what is cognitive neuroscience?€¦ · 1) pretty good spatial resolution. 2) one can tag other...

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9.63 - Fall 2005 Lecture 7 What is cognitive neuroscience? l characterizi l terms. Experimental Psychology is more or less the study of subjects’ behavior subject to various manipulations of stimuli or environment. Cognitive Science is an outgrowth of this field that is particular y interested in ng the mind in computationa Cognitive Neuroscience is a further extension of that philosophy, explicitly aimed at discovering the neural substrates that support various cognitive processes. 1 Courtesy of Ben Balas. Used with permission. Ben Balas

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Page 1: What is cognitive neuroscience?€¦ · 1) Pretty good spatial resolution. 2) One can tag other substances than blood to look for neurotransmitters. 1) Pretty expensive. 2) Radioactive

What is cognitive neuroscience?

9.63 - Fall 2005 Lecture 7

What is cognitive neuroscience?

lcharacterizi l terms.

Experimental Psychology is more or less the study of subjects’ behavior subject to various manipulations of stimuli or environment.

Cognitive Science is an outgrowth of this field that is particular y interested in

ng the mind in computationa

Cognitive Neuroscience is a further extension of that philosophy, explicitly aimed at discovering the neural substrates that support various cognitive processes.

1

Courtesy of Ben Balas. Used with permission.

Ben Balas

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What is cognitive neuroscience?

Roadmap

What is cognitive neuroscience?

and

i

• Cog. Neuro. = What does the brain do?

• Q: But how do we study brain behavior?

• A: F nd ways to look at brain activity…

2. 3.

Roadmap

1. Lesion Studies – The birth of cog. neuro. MEG and EEG - When does your brain process stuff? PET and fMRI – Where does your brain process stuff?

4. TMS – Do you need that part of your brain to do that? 5. The view from here…

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Brain Lesions – Necessity

But what about normal subjects?

In a sense, brai

Image removed due to copyright reasons.

Brain Lesions – Necessity

n lesions and their effects on behavior and perception gave birth to cog. neuro.

HM – Dissociation of memory systems (episodic v. procedural)

DF – Dissociation of visual systems for recognition v. action

Phineas Gage – Frontal lobe as the seat of “personality”

and many many others.

But what about normal subjects?

Wi

li

We can’t just wait around for people to have brain damage to learn about neural function.

th rats and other animals, we can just use single unit recording to work out what’s going on. This is still the “Gold Standard” for work in neuroscience…unfortunate y, it is unavailable to us for work w th humans…

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Image removed due to copyright reasons.

Page 5: What is cognitive neuroscience?€¦ · 1) Pretty good spatial resolution. 2) One can tag other substances than blood to look for neurotransmitters. 1) Pretty expensive. 2) Radioactive

EEG and MEG – Passive Recording

EEG and MEG – Passive Recording

WHEN various things

Image removed due to copyright reasons.

EEG and MEG – Passive Recording

Both EEG and MEG are ways to measure happen in the brain. They are called passive recording techniques because they do not alter the brain in any way.

wi i

What would make us choose between measuring

Image removed due to copyright reasons.

EEG and MEG – Passive Recording

The general idea in both of these methodologies is to present subjects th stimuli, and record the changes n the local electric or magnetic

fields at the surface of the scalp.

an E-field v. a B-field?

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What are you measuring?

The gear…

What are you measuring?

l

The EEG is sensitive to all the three components of the electric activity of the brain. The MEG is sensitive on y to the two tangential components.

This means that the MEG is especially good for getting information from sulci, whereas the EEG is good for getting information from gyri as well.

Image removed due to copyright reasons.

Image removed due to copyright reasons.

The gear…

Typical EEG caps

Typical MEG “hairdryer” set-up.

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Image by MIT OCW.

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So what kind of stuff can you learn?

So what kind of stuff can you learn?

ill ll l

i

Image removed due to copyright reasons.

So what kind of stuff can you learn?

On a particular trial, the data from any given electrode w ook very noisy. This is because the changes in e ectric field potentia brought on by your brain activity are l ke whisper in a VERY loud room.

Both your heartbeat, eyeblinks, and nearby muscle movements can more or less obliterate the signal.

l

Note that all of these

So what kind of stuff can you learn?

What we can do is average the response over many hundreds of trials. The noise should come out in the wash, and the signashould be all that remains.

This way we can see any consistent changes in potential at a given site.

peaks are time-locked to the stimulus presentation.

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“When” not “Where”

“When” not “Where”

ill tell

itude).

either technil i

“When” not “Where”

A crucial point to remember is that these peaks of activity w you only WHEN something was happening at that electrode (latency), and HOW MUCH activity you saw (magn

What we don’t know much about from que is where exactly in the

brain the signa was com ng from.

Image removed due to copyright reasons.

“When” not “Where”

“But wait!” You say. “Aren’t there tons of electrodes at different places on the scalp? Doesn’t that tell us where this stuff is happening?”

The answer is yes and no. The reason for the “No” is that you’re not ONLY listening to one set of neurons at any one electrode.

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“When” not “Where”

l

“When” not “Where”

A good metaphor for this is to imagine that you’re listening to the Super Bow from the roof of the stadium. You’ll know when big plays happen, but just try to work out field position…I dare you.

Dipole fitting

Image removed due to copyright reasons.

Dipole fitting

Are we totally out of luck? Not entirely…you can do some fancy stuff by reasoning about the potential across the entire head to do what is called dipole fitting. A nice try, but this is something of a black art still.

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EEG/MEG recap

Where are you thinking? – PET and fMRI

l ive

i

EEG/MEG recap

• Passive methods for recording brain activity to different stimuli • Extremely good temporal resolution • Poor spatial resolution • Complete y non-invas• Useful for children or other special populations • EEG can take a lot of prep time (electrode goo) • MEG is less involved in terms of prep, but needs more gear. • Also, B-fields and E-fields are measuring activity in d fferent places

i i

1) )

2)

i i

Where are you thinking? – PET and fMRI

So, we can learn when d fferent things happen in the bra n, but how do we find out about where? The answer comes in the form of two similar techniques for cortical localization called:

PET (Positron Emission Tomography

fMRI (function Magnetic Resonance Imaging)

Both of which fall under the category of active recording techniques due to the ways in which they “interfere” w th normal bra n metabolism.

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From electrical fields to blood flow…

PET – injecting you with science

From electrical fields to blood flow…

li

Images removed due to copyright reasons.

One thing that is different about these techniques is that our dependent variable is no longer e ectric field potentials…we instead will be using blood flow as a proxy for neuronal activ ty.

iill be distributed

i

accompli

Image removed due to copyright reasons.

PET – injecting you with science

PET works by injecting you w th a tracer substance that wthroughout your bloodstream and that gives off positrons. When they decay, one can use a detector to work out where they were, allow ng a researcher to determine where blood went in one condition vs. the others. This is

shed by means of a subtraction analysis.

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PET – injecting you with science

PET – injecting you with science

PET – injecting you with science

PROS:

CONS:

ll

PET – injecting you with science

1) Pretty good spatial resolution. 2) One can tag other substances than blood to look for neurotransmitters.

1) Pretty expensive. 2) Radioactive tracer means a subject can on y participate occasionally. 3) Bad tempora resolution.

PET really isn’t used a lot anymore in Cog. Neuro., but a lot of seminal work was done using it, so you should know how it works.

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Radiation Detector

Coincidence Circuit

Electron180o

511 KeV Annihilation XRay

511 KeV Annihilation XRay

Atomic Nucleus Positron

Radiation Detector

Principles of Decay and Detection PET Detector Ring Coincidence Imaging

HOW DOES PET WORK?

Figure by MIT OCW.

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fMRI – Brain mapping in the modern era

fMRI – Brain mapping in the modern era

__________________________

…to brain function

Image removed due to copyright reasons.

Image removed due to copyright reasons.

fMRI – Brain mapping in the modern era

fMRI has become the method of choice for relating brain anatomy…

fMRI – Brain mapping in the modern era

In case you’ve never seen one…

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Photo courtesy of the National Institute of Mental Health.

