autism to adhd computational simulations从自闭症到注意力缺陷多动症的计算模拟课件 54页

Plan:Howcanweunderstandneurodegenerativedisease,suchasautism,ADHDorepilepsy?Whoisinthebestpositiontodoit?Theories,mistakingsymptomsforcauses.Whatdowehopefor?Computationalexperiments.Experimentalevidence,geneticsSomeideasforneurorehabilitation&ICNT.Apriliscelebratedastheautismawarenessmonthsince1970. InterdisciplinaryCenterofInnovativeTechnologiesWhyamIinterestedinthis?ICITinconstruction,endof2012?Neurocognitivelab,5rooms,manyprojectsrequiringexperiments.WorkingonEUgrant.Understandingbrainplasticity,mindstates. AbitofASDhistoryASD:AutismSpectrumDisorder,includesmanyformsofautism.Describedforthefirsttimein1943byLeoKanner:“extremealonenessfromthebeginningoflifeandanxiouslyobsessivedesireforthepreservationofsameness.”“…thesechildrenhavecomeintotheworldwithinnateinabilitytoformtheusual,biologicallyprovidedaffectivecontactwithpeople…”.Commondeficit:lackofthetheoryofmind.Initialtheories:badparents,refrigeratormothers...abehavioralsyndrome…adevelopmentalsyndrome...multiplediseaseentities,multipleetiologies,includingmetabolicandimmunesystemderegulation,genetics.2008:However,asinmanyareasofneuroscience,weare‘‘datarichandtheorypoor’’(Zimmerman,Autism–currenttheories). ASDAutismSpectrumofDisordersincludes:Autism,Aspergersyndrome,pervasivedevelopmentaldisordernototherwisespecified(PDD-NOS),atypicalformsofchildhooddisintegrativedisorder,Rettsyndrome,InfantileAutisticBipolarDisorder(IABD),purineautism.4-5timesmoreboysthangirls.CDCestimates:averageabout1%,boysabout2%.AutisticSavants:fewpercentofpeoplewithASDlearnunusualmemoryormotorskills,butareimpairedinmanyotherways. AutismSymptoms...Epidemics?Notclearwhy:moreattention,betterdiagnostics?Verydiverse,notasingledisease,butmorelikedementia.Geneticcomponent,butsearchfor“autismgenes”nottoosuccessful,toomanyareinvolved.Geneticscannotexplainrecentrapidincrease. ADHDAttentionDeficitHyperactivityDisorder,3-5%ofpopulation(alsoadults).Problemswithattention:usuallyimpulsive-hyperactive,inattentive(ADD)Lackofimpulsecontrol,easilydistracted,missdetails,forgetthings,frequentlyswitchbetweenactivity,can’tfocusononething…Motorrestlessness,runnon-stop,losethings,areveryimpatient,displaystrongemotions,actwithoutthinkingaboutconsequences.Boredquickly,daydream,difficultyinlearningnewthings,completehomework.ADHDinvolvesfunctionaldisconnectionsbetweenfrontalandoccipitalcortex(A.Mazaherietal,BiologicalPsychiatry67,617,2010);psychologisttalkaboutdeficitin"top-down"attentioncontrol.InmanyrespectsitistheoppositeofASD. Eyesaccades Autism:hiperspecificityStevenWiltshire,http://www.stephenwiltshire.co.ukSeealso:GrandinTemple,ThinkinginpicturesandOtherReportsfromMyLifewithAutism(VintageBooks,1996) ReadingintentionsAnimationshowsthecircleasavictim,Smalltriangletriestohelp,bigoneisaggressive.Autism,Aspergersyndromeandbrainmechanismsfortheattributionofmentalstatestoanimatedshapes.F.Castelli&etal.Brain2002,125:1839-49 Source:BrunoWicker(CNRS) Theories,theoriesBestbookonASDsofar:AndrewW.Zimmerman(Ed.)Autism;currenttheoriesandevidence.HumanaPress2008.20chaptersdividedintosixsections:MolecularandClinicalGenetics(4chapters);NeurotransmittersandCellSignaling(3chapters);Endocrinology,Growth,andMetabolism(4chapters);Immunology,Maternal-FetalEffects,andNeuroinflammation(4chapters);Neuroanatomy,Imaging,andNeuralNetworks(3chapters);EnvironmentalMechanismsandModels(2chapters).Other:GrossbergARTmodel.Atwhichlevelcanweunderstandnotjustcorrelations,butrealmechanismsresponsibleforbehavioralsymptoms?