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METHODS: HOW WE KNOW WHAT WE KNOW SEPT 2, 2015 – DAY 5 Brain & Language LING 4110-4890-5110-7960 NSCI 4110-4891-6110 Fall 2015

METHODS: HOW WE KNOW WHAT WE KNOW SEPT 2, 2015 – DAY 5 Brain & Language LING 4110-4890-5110-7960 NSCI 4110-4891-6110 Fall 2015

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Page 1: METHODS: HOW WE KNOW WHAT WE KNOW SEPT 2, 2015 – DAY 5 Brain & Language LING 4110-4890-5110-7960 NSCI 4110-4891-6110 Fall 2015

METHODS: HOW WE KNOW WHAT WE KNOWSEPT 2, 2015 – DAY 5

Brain & Language

LING 4110-4890-5110-7960

NSCI 4110-4891-6110

Fall 2015

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Course organization• http://www.tulane.edu/~howard/BrLg/• Fun with https://www.facebook.com/BrLg15/

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MICROSTRUCTURE OF THE BRAINReview

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A pyramidal neuron

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Layout of dendrites of pyramidal cells

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apical dendrites

basaldendrites

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Horizontal organization: minicolumn

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Vertical organization: lamination

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METHODS

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Short history of researchDate Event

1836 Abercrombie?

1836 Marc Dax claimed that the LH of right-handers has “memory for words”

1861 Paul Broca claimed that the LH of right-handers has “faculty of articulate speech”

1874Karl Wernicke discovered that damage to a certain area could cause receptive aphasia.John Hughlings Jackson claimed that the LH is responsible for language, while the RH is responsible for visual cognition (recognition, discrimination, recall).

WWI-II Many observations of the cognitive results of head injuries

end WWII

Juhn A. Wada developed test for cerebral dominance for speech by injecting an anesthetic into the right or left internal carotid artery

1950sPenfield & Wilder use cortical stimulation to map the cortex > treat epilepsy, discover the motor-sensory homunculus

1960s Corpus callosotomy (commissurotomy) > split-brain patients

1970s Hemifield tachistoscopy, dichotic listening > laterality research

1980s Noninvasive imaging techniques

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Overview of methodologies in nearly chronological order of appearance• Lesions• Wada test• Craniotomy & cortical stimulation• Corpus callosotomy & split-brain patients• Hemifield tachistoscopy• Dichotic listening• Imaging: C(A)T, PET, (f)MRI• Electromagnetic: EEG, MEG• Transcranial magnetic stimulation (TMS), but not today

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Lesions

• A lesion is a non-specific term referring to abnormal tissue in the body. It can be caused by any disease process including trauma (physical, chemical, electrical), infection, neoplasm, metabolic and autoimmune.

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Wada test

• The Wada test (named for a neurologist, Juhn A. Wada) consists of behavioral testing after the injection of an anesthetic (such as sodium amobarbital or sodium methohexital) into the right or left internal carotid artery.

• Depending on how the injection is made (and the quantity), there is a certain amount of time during which the activities of one of the cerebral hemispheres are suspended, so the abilities subserved by the other hemisphere can be tested in isolation.

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Craniotomy & cortical stimulation

• A craniotomy is a surgical operation in which part of the skull, called a skull flap, is removed in order to access the brain.

• Craniotomies are necessary for many types of surgery; they are also widely used in neuroscience in techniques such as extracellular recording, brain imaging, and manipulations such as electrical stimulation and chemical titration.

• Human craniotomy is usually performed under general anesthesia but can be also done with the patient awake using a local anaesthetic and generally does not involve significant discomfort for the patient.

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Corpus callosotomy (split-brain patients)

• “Split-brain” is a lay term to describe the result of severing the corpus callosum to some degree.

• The surgical operation to produce this condition is called corpus callosotomy.

• It is rarely performed, usually only in the case of epilepsy, in order to mitigate the risk of accidental physical injury by reducing the severity and violence of epileptic seizures.

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Corpus callosotomy (split-brain patients), cont.

• A patient with a split brain, when shown an image in his or her left visual field (the left half of what each eye sees), will be unable to name what he or she has seen.

• This is because the speech control center is in the left side of the brain in most people and the image from the left visual field is sent only to the right side of the brain.

• Since the two sides of the brain cannot communicate, the patient can't name what he or she is seeing.

• The person can, however, pick up a corresponding object with their left hand, since that hand is controlled by the right side of their brain.

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Divided visual-field (hemifield) tachistoscopy

• A tachistoscope is a device that displays an image for a specific amount of time.

• It can be used to increase recognition speed, to show something too fast to be consciously recognized, or to test which elements of an image are memorable.

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Dichotic listening• Dichotic listening is a procedure

commonly used for investigating selective attention in the auditory domain.

• Two messages are presented to both the left and right ears (one message to each ear), normally using a set of headphones. Normally, participants are asked to pay attention to either one, or both (divided attention condition) of the messages and may later be asked about the content of both.

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Computerized (Axial) Tomography (CT/CAT)

• Computed tomography (CT), originally known as computed axial tomography (CAT or CT scan), employs tomography (digital geometry processing) to generate a 3D image of the internals of an object from a large series of two-dimensional X-ray images taken around a single axis of rotation.

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Positron Emission Tomography (PET)

To produce a PET scan, a patient is administered a solution of a metabolically-active substance, such as glucose, tagged with a positron-emitting isotope. The substance eventually makes its way to the brain and concentrates in areas of high metabolism and blood flow, which are presumably triggered by increased neural activity. The positrons emitted by the isotopes are collected by detectors arrayed around the patients’ body and converted into signals which are amplified and sent to a computer for construction of an image.