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fMRI Setup

Equipment

Figure removed due to copyright reasons.

fMRI Setup

RF Coil

Equipment

Image removed due to copyright reasons.

Image removed due to copyright reasons.

Magnet Gradient Coil

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The BIG magnet

Magnet Safety

÷

R

l

S

)

0

B0

The BIG magnet

Images removed due to copyright reasons.

4 Tesla = 4 x 10,000 0.5 = 80,000X Earth’s magnetic field

Very strong

Continuous y on

1 Tesla (T = 10,000 Gauss

Earth’s magnetic field = 0.5 Gauss

Main field = B

Images removed due to copyright reasons.

The whopping strength of the magnet makes safety essential. Things fly – Even big things!

Magnet Safety

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Artifacts from metal

MRI v. fMRI

i i i ii i

Th s subject was wear ng a ha r band w th a ~2 mm copper clamp. Left: w th hair band. Right: w thout.

Source: Jorge Jovicich

Artifacts from metal

↑ Î ↑ blood oxygen Î ↑ fMRI signal

MRI

Blood O Level D (BOLD

MRI v. fMRI

fMRI

Images removed due to copyright reasons.

neural activity

fMRI

xygenation ependent ) signal indirect measure of neural activity

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Courtesy of Jorge Jovicich. Used with permission.

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Proton Alignment

Hemoglobin (deOxygenated)

to B0 ) along B0

ith field

Proton Alignment

Outside magnetic field

Inside magnetic field

randomly oriented

• spins tend to align parallel or anti-parallel

• net magnetization (M• spins precess with random phase • no net magnetization in transverse plane • only 0.0003% of protons/T align w

)

Hemoglogin (Hgb): - globi

l i)

(O2) 2) i → no ∆

i → if [ ] ↓ → l ∆B ↓

Figures removed due to copyright reasons.

Hemoglobin (deOxygenated

four n chains - each g ob n chain contains a heme group - at center of each heme group is an iron atom (Fe- each heme group can attach an oxygen atom- oxy-Hgb (four O s diamagnetic B effects - deoxy-Hgb s paramagnetic deoxy-Hgb loca

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Applied MagneticField

M

Image by MIT OCW.

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Recipe for fMRI

Statistical Analysis

(leave him there) i [about 3 ms]

– interval ]

6) Process raw data to reconstruct images

1) Put subject in big magnetic field 2) Transmit radio waves nto subject 3) Turn off radio wave transmitter 4) Receive radio waves re-transmitted by subject

Manipulate re-transmission with magnetic fields during this readout [10-100 ms: MRI is not a snapshot

5) Store measured radio wave data vs. time Now go back to 2) to get some more data

7) Allow subject to leave scanner (this is optional)

Source: Robert Cox’s web slides

Recipe for fMRI

superimposed on anatomical MRI

image

~ fMRI

Signal ROI Time

Statistical Analysis

Images removed due to copyright reasons. Statistical Map

Time

(% change) Course

Condition

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Visualizing brains – What about the folds?

Visualizing brains – Across-subject analysis

lly)

Image removed due to copyright reasons.

Visualizing brains – What about the folds?

“Inflated Brains” (This used to be done physically, but now we can do it mathematica

standard

this.

Image removed due to copyright reasons.

Visualizing brains – Across-subject analysis

Talairach coords.

1) Based on one French woman.

2) Widely used

3) Many tools and atlases to support

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Visualizing brains – Across-subject analysis

Visualizing brains – Across-subject analysis

ii

Images removed due to copyright reasons.

Visualizing brains – Across-subject analysis

Brodmann’s Areas – Cytoarchitectonic designations for brain reg ons. Allows one to parcel up the cortex into regions w th uniform characteristics.

i

Images removed due to copyright reasons.

Visualizing brains – Across-subject analysis

Spherical bra n registry

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ROI analysis – functionally defined regions

ROI analysis – looking at other stimuli

and MEG/EEG studies is ROIFigure removed due to copyright reasons. Please see: Kanwisher, Nancy, Josh McDermott, and Marvin M. Chun. Figure 3 in "The Fusiform Face Area: A Module in Human Extrastriate Cortex Specialized for Face Perception." J Neurosci 17 (1997): 4302 - 4311

ROI analysis – functionally defined regions

Another strategy employed by many researchers both in fMRI

analysis.

