fundamentals of neuroscience neuroimaging in cognitive neuroscience

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Fundamentals of Neuroscience Neuroimaging in Cognitive Neuroscience. James Danckert PAS 4040 jdancker@watarts.ca. Functional Neuroimaging. Electrical activity Event-related potentials (ERP), visual evoked potentials (VEP) all derivative from EEG Stimulation - PowerPoint PPT Presentation

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  • Fundamentals of NeuroscienceNeuroimaging in Cognitive NeuroscienceJames DanckertPAS 4040 jdancker@watarts.ca

  • Functional NeuroimagingElectrical activityEvent-related potentials (ERP), visual evoked potentials (VEP) all derivative from EEG

    StimulationTrans-cranial magnetic stimulation single vs. rapid pulse TMS

    MetabolismPositron Emission Tomography (PET) and Blood Oxygenated Level Dependent (BOLD) functional MRI (fMRI)

  • EEGLarge populations of neurons firing produce electrical potentials that can be measured at the scalpSignals are passively conducted through the skull and scalp and can be amplified and measuredDifference between reference (ground) and recording electrodes are measured to give the electrical potential electroencephalogram (EEG)

  • ERPs and VEPsEEG tends to record global brain activityERPs (and VEPs) are a special case of EEGaverage EEG trace from a large number of trials align signal to onset of a stimulus or response hence event-related potential (ERP)

  • Pros and cons of ERPs.Good temporal resolutionLinked to specific physiological markers (e.g., N1, P3 etc. which in turn can be linked to known cognitive processes)Poor spatial resolutionDifficult to get at some brain regions (OFC, temporal cortex)

    ConsPros

  • Transcranial Magnetic Stimulation (TMS) Thompson (1910) placed head between two coils and stimulated at ~ 42 Hz saw flashing lights magnetophosphenes was probably stimulating the retina and not the visual cortexCowey and Walsh, 2001

  • TMSTMS applies a magnetic pulse to a certain brain region to temporarily modulate the function of that region

  • TMS the induced current in the tissue is in the opposite direction to that of the coil

    the intensity of the signal drops off towards the centre and outside of the coilcircular coilinduced currentCowey and Walsh, 2001

  • TMS the flow of the current must cross the axon to cause stimulation or interruption of function (N3 will not be stimulated)maximum depolarizationmaximum hyperpolarizationCowey and Walsh, 2001little or no change

  • TMS

  • Spatial extent of TMS spatial extent of induced electric field drops ~ 75% within 10 mm affects 600 mm2 of neural tissue

  • Rapid vs. Single Pulse TMS for single pulse TMS duration of stimulation = 1 msec, but affects motor cortex for up to 100 msec

    for rapid or repetitive pulse TMS stimuli are delivered in trains with frequencies from 1 to 25 Hz (1 25 times per second)

    duration of after-effects for rapid pulse TMS anywhere from msec to several seconds

  • excitatory or inhibitory reversible effects depending on site and parameters of stimulation (e.g. frequency of pulses) -> facilitates or slows down cognitive process/behavior

    when inhibitory, referred to as virtual lesion technique

    can give precise timing information (msec level) due to transient nature of effects

    rTMS is beginning to be used as a treatment for depression (focus is on DLPFC)Transcranial magnetic stimulation (TMS / rTMS)

  • TMSPoor spatial localisation how focal is the stimulation?Cant stimulate certain areas (e.g., temporal lobe) and can only stimulate cortical surfaceGood temporal resolutionCan presumably disrupt individual processes within a task.Distance effects changed interactions due to stimulationCan induce seizures (particularly rTMS)

  • Frameless stereotaxy and fMRI areas can be identified functionally and then used to position the coil in a TMS study using the frameless stereotaxy method

    Paus is attempting to directly combine fMRI and TMS with TMS pulses delivered in between fMRI runs

  • Metabolic ImagingTwo main techniques positron emission tomography (PET) and functional MRI (fMRI)Activity in cells requires energy (oxygen and glucose)Increased neural activity will lead to changes in cerebral blood volume (CBV), cerebral blood flow (CBF) and the rate of metabolism of glucose and oxygen (CRMGl and CRMO)These changes in blood flow and metabolism can be measured using PET and fMRI

  • Positron Emission Tomography (PET)Measures local changes in cerebral blood flow (CBF) or volume and can also be used to trace certain neurotransmitters (but can only do one of these at a time)Radioactive isotopes are used as tracersThe isotopes rapidly decay emitting positronsWhen the positrons collide with electrons two photons (or gamma rays) are emittedThe two photons travel in opposite directions allowing the location of the collision to be determined

  • Positron Emission Tomography (PET)

  • PET and subtractionRun two conditions stimulation (e.g., look at visual images) vs. control (e.g., look at blank screen)Measure the difference in activation between the two images (i.e., subtract control from stimulation)This provides a picture of regional cerebral blood flow relative to visual stimulation.

