland peripheralnervoussystems,andinresponseitgeneratesandsendsnewsignalsthatinstructthe correspondingpartsofthebodytomoveorreactinsomeway.Italsointegratessignalsreceived from the body with signals from adjacent areas of the brain, giving rise to perception and consciousness.Thebrainweighsabout1,500grams(3pounds)andconstitutesabout2percent oftotalbodyweight.Itconsistsofthreemajordivisions; Themassivepairedhemispheresofthecerebrum The brainstem, consisting of the thalamus, hypothalamus, epithalamus, subthalamus, midbrain,andmedullaoblongata Thecerebellum.

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The human ability to feel, interpret and even see is controlled, in computer like calculations,bythemagicalnervoussystem.Thenervoussystemisquitelikemagicbecausewe cantseeit,butitsworkingthroughelectricimpulsesthroughyourbody.Oneoftheworldsmost intricatelyorganizedelectronmechanismsisthenervous

system.Notevenengineershavecomeclosetomakingcircuitboardsandcomputersasdelicate andpreciseasthenervoussystem.Tounderstandthissystem,onehastoknowthethreesimple functionsthatitputsintoaction;sensoryinput,integration&motoroutput.

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Fig. 2.1. Medial view of the left hemisphere of human brain

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2.1.1SensoryInput
Whenoureyesseesomethingorourhandstouchawarmsurface,thesensorycells,also knownasNeurons,sendamessagestraighttoyourbrain.Thisactionofgettinginformation fromyoursurroundingenvironmentiscalledsensoryinputbecauseweareputtingthingsinyour brainbywayofyoursenses.

2.1.2Integration
Integrationisbestknownastheinterpretationofthingswehavefelt,tasted,andtouched withoursensorycells,alsoknownasneurons,intoresponsesthatthebodyrecognizes.This processisallaccomplishedinthebrainwheremany,manyneuronsworktogethertounderstand theenvironment.

2.1.3MotorOutput
Onceourbrainhasinterpretedallthatwehavelearned,eitherbytouching,tasting,or usinganyothersense,thenourbrainsendsamessagethroughneuronstoeffectercells,muscle orglandcells,whichactuallyworktoperformourrequestsandactuponourenvironment.

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2.2Howwesee,hear,feel,&smell?
2.2.1Nose
Oncethesmelloffoodhasreachedyournose,whichislinedwithhairs,ittravelstoan olfactorybulb,asetofsensorynerves.Thenerveimpulsestravelthroughthe olfactorytract, around,inacircularway,thethalamus,andnallytothesmellsensorycortexofourbrain, locatedbetweenoureyeandear,whereitisinterpretedtobeunderstoodandmemorizedbythe body.

2.2.2Eye
Seeingisoneofthemostpleasingsensesofthenervoussystem.Thischerishedaction primarilyconductedbythelens,whichmagniesaseenimage,vitreousdisc,whichbendsand rotatesanimageagainsttheretina,whichtranslatestheimageandlightbyasetofcells.The retinaisatthebackoftheeyeballwhererodsandconesstructurealongwithothercellsand tissuescoverttheimageintonerveimpulseswhicharetransmittedalongtheopticnervetothe brainwhereitiskeptformemory.

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2.2.3Tongue

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Asetofmicroscopicbudsonthetonguedivideeverythingweeatanddrinkintofour kindsoftaste:bitter,sour,salty,andsweet.Thesebudshavetastepores,whichconvertthetaste intoanerveimpulseandsendtheimpulsetothebrainbyasensory

nerveber.Uponreceivingthemessage,ourbrainclassiesthedifferentkindsoftaste.Thisis howwecanreferthetasteofonekindoffoodtoanother.

2.2.4Ear
Oncethesoundorsoundwavehasenteredthedrum,itgoestoalargestructurecalledthe cochlea.Inthissnaillikestructure,thesoundwavesaredividedintopitches.Thevibrationsof the pitches in the cochlea are measured by the Corti. This organ transmits the vibration informationtoanerve,whichsendsittothebrainforinterpretationandmemory.

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BRAIN SIMULATION

AcomparativediscussionofNaturalBrainandSimulatedBrainisgivenbelow.

Sl N o

NATURAL BRAIN

SIMULATED BRAIN

INPUT: In the nervous system in our INPUT: In a similar way the articial
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bodytheneuronsareresponsibleforthe nervous system can be created. The messagepassing.Thebodyreceivesthe scientist has already created articial input by the sensory cells. These neurons by replacing them with the sensorycellsproduceelectricimpulses siliconchip.Ithasalsobeentestedthat whicharereceivedbytheneurons.The theseneuronscanreceivetheinputfrom neuronstransfertheseelectricimpulses the sensory cells. So, the electric tothebrain. impulses from the sensory cells can be

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received throughthesearticial neurons and send to a super computer for the interpretation.

INTERPRETATION: The electric INTERPRETATION:The interpretation

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impulsesreceivedbythebrainfromthe oftheelectric impulses received by the neuronsareinterpretedinthebrain.The articialneuroncanbedonebymeansof interpretation in the brain is asetofregister.Thedifferentvaluesin accomplished by the means of certain these register will represent different statesofmanyneurons. statesofthebrain.

OUTPUT: Based on the states of the OUTPUTSimilarlybasedonthestatesof

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neurons the brain sends the electric theregistertheoutputsignalcanbegiven impulses representing the responses tothearticialneuronsinthebodywhich which are further received by the willbereceivedbythesensorycell. sensorycellofourbodytorespond.The sensorycellsofwhichpartofourbody isgoingtoreceivethat,itdependsupon thestateoftheneuronsinthebrainat thattime. MEMORY. There are certain neurons MEMORY It is notimpossible to store

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in our brain which represent certain the data permanently by using the states permanently. When required secondary memory. In the similar way these state is interpreted by our brain therequiredstatesoftheregisterscanbe andwecanremember thepastthings. stored permanently. And when required To remember thing we force the these information can be retrieved and neuronstorepresentcertainstatesofthe used. brainpermanentlyorforanyinteresting or serious matter this is happened implicitly.

. PROCESSINGWhenwetakedecision, PROCESSING In a similar way the

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think about something, or make any decision making can be done by the computation, Logical and arithmetic computerbyusingsomestoredstatesand calculations are done in our neural thereceivedinput&byperformingsome circuitry. The past experience stored arithmeticandlogicalcalculations. andthecurrentinputreceivedareused and the states of certain neurons are changedtogivetheoutput

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4.

HOW THE BLUE BRAIN PROJECT WILLWORK?

4.1Goals&Objectives
The Blue Brain Project is the rst comprehensive attempt to reverseengineer the mammalian brain, in order to understand brain function and dysfunction through detailed simulations. The mission in undertaking The Blue Brain Project is to gather all existing knowledgeofthebrain,acceleratetheglobalresearcheffortofreverseengineeringthestructure andfunctionofthecomponentsofthebrain,andtobuildacompletetheoreticalframeworkthat canorchestratethereconstructionofthebrainofmammalsandmanfromthegenetictothe wholebrainlevels,intocomputermodelsforsimulation,visualizationandautomaticknowledge archivingby2015.Biologicallyaccuratecomputermodelsofmammalianandhumanbrains couldprovideanewfoundationforunderstandingfunctionsandmalfunctionsofthebrainand foranewgenerationofinformationbased,customizedmedicine.

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4.2ArchitectureofBlueGene

Fig. 4.1. The Blue Gene/L supercomputer architecture BlueGene/Lisbuiltusingsystemonachiptechnologyinwhichallfunctionsofanode (except formainmemory) areintegrated ontoasingleapplicationspecic integrated circuit (ASIC).ThisASICincludes2PowerPC440coresrunningat700MHz.Associatedwitheach coreisa64bitdoubleoatingpointunit(FPU)thatcanoperateinsingleinstruction,multiple data(SIMD)mode.Each(single)FPUcanexecuteupto2multiplyaddspercycle,which meansthatthepeakperformanceofthechipis8oatingpointoperationspercycle(4under normalconditions,withnouseofSIMDmode).Thisleadstoapeakperformanceof5.6billion oatingpointoperationspersecond(gigaFLOPSorGFLOPS)perchipornode,or2.8GFLOPS innonSIMDmode.ThetwoCPUs(centralprocessingunits)canbeusedincoprocessor mode(resultinginoneCPUand512MBRAM(randomaccessmemory)forcomputation,the otherCPUbeingusedforprocessingtheI/O(input/output)ofthemainCPU)orinvirtual

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node

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mode(inwhichbothCPUswith256MBeachareusedforcomputation).So,theaggregate performanceofaprocessorcardinvirtualnodemodeis:2xnode=2x2.8GFLOPS=5.6 GFLOPS,anditspeakperformance(optimaluseofdoubleFPU)is:2x5.6GFLOPS=11.2 GFLOPS.Arack(1,024nodes=2,048CPUs)thereforehas2.8teraFLOPSorTFLOPS,anda peakof5.6TFLOPS.TheBlueBrainProjectsBlueGeneisa4racksystemthathas4,096 nodes,equalto8,192CPUs,withapeakperformanceof22.4TFLOPS.A64rackmachine shouldprovide180TFLOPS,or360TFLOPSatpeakperformance.

4.3ModellingtheMicrocircuit
Theschemeshowstheminimalessentialbuildingblocksrequiredtoreconstructaneural microcircuit. Microcircuits are composed of neurons and synaptic connections. To model neurons, the threedimensional morphology, ion channel composition, and distributions and electricalpropertiesofthedifferenttypesofneuronarerequired,aswellasthetotalnumbersof neuronsinthemicrocircuitandtherelativeproportionsofthedifferenttypesofneuron.To modelsynapticconnections,thephysiologicalandpharmacologicalpropertiesofthedifferent typesofsynapsethatconnectanytwotypesofneuronarerequired,inadditiontostatisticson whichpartoftheaxonalarborizationisused(presynapticinnervationpattern)tocontactwhich regionsofthetargetneuron(postsynapticinnervationspattern),howmanysynapsesareinvolved in forming connections, and the connectivity statistics between any two types of neuron. Neuronsreceiveinputsfromthousandsofotherneurons,whichareintricatelymappedonto

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different branches of highly complex dendritic trees and require tens of thousands of compartmentstoaccuratelyrepresentthem.Thereisthereforeaminimalsizeofamicrocircuit andaminimalcomplexityofaneuronsmorphologythatcanfullysustainaneuron.Amassive increase in computational poweris required to make this quantum leap an increase that is providedbyIBMsBlueGenesupercomputer.ByexploitingthecomputingpowerofBlueGene, the Blue Brain Project1 aims to build accurate models of the mammalian brain from rst principles.Therstphaseoftheprojectistobuildacellularlevel(asopposedtoageneticor molecularlevel) model of a 2weekold rat somatosensory neocortex corresponding to the dimensionsofaneocorticalcolumn(NCC)asdenedbythedendriticarborizationsofthelayer 5pyramidalneurons.Thecombinationofinfrareddifferentialinterferencemicroscopyinbrain slicesandtheuseofmultineuronpatchclampingallowedthesystematicquanticationofthe molecular,morphologicalandelectricalpropertiesofthedifferentneuronsandtheirsynaptic pathwaysinamannerthatwouldallowanaccuratereconstructionofthecolumn.Overthepast 10years,thelaboratoryhaspreparedforthisreconstructionbydevelopingthemultineuron patchclamp approach, recording from thousands of neocortical neurons and their synaptic connections,anddevelopingquantitativeapproachestoallowacompletenumericalbreakdown oftheelementarybuildingblocksoftheNCC.Therecordingshavemainlybeeninthe1416 dayold rat somatosensory cortex, which is a highly accessible region on which many researchershaveconvergedfollowingaseriesofpioneeringstudiesdrivenbyBertSakmann. Muchoftherawdataislocatedinourdatabases,butamajorinitiativeisunderwaytomakeall thesedatafreelyavailableina

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publicly accessible database. Thesocalledblueprintofthecircuit, although notentirely complete,hasreachedasufcientlevelofrenementtobeginthereconstructionatthecellular level.Highlyquantitativedataareavailableforratsofthisage,mainlybecausevisualizationof thetissueisoptimalfromatechnicalpointofview.Thisagealsoprovidesanidealtemplate becauseitcanserveasastartingpointfromwhichtostudymaturationandageingoftheNCC. AsNCCsshowahighdegreeofstereotypy,theregionfromwhichthetemplateisbuiltisnot crucial,butasensoryregionispreferredbecausetheseareascontainaprominentlayer4with cellsspecializedtoreceiveinputtotheneocortexfromthethalamus;thiswillalsoberequired for later calibration with in vivo experiments. The NCC should not be overly specialized, becausethiscouldmakegeneralizationtootherneocorticalregionsdifcult,butareassuchas thebarrelcortexdooffertheadvantageofhighlycontrolledinvivodataforcomparison.The mousemighthavebeenthebestspeciestobeginwith,becauseitoffersaspectrumofmolecular approacheswithwhichtoexplorethecircuit,butmouseneuronsaresmall,whichpreventsthe detailed dendriticrecordingsthatareimportantformodellingthenonlinearpropertiesofthe complex dendritic trees of pyramidal cells (7580% of the neurons). The image shows the Microcircuitinvariousstagesofreconstruction.Onlyasmallfractionofreconstructed,three dimensionalneuronsisshown.Redindicatesthedendriticandbluetheaxonalarborizations.The columnarstructureillustratesthelayerdenitionoftheNCC.

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Fig. 4.2. Elementary building blocks of neural microcircuits.

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Fig. 4.3. Reconstructing the neocortical column. Themicrocircuits(fromlefttoright)forlayers2,3,4and5. Asinglethicktuftedlayer5pyramidalneuronlocatedwithinthecolumn. Onepyramidalneuroninlayer2,asmallpyramidalneuroninlayer5andthelargethick tuftedpyramidalneuroninlayer AnimageoftheNCC,withneuronslocatedinlayers2to5.

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Blue Brain 4.4SimulatingtheMicrocircuit

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Oncethemicrocircuitisbuilt,theexcitingworkofmakingthecircuitfunctioncanbegin. All the 8192 processors of the Blue Gene are pressed into service, in a massively parallel computationsolvingthecomplexmathematicalequationsthatgoverntheelectricalactivityin each neuronwhen astimulus is applied. As the electrical impulse travels fromneuron to neuron,theresultsarecommunicatedviainterprocessorcommunication(MPI).Currently,the timerequiredtosimulatethecircuitisabouttwoordersofmagnitudelargerthantheactual biologicaltimesimulated.TheBlueBrainteamisworkingtostreamlinethecomputationsothat thecircuitcanfunctioninrealtimemeaningthat1secondofactivitycanbemodeledinone second.

4.5InterpretingtheResults
Running the Blue Brain simulation generates huge amounts of data. Analyses of individualneuronsmustberepeatedthousandsoftimes.Andanalysesdealingwiththenetwork activitymustdealwithdatathateasilyreacheshundredsofgigabytespersecondofsimulation. Usingmassivelyparallelcomputersthedatacanbeanalyzedwhereitiscreated(serverside analysisforexperimentaldata,onlineanalysisduringsimulation). Giventhegeometriccomplexityofthecolumn,avisualexplorationofthecircuitisan importantpartoftheanalysis.Mappingthesimulationdataontothemorphologyisinvaluable foranimmediatevericationofsinglecellactivityaswellasnetworkphenomena.Architectsat EPFLhaveworkedwiththeBlueBraindeveloperstodesign

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avisualizationinterfacethattranslatestheBlueGenedataintoa3Dvisualrepresentationofthe column. A different supercomputer is used for this computationally intensive task. The visualizationoftheneuronsshapesisachallengingtaskgiventhefactthatacolumnof10,000 neuronsrenderedinhighqualitymeshaccountsforessentially1billiontrianglesforwhichabout 100GB of management data is required. Simulation data with a resolution of electrical compartmentsforeachneuronaccountsforanother150GB.Astheelectricalimpulsetravels throughthecolumn,neuronslightupandchangecolorastheybecomeelectricallyactive.A visualinterfacemakesitpossibletoquicklyidentifyareasofinterestthatcanthenbestudied moreextensivelyusingfurthersimulations.Avisualrepresentationcanalsobeusedtocompare thesimulationresultswithexperimentsthatshowelectricalactivityinthebrain

4.6DataManipulationCascade
BuildingtheBlueColumnrequiresaseriesofdatamanipulations.Therststepisto parseeachthreedimensionalmorphologyandcorrecterrorsduetotheinvitropreparationand reconstruction. The repaired neurons are placed in a database from which statistics for the different anatomical classes of neurons are obtained. These statistics are used to clone an indenitenumberofneuronsineachclasstocapturethefullmorphologicaldiversity.Thenext step is totakeeachneuronandinsertionchannelmodels inordertoproducethearray of electricaltypes.Theeldhasreachedasufcientstageofconvergencetogenerateeffortsto classify neurons, such as the Petilla Convention a conference held in October 2005 on anatomicalandelectrical

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types of neocortical interneuron, established by the community. Singlecell gene expression studiesofneocorticalinterneuronsnowprovidedetailedpredictionsofthespeciccombinations ofmorethan20ionchannelgenesthatunderlieelectricaldiversity.Adatabaseofbiologically accurateHodgkinHuxleyionchannelmodelsisbeingproduced.ThesimulatorNEURONis usedwithautomatedttingalgorithmsrunningonBlueGenetoinsertionchannelsandadjust theirparameterstocapturethespecicelectricalpropertiesofthedifferentelectricaltypesfound ineachanatomicalclass.Thestatisticalvariationswithineachelectricalclassarealsousedto generatesubtlevariationsindischargebehaviourineachneuron.So,eachneuronismorpho logicallyandelectricallyunique.Ratherthantaking10,000daystoteachneuronselectrical behaviourwithauniqueprole,densityanddistributionofionchannels,applicationsarebeing preparedtouseBlueGenetocarryoutsuchatinaday.Thesefunctionalizedneuronsare stored in a database. The threedimensional neurons are then imported into Blue Builder, a circuitbuilderthatloadsneuronsintotheirlayersaccordingtoarecipeofneuronnumbersand proportions.Acollisiondetectionalgorithmisruntodeterminethestructuralpositioningofall axodendritic touches, and neurons are jittered and spun until the structural touches match experimentallyderivedstatistics.Probabilitiesofconnectivitybetweendifferenttypesofneuron areusedtodeterminewhichneuronsareconnected,andallaxodendritictouchesareconverted into synaptic connections. The manner in which the axons map onto the dendrites between specicanatomicalclassesandthedistributionofsynapsesreceivedbya