(genes,proteins,biochemistry,ionchannels,synapses,membranes)(neuralproperties,networks)(behavior,syndromes,disease). MirrorNeuronSystemMNS:observingactionelicitssimilarmotoractivationsasifithadbeenperformedbyoneself;visuo-motorneurons.Thishelpstounderstandactionsofothers,modelingbehaviorviaembodiedsimulationoftheiractions,intentions,andemotions.MNStheoryofautism(Williamsetal,2001):distortioninthedevelopmentoftheMNSinterfereswiththeabilitytoimitate,leadstosocialimpairmentandcommunicationdifficulties.CorrelationsbetweenreducedMNSactivityandseverityofASDarestrong.Problems:InASDabnormalbrainactivationisseeninmanyothercircuits;performanceofautisticchildrenonvariousimitationtasksmaybenormal.MNSisusedtoexplainalmosteverythinginsocialneuroscience,butMNSisnotreallyaspecialsubsystem,justmultimodalneurons. MNSEEGEEGoncontrolsandautisticson4differenttasks,comparingmurhythms.Baseline:largeamplitudemuoscillationsinsynchrony.Seeinganactioncausesmurhythmstofireasynchronouslyresultinginmusuppression.Muwavesuppressionreflectsactivityofthemirrorneuronsystem.Inautisticsmuissuppressedforownhandmovements(Oberman2005),butnotfortheobservedhandmovementsofothers(handvs.move). ReducedfunctionalconnectivityTheunderconnectivitytheoryofautismisbasedonthefollowing:Excessoflow-level(sensory)processes.Underfunctioningofhigh-levelneuralconnectionsandsynchronization,fMRIandEEGstudysuggeststhatadultswithASDhavelocaloverconnectivityinthecortexandweakfunctionalconnectionsbetweenthefrontallobeandtherestofthecortex.Underconnectivityismainlywithineachhemisphereofthecortexandthatautismisadisorderoftheassociationcortex.Patternsoflowfunctionandaberrantactivationinthebraindifferdependingonwhetherthebrainisdoingsocialornonsocialtasks.“Defaultbrainnetwork”involvesalarge-scalebrainnetwork(cingulatecortex,mPFC,lateralPC),showslowactivityforgoal-relatedactions;itisactiveinsocialandemotionalprocessing,mindwandering,daydreaming.Activityofthedefaultnetworkisnegativelycorrelatedwiththe“actionnetwork”(consciousgoal-directedthinking),butthisisnotthecaseinautism–perhapsdisturbanceofself-referentialthought? ReducedfunctionalconnectivityTheunderconnectivitytheoryofautismisbasedonthefollowing:Excessoflow-level(sensory)processes.Underfunctioningofhigh-levelneuralconnectionsandsynchronization,fMRIandEEGstudysuggeststhatadultswithASDhavelocaloverconnectivityinthecortexandweakfunctionalconnectionsbetweenthefrontallobeandtherestofthecortex.Underconnectivityismainlywithineachhemisphereofthecortexandthatautismisadisorderoftheassociationcortex.Patternsoflowfunctionandaberrantactivationinthebraindifferdependingonwhetherthebrainisdoingsocialornonsocialtasks.