ROI = “Region of Interest” The idea is to isolate a part of the brain using functional criteria, and then only look at what happens there when you show other stimuli.

Images removed due to copyright reasons.

Tong, F., K. Nakayama, M. Moscovitch, O. Weinrib, and N. Kanwisher. "Response properties of the human fusiform face area." Cogn Neuropsychol 17 (2000): 257–279.

ROI analysis – looking at other stimuli

Please see:

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ROI analysis – looking at other stimuli

ROI analysis – looking at other stimul

Tong, F., K. Nakayama, M. Moscovitch, O. Weinrib, and N. Kanwisher. "Response properties of the human fusiform face area." Cogn Neuropsychol 17 (2000): 257–279.

Figure removed due to copyright reasons.

ROI analysis – looking at other stimuli

Please see:

Tong, F., K. Nakayama, M. Moscovitch, O. Weinrib, and N. Kanwisher. "Response properties of the human fusiform face area." Cogn Neuropsychol 17 (2000): 257–279.

Figure removed due to copyright reasons. Please see:

ROI analysis – looking at other stimuli

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fMRI – sufficiency and necessity?

Well…lesions were useful for this…

i

necessity wi

Image removed due to copyright reasons.

fMRI – sufficiency and necessity?

So fMRI is a great tool for discovering what brain reg ons show activity for various kinds of tasks. But…are we able to really make claims about the of a particular area for some process

th fMRI?

Image removed due to copyright reasons.

Well…lesions were useful for this…

But we can’t just give subjects lesions!

Or can we?

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TMS – “Virtual Lesions”

“Lesioning” a subject with TMS

Enter TMS, or

brain activi i

Image removed due to copyright reasons.

TMS – “Virtual Lesions”

“Transcranial Magnetic Stimulation”

TMS uses transient magnetic fields to either stimulate or suppress ty n a focused region…

Image removed due to copyright reasons.

“Lesioning” a subject with TMS

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A simple experiment

A simple experiment

A simple experiment

F P W

A simple experiment

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A simple experiment

Visual suppression

F P W

A simple experiment

Visual suppression

Figure removed due to copyright reasons.

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Is it safe?

Roadmap

Is it safe?

1. l

2. lso

3. /l effects and the

If used properly, single-pulse TMS has no known harmfuside effects. TMS has been used since 1985 and today some 3,000 stimulators are in use.

If used properly, a repetitive TMS (rTMS) is thought to be safe. Beginners should consult literature and competent personnel, since rTMS can cause seizures.

It is extremely important for the future of TMS rTMS that the experimenters document all harmfustimulation parameters that produced them.

From: International Federation of Clinical Neurophysiology (IFCN)

2. 3.

Q:

A:

Roadmap

1. Lesion Studies – The birth of cog. neuro. MEG and EEG - When does your brain process stuff? PET and fMRI – Where does your brain process stuff?

4. TMS – Do you need that part of your brain to do that? 5. The view from here…

What’s left for these methods? And what’s left for cog. neuro?

Plenty.

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Technological advances

Technological advances

Technological advances

EEG/MEG •

i

Images removed due to copyright reasons.

More and more electrodes, and thus better dipole fitting. • Better mathematical tools for combating no se in measurements. • Better analytical solutions for source localization. • New kinds of analysis.

Technological advances

fMRI

• i

Images removed due to copyright reasons.

• New pulse sequences to get better resolution. • Bigger and bigger magnets • Clever ways to get more out of the BOLD signal

ntegrating fMRI and MEG

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Methodological advancesMethodological advances

lIs Cog. Neuro. just legitimized

i

wi

Image removed due to copyright reasons.

Are we real y making progress?

phrenology?

On some level, it is…and we need to decide if we’re okay with that, or if we want to do something more than geography. F nding other ways to use the technology we have is where the real fun

ll be in the next decade or so.

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