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PET vs CT• PET differs from CT in that it uses the body’s basic

biochemistry to produce images. • The positron-emitting isotope is chosen from elements

that the body already uses, such as carbon, nitrogen, oxygen, and fluorine.

• By relying on normal metabolism, PET is able to show a biochemical change even in diseases such as Alzheimer’s in which there is no gross structural abnormality.

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Magnetic Resonance Imaging (MRI)

• In 1977, a team lead by Raymond Damadian produced the first image of the interior of the human body with a prototype device using nuclear magnetic resonance.

• Damadian’s device uses liquid helium to supercool magnets in the walls of a cylindrical chamber.

• A subject is introduced into the chamber and so exposed to a powerful magnetic field.

• This magnetic field has a particular effect on the nuclei of hydrogen atoms in the water which all cells contain that forms the basis of the imaging technique.

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Magnetic Resonance Imaging (MRI)

All atoms spin on their axes. Nuclei have a positive electronic charge, and any spinning charged particle will act as a magnet with north and south poles located on the axis of spin. The spin-axes of the nuclei in the subject line up with the chamber’s field, with the north poles of the nuclei pointing in the ‘southward’ direction of the field. Then a radio pulse is broadcast toward the subject. The pulse causes the axes of the nuclei to tilt with respect to the chamber’s magnetic field, and as it wears off, the axes gradually return to their resting position (within the magnetic field). As they do so, each nucleus becomes a miniature radio transmitter, giving out a characteristic pulse that changes over time, depending on the microenvironment surrounding it. For example, hydrogen nuclei in fats have a different microenvironment than do those in water, and thus transmit different pulses. Due to such contrasts, different tissues transmit different radio signals. These radio transmissions can be coordinated by a computer into an image. This method is known as magnetic resonance imaging (MRI), and it can be used to scan the human body safely and accurately

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functional Magnetic Resonance Imaging (fMRI)

An elaboration of MRI called functional MRI (fMRI) has become the dominant technique for the study of the functional organization of the human brain during cognitive, perceptual, sensory, and motor tasks. As Gregg (2002) explains it, the principle of fMRI imaging is to take a series of images in quick succession and then to analyze them statistically for differences. For example, in the blood-oxygen-level dependent (BOLD) method introduced by Ogawa et al. (1990), the fact that hemoglobin and deoxyhemoglobin are magnetically different is exploited. Hemoglobin shows up better on MRI images than deoxyhemoglobin, which is to say that oxygenated blood shows up better then blood whose oxygen has been depleted by neural metabolism. This has been exploited in the following type of procedure: a series of baseline images are taken of the brain region of interest when the subject is at rest. The subject then performs a task, and a second series is taken. The first set of images is subtracted from the second, and the areas that are most visible in the resulting image are presumed to have been activated by the task.

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EEG & MEG

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Scalp EEG

• Scalp EEG is collected from tens to hundreds of electrodes positioned on different locations at the surface of the head.

• EEG signals (in the range of millivolts) are amplified and digitalized for later processing.

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Magnetoencephalography (MEG)

• … records magnetic fields produced by using arrays of SQUIDs (superconducting quantum interference devices).

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An EEG

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Electrical-chemical-electrical communication at the synapse

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Pre- and post-synaptic currents

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Currents and fields

• Primary or intracellular current (what we want to know about) does not summate across axons.

• Summation of parallel dendrites in cortical sheet creates:• Secondary or

extracellular or volume currents

• Magnetic field perpendicular to primary current

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The paired positive and negative ‘ends’ of the volume current are known

as a dipole.

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Currents, fields and a dipole

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Another take on currents and fields

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Axons vs. apical dendrites

• Axons are oriented randomly along the cortical sheet, which results in their potentials cancelling one other out.

• Apical dendrites are oriented in parallel along the cortical sheet, which results in their potentials to reinforce one another and sum together, creating a large “dipole”, which is measurable with EEG/MEG.

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The basic fact about dipoles

A dipole has a direction … … which in cortex is perpendicular to its surface

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But, what do we know about the shape of the cortex?

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Another dipole

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Inverse problems• Ideally, one would like to localize the precise neural sources that generate ERPs.

• This is an example of an “inverse problem”, because it tries to deduce the cause of an observation from the observation itself:• “An inverse problem is a general framework that is used to convert

observed measurements into information about a physical object or system that we are interested in.”

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How to calculate the source of a dipole

• How do we know which one is correct?• We can’t. There is no correct answer. • Dipole source localization is an ill-defined problem.

• That is to say, the inverse solution to the dipole source-localization problem is impossible to compute with certainty, because any given scalp distribution could, in principle, be generated by any number of source configurations within the brain.

+ -

+

-

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But …• … researchers have developed powerful tools that

provide good estimates of dipole localization, given some reasonable assumptions.

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LORETA

• One such method is known as LORETA (low resolution brain electromagnetic tomography), which provides an estimate of the current distribution throughout the entire 3-dimensional space within the brain.

• It does so by taking into account what is known about the structure of the brain and skull.

• An example of a LORETA solution, mapped onto a normalized brain space, is provided above.

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Comparison of EEG & MEG

EEG MEGSignal measured from electrical fields generated by

secondary (volume) currentsmagnetic fields generated by primary currents

Signal magnitude large (10 mV), easy to detect tiny (10 fT), difficult to detect

Dipole orientation sensitive to tangential and radial dipoles

sensitive only to tangential dipoles

Signal purity affected by skull, scalp, etc. unaffected by skull, scalp, etc.

Temporal resolution ~ 1 ms ~ 1 ms

Spatial resolution ~ 1 cm ~ 1 mm

Experimental flexibility allows some movement requires complete stillness

Cost cheap expensive

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NEXT TIMEP1 in class

Auditory induction

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