Week 3 Lecture Notes

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Q551 Brain and Cognition

Cognitive Neuroscience

“If the brain were simple enough to understand, we would be too stupid to understand it”

Brain and Cognition Week 3

Gross Brain Anatomy and PhysiologySynaptic transmissionEEG/MEG/PET/fMRI

The Chemical Synapse

Chemical Neurotransmission

“At rest”, the synapse (presynaptic side) contains numerous synaptic vesicles filled with neurotransmitter, intracellular calcium levels are very low (1).

Arrival of an action potential: voltage-gated calcium channels open, calcium enters the synapse (2).

Calcium triggers exocytosis and release of neurotransmitter (3).

Vesicle is recycled by endocytosis (4).

Chemical Neurotransmission

Once released, the neurotransmitter molecules diffuse across the synaptic cleft (about 20-50 nm wide).

When they “arrive” at the postsynaptic membrane, they bind to neurotransmitter receptors (“lock-and-key” mechanism).

Two main classes of receptors:

Transmitter-gated ion channels

G-protein-coupled receptors

Transmitter-gated ion channels: transmitter molecules bind on the outside, cause the channel to open and become permeable to either Na+ (depolarizing, excitatory effect) or Cl– (hyperpolarizing, inhibitory effect).

G-protein-coupled receptors have slower, longer-lasting and diverse postsynaptic effects. They can have effects that change an entire cell’s metabolism.

Excitatory Effects of Neurotransmitters

EPSP = ExcitatoryPost-SynapticPotential

Inhibitory Effects of Neurotransmitters

IPSP = InhibitoryPost-SynapticPotential

Integration of Synaptic Inputs

In the CNS, many EPSP’s are needed to generate an AP in a single neuron.

A single EPSP has, in general, very little effect on the state of a neuron (this makes computational sense).

On average, the dendrite of a cortical pyramidal cell receives ~10000 synaptic contacts, of which several hundred to a thousand are active at any given time.

The adding together of many EPSP’s in both space and time is called synaptic integration.

Synaptic Integration

(a)Single input → single EPSP.

(b)Three APs arriving simultaneously at different parts of the dendrite add together to produce a larger response (spatial summation).

(c) Three APs arriving in quick succession in the same fiber can also result in a larger response (temporal summation).

Integration of Synaptic Inputs

Distal and proximal synaptic inputs:

Learning and Plasticity

We will return to these topics in a future week

Anatomy-Exterior View

Anatomy-Major Structures

Anatomy-Interior View

Anatomy-Four Lobes

Anatomy-Major Areas

Four Lobes:

• Frontal Lobe

• Parietal Lobe

• Temporal Lobe

• Occipital Lobe

• Thalamus

• Cerebellum

Anatomy-Association Corti

Major Areas- Speech Pathways

Cortical Anatomy

Representation of Imaging Data Sets:- 3-D based- Surface based

Broca’s Area

Motor Cortex

Visual Cortex

Auditory Cortex

sulcus

Cortical Anatomy

The macaque monkey cortex - unfolded.

Felleman and Van Essen, 1991.

Cortical Anatomy

“Brain Flattening”

25Source: Marty Sereno, UCSD

26Source: Marty Sereno, UCSD

“Brain Averaging”

Standardized Brain Atlas

Methods of Cognitive Neuroscience

Neurobiology:NeuroanatomyNeurophysiology

Neuroimaging TechniquesPETMRI/fMRIEEGMEG

Evidence from DysfunctionLesionsDiseases of the CNS

Cognitive Psychology

Computational Approaches

Methods of Cognitive Neuroscience

Neurobiology

Neuroanatomy and neurophysiologyare often conducted in animalsystems (monkey, cat, etc.).

Neuroanatomy:

- Large-scale anatomy of the brain- Subdivisions of the cortex- Neuronal subtypes, layers- Morphology of single neurons

Neurobiology

Neurophysiology:

- Recording of neural activity, often in the context of a stimulus or task (single-cell recording, local field potential recording, multi-electroderecording).- Electrical stimulation of neurons to study their role in perception or movement (micro-stimulation, surface stimulation)

Methods ComparisonMethod Space Time Neural Correlate-------------------------------------------------------------PET coarse coarse “brain activation”, metabolic

(5 mm) (sec.) rate of tissue, incorporation of glucose, oxygen utiliz., receptor distribution, 2D-3D capable.

fMRI coarse coarse “blood oxygenation state”,(2 mm) (1 sec.) “regional blood flow”,

oxygenated/deoxygenated hemoglobin, 2D-3D, in register with struct. Scan.

EEG coarse fine “electrical (field) potentials”,(?) (msec) surface electrodes arranged

on skull, limited depth, inverseproblem, unknown source locations, allows correlationmeasures.

MEG coarse fine “magnetic (field) potentials”,(?) (msec) SQUIDs arranged around head,

sensitive to noise, similar advantages and drawbacks as EEG.

A New Method…Transcranial Magnetic Stimulation (TMS)

The electroencephalogram (EEG) measures the activity of large numbers (populations) of neurons.

First recorded by Hans Berger in 1929.

EEG recordings are noninvasive, painless, do not interfere much with a human subject’s ability to move or perceive stimuli, are relatively low-cost.

Electrodes measure voltage-differences at the scalp in the microvolt (μV) range.

Voltage-traces are recorded with millisecond resolution – great advantage over brain imaging (fMRI or PET).

Standard placements of electrodes on the human scalp: A, auricle; C, central; F, frontal; Fp, frontal pole; O, occipital; P, parietal; T, temporal.

Many neurons need to sum their activity in order to be detected by EEG electrodes. The timing of their activity is crucial. Synchronized neural activity produces larger signals.

The Electroencephalogram

A simple circuit to generate rhythmic activity

The Electroencephalogram

Two ways of generating synchronicity:

a) pacemaker; b) mutual coordination

1600 oscillators (excitatory cells)

un-coordinated coordinated

EEG potentials are good indicators of global brain state. They often display rhythmic patterns at characteristic frequencies

EEGEEG suffers from poor current source localization and the “inverse problem”

EEG rhythms correlate with patterns of behavior (level of attentiveness, sleeping, waking, seizures, coma).

Rhythms occur in distinct frequency ranges:

Gamma: 20-60 Hz (“cognitive” frequency band)

Beta: 14-20 Hz (activated cortex)

Alpha: 8-13 Hz (quiet waking)

Theta: 4-7 Hz (sleep stages)

Delta: less than 4 Hz (sleep stages, especially “deep sleep”)

Higher frequencies: active processing, relatively de-synchronized activity (alert wakefulness, dream sleep).

Lower frequencies: strongly synchronized activity (nondreaming sleep, coma).

EEGPower spectrum:

EEG - ERP

ERP’s are obtained after averaging EEG signals obtained over multiple trials (trials are aligned by stimulus onset).

MEGThe MEG laboratory

Images courtesy of CTF Systems Inc.

MEGMeasures changes in magnetic fields that accompany electrical activity.

An example (auditory task):

MEGThree task conditions: MEG results

1 -- Listening to tones that were delivered with a delay of about 5s. A random time was added to prevent stimulus prediction. The signal is an average over about 80 stimulus presentations.

2 -- Reacting to acoustic stimuli. The same stimulus presentation as in (1) but now the subject was told to press on an air cushion as soon as possible after the tone was heard.

3 -- Synchronizing with a rhythm. Here the tones were presented regularly with a frequency of 1 Hz. The subject was told to press the air cushion in synchrony with the stimulus.

