The Cognitive Neuroscientist’s Toolkit

The Cognitive Neuroscientist’s ToolkitJesse RissmanCS 182 Guest Lecture, 2/1/07QuickTimeª and aTIFF (Uncompressed) decompressorare needed to see this picture.LESIONPETfMRIEEG/MEGTMS

A little history Galen (129-200 AD)Ventricular theory of brain function* Anterior ventricle controls perception* Middle ventricle controls cognition* Posterior ventricle controls memory

Could he have been right?Don’t believe everything you read in Glamour Magazine!

Phrenology: the start of localizationismFranz Joseph Gall(1758-1828)

Some people still believe in phrenology to this day.Mr. Burns: Who could forget such a monstrous visage?She has the sloping brow and cranial bumpage of thecareer criminal.”Smithers: "Uh, Sir? Phrenology was dismissed asquackery 160 years ago.”Mr. Burns: (measuring Smithers' head) "Of courseyou'd say that. you have the brainpan of astagecoach tilter!"

Lesions as tool to gain insight into brain functionThe brain of patient “tan”Broca’sArea

Another landmark caseCarl Wernicke(1848-1904)

Cytoarchitectonic Areas (Brodmann, early 1900s)

Electrocortical Stimulation Mappingthe motorhomunculus

The First “Brain Imaging” Experiment and probably the cheapest one too!Angelo MossoItalian physiologist(1846-1910)E mc2?“[In Mosso’s experiments] the subject to be observed lay on a delicately balanced tablewhich could tip downward either at the head or at the foot if the weight of either end wereincreased. The moment emotional or intellectual activity began in the subject, down went thebalance at the head-end, in consequence of the redistribution of blood in his system.”-- William James, Principles of Psychology (1890)Source: Jody Culham’s fMRI for Dummies web site

Positron Emission Tomography (PET) Subjects injected with radioactive isotope, which emits positronsPositrons collide with electrons, emitting two photons (gamma rays) inopposite directionsDetectors surrounding brain register simultaneous photons and computelikely sourceNeural activity increased metabolic demand local increase inblood flow the active region

PET Compares regional cerebral bloodflow (rCBF) between cognitive states(experimental conditions) Integrates signal over 45-60 sec Need to wait a number of half-livesbefore next injection

The first cognitive PET studyPassively viewing wordsListening to wordsSpeaking wordsGenerating verbsPetersen et al. (1988). Positron emission tomographic studies of the cortical anatomy of single-word processing. Nature.

PET: Pros and Cons PROs– Decent spatialresolution (5-10mm3)– Can also measureneurotransmittermetabolism.– Can be used as atool to aid in earlydiagnosis ofdisorders such asAlzheimer’s disease CONs– Invasive(radioactiveinjection)– Very expensive– Poor temporalresolution– Cannot detect theneural response todiscrete cognitiveevents.

MRI vs. fMRIMRI studies brain anatomy.Functional MRI (fMRI)studies brain function.Source: Jody Culham’s fMRI for Dummies web site

Berkeley’s 4 Tesla Magnet1 Tesla (T) 10,000 GaussEarth’s magnetic field 0.5 Gauss4 Tesla 4 x 10,000 0.5 80,000 X Earth’s magnetic fieldB0

Magnets attract metal objects

Necessary Equipmentgiant magnetRF Coilgradient coil(inside)MagnetGradient Coil very strong magnetic field enables spatial encodingSource for Photos: Joe GatiRadio Frequency Coil receives and transmits radiofrequenciesfMRI for Dummies

Very Basic MRI Physics

MRI vs. fMRIMRIhigh resolution(1 mm)fMRIlow resolution( 3 mm but can be better)one imagefMRIBlood Oxygenation Level Dependent (BOLD) signalindirect measure of neural activity neural activity many images(e.g., every 2 sec for 20-60 mins) blood oxygen fMRI signalSource: Jody Culham’s fMRI for Dummies web site

As the ratio of oxygenated to deoxygenatedhemoglobin increased, BOLD fMRI signal increases

Hemodynamic ResponseFunction (HRF)peak BOLD response(4-6 sec post-stimulus)signal decayundershootbrief stimulus

fMRI Setup

A basic fMRI experimental tedBOLD signaltime Subject is given sensory stimulation or task,interleaved with control or rest condition Acquire BOLD-sensitive MRI images during stimulation Analyze image timeseries to determine where signalchanged in response to stimulation