classofneuronsareusedtoverifyandnetunethebiologicalaccuracyofthesynapticmapping

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between neurons.It is therefore possible toplace 1050million synapses inaccurate three dimensionalspace,distributedonthedetailedthreedimensionalmorphologyofeachneuron. Thesynapsesarefunctionalizedaccordingtothesynapticparametersfordifferentclassesof synapticconnectionwithinstatisticalvariationsofeachclass,dynamicsynapticmodelsareused tosimulatetransmission,andsynapticlearningalgorithmsareintroducedtoallowplasticity.The distancefromthecellbodytoeachsynapseisusedtocomputetheaxonaldelay,andthecircuit congurationisexported.ThecongurationleisreadbyaNEURONsubroutinethatcallsup eachneuronandeffectivelyinsertsthelocationandfunctionalpropertiesofeverysynapseonthe axon,somaanddendrites.Oneneuronisthenmappedontoeachprocessorandtheaxonaldelays areusedtomanagecommunicationbetweenneuronsandprocessors.Effectively,processorsare convertedintoneurons,andMPI(messagepassinginterface)basedcommunicationcablesare converted into axons interconnecting the neurons so the entire Blue Gene is essentially convertedintoaneocorticalmicrocircuit.Wedevelopedtwosoftwareprogramsforsimulating such largescale networks with morphologically complex neurons. A new MPI version of NEURONhasbeenadaptedbyMichaelHinestorunonBlueGene.Thesecondsimulatoruses the MPImessagingcomponentofthelargescaleNeoCortical Simulator(NCS),which was developed by Philip Goodman, to manage the communication between NEURONsimulated neuronsdistributedondifferentprocessors.Thelattersimulatorwillallow

embeddingofadetailedNCCmodelintoasimpliedlargescalemodelofthewholebrain. Bothofthesesoftwareshavealreadybeentested,produceidenticalresultsandcansimulatetens

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of thousands of morphologically and electrically complex neurons (as many as 10,000 compartments per neuron with more than a dozen HodgkinHuxley ion channels per compartment).Upto10neuronscanbemappedontoeachprocessortoallowsimulationsofthe NCC with as many as 100,000 neurons. Optimization of these algorithms could allow simulations torunat closeto real time. Thecircuit conguration is alsoread bya graphic application,whichrenderstheentirecircuitinvariouslevelsoftexturedgraphicformats.Real time stereo visualization applications are programmed to run on the terabyte SMP (shared memoryprocessor)ExtremeseriesfromSGI(SiliconGraphics,Inc.).TheoutputfromBlue Gene(anyparameterofthemodel)canbefeddirectlyintotheSGIsystemtoperforminsilico imagingoftheactivityoftheinnerworkingsoftheNCC.Eventually,thesimulationoftheNCC willalsoincludethevasculature,aswellastheglialnetwork,toallowcaptureofneuronglia interactions. Simulations of extracellular currents and eld potentials, and the emergent electroencephalogram(EEG)activitywillalsobemodelled.

4.7WholeBrainSimulations
Themainlimitationsfordigitalcomputersinthesimulationofbiologicalprocessesare theextremetemporalandspatialresolutiondemandedbysomebiologicalprocesses,andthe limitationsofthealgorithmsthatareusedtomodel

biologicalprocesses.Ifeachatomiccollisionissimulated,themostpowerfulsupercomputers stilltakedaystosimulateamicrosecondofproteinfolding,soitis,ofcourse,notpossibleto

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simulatecomplexbiologicalsystemsattheatomicscale.However,modelsathigherlevels,such asthemolecularorcellularlevels,cancapturelowerlevelprocessesandallowcomplexlarge scalesimulationsofbiologicalprocesses.TheBlueBrainProjectsBlueGenecansimulatea NCCofupto100,000highlycomplexneuronsatthecellularorasmanyas100millionsimple neurons (about the same number of neurons found in amouse brain). However, simulating neuronsembeddedinmicrocircuits,microcircuitsembeddedinbrainregions,andbrainregions embeddedinthewholebrainaspartoftheprocessofunderstandingtheemergenceofcomplex behaviors of animals is an inevitable progression in understanding brain function and dysfunction, and the question is whether wholebrain simulations are at all possible. Computationalpowerneedstoincreaseabout1millionfoldbeforewewillbeabletosimulate thehumanbrain,with100billionneurons,atthesamelevelofdetailastheBlueColumn. Algorithmic and simulation efciency (which ensure that all possible FLOPS are exploited) couldreducethisrequirementbytwotothreeordersofmagnitude.SimulatingtheNCCcould alsoactasatestbedtorenealgorithmsrequiredtosimulatebrainfunction,whichcanbeused to produce eld programmable gate array (FPGA)based chips. FPGAs could increase computational speeds by as much as two orders of magnitude. The FPGAs could, in turn, provide the testing ground for the production of specialized NEURON solver application specicintegratedcircuits(ASICs)thatcouldfurtherincreasecomputationalspeedbyanother onetotwoordersof

magnitude.Itcouldthereforebepossible,inprinciple,tosimulatethehumanbrainevenwith current technology.Thecomputer industryisfacingwhatisknownasadiscontinuity, with

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increasing processor speed leading to unacceptably high power consumption and heat production.Thisispushingaqualitativelynewtransitioninthetypesofprocessortobeusedin futurecomputers.Theseadvancesincomputingshouldbegintomakegeneticandmolecular levelsimulationspossible.Softwareapplicationsanddatamanipulationrequiredtomodelthe brainwithbiologicalaccuracy.Experimentalresultsthatprovidetheelementarybuildingblocks of themicrocircuit arestoredinadatabase. Beforethreedimensional neuronsaremodelled electrically,themorphologyisparsedforerrors,andforrepairofarborizationsdamagedduring slicepreparation.Themorphologicalstatisticsforaclassofneuronsareusedtoclonemultiple copiesofneuronstogeneratethefullmorphologicaldiversityandthethousandsofneurons required in the simulation. A spectrum of ion channels is inserted, and conductances and distributionsarealteredtottheneuronselectricalpropertiesaccordingtoknownstatistical distributions, to capture the range of electrical classes and the uniqueness of each neurons behaviour(modeltting/electricalcapture).Acircuitbuilderisusedtoplaceneuronswithina threedimensional column, to perform axodendritic collisions and, using structural and functionalstatisticsofsynapticconnectivity,toconvertafractionofaxodendritictouchesinto synapses.ThecircuitcongurationisreadbyNEURON,whichcallsupeachmodelledneuron andinsertstheseveralthousandsynapsesontoappropriatecellularlocations.Thecircuitcanbe insertedintoabrainregionusingthebrainbuilder.Anenvironmentbuilderisusedtoset

upthestimulusandrecordingconditions.Neuronsaremappedontoprocessors,withinteger numbersofneuronsperprocessor.Theoutputisvisualized,analysedand/orfedintorealtime algorithmsforfeedbackstimulation.

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Fig. 4.4. The data manipulation cascade

5.

APPLICATIONS OF BLUE BRAIN PROJECT

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Detailed,biologicallyaccuratebrainsimulationsoffertheopportunitytoanswersome fundamentalquestionsaboutthebrainthatcannotbeaddressedwithanycurrentexperimentalor theoreticalapproaches.Theseinclude,

5.1.1Deningfunctionsofthebasicelements
Despiteacenturyofexperimentalandtheoreticalresearch,weareunabletoprovidea comprehensive denition of the computational function of different ion channels, receptors, neuronsorsynapticpathwaysinthebrain.Adetailedmodelwillallownecontrolofanyof these elements and allow a systematic investigation of their contribution to the emergent behaviour.

5.1.2Understandingcomplexity
Atpresent,detailed,accuratebrainsimulationsaretheonlyapproachthatcouldallowus toexplainwhythebrainneedstousemanydifferentionchannels,neuronsandsynapses,a spectrum of receptors, and complex dendritic and axonal arborizations, rather than the simplied,uniformtypesfoundinmanymodels.

5.1.3Exploringtheroleofdendrites.
Thisistheonlycurrentapproachtoexplorethedendriticobjecttheory,whichproposes that threedimensional voltage objects are generated continuously across dendritic segments regardless ofthe originofthe neurons,andthat spikes are usedto maintain such dendritic

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objects.