“Defaultbrainnetwork”involvesalarge-scalebrainnetwork(cingulatecortex,mPFC,lateralPC),showslowactivityforgoal-relatedactions;itisactiveinsocialandemotionalprocessing,mindwandering,daydreaming.Activityofthedefaultnetworkisnegativelycorrelatedwiththe“actionnetwork”(consciousgoal-directedthinking),butthisisnotthecaseinautism–perhapsdisturbanceofself-referentialthought? EffectivebrainconnectionsB.Wickeretal.SCAN2008 ExecutivedysfunctionHypothesis:autismresultsmainlyfromdeficitsinworkingmemory,planning,inhibition,andotherexecutivefunctions.Executiveprocessesdonotreachtypicaladultlevels,resultinginstereotypedbehaviorandnarrowinterests.Butexecutivefunctiondeficitshavenotbeenfoundinyoungautisticchildren.Weakcentralcoherencetheoryhypothesizesthatalimitedabilitytoseethebigpictureunderliesthecentraldisturbanceinautism.Thispredictsspecialtalentsinperformanceofautisticpeople.Enhancedperceptualfunctioningtheoryfocusesmoreonthesuperiorityoflocallyorientedandperceptualoperationsinautisticindividuals.Thesetheoriesagreewiththeunderconnectivitytheoryofautism.Socialcognitiontheoriespoorlyaddressautism"srigidandrepetitivebehaviors,whilethenonsocialtheorieshavedifficultyexplainingsocialimpairmentandcommunicationdifficulties. FunctionconnectivitytheoryModeldevelopedover20years(NancyJ.Minshew):autismaswidespreaddisorderofassociationcortex,developmentofconnectivity,onlysecondarilyasabehavioraldisorder.Fine,butstillquitegeneral.AbnormalitiesingeneticcodeforbraindevelopmentAbnormalmechanismsofbraindevelopmentStructuralandfunctionalabnormalitiesofbrainCognitiveandneurologicabnormalitiesBehavioralsyndromeGoal:understandthepathophysiologyfromgenetobehavior,eventuallytheinfluenceofetiologiesonthissequence,ultimatelysupportthedevelopmentofinterventionsatmultiplelevelsofthepathophysiologicsequence. Temporo-spatialprocessingdisordersB.Gepner,F.Feron,Autism:Aworldchangingtoofastforamis-wiredbrain?NeuroscienceandBiobehavioralReviews(2009). FromGenestoNeuronsGenes=>Proteins=>receptors,ionchannels,synapses=>neuronproperties,networks,neurodynamics=>cognitivephenotypes,abnormalbehavior,syndromes. FromNeuronstoBehaviorGenes=>Proteins=>receptors,ionchannels,synapses=>neuronproperties,networks=>neurodynamics=>cognitivephenotypes,abnormalbehavior! NeuropsychiatricPhenomicsLevelsAccordingtoTheConsortiumforNeuropsychiatricPhenomics(CNP)http://www.phenomics.ucla.eduFromgenestomoleculestoneuronsandtheirsystemstotasks,cognitivesubsystemsandsyndromes.Neuronsandnetworksarerightinthemiddleofthishierarchy. StrategyforNeurophenomicsResearchTheConsortiumforNeuropsychiatricPhenomics:bridgealllevels,oneatatime,fromenvironmenttosyndromes.Ourstrategy:identifybiophysicalparametersofneuronsrequiredfornormalneuralnetworkfunctionsandleadingtoabnormalcognitivephenotypes,symptomsandsyndromes.Startfromsimpleneuronsandnetworks,increasecomplexity.Createmodelsofcognitivefunctionthatmayreflectsomeofthesymptomsofthedisease,forexampleproblemswithattention.Testandcalibratethestabilityofthesemodelsinanormalmode.Determinemodelparameterrangesthatleadtosimilarsymptoms.Relatetheseparameterstothebiophysicalpropertiesofneurons.Result:mentaleventsatthenetworklevelaredescribedinthelanguageofneurodynamicsandrelatedtolow-levelneuralproperties.Example:relationofASD/ADHDsymptomstoneuralaccommodation. ComputationalModelsModelsatvariouslevelofdetail.Minimalmodelincludesneuronswith3typesofionchannels.Modelsofattention:Posnerspatialattention;attentionshiftbetweenvisualobjects.Modelsofwordassociations:sequenceofspontaneousthoughts.Modelsofmotorcontrol.Critical:controloftheincreaseinintracellularcalcium,whichbuildsupslowlyasafunctionofactivation.Initialfocusontheleakchannels,2-poreK+,lookingforgenes/proteins. VisionFromretinathroughlateralgeniculatebody,LGN(partofthalamus)informationpassestotheprimaryvisualcortexV1andthensplitsintotheventralanddorsalstreams. SimplemodelofPosnerexperimentsCue(brightbox)isinthesamepositionastarget(validtrial),orinanotherposition(invalidtrial),orthereisnocue(neutral),justtarget.Testoftheobjectrecognition/localization. PosnerspatialattentionCue(brightbox)isinthesamepositionastarget(validtrial),orinanotherposition(invalidtrial),orthereisnocue(neutral). PosnerspatialattentionMorecomplexcue=strongerlocalattractor=>canbindASDlonger?Cuepulsatingwithdifferentfrequenciesmaycreateresonances?Whatchangesinthenetworkwillleadtofasterattentionshifts?Broadeningofattractorbasins=>helpstodecreasesymptoms?Diagnosticvalue?Explainsfevereffects?Suggestpharmacotherapy?ModelinGENESISisinconclusive.SpatialattentionshiftsinPosnerexperimentsasafunctionofleakchannelconductancechangebetween20-120ms. RecognitionofmanyobjectsVisionmodelincludingLGN,V1,V2,V4/IT,V5/MTTwoobjectsarepresented.Connectivityoftheselayers:Spat1V2,Spat2Spat1V2,Spat2Spat2V2.Spat1hasrecurrentactivationsandinhibition,focusingonasingleobject.Innormalsituationsneuronsdesynchronizeandsynchronizeonthesecondobject=attentionshift. ModelofreadingLearning:mappingoneofthe3layerstotheothertwo.Fluctuationsaroundfinalconfiguration=attractorsrepresentingconcepts.Howtoseepropertiesoftheirbasins,theirrelations?Emergentneuralsimulator:Aisa,B.,Mingus,B.,andO"Reilly,R.Theemergentneuralmodelingsystem.NeuralNetworks,21,1045-1212,2008.3-layermodelofreading:orthography,phonology,semantics,ordistributionofactivityover140microfeaturesofconcepts.Hiddenlayersinbetween. FuzzySymbolicDynamics(FSD)Trajectoryofdynamicalsystem(neuralactivities),usingrecurrentplots(RP):RPplotsS(t,t0)valuesasamatrix.FSDshowstrajectoriesin2Dor3D:findreferencecentersm1,m2,m3onstandardizeddataandoptimizetheirpositiontoseeclearlyimportantfeaturesoftrajectoriesdespitereduceddimensionality.Thiscreateslocalizedmembershipfunctionsyk(t;W).Sharpindicatorfunctions=>symbolicdynamics;x(t)=>stringsofsymbols.Softmembershipfunctions=>fuzzysymbolicdynamics,dimensionalityreductionY(t)=(y1(t;W),y2(t;W))=>visualizationofhigh-Ddata.DoboszK,DuchW,NeuralNetworks23,487-496,2010;CognitiveNeurodynamics5(2),145-160,2011 NeurodynamicsTrajectoriesshowattentioneffectsasapropertyofneurodynamics,itdependson:synapticconnections:inhibitorycompetition,bidirectionalinteractiveprocessing,multipleconstraintsatisfaction;neuralproperties:thresholds,accommodation,ionchannels…Inputactivations=>basinsofattractors=>objectrecognitionNormalcase:relativelylargebasins,generalization,averagedwelltime,movingtootherbasinofattraction,exploringtheactivationspace.Withoutaccommodation(inactiveoutwardrectifyingionchannels):deep,narrowbasins,hardtomoveoutofthebasin,associationsareweak.Accommodation:basinsofattractorsshrinkandvanishbecauseneuronsdesynchronizeduetotheneuralfatigue.Thisallowsotherneuronstosynchronizeonnewstimuli,guidedbySpat=>V2=>V1feedback.Thisleadstosuddenspontaneousweaklyrelatedchainsofthoughts. AttractorsforwordsModelforreadingincludesphonological,orthographicandsemanticlayerswithhiddenlayersinbetween.Non-linearvisualizationofactivityofthesemanticlayerwith140units.Costandrenthavesemanticassociations,attractorsareclosetoeachother,butwithoutaccommodationtransitionsbetweenbasinsofattractionsarehard.Willitmanifestinverbalprimingtests?Freeassociations?Willbroadeningofphonological/writtenformrepresentationshelp?Forexample,willtrainingASDchildrenwithcharactersthatvaryinmanyways(shapes,colors,size,rotations)helpthem? Howstrongareattractors?Variancearoundthecenterofaclustergrowswithsynapticnoise;fornarrowanddeepattractorsitwillgrowslowly,butforwidebasinsitwillgrowfast.Jumpingoutoftheattractorbasinreducesthevarianceduetoinhibitionofdesynchronizedneurons.Morevariedencodingofconcretenounsseemstohelpcreatinglargerattractorbasins,butabstractconceptsshownarrowanddeepbasins. Normal-ADHDAllplotsfortheflagword,differentvaluesofb_inc_dtparameterintheaccommodationmechanism.b_inc_dt=0.01&b_inc_dt=0.02b_inc_dt=timeconstantforincreasesinintracellularcalciumwhichbuildsupslowlyasafunctionofactivation.http://kdobosz.wikidot.com/dyslexia-accommodation-parameters Normal-AutismAllplotsfortheflagword,differentvaluesofb_inc_dtparameterintheaccommodationmechanism.b_inc_dt=0.01&b_inc_dt=0.005b_inc_dt=timeconstantforincreasesinintracellularcalciumwhichbuildsupslowlyasafunctionofactivation.http://kdobosz.wikidot.com/dyslexia-accommodation-parameters InhibitionIncreasinggifrom0.9to1.1reducestheattractorbasinsizesandsimplifiestrajectories.Stronginhibition,emptyhead… ConnectivitySamesituation,withstrongerrecurrentconnectionswithinlayers;fewerbutlargerattractorbasinsarecreated,andmoretimeisspentineachbasin.Withsmallsynapticnoise(var=0.02)thenetworkstartsfromreachinganattractorandmovestoanotherone(frequentlyquitedistant),creatinga“chainofthoughts”. RecurrenceplotsSametrajectoriesdisplayedwithrecurrenceplots,showingroughly5largerbasinsofattractorsandsometransientpoints.Startingfromtheword“flag”,withsmallsynapticnoise(var=0.02),thenetworkstartsfromreachinganattractorandmovestoanotherone(frequentlyquitedistant),creatinga“chainofthoughts”. ProbabilityofrecurrenceProbabilityofrecurrencemaybecomputedfromrecurrenceplots,allowingforevaluationhowstronglysomebasinsofattractorscaptureneurodynamics. FasttransitionsAttentionisfocusedonlyforabrieftimeandthanmovedtothenextattractorbasin,somebasinsarevisitedforsuchashorttimethatnoactionmayfollow,correspondingtothefeelingofconfusionandnotbeingconsciousoffleetingthoughts. SomespeculationsAttentionshiftsmaybeimpairedduetoseveralfactors:Deepandnarrowattractorsthatentrapdynamics–duetoleakchannels?ExplainsoverspecificmemoryinASD,unusualattentiontodetails,theinabilitytogeneralizevisualandotherstimuli,alsofevereffects?Accommodation:voltage-dependentK+channels(~40types)donotdecreasedepolarizationinanormalway,attractorsdonotshrink.Thiseffectshouldalsoslowdownattentionshiftsandreducejumpstounrelatedthoughtsortopicsrelativelytoaverageperson–neuralfatiguewilltemporarilyswitchthemoffpreventingactivationofattractorsthatcodesignificantlyoverlappingconcepts.Whatbehavioralchangesareexpected?Howtotestsit? Research/diagnosticconsequencesManyproblemsatgenetic/molecularlevelmayleadtothesamebehavioralsymptoms=>problemsforstatistically-orientedresearchmethods.Geneticmutationshouldgiveweaksignals:inagivenpopulationofautisticpatientsonlysmallfractionwillhaveagivenmutation.Inconclusiveresultsondiet:severalstudiesshowsomeimprovement,otherstudiesshownoeffect.Pharmacologicalandothertreatmentswillhavelimitedsuccess.Needforabetterdiagnosticsatmolecular/geneticlevel!Strategy:behavior<=neuralproperties;findneuralparametersthataffectbehaviorinaspecificway;trytorelatethemtomolecularpropertiesinsynapses,variousreceptors,ionchannels(poreformingproteins),membraneproperties;trytofindmarkersforspecificabnormalities. BehavioralconsequencesDeep,localizedattractorsareformed;whataretheconsequences?Problemswithdisengagementofattention;hyperspecificmemoryforimages,words,numbers,facts,movements;strongfocusonsinglestimulus,absorption,easysensoryoverstimulation;gazefocusedonsimplestimuli,notfaces,contactisdifficult;echolalia,repeatingwordswithoutunderstanding(noassociations);nounsareacquiredmorereadilythanabstractwordslikeverbs;playisschematic,fastchangesarenotnoticed(stablestatescannotarise);playwithotherchildrenisavoidedinfavorofsimpletoys;generalizationandassociationsarequitepoor;integrationofdifferentmodalitiesthatrequiressynchronizationisimpaired,connectionsareweak;normaldevelopment–theoryofmind,MNS,relations–isimpaired.Simplebasicdeficit=>hostofproblems,manyinsightsfromsimplemechanism.Expectgreatdiversity,dependingonlocalexpressionandseverity. Experimentalevidence:behaviorKawakuboY,etal.Electrophysiologicalabnormalitiesofspatialattentioninadultswithautismduringthegapoverlaptask.ClinicalNeurophysiology118(7),1464-1471,2007.“TheseresultsdemonstrateelectrophysiologicalabnormalitiesofdisengagementduringvisuospatialattentioninadultswithautismwhichcannotbeattributedtotheirIQs.”“Wesuggestthatadultswithautismhavedeficitsinattentionaldisengagementandthephysiologicalsubstratesunderlyingdeficitsinautismandmentalretardationaredifferent.”LandryR,BrysonSE,Impaireddisengagementofattentioninyoungchildrenwithautism.JournalofChildPsychologyandPsychiatry45(6),1115-1122,2004“Childrenwithautismhadmarkeddifficultyindisengagingattention.Indeed,on20%oftrialstheyremainedfixatedonthefirstoftwocompetingstimulifortheentire8-secondtrialduration.”Severalnewerstudies:MayadaElsabbagh. Experimentalevidence:behaviorD.P.Kennedy,E.Redcay,andE.Courchesne,Failingtodeactivate:Restingfunctionalabnor-malitiesinautism.PNAS103,8275-8280,2006.Defaultnetworkinautismgroupfailedtodeactivatebrainregions,strongcorrelationbetweenaclinicalmeasureofsocialimpairmentandfunctio-nalactivitywithintheventralMPF.Mistakingsymptomsforrealproblems:Wespeculatethatthelackofdeactivationintheautismgroupisindicativeofabnormalinternallydirectedprocessesatrest. MistakingsymptomsforcausesVariousbrainsubsystemsdevelopinanabnormalway:1.Abnormalfunctionalconnectivitybetweenextrastriateandtemporalcorticesduringattributionofmentalstates,andexecutivetaskssuchasmemoryfororattentiontosocialinformation(Castellietal.,2002;Justetal.,2004,2007;Kanaetal.,2007a,b;Dichteretal.,2007;Kleinhansetal.,2008).2.Underconnectivity:workingmemory,faceprocessing(Justetal.,2007;Koshinoetal.,2008;Birdetal.,2006),cortico-corticalconnectivity(Barnea-Goralyetal.,2004;Herbertetal