Behaviour and the Brain 2:

Cognitive Neuroscience
Johannes Fahrenfort
[email protected]
Medical Faculty, room B563

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Exam viewing moment
BB part 1

• Next Thursday the 15th at 11:00 in the

morning. This is right after the lecture of
part 2, for those that follow both parts.
Students can come to HG-5A36.

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How to investigate brain
mechanisms?

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 Mutual manipulability
measure Top-down manipulate
behavior/ experiment behavior/task/
mental Detect effect Manipulation stimulus/mental

manipulate Manipulation Detect effect measure

interfere/ Bottom-up correlation
stimulate experiment structure/connect.
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 How to investigate brain mechanisms

• Correlational methods • Stimulation methods

‣ fMRI ‣ Electrophysiology ‣ TMS
‣ MEG/EEG ‣ Brain stimulation (Pen eld)
‣ eCog ‣ tDCS (anodal)
• Connect. / struct. methods • Inhibition/interference methods
‣ DTI ‣ Lesions ‣ TMS
‣ VBM ‣ Strokes ‣ tDCS (cathodal)
‣ Tracers ‣ Tumors ‣ Cooling
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Correlational methods

• fMRI
• MEG/EEG
• eCog

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 A short history of fMRI
• In 1890 a paper called 'On the regulation of blood supply of
the brain' suggested that neural activity was accompanied by
a regional increase in cerebral blood ow.
• Discovery of the Nuclear Magnetic Resonance (NMR)
phenomenon: 1946
• First 3D images generated using NMR: 1973
• The rst successful Magnetic Resonance Imaging (MRI) of a
human body: 1977
• The rst functional MRI (fMRI): Ogawa & Kwong (1992)
• fMRI is an rather young technique
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 The rst MRI

Raymond Damadian (1973)

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 Hardware

Radio Participant
Frequency coil
Participant
Gradient coils Table
(X-Y-Z direction)

Magnet
Scanner
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How does MRI work?

Protons (the nuclei of atoms) spin (precess)

around their axes in random directions
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Magnet

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 How does MRI work?

B0 eld A huge superconducting

magnet (e.g. 3 Tesla) in
aligns protons in
hydrogen (water) atoms
in the body, to align with
the direction of the
magnetic eld. This is
called the B0 eld.

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 How does MRI work?
B0 eld Somewhat like a sonar

A radio frequency pulse

is sent out by the RF
coil, so that the protons
are moved out of the
direction of the main B0
B1 eld eld.

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 How does MRI work?
B0 eld Somewhat like a sonar

When these protons

align back to the
direction of the B0 eld,
they release the energy
from the RF pulse, which
gets picked up by the
B1 eld coil to form a 3D image.

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 Hardware

Radio Participant
Frequency coil
Participant
Gradient coils Table
(X-Y-Z direction)

Magnet
Scanner
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Radio Frequency Head coil

Broadcasts the RF pulse and has

antenna to pick it up again
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B0 Not bad for your health, but...

1 Tesla is 20.000 times the strength of the earth’s magnet eld

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Demonstration

c t s
t t ra
l a l t ! )
et a b e
l m i n g
Al clud
(in
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Mirror to watch stimuli

shielded wall
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 fMRI vs MRI?
fMRI: Brain function MRI: Brain anatomy

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 fMRI - what is it?
• functional MRI allows you to build a 4D
model of brain activations during tasks or
perception (hence the word functional)

f MRI
f

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 MRI: T1 weighted

• Longitudinal relaxation
(spin-lattice relaxation): realignment with B0
• Occurs because of the protons ipping back
to their lower energy state
• Tissue type is fat
• Anatomical images
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 MRI: T2 weighted
• Transverse relaxation
(spin-spin relaxation): loss of phase alignment
• Occurs due to the proton’s interaction with
its environment
• Tissue type is fat and
water: bright

Cerebrospinal uid
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fMRI: T2* weighted
• Transverse relaxation
(spin-spin relaxation): loss of phase alignment
• Occurs due to the proton’s interaction with
its environment
• Tissue type is fat and water
• T2* is sensitive to blood
oxygenation, functional images