  • Motion vs. colour.Subject views coloured screen (left) vs. moving random black and white dots (right)Both task activate early visual areas (V1 and V2)Subtracting the two images reveals different brain areas for colour (V4) vs. motion (V5) processing

  • PET vs. fMRIPET allows you to track multiple metabolic processes so long as the emitted photon can be detected allows imaging of some neurotransmittersPET is invasive radioactive isotopes can only be administered (at experimental levels) every 4 5 yearsfMRI has much greater spatial resolution (~ mms)fMRI has greater temporal resolution can detect activation to stimuli appearing for less than a second (PET is limited by the half life of the isotope used)

  • fMRI

  • Magnet safetyvery strong magnetic fields even large and heavy objects can fly into the magnet bore

  • Cerebral blood supply.ArteriolesY=95% at rest.Y=100% during activation.25 mm diameter.
  • Cerebral blood supply.

  • fMRIDeoxyhaemoglobin is paramagneticWhen neural activity increases more oxygenated blood than is needed is delivered to the siteThis leads to an imbalance in oxyhaemoglobin and deoxyhaemoglobin more oxy than deoxyfMRI is able to measure this difference due to the different magnetic properties of oxy and deoxyhaemoglobin

  • fMRI and BOLDblood oxygenated level dependent (BOLD) signal is actually a complex combination of:rate of glucose and oxygen metabolismCBVCBFsame subtraction logic used in PET is used in fMRI

  • fMRI block designfMRI (like PET) began examining brain activity using block designs

  • fMRI event-related designallows randomization of stimuli (not possible in PET)

  • fMRI event-related designBOLD response has a predictable form

    In rapid event-related designs the signal to a given trial type is deconvolved using models of the BOLD response

  • Linearity of BOLD responseDale & Buckner, 1997Linearity:Do things really add up?

    Not quite linear but good enough !

  • Fixed vs. Random Intervals If trials are jittered, ITI power Source: Burock et al., 1998

  • fMRI spatial resolutionimages can be co-registered to the subjects own brain (not an average brain as in PET)PETfMRI

  • fMRI and topologiesUsing fMRI to map different brain functionsPenfields mapsServos et al., 1998red = wrist; orange = shoulder

  • Retintopy 8 Hz flicker (checks reverse contrast 8X/sec) good stimulus for driving visual areas subjects must maintain fixation (on red dot)Source: Jody Culham

  • Source: Jody Culhamtime = 0time = 20 sectime = 60 sectime = 40 sec0204060TIME STIMULUSEXPECTED RESPONSE PROFILE OF AREA RESPONDING TO STIMULUSTo analyze retinotopic data:

    Analyze the data with a set of functions with the same profile but different phase offsets.

    For any voxels that show a significant response to any of the functions, color code the activation by the phase offset that yielded maximum activation (e.g., maximum response to foveal stimulus = red, maximum response to peripheral stimulus = pink)

  • Retintopy: Eccentricitycalcarinesulcusleft occipitalloberight occipitallobe foveal area represented at occipital pole peripheral regions represented more anteriorly

  • Retinotopy Source: Sereno et al., 1995

  • Other Sensory -topies

  • SaccadotopySource: Sereno et al., 2001delayed saccades

    move saccadic target systematically around the clockhttp://kamares.ucsd.edu/~sereno/LIP/both-closeup+stim.mpgMarty Serenos web page

  • Break

  • Finding the human homologue of monkey area X!recent research has used monkey neurophys to guide fMRI in humansDukelow et al. 2001

  • Problems with the search for homologuesAbsence of activation doesnt mean the absence of functionPresence of activation doesnt imply sole locus of functionBut our brains are different!Confirmatory hypothesesDukelow et al. 2001

  • fMRI and diagnosisfMRI is starting to be used in patients with epilepsyone goal is to use this as a tool to localise language, memory etc. prior to surgeryanother goal would be to use fMRI to study the propogation of seizures

    in stroke patients fMRI can be used to chart recovery of function

  • Patient SP congenital porencephalic cyst

  • SP - motor strip

  • SP somatosensory strip

  • 6.04.02.00.0-2.0% signal change12141images

  • fMRI and cognitionWhat not to do poorly designed tasks!

    What is the right inferior parietal lobes contribution to movement control?

    spatial component of movements

    compare imagined movements with only a spatial component vs. movements with a sequential component

  • Supplementary Motor Area (SMA)

  • Bilateral superior p

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