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5.1.4Revealingfunctionaldiversity
Mostmodels engineeraspecicfunction,whereas aspectrumoffunctions mightbe possiblewithabiologicallybaseddesign.Understandingmemorystorageandretrieval.This approach offers the possibility of determining the manner in which representations of informationareimprintedinthecircuitforstorageandretrieval,andcouldrevealthepartthat differenttypesofneuronplayinthesecrucialfunctions.

5.1.5Trackingtheemergenceofintelligence
Thisapproachoffersthepossibilitytoretracethestepstakenbyanetworkofneuronsin theemergenceofelectricalstatesusedtoembodyrepresentationsoftheorganismanditsworld.

5.1.6Identifyingpointsofvulnerability Althoughtheneocortexconfersimmensecomputationalpowertomammals,defectsare common,withcatastrophiccognitiveeffects.Atpresent,adetailedmodelistheonlyapproach thatcouldproducealistofthemostvulnerablecircuitparameters,revealinglikelycandidatesfor dysfunctionandtargetsfortreatment.

5.1.7Simulatingdiseaseanddevelopingtreatments
Suchsimulationscouldbeusedtotesthypothesesforthepathogenesisofneurological andpsychiatricdiseases,andtodevelopandtestnewtreatmentstrategies.

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5.1.8Providingacircuitdesignplatform

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Detailedmodelscouldrevealpowerfulcircuitdesignsthatcouldbeimplementedinto siliconechipsforuseasintelligencedevicesinindustry.

5.2ApplicationsofBlueBrain
5.2.1GatheringandTesting100YearsofData
Themostimmediatebenetistoprovideaworkingmodelintowhichthepast100years knowledgeaboutthemicrostructureandworkingsoftheneocorticalcolumncanbegatheredand tested. The Blue Column will therefore also produce a virtual library to explore in 3D the microarchitecture of the neocortex and access all key research relating to its structure and function.

5.2.2CrackingtheNeuralCode
TheNeuralCodereferstohowthebrainbuildsobjectsusingelectricalpatterns.Inthe samewaythattheneuronistheelementarycellforcomputinginthebrain,theNCCisthe elementarynetworkforcomputingintheneocortex.Creatinganaccurate

replicaoftheNCCwhichfaithfullyreproducestheemergentelectricaldynamics ofthereal microcircuit,isanabsoluterequirementtorevealinghowtheneocortexprocesses,storesand retrievesinformation.

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5.2.3UnderstandingNeocorticalInformationProcessing

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Thepowerofanaccuratesimulationliesinthepredictionsthatcanbegeneratedabout theneocortex.Indeed,iterationsbetweensimulationsandexperimentsareessentialtobuildan accurate copy of the NCC. These iterations are therfore expected to reveal the function of individual elements (neurons, synapses, ion channels, receptors), pathways (monosynaptic, disynaptic, multisynaptic loops) and physiological processes (functional properties, learning, reward,goaloreintedbehavior).

5.2.4ANovelToolforDrugDiscoveryforBrainDisorders
UnderstandingthefunctionsofdifferentelementsandpathwaysoftheNCCwillprovide a concrete foundation to explore the cellular and synaptic bases of a wide spectrum of neurologicalandpsychiatricdiseases.Theimpactofreceptor,ionchannel,cellularandsynaptic decitscouldbetestedinsimulationsandtheoptimalexperimentaltestscanbedetermined.

5.2.5AGlobalFacility
A software replica of a NCC will allow researchers to explore hypotheses of brain functionanddysfunctionacceleratingresearch.Simulationrunscoulddeterminewhich

parameters shouldbeusedand measuredin theexperiments. Anadvanced 2D,3D and 3D immersivevisualizationsystemwillallowimagingofmanyaspectsofneuraldynamicsduring processing,storageandretrievalofinformation.Suchimagingexperimentsmaybeimpossible

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inrealityormaybeprohibitivelyexpensivetoperform.

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5.2.6AFoundationforWholeBrainSimulations
With current and envisageable future computer technology it seems unlikely that a mammalian brain can be simulated with full cellular and synaptic complexity (above the molecular level). An accurate replica of an NCC is therefore required in order to generate reduced models that retain critical functions and computational capabilities, which can be duplicated and interconnected to form neocortical brain regions. Knowledge of the NCC architecturecanbetransferredtofacilitatereconstructionofsubcorticalbrainregions.

