2011.10.15.. 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 2011.10.15. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 2 Peter Pazmany Catholic University Faculty of Information Technology BEVEZETÉS A FUNKCIONÁLIS NEUROBIOLÓGIÁBA INTRODUCTION TO FUNCTIONAL NEUROBIOLOGY www.itk.ppke.hu By Imre Kalló Contributed by: Tamás Freund, Zsolt Liposits, Zoltán Nusser, László Acsády, Szabolcs Káli, József Haller, Zsófia Maglóczky, Nórbert Hájos, Emilia Madarász, György Karmos, Miklós Palkovits, Anita Kamondi, Lóránd Erõss, Róbert Gábriel, Zoltán Kisvárdai, Zoltán Vidnyánszky Introduction to functional neurobiology: Functional imaging techniques 2011.10.15. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 3 www.itk.ppke.hu Functional imaging techniques Éva Bankó, Viktor Gál, István Kóbor & Zoltán Vidnyánszky Pázmány Péter Catholic University, Faculty of Information Technology I. Functional Magnetic Resonance Imaging (fMRI) Image acquisition, processing and analysis What fMRI can do and what it can not do? II. Investigation of Sensory processing Neural Plasticity Cognitive functions Introduction to functional neurobiology: Functional imaging techniques 2011.10.15. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 4 www.itk.ppke.hu The MR system (1.5/3.0T ) Main components: external magnet gradient coils RF coils computers 030805-056-km Introduction to functional neurobiology: Functional imaging techniques 2011.10.15. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 5 www.itk.ppke.hu Functional Magnetic Resonance Imaging (fMRI) • The Blood OxygenationLevel Dependent (BOLD, Ogawa et al, 1990Magn. Reson.Med.) Method: Introduction to functional neurobiology: Functional imaging techniques 2011.10.15. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 6 www.itk.ppke.hu Factors defining local deoxyhemoglobin-concentration Local neuronal activity Local concentration of deoxy- hemoglobin Vasodilators Blood flow Blood volume Metabolic changes Diffuse projections Vasoconstrictors Introduction to functional neurobiology: Functional imaging techniques 2011.10.15. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 7 www.itk.ppke.hu Activity dependent changes in deoxy-and oxyhemoglobin levels 0 Time Relativeconcentration Hb dHb 0 14 • Quite distinct changes in oxygenated(Hb)and deoxygenated hemoglobin(dHb)following neuronal activation. • Unlike weak deoxygenated hemoglobin signal spatial pattern of oxygenated hemoglobin did not reflect the pattern of neuronal activity Introduction to functional neurobiology: Functional imaging techniques 2011.10.15. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 8 www.itk.ppke.hu Functional Magnetic Resonance Imaging (fMRI) BOLD response correlates with the strength of the neural local field potentials (LFP) Spatial resolution of the BOLD method: 1-3 mm. Temporal resolution of the BOLD method: seconds Logothetis et al, Journal of Neuroscience, 2003, Introduction to functional neurobiology: Functional imaging techniques 2011.10.15. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 9 www.itk.ppke.hu Acquired Data • 3D T1 anatomy– 1×1×1 mm resolution • 4D T2* EPI images– 3D timeseries collected at each TR (1-2 s) – ~4×3.5×3.5 mm resolution Introduction to functional neurobiology: Functional imaging techniques Preprocessing and Processing Steps • Anatomical images– Intensity normalization – Skull-stripping – 3D reconstruction – Normalization (MNI or Talairach) • Functional images– Coregistration – 3D motion correction – Slice-time correction – Smoothing – Defining ROIs – Regression analysis 2011.10.15. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 10 www.itk.ppke.hu + Introduction to functional neurobiology: Functional imaging techniques 2011.10.15. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 11 www.itk.ppke.hu Anatomical PreprocessingI. • Intensity normalization– make white matter (WM) homogenous to aid segmentation • Skull-stripping– remove all non-brain tissues – caveat: shouldn’t accidentally removegrey matter (GM) • Segmentation– separate hemispheres, then separateGM from WM, so analysis can berestricted to GM Introduction to functional neurobiology: Functional imaging techniques 2011.10.15. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 12 www.itk.ppke.hu Anatomical Preprocessing II. • Surface creation– make surfaces out of the segmentedGM and WM • Inflation– inflate WM surface to better visualize activations in sulci • Flattening– cut a patch and flatten or cut at predefined sulci to flatten the whole brain WM surfaceGM surface Introduction to functional neurobiology: Functional imaging techniques 2011.10.15. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 13 www.itk.ppke.hu Anatomical Preprocessing III. • Normalization– transform each individual brain into a standard space by predefined algorithms so 2nd-level (group-level) analysis can be performed – standard spaces: • Talairach space based on one post-mortem brain • Montreal Neurological Institute (MNI) space based on a large series of MRI scans on normal controls individual spaceMNI space Introduction to functional neurobiology: Functional imaging techniques 2011.10.15. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 14 www.itk.ppke.hu Functional Preprocessing I. • Coregistration– 3Danatomyandthefunctionalimagesareacquiredinadifferentspace;moreovertheEPIsequencedistortsthebrainintheneighborhoodofcavities – alinear(ornon-linear)warpingalgorithmisrequiredtoregisterbothinthesamespacesostatisticalactivationscanbeprojectedtotheanatomicalsurface + = EPI distortion Introduction to functional neurobiology: Functional imaging techniques 2011.10.15. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 15 www.itk.ppke.hu Functional PreprocessingII. • 3D Motion correction– alignallfunctionalimagestoareferenceimage(usuallythefirstimageortheimageinthemiddleofthescan)sincetheirlocationcouldhaveslightlychangedduetosubjectmotionandallstatisticalanalysesassumethatthelocationofagivenvoxelwithinthebraindoesnotchangeovertime • Slice-timing correction– withacontinuousdescendingEPIsequence,thebottomsliceisacquiredaTRlaterthanthesliceonthetop,sothereisashiftintheonsetofthehaemodynamicfunction.Onesolutiontothisproblemistointerpolatethedataduringpreprocessingasifthesliceswereacquiredsimultaneously • Smoothing– spatiallysmoothingeachoftheimagesimprovesthesignal-to-noiseratio(SNR),butwillreducetheresolutionineachimage Introduction to functional neurobiology: Functional imaging techniques 2011.10.15. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 16 www.itk.ppke.hu Statistical Analysis of Functional ImagesI. • Aims:– find and describe the effect of stimulation if there is any • Based on the spatial complexity of the signal, there are:– one-dimensional methods• doing the statistics separately on a voxel-by-voxel basis (classic GLM regression method) • averaging the timecourse of predefined voxels in a certain area (region-of-interest: ROI) and doing the statistics on that (increases signal-to-noise ratio (SNR) – multi-dimensional (multi-variate) methods• finding patterns in time andspace Introduction to functional neurobiology: Functional imaging techniques 2011.10.15. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 17 www.itk.ppke.hu Statistical Analysis of Functional ImagesII. • Fitting models to the data:– find models that describe the signal and the noise and evaluate the fit • Parametric models:– linear correlation – t-tests – event-related averaging – general linear models (GLM) • Non-parametric models– bootstrap – Monte-Carlo simulations – multi-variate models Introduction to functional neurobiology: Functional imaging techniques 2011.10.15. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 18 www.itk.ppke.hu Statistical Analysis of Functional ImagesIII. • Noise integration into models– models should take noise into account either as a separate term – there are models devoted to noise estimation (nuisance variability models) such as time autocorrelation or drift • Univariate models treating each voxel separately need to be statistically corrected for– correction for the multiple comparison problem • Group-level statistics model the population not particular individuals– Random effects models Introduction to functional neurobiology: Functional imaging techniques 2011.10.15. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 19 www.itk.ppke.hu Linear Transform Hypothesis • ItisassumedthattheprocessesfromneuronalfiringtoBOLDresponseconstituteatime-invariantlinearsystem,sothefMRIsignalisapproximatelyproportiontoameasureoflocalneuralactivity,averagedoveraspatialextentofseveralmillimetersandoveratimeofseveralseconds. • Haemodynamicimpulseresponsefunction:(HIRForHRF)themeasurablefMRIsignalforabriefstimuluspresentation. Introduction to functional neurobiology: Functional imaging techniques 2011.10.15. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 20 www.itk.ppke.hu Haemodynamic Response Function Nervous system Haemodynamics MR scanner VASO man2 Series of stimulation modeled by the HRF Regressorconvolved with the HRF Introduction to functional neurobiology: Functional imaging techniques 2011.10.15. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 21 www.itk.ppke.hu • Functional Contrast:– Blood volume – Blood flow/perfusion – Blood oxygenation • Spatial resolution: – Typical: 3 mm3 – Upper: 0.5 mm3 • Temporal resolution:– Typical: 2-3sec – Stimuli can be detected:– Minimum duration(single slice): < 16 ms – Minimum onset diff: 100 ms to 2 sec • Interpretability:– Neurovascular coupling, vascular sampling, blood, physiologic noise, motion and other artifacts, etc. Overview of fMRI Introduction to functional neurobiology: Functional imaging techniques 2011.10.15. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 22 www.itk.ppke.hu Why fMRIis so popular? • Powerful– Improved ability to understand cognition – Better spatial resolution than PET – Allows new forms of analysis • High benefit/risk ratio– Non-invasive (no contrast agents) – Repeated studies (multisession, longitudinal) • Accessible– Uses clinically prevalent equipment – No isotopes required – Little special training for personnel Introduction to functional neurobiology: Functional imaging techniques 2011.10.15. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 23 www.itk.ppke.hu Help in understanding healthy brain organization – map networks involved with specific behavior, stimulus, or performance – characterize changes over time (seconds to years) – determine correlates of behavior (response accuracy, etc…) Current Clinical Applications – presurgicalmapping – better understanding mechanism of pathology for focused therapy – drug effect assessment – assessment of therapy progress, biofeedback – epileptic foci mapping – neurovascular physiology assessment Current Clinical Research – assessment of recovery and plasticity – clinical population characterization with probe task or resting state What fMRICan Do Introduction to functional neurobiology: Functional imaging techniques 2011.10.15. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 24 www.itk.ppke.hu What fMRICan’t Do • Too low SNR for routine clinical use (takes too long) • Requires patient cooperation (too sensitive to motion) • Too low spatial resolution (each voxelhas several million neurons) • Too low temporal resolution (hemodynamicsare variable and sluggish) • Too indirectly related to neuronal activity • Too many physiologic variables influence signal • Requires a task (BOLD cannot look at baseline maps) • Too confined space and high acoustic noise. Introduction to functional neurobiology: Functional imaging techniques 2011.10.15. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 25 www.itk.ppke.hu InvestigatingBrain Functions with fMRI • Sensory Processing– early level – higher-order • Neural Plasticity– short-term plasticity – long-term cortical reorganization – developmental plasticity • Cognitive Function– attentional network – decision making – memory Introduction to functional neurobiology: Functional imaging techniques 2011.10.15. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 26 www.itk.ppke.hu Sensory Processing Introduction to functional neurobiology: Functional imaging techniques 2011.10.15. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 27 www.itk.ppke.hu RetinotopicalMapping Aim is to separate early and mid-level visual areas Visual areas in the brain are defined by – Physiology – Cellular architecture – Connections to other areas – Topographical representationof the world Neuralrepresentationofthestimulusintheprimaryvisualcortexofamacaquemonkey(Tootelletal.1988,JNeurosci.). Introduction to functional neurobiology: Functional imaging techniques 2011.10.15. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 28 www.itk.ppke.hu Visual field representation in human primary visual cortex (V1) Introduction to functional neurobiology: Functional imaging techniques 2011.10.15. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 29 www.itk.ppke.hu Protocol for Retinotopy • Phase reversing checkerboard stimulus for strong excitation • Aim is to probe the entire visual field:– Rotating wedge to get information about visual field quadrants – Contracting-expanding ring to get informationabout eccentricity polar_stimuli ecc_stimuli CW/CCW rotating wedge Contracting/expanding ring Introduction to functional neurobiology: Functional imaging techniques 2011.10.15. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 30 www.itk.ppke.hu Defining visual areas on flattened cortex Phase map – Phasereversaldelineates areas Eccentricity map – Tells about fovealand peripheralrepresentation of each area dorsal ventral medial lateral lateral medial Left hemisphere Right hemisphere UVM LHM RHM LVM UVM LHM RHM LVM Introduction to functional neurobiology: Functional imaging techniques 2011.10.15. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 31 www.itk.ppke.hu Retinotopy Demo Flattened right hemisphere, cut through the calcarine sulcus polar_lag0-6 LVF B B M M U U occipital pole ventral-dorsal uppermiddlebottom visual field Introduction to functional neurobiology: Functional imaging techniques 2011.10.15. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 32 www.itk.ppke.hu • As a result the voxels are assigned to areas,so the activation pattern of each area in a specific experimental design can be studied separately. • Topographic mapping can also be done in somatosensory and auditory cortices. 2hemishpere Introduction to functional neurobiology: Functional imaging techniques 2011.10.15. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 33 www.itk.ppke.hu Category-specific higher-order cortical areas Therearetwovisualprocessingstreamsexistinginthecortexforprocessingdifferentvisualpercepts: • Ventral(“what”)pathway–enablesthevisualidentificationofobjects– maininputfrom“slowanddetailed”parvosystemofLGN – ends in object-selective inferior temporal cortex • Dorsal (“where”) pathway–spatial perception, visual location of objects– main input from “quick and dirty” magnosystem of LGN – ends in posterior parietal cortex, comprises motion selective area MT+ (Mischkin& Ungerleider1983, Trends Neurosci) Introduction to functional neurobiology: Functional imaging techniques 2011.10.15. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 34 www.itk.ppke.hu Functional Localizers • Higher-ordercorticalareaslackingtopographicalorganizationbutbeingcategory-specificcanstillbedeterminedbasedonfunctionalcontrasts– E.g. Face-localizer: probingthe selectivity of object-selectiveinferotemporal cortex using the contrast of non-sense objects and faces LO: Lateral Occipital Complex OFA: Occipital Face Area FFA: FusiformFace Area Introduction to functional neurobiology: Functional imaging techniques 2011.10.15. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 35 www.itk.ppke.hu Face processing network Haxby Mainly the posterior part of STS (pSTS) i.e. Fusiform Face Area, strongly right lateralized Activation due to presentation of faces w/ both emotionaland neutral expressions Activation due to presentation of faces w/ emotionalexpressions (Haxby et al, 2000, Trends Cog Sci) (Grill-Spectoret al, 2004, Nature Neurosci) Introduction to functional neurobiology: Functional imaging techniques 2011.10.15. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 36 www.itk.ppke.hu • specialized in the processing of visual motion information: its response to coherent motion is higher than to incoherent motion • block design: coherently and incoherentlymoving dotsare presented in interleavedorder LOCALIZE + + > + + – hMT+ (V5) localizer: probing the motion-selectivity of the dorsal visual pathway Introduction to functional neurobiology: Functional imaging techniques 2011.10.15. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 37 www.itk.ppke.hu Localizers as means of studying homology between species It was shown that both face-selective patches in macaque cortex (Tsao et al. 2003, Nat Neurosci; Pinsk et al. 2005, PNAS) correspond to existing structures in humans. MacaqueHuman (Rajimehr et al., 2009, PNAS) PTFP: Post. Temp. Face PatchFFA: Fusiform Face Area ATFP: Ant. Temp. Face Patch Introduction to functional neurobiology: Functional imaging techniques 2011.10.15. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 38 www.itk.ppke.hu Somatosensorystimulation: self-produced or external? •Somatosensorycortex: increased BOLD signal to baseline in the case of externally-produced tactile stimulation, while reduced BOLD signal compared to baseline in the case of self-produced tactile stimulation › mediated by the cerebellum tactile2.jpg tactile1.jpg •Significantly decreased activity in right anterior cerebellarcortex associated with the interaction between the effects of self-generated movement and tactile stimulation(external input) (Blakemore et al., 1998, Nature Neurosci) Introduction to functional neurobiology: Functional imaging techniques 2011.10.15. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 39 www.itk.ppke.hu Neuronal Plasticity Introduction to functional neurobiology: Functional imaging techniques 2011.10.15. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 40 www.itk.ppke.hu Plasticity Underlying Short-term Learning Long-termpracticeonsequenceperformance(motorskilllearning) •Inacomplexfingermovingparadigmaftertrainingimprovedratesofperformanceinducedincreasedactivationoftheprimarysensorimotorcortex,whichdidnotgeneralizetothecontralateralhand. (Karni et al. 1998, PNAS) Time (weeks) Performance Rate (sequences/30s) Introduction to functional neurobiology: Functional imaging techniques 2011.10.15. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 41 www.itk.ppke.hu Enhancement of relevant information during perceptual learning •Perceptuallearningisdefinedasperformanceorsensitivityincreaseinasensoryfeatureasaresultofrepetitivetrainingorexposuretothefeatureandisregardedasmanifestationofsensoryplasticity. •Visualtexturediscriminationinduceslong-lastingbehavioralimprovementrestrictedtothetrainedeyeandtrainedlocationinvisualfield.Within-subjectcomparisonsbetweentrainedanduntrainedeye for targets presented withinthe same quadrant revealed higher activity in a corres-pondingretinotopicarea of visual cortex. ›learning leads to enhanced perceptual and neural responses for the learned relevant stimulus (Schwarz et al. 2002, PNAS) (©2002 The National Academy of Sciences) Introduction to functional neurobiology: Functional imaging techniques 2011.10.15. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 42 www.itk.ppke.hu Learning to suppress irrelevant stimuli •Beforetraining:nodifferencebetweenthefMRIresponsesevokedbythetask-relevantandtask-irrelevantmotiondirections •Aftertraining:task-irrelevantdirection(i.e.distractorstimulus)evokedsignificantlysmallerfMRIresponsesthantask-relevantdirection ›learningleadstosuppressedperceptualandneuralresponsesfortask-irrelevantinformation,whichcompeteswiththeprocessingofthetask-relevantinformationduringtraining (Gál et al.,2009, E J Neurosci) Introduction to functional neurobiology: Functional imaging techniques 2011.10.15. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 43 www.itk.ppke.hu Studying Long-Term Cortical Reorganization • in congenitally and early blind people retinotopic visual cortex is activated when reading Braille, as opposed to late blind people who show much less activation Burton 2003, J Neurosci Introduction to functional neurobiology: Functional imaging techniques 2011.10.15. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 44 www.itk.ppke.hu • Visual cortex activation in verbal tasks in blind people also correlates with verbal memory performance Fig 2 full size Fig 7 full size (Amediet al, 2003, Nature Neurosci) Introduction to functional neurobiology: Functional imaging techniques 2011.10.15. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 45 www.itk.ppke.hu Cross-modal plasticity in congenitally deaf: • Auditorycortexactivatesforsimplevisualstimuli(movingdotpattern)inearlydeafsubjects,demonstratingthatearlydeafnessresultsintheprocessingofvisualstimuliinprimaryauditorycortex. (Finneyet al. 2001, Nature Neurosci) Introduction to functional neurobiology: Functional imaging techniques 2011.10.15. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 46 www.itk.ppke.hu • Bothbilateralinferiorprefrontalregions(includingBroca’sarea)andbilateralsuperiortemporalregions(includingWernicke’sarea)wereactivatedbyviewingsignlanguage(BSL)incongenitallydeafsigners.DeafnativesignersalsodemonstratedgreateractivationintheleftsuperiortemporalgyrusinresponsetoBSLthanhearingnativesigners(A),whichsuggeststhatlefttemporalauditoryregionsmaybeprivilegedforprocessingheardspeecheveninhearingnativesigners.However,intheabsenceofauditoryinputthisregioncanberecruitedforvisual processing. (MacSweeneyet al. 2002, Brain) Introduction to functional neurobiology: Functional imaging techniques 2011.10.15. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 47 www.itk.ppke.hu Studying Developmental Plasticity Dyslexia, a developmental disorder • Functional neuroimagingstudies have revealed differences in brain function and connectivity that are characteristic of dyslexia, e.g.– children and adults with dyslexia exhibit reduced or absent activation in the left temporo-parietal cortex – left temporo-parietal region supports the cross-modal relation of auditory and visual processes during reading – atypical activations in left middle and superior temporal gyriassociated with receptive language, and left occipito-temporal regions associated with visual analysis of letters and words Introduction to functional neurobiology: Functional imaging techniques 2011.10.15. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 48 www.itk.ppke.hu Brain Plasticity Associated with Treatment Duringphonologicalprocessingthereisamarkedfrontal(redcircles)andtemporo-parietal(bluecircles)hypoactivationindyslexicreaderscomparedtotypicallydevelopingreaders,whichbecamemoreactiveafterremediation. dyslexic_child.jpg © 2003 The National Academy of Sciences (Templeet al., 2003, PNAS) Introduction to functional neurobiology: Functional imaging techniques 2011.10.15. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 49 www.itk.ppke.hu Cognitive Functions Introduction to functional neurobiology: Functional imaging techniques 2011.10.15. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 50 www.itk.ppke.hu Studying the Organization of Attention System Attentionsystems: •Dorsalgoal-directedattentionalnetwork(blue)isinvolvedinpreparingandapplyinggoal-directed(top-down)selectionforstimuliandresponses.(rightwardbias) •Ventralstimulus-drivenattentionalnetwork(orange)isnotinvolvedintop-downselection.Instead,thissystemisspecializedforthedetectionofbehaviourallyrelevantstimuli,particularlywhentheyaresalientorunexpected.(reorientingdeficit) (Corbettaand Shulman, 2002, Nature Rev Neurosci) Introduction to functional neurobiology: Functional imaging techniques 2011.10.15. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 51 www.itk.ppke.hu Basis of Attentional Selection: Location Spatial attentionalselection: Whensubjectsarecuedtoshifttheirattentionbetweentwolocationsofthevisualfield,striateandextrastriatecortexresponsesmodulatewiththealternationoftheattentionalcue:responsesaregreaterwhenthesubjectsattendtothestimuliinthecontralateralhemifield. (Matrínezet al., 1999, Nature Neurosci) Introduction to functional neurobiology: Functional imaging techniques 2011.10.15. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 52 www.itk.ppke.hu Basis of Attentional Selection: Features Globalattentionalselection:attentiontoastimulusfeature(colorordirectionofmotion)increasedtheresponseofcorticalvisualareasnotonlytothestimuliattheattendedlocationbutalsotoaspatiallydistant,ignoredstimulusthatsharedthesamefeature. attended side Motion Color (Saenz et al., 2002, Nature Neurosci) Introduction to functional neurobiology: Functional imaging techniques 2011.10.15. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 53 www.itk.ppke.hu Basis of Attentional Selection: Objects Withstimuliconsistingofafacetransparentlysuperimposedonahouse,withonemovingandtheotherstationaryorviceversa,attendingtothemovingobjectresultedinhigheractivationnotonlyinmotionprocessingareaMTbutalsointhecorticalareaselectiveforthemovingobject.Thisprovidesphysiologicalevidencethatwholeobjectsareselectedevenwhenonlyonevisualattributeisrelevant,insteadoflocationsorfeaturebeingtheunitsofattentionalselection. (O’Craven et al., 1999, Nature) Introduction to functional neurobiology: Functional imaging techniques 2011.10.15. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 54 www.itk.ppke.hu Studying Areas Involved in Decision Making •Perceptualdecisionmakingistheactofchoosingoneoptionorcourseofactionfromasetofalternativesonthebasisofavailablesensoryevidence.Thecorticalareasinvolvedi)representsensoryevidenceii)accumulateandcomparesensoryevidencetocomputeadecisionvariableiii)monitorperformancedetectingerrorstosignalforadjustmentofdecisionstrategies. Stimulus (Heekerenet al. 2008, Nature Rev Neurosci) Introduction to functional neurobiology: Functional imaging techniques 2011.10.15. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 55 www.itk.ppke.hu •Value-baseddecisionmakingistheactofchoosingfromseveralalternativesonthebasisofasubjectivevaluethattheindividualplacesonthem. (Rangel et al. 2008, Nature Rev Neurosci) Introduction to functional neurobiology: Functional imaging techniques 2011.10.15. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 56 www.itk.ppke.hu Sensory evidence representation in perceptual decision making •Forthepreferredcategory,bothface-(FFA)andhouse-selectiveregions(PPA)respondedmoretosuprathresholdthantoperi-thresholdimageswhereastheoppositewastrueforthenon-preferredcategory,indicatingthatface-andhouse-selectiveregionsininferotemporalcortexrepresentedthesensoryevidenceforthetworespectivecategories. FFA PPA (Heekerenet al., 2004, Nature) Introduction to functional neurobiology: Functional imaging techniques 2011.10.15. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 57 www.itk.ppke.hu Studying the Neural Network Associated with Memory Long-term memory systems: • Declarative (explicit) memory affords the capacity for conscious recollections about facts and events– subtypes: semantic memory; episodic memory – structures involved are medial-temporal lobe, prefrontal cortex, diencephalon and basal forebrain • Non-declarative (implicit) memory, a heterogeneous collection of nonconscious abilities that includes the learning of skills and habits, priming and some forms of classical conditioning. Short-term memory: • Working memory Introduction to functional neurobiology: Functional imaging techniques 2011.10.15. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 58 www.itk.ppke.hu • Encodingandretrievaldifferenceswerefoundwithinthe:– medialtemporallobes(MTLs):encoding(ESA)inducedgreateractivityintheanteriorhippocampus,whileretrieval(RSA)wasassociatedwithgreateractivityintheposteriorparahippocampalcortex/hippocampus(encoding-retrievalgradientalongthelongitudinalMTLaxis). – prefrontalcortex(PFC):encodinginducedgreateractivityinventrolateralPFC,whileretrievalwasassociatedwithgreateractivityindorsolateralandanteriorPFC. • Onlythelefthippocampuswasassociatedwithrelationalmemoryingeneral(i.e.,forbothsemanticandperceptualencodingandretrieval) Encoding and retrieval of semantic and perceptual associations (Princeet al., 2005, J Neurosci) © 2005 Society for Neuroscience Introduction to functional neurobiology: Functional imaging techniques 2011.10.15. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 59 www.itk.ppke.hu Working memory for emotional expressions • Althoughinitialprocessingofemotionandidentityisaccomplishedinanatomicallysegregatedtemporalandoccipitalregions,activemaintenanceofbothfacialemotionsandidentityisassociatedwithasustaineddelay-periodactivityinorbitofrontalcortex(OFC),amygdalaandhippocampus. (LoPrestiet al., 2008, J Neurosci) © 2008 Society for Neuroscience Introduction to functional neurobiology: Functional imaging techniques 2011.10.15. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 60 www.itk.ppke.hu WorkingmemoryforemotionalexpressionsII • Short-termencodingandretrievaloffacialexpressionsdependontheactivationlevelofrightpSTS,whichpredominantlyprocesseschangeablefacialfeaturessuchasfacialexpressions • Correlation only existed if expression wasattended and disappeared when identity wasrelevant Attend to emotion > attend to identity AllSubs avgRun_Emo_STS_groupROI_BVQX_cikk (Bankó et al., 2009, J Vision) Introduction to functional neurobiology: Functional imaging techniques © 2008 The National Academy of Sciences 2011.10.15. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 61 www.itk.ppke.hu Resting State fMRI –Default Network • A baseline or control state is fundamental to the understanding of most complex systems. • Defaultnetwork:areasthatconsistentlyexhibitdecreasesfromthisbaseline,duringawidevarietyofgoal-directedbehaviors.Thesedecreasessuggesttheexistenceofanorganized,baselinedefaultmodeofbrainfunctionthatissuspendedduringspecificgoal-directedbehaviors.Overdevelopment,theseregionsintegrateintoacohesive,interconnectednetwork. (Fair et al. 2008, PNAS ) Introduction to functional neurobiology: Functional imaging techniques 2011.10.15. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 62 www.itk.ppke.hu Other fMRI applications Introduction to functional neurobiology: Functional imaging techniques 2011.10.15. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 63 www.itk.ppke.hu “Mindreading” –Decoding Cortical Activity •EnsemblefMRIsignalsinearlyvisualareascanreliablypredictonindividualtrialswhichofeightstimulusorientationsthesubjectwasseeing. •Feature-basedattentionstronglybiasedensembleactivitytowardstheattendedorientation ›fMRIactivitypatternsinearlyvisualareas,includingprimaryvisualcortex(V1),containdetailedorientationinformationthatcanreliablypredictsubjectiveperception. (Kamitaniand Tong, 2005, Nature Neurosci) Introduction to functional neurobiology: Functional imaging techniques 2011.10.15. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 64 www.itk.ppke.hu “Mindreading” –Decoding Cortical Activity II RepresentationofBehavioralChoiceforMotioninHumanVisualCortex •Multivoxelpatternanalysis(MVPA)enablestodiscriminatewith60-70%accuracybetweenleftwardandrightwardmotioninthecaseof100%motioncoherenceinallareasregardlessofitsmotionselectivity.HoweveronlymotionsensitiveareahMT+wasabletodiscriminatebetweenperceiveddirectionofmotion(ambiguosstimulus)makingthisareathecandidatewhichtheconsciousexperienceisbasedon. (Serences and Boynton, 2007, J Neurosci) © 2007 Society for Neuroscience Introduction to functional neurobiology: Functional imaging techniques 2011.10.15. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 65 www.itk.ppke.hu “Mindreading” –Perception w/o awareness fMRIisausefultootoinvestigateperceptionwithoutawareness,becausetheneurallocusofanyactivationthatoccuroutsideofawarenessprovidessomeinformationaboutthenatureoftheinformationrepresented: •Thepresentationoffearfulfacesmaskedwithneutralfaceselicitsastrongeramygdalaresponsethanwhenhappyfacesarepresentedbeforeneutralfaces,eventhoughsubjectsfailedtoseeanyexpressivefaces. ›amygdalarespondstononconsciousstimuli (Whalen et al. 1998, J Neurosci) © 1998 Society for Neuroscience