Week 3 Lecture Notes
84