24 Ogawa & Kwong (1992)

 The BOLD response
• fMRI uses EPI (echo planar imaging) in which
a number of echoes are acquired in a row
→ slices
• EPI scans pick up changes in the level of
oxygen in the blood of the brain
• EPI scans measure what is commonly
referred to as the BOLD response
(Blood Oxygenation Level Dependent response)

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 The BOLD response
Blood Oxygenation Level Dependent response
• Neural activity requires oxygen, supplied by blood
• Oxygenated blood is diamagnetic and does not result in signal loss
• Deoxygenated blood is paramagnetic: distorts the magnetic eld
and results in signal loss → local changes in signal loss are picked up

Ratio oxygenated-
deoxygenated is
important
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 The BOLD response
Blood Oxygenation Level Dependent response
• Neural activity requires oxygen, supplied by blood
• Oxygenated blood is diamagnetic and does not result in signal loss
• Deoxygenated blood is paramagnetic: distorts the magnetic eld
and results in signal loss → local changes in signal loss are picked up

sustained
response

early dip post undershoot

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Relation to neural activity
The BOLD signal is highly
correlated both with
spiking activity (outputs) and with
Local Field Potentials (inputs)

Although much slower

(5 or 6 seconds to peak)
the BOLD response re ects neural
activity

28 Logothetis et al. (2001) Nature

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Correlational methods

• fMRI
• MEG/EEG
• eCog

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 Electroencephalography (EEG)

• On July 6, 1924, Hans Berger (after 30 years of trying) for the

rst time recorded EEG from a human subject:

EEG
10 Hz timing
First EEG ever recorded in the history of mankind

Recommended reading about the history of Hans Berger:

https://doi.org/10.1300/J184v03n02_01

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Electroencephalography (EEG)

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What does EEG measure?

Pyramidal cells

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 Source of electric signal:
cell depolarization of pyramidal neurons
• Resting potential: negative
inside, positive outside:
-70mV
• Excitatory
neurotransmitter released
LFP on apical dendrites causes
positive charges to ow
into dendrite
(depolarization)
• When threshold is crossed:
net negative on outside of
dendrite → spiking activity
spiking
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Action potential

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 LFPs generate dipoles

Electric dipole eld Equipotential lines

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 Spiking activity versus
local eld potential (LFP)

• Spiking activity: the output activity of a

neuron or group of neurons
• Local Field Potential (LFP): the result of
su re ?
synchronized input activity of many e a
dendrites into neurons m
EG
s E
o e
t d
h a
W
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 Cortical fold
cortical surface

white matter

• Large numbers of
neurons must have
unidirectional voltage
elds
• Folding can cause
local cancellation
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Source of EEG
• Local Field Potentials
(summation of synaptic
inputs)
NOT spiking activity
• Scalp-recorded potentials
only possible for layered
structures with consistent
orientations, which are
mostly cortical (not
subcortical)

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Source of EEG
• Voltage everywhere
except at negative-
positive transition
• Voltages spread through
the head through
volume conduction
• This results in
smearing / blurring
• Many sources contribute
to the voltage measured
at any given point:
Signal summation
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Three requirements for EEG
1. An LFP needs to result from large groups of neurons to
create a suf ciently strong dipole (synchronous activity of
many neurons) also called signal summation

2. Dipoles (and thus neurons) need to have

the same orientation
radial

3. Measures radial dipoles. tangential

Neurons that are oriented
perpendicular to the cortical surface
contribute strongest to the signal

Note: a lot of event-related neural activity does not meet these

requirements; what does that mean for the interpretation of EEG?
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 Electrode placement
(anywhere between 2 and 256)
Standard 10-20 system
Optional electrodes

Gel between
electrode and scalp
for conduction
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EEG channels → topomap

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EEG source reconstruction
• Inverse problem: where do the
voltage differences come from?