.,2004;Kelleretal.,2007).3.Defaultmodenetwork:“Resultsrevealedthatwhiletypicallydevelopingindividualsshowedenhancedrecallskillsfornegativerelativetopositiveandneutralpictures,individualswithASDrecalledtheneutralpicturesaswellastheemotionalones.FindingsofthisstudythuspointtoreducedinfluenceofemotiononmemoryprocessesinASDthanintypicallydevelopingindividuals,possiblyowingtoamygdaladysfunctions.”C.Deruelleetal.,Negativeemotiondoesnotenhancerecallskillsinadultswithautisticspectrumdisorders.AutismResearch1(2),91–96,2008 Experimentalevidence:molecularWhattypeofproblemswithneuronscreatethesetypesofeffects?Neuralself-regulationmechanismsleadtofatigueoraccommodationofneuronsthroughleakyK+channelsopenedbyhighCa++concentration,orlongeractingGABA-Binhibitorysynapticchannel.Thisleadstoinhibitionofneuronsthatrequirestrongeractivationtofire.Neuronsaccommodateorfatigueandbecomelessandlessactiveforthesameamountofexcitatoryinput.Dysregulatedcalciumsignaling,mainlythroughvoltage-gatedcalciumchannels(VGCC)isthecentralmoleculareventthatleadstopathologiesofautism.http://www.autismcalciumchannelopathy.com/Calciumhomeostasisincriticalstagesofdevelopmentmaybeperturbedbygeneticpolymorphismrelatedtoimmunefunctionandinflammatoryreactionsandenvironmentalinfluences(perinatalhypoxia,infectiousagents,toxins).Geneticmutations=>proteinsbuildingincorrectpotassiumchannels(CASPR2gene)andsodiumchannels(SCN2Agene). Genes&functionshttp://www.sciencebasedmedicine.org/?p=5662Pinto,D.+180coauthors...(2010).FunctionalimpactofglobalrarecopynumbervariationinautismspectrumdisordersNatureDOI:10.1038/nature09146 Questions/IdeasNeurodynamicsisanewusefullanguagetospeakaboutmentalprocesses.Therearemanyparameterscharacterizingbiophysicalpropertiesofneuronsandtheirconnectionswithindifferentlayersthatcontrolbehavior.Howdoesdepth/sizeofbasinsofattractorsdependontheseparameters?Howtomeasureand/orvisualizeattractors?Stabilityofdetailedneuralmodels,realeffectsorartifacts?Howdoattractorsdependonthedynamicsofneuronaccommodation?Noise?Inhibitionstrength,localexcitations,long-distancesynchronization?Howwillsymptomsdifferdependingonspecificbrainareas?Forexample,musuppressionmaybeduetodeepattractors…Whatarepreciserelationstoionchannelsandproteinsthatbuildthem?Howcantheybechangedbypharmacologicalinterventions? Morequestions/ideasHowlearningproceduresmayinfluenceformationofbasinsofattractors?Forexample,learningtoreadmaydependonthevariabilityoffonts,handwritingmaybemuchmoredifficultetc.Slowbroadeningofattractorbasins?Spontaneousthoughts,localenergywithlowneuralaccommodation?Canonedrawusefulsuggestionshowtocompensateforsuchdeficits?SpatialattentionshiftsinPosnerexperiments–resonancesdependingonthetiming,maskingeffects,flickeringwithdifferentfrequencies?Precisediagnostics,whattypeofproblemsatgenetic/molecularlevel?Compensationeffects:whatchangesinthenetworkwillleadtofasterattentionshifts?Willithelpindiagnostics/therapy?Neurofeedback?Weneedtofinishcomputationalsimulationsandthendorealtestofsomepredictions. Neuromania,andNeurohistoryofartinMay/June2013;Trendsininterdisciplinarystudies8-10.11.2013http://www.kognitywistyka.umk.pl4CSconferencesin2013:Homocommunicativus, ThankyouforlendingyourearsGoogle:W.Duch=>papers,talks,lecturenotes…