5.2.7AFoundationforMolecularModelingofBrainFunction
Anaccuratecellularreplicaoftheneocorticalcolumnwillprovidetherstandessential steptoagradualincreaseinmodelcomplexitymovingtowardsamolecularleveldescriptionof theneocortexwithbiochemicalpathwaysbeingsimulated.AmolecularlevelmodeloftheNCC will provide the substrate for interfacing gene expression with the network structure and function.TheNCCliesattheinterfacebetweenthegenesandcomplexcognitivefunctions. Establishingthislinkwillallow

predictions of the cognitive consequences of genetic disorders and allow reverse engineeringofcognitivedecitstodeterminethegeneticandmolecularcauses.Thislevelof simulationwillbecomearealitywiththemostadvancedphaseofBlueGenedevelopment.

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6. ADVANTAGES AND LIMITATIONS

6.1Advantages
Wecanrememberthingswithoutanyeffort.

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Decisioncanbemadewithoutthepresenceofaperson. Evenafterthedeathofamanhisintelligencecanbeused.

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Theactivityofdifferentanimalscanbeunderstood.Thatmeansbyinterpretation of the electric impulses from the brain of the animals, their thinking can be understoodeasily.

Itwouldallowthedeaftohearviadirectnervestimulation,andalsobehelpful formanypsychologicaldiseases.Bydownloadingthecontentsofthebrainthat wasuploadedintothecomputer,themancangetridfromthemadness.

6.2Limitations
Further,therearemanynewdangersthesetechnologieswillopen.Wewillbesusceptible tonewformsofharm. Webecomedependentuponthecomputersystems. Othersmayusetechnicalknowledgeagainstus.

Computerviruseswillposeanincreasinglycriticalthreat. Therealthreat,however,isthefearthatpeoplewillhaveofnewtechnologies.Thatfear mayculminateinalargeresistance.Clearevidenceofthistypeoffearisfoundtoday withrespecttohumancloning.

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7.

FUTUREPERSPECTIVE

ThesynthesiserainneurosciencestartedwiththelaunchoftheHumanBrainProjectandis aninevitablephasetriggeredbyacriticalamountoffundamentaldata.Thedatasetdoesnot

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needtobecompletebeforesuchaphasecanbegin.Indeed,itisessentialtoguidereductionist researchintothedeeperfacetsofbrainstructureandfunction.Asacomplementtoexperimental research, it offers rapid assessment of the probable effect of a new nding on preexisting knowledge,whichcannolongerbemanagedcompletelybyanyoneresearcher.Detailedmodels willprobablybecomethenalformofdatabasesthatareusedtoorganizeallknowledgeofthe brainandallowhypothesistesting,rapiddiagnosesofbrainmalfunction,aswellasdevelopment oftreatmentsforneurologicaldisorders.Inshort,wecanhopetolearnagreatdealaboutbrain functionanddisfunctionfromaccuratemodelsofthebrain.Thetimetakentobuilddetailed modelsofthebraindependsonthelevelofdetailthatiscaptured.Indeed,therstversionofthe Blue Column, which has 10,000 neurons, has already been built and simulated; it is the renementofthedetailedpropertiesandcalibrationofthecircuitthattakestime.Amodelofthe entirebrainatthecellularlevelwillprobablytakethenextdecade.Thereisnofundamental obstacletomodelingthebrainanditisthereforelikelythatwewillhavedetailedmodelsof mammalianbrains,includingthatofman,inthenearfuture.Evenifoverestimatedbyadecade ortwo,thisisstilljustablinkofaneye

inrelationtotheevolutionofhumancivilization.AswithDeepBlue,BlueBrainwillallow ustochallengethefoundationsofourunderstandingofintelligenceandgeneratenewtheoriesof consciousness.

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CONCLUSION
Inconclusion,wewillbeabletotransferourselvesintocomputersatsomepoint.Most arguments against this outcome are seemingly easy to circumvent. They are either simple

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minded,orsimplyrequirefurthertimefortechnologytoincrease.Theonlyseriousthreatsraised arealsoovercomeaswenotethecombinationofbiologicalanddigitaltechnologies.

REFERENCES

1)

EngineeringinMedicineandBiologySociety,2008.EMBS2008.30th

AnnualInternationalConferenceoftheIEEE

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2) 2006February. 3) SimulatedbrainclosertothoughtBBCNews22April2009. 4) ProjectMilestones.BlueBrain. http://bluebrain.ep.ch/Jahia/site/bluebrain/op/edit/pid/19085 5)

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HenryMarkram,TheBlueBrainProject,NatureReviewsNeuroscience

GrahamRowe,Duncan.Missiontobuildasimulatedbrainbegins,New

Scientist,June2005.pp.187985. 6) BlueGene:http://www.research.ibm.com/bluegene 7) TheBlueBrainProject:http://bluebrainproject.ep.ch 8) www.ieee.org/bluebrain/project

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