‣ Cortical surface > 3D sources:

many solutions are possible

‣ Problem is underdetermined
(more than one pattern of activity
can cause the result)

‣ Reasons: signal summation,

cortical folding, blurring etc
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 Inverse problem

hypothetical dipoles

Different neural generators can lead to

the same distribution of measured EEG!

44 https://doi.org/10.1002/hbm.21358
Forward problem versus
Inverse problem
Forward problem
(solvable, relatively easy)

Inverse problem
(ill-posed / underdetermined)

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 Magnetoencephalography (MEG)

No blurring
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 Magnetoencephalography (MEG)
Only sensitive to tangential sources

radial

tangential
Right hand grip rule

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Relationship EEG / MEG

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Correlational methods

• fMRI
• MEG/EEG
• eCog (intracranial EEG)

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 Electrocorticography (ECoG):
solves (some of) the inverse problem

Brain is only
organ without
nociceptors

Wilder Pen eld 50

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 ECoG / Intracranial EEG:
Find the focus of epilepsy

• Extent of recording limited

• Very high quality signals for
researchers
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 Connectional/
structural methods

• DTI
• VBM
• Tracers

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Diffusion Tensor Imaging (DTI)

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Brownian motion

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 Diffusion Tensor
Imaging (DTI)

• Water diffusion in white matter is anisotropic

(directionally restricted)
• Diffusion is high along the length of an axon
• Fractional anisotropy (FA) is a scalar value
between zero and one that describes the
degree of anisotropy
• FA can be measured using a DTI sequence
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 DTI

Colors often (but not always) refer to the degree

or to the direction of anisotropy
Fiber tracking

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 Connectional/
structural methods

• DTI
• VBM
• Tracers

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Voxel Based Morphometry:VBM

How much grey

matter (volume) and
thus how many
neurons are present
in a given location? ?
c e
e n
q u
se
2 *
r T
1 o
59 T
 Stimulation methods

• TMS
• Brain stimulation (Pen eld)
• tDCS

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Transcranial Magnetic Stimulation (TMS)

Seriously in neuroscience:
Magnussen &
from 1985
Stevens, 1911
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How does TMS work?
Induce currents!

Right hand grip rule

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 TMS

Exact location guided by MRI and fMRI measurements

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 TMS
• Single pulse TMS causes neurons to
depolarize and discharge an action potential.
‣ Primary motor cortex produces muscle activity
‣ Phosphenes in visual cortex
‣ Can also disrupt cortical processing
• Repetitive TMS (rTMS) produces longer-
lasting effects: increases or decreases the
excitability of the corticospinal tract.
‣ Used for treatment of depression.
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 Stimulation methods

• TMS
• Brain stimulation (Pen eld)
• tDCS

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 Brain stimulation

Wilder Pen eld 67

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 Stimulation methods

• TMS
• Brain stimulation (Pen eld)
• tDCS

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Transcranial Direct Current
Stimulation (tDCS)

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 tDCS
• Anodal stimulation (positive stimulation)
‣ Excites/enhances neuronal activity
• Cathodal stimulation (negative stimulation)
‣ Inhibits/reduces neuronal activity
• Sham stimulation
‣ brief current but then remains off for the
remainder of the stimulation time

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tDCS

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 tDCS impacts
• Depression
• Movement
• Perception
• Improve working memory and attention
• Emotion regulation
• Impulsivity

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 Inhibition/interference
methods
• Cathodal tDCS
• TMS
• Lesions
• Strokes
• Tumors
• Cooling

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 Lesion methods: cooling

• Methanolpump
• Only used in animals
• Cooling is reversible
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 Mutual manipulability
measure Top-down
experiment
manipulate
behavior/ Detect effect Manipulation behavior/task
mental mental

manipulate Manipulation Detect effect measure

interfere/ Bottom-up correlation
stimulate experiment structure/connect.
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Time versus spatial resolution
MEG & EEG fMRI

TMS

lesions

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 The brain

EEG

fMRI MEG
TMS
tDCS

77 https://en.wikipedia.org/wiki/Blind_men_and_an_elephant
Questions?

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