Viktor Jirsa (FAU): http://www.ccs.fau.edu/~jirsa/Imaging.html

Sensing Techniques-Cat Scans

• Cat Scans use x-rays to show structures

• Really precise maps

• Hard to determine functions

Positron Emission Tomography

Requires the injection of a positron-emittingradioactive isotope (tracer)

Examples: C-11 Glucose analogs (metabolism)O-15 water (blood flow or volume)C-11 or O-15 carbon monoxide

PET tracers must have short half-life, e.g. C-11 (20 min.), O-15 (2 min.). Cyclotron!

Positron + electron 2 gamma ray beams.

Gamma radiation is detected by ring of detectors, source is plotted in 2-D producingan image slice.

Sensing Techniques-PETRadioactive element decays, gives off positron

Positron moves a short distance and gives off two gamma rays in opposite directions

Sensing Techniques-PET

PET Scans

Eyes Closed White Light Complex Scene

PET Scans

EpisodicTask

SemanticTask

Difference

PET Scans

PET - Examples

In cognitive studies, a subtraction paradigm is often used.

PET - Examples

Another example of control and taskstates, and of averaging over subjects:

Marc Raichle

PET - Examples

M. Raichle(a) Passive viewing of nouns; (b) Hearing of nouns; (c ) Spoken nouns minus viewed or heard nouns; (d) Generating verbs.

PET - Examples

M. Raichle

PET - Examples

M. Raichle

PET images taken at different times, e.g. during learning, can be compared.

PET - ExamplesPET images are pretty to look at ...

… and can be combined with other imaging modalities, here MRI.

Functional Magnetic Resonance Imaging

Typical MRI Scanner

MRI - fMRI

Subjects are placed in a strong external magnetic field. Spin axes of nuclei orient within the field. External RF pulseis applied. Spin axes reorient, then relax. During relaxation time, nuclei send out pulses, which differ depending on the microenvironment (e.g. water/fat ratio).

The Physics (sort of) ...

fMRI – functional MRIAllows fast acquisition of a complete image slice in as little as 20 ms. Several slices are acquired in rapid succession and the data is examined for statistical differences.

Hemoglobin is “brighter” than deoxyhemoglobin. Oxygenated blood is “brighter” - active areas are “brighter”.

BOLD-fMRI

PET - MRI in Comparison

Sensing Techniques-fMRI

• Functional Magnetic Nuclear Resonance Imaging• Similar to Pet, uses radio frequency information

given off by water• Gives better time (6 seconds) and spatial (2 mm)

resolution than Pet or Cat scans• Technology still under revision• Slight danger to subjects• Expensive ($300 an hour)

fMRI Method

MRI Scans

fMRI - Examples

Stimulus: “checkerboard pattern”V1 responsesJezzard/Friston 1994

fMRI High-Resolution Mapping

Kim et al., 2000

BOLD fMRI in cat cortex (level of area 18)

fMRI High-Resolution Mapping

Kim et al., 2000

PET and fMRI - Similarities and Differences

- Different biological signal. Yet, both pick up a signal related to bulk metabolism (not electricity).- fMRI has better temporal (<100 ms) and spatial resolution (1 mm and less)- fMRI does not involve radioactive tracers and subjects can be measured repeatedly, over many trials.- PET images generally represent “idealized averages”. fMRI images are often registered with structural scans to show individual anatomy.- For both, images can be aligned for multiple subjects.- fMRI is widely available, PET is not.- fMRI does not allow localization of neurotransmitters or receptors etc.- For both, it can be tricky to get stimuli to the subject.

Data Analysis Issues

Neuroimaging (PET/fMRI): Activation values, spatial resolution, averaging, image alignment and registration.

EEG/MEG: Current source localization (inverse problem), time domain data sets, frequency power spectrum, correlation and coherency.

Summary

• Appropriate technology depends on question

• ERP has good temporal resolution

• CAT, Pet, MRI have good to fair spatial resolution, only PET has any functional capture

• fMRI has reasonably good spatial, reasonably good temporal, but is expensive

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