The first fMRI ExperimentFlickering CheckerboardOFF (60 s) - ON (60 s) -OFF (60 s) - ON (60 s) - OFF (60 s)BrainActivityTime Source: Kwong et al., 1992

BOLD signal change during presentationof static and moving visual stimuliQuickTimeª and aTIFF (LZW) decompressorare needed to see this picture.W. W. Norton

Blocked vs. Event-Related Designs

Advantages of event-related designsCharacterize individual trialsafter-the-fact, based on thesubject’s behavioral responseWagner et al., 1998, ScienceCorrect trials vs. Incorrect trialsBlumenfeld et al., 2006 J Neuroscience

Modularity vs. NetworksFunctionalSegregationLocalization of category-specificvisual processing regionsFunctionalIntegrationStatistical modeling of functionalinteractions between brain regions

Diffusion Tensor Imaging (DTI)zxyColor-coded directionsTract-basedconnectivity Water diffusion restrictedalong white matter pathways Tractography: tracing whitematter pathways betweengray matter regions

Can fMRI read your mind?

The Era of Neuromarketing Has Begun

A more reasonable examplePPAFFAO’Craven & Kanwisher, 2001FFA- Fusiform Face AreaPPA- Parahippocampal Place Area

But we still have a long way to go

Spatial and Temporal Resolution

Single-unit recording:Identifying neuronal receptive fields

Memory Cells in the Prefrontal Cortex

A Face Area in the Monkey BrainAn area of the monkey’s brainthat responds to faces

A Halle Berry neuron?Quiroga et al., 2005, Nature

Electroencephalography (EEG) fMRI does not provideprecise info about thetiming of neural activity. Single-unit recordings canonly measure activity inone brain region at a time. EEG can record electricalpotentials of largepopulations ofsimultaneously activeneurons at the scalp withmillisecond resolution. Plus, EEG is a directmeasure of neural activity.

Arousal states of the brain:characteristic waveform patternsW. W. Norton

What about electrical activity forspecific cognitive events?Event-Related Potentials (ERPs)

ERP example:The face-sensitive N170QuickTimeª and aTIFF (LZW) decompressorare needed to see this picture.

Magnetoencephalography (MEG)SQUID Array:64 to 275 Sensing Locations

Cortical surface rendering of MEG activityGonsalves et al.(2005) Neuron

Electrocorticography (ECoG):Direct recordings from the cortical surface

Transcranial Magnetic Stimulation(TMS) Brief powerful (severalthousand amperes)electrical charge iscreated in coil Creates a 1.5-2.0 Teslamagnetic field capable ofinducing eddy currents intissue 1-2 cm deepQuickTimeª and aTIFF (Uncompressed) decompressorare needed to see this picture.

Transcranial Magnetic Stimulation(TMS)– Disrupts normal neural function byadding noise– In essence, TMS creates atemporary “virtual patient”– Unlike fMRI and PET, TMS canassess the causal influence of aregion on behavior.– Unlike naturally-occurring lesions,TMS gives the researcher morecontrol, better temporal resolution,and the ability to create multiplevirtual patients in the sameindividual.

Safety Issues Generally thought to be free from harmfuleffects Examination of brain tissue submitted tothousands of TMS pulses has shown nodetectable structural changes It is possible in unusual circumstances totrigger a seizure in healthy subjects, but usingthe proper guidelines eliminates this risk

A simple TMS experiment Coil placed over target brain regionCognitive failures recorded

Establishing causal links between brain activity and behaviorReal lesionHamilton et al., 2000.Reported case of blindwoman who lost abilityto read braille followingbilateral occipital lesionsTMS “lesion”Cohen et al., 1997.Occipital TMSdisrupts braillereading in earlyblind, but notcontrol subjectsBlue sighted;Red early blind

fMRI-guided TMS stimulation

TMSConverging Methodolgies:fMRI 10-12-14-16050100 150 200 250 300 350 400[ms]N170 ERP

Thanks for your attention!

Feb 01, 2007 · MRI vs. fMRI neural activity blood oxygen fMRI signal MRI fMRI one image many images (e.g., every 2 sec for 20-60 mins) high resolution (1 mm) low resolution ( 3 mm but can be better) fMRI Blood Oxygenation Level Dependent (BOLD) signal indirect measure of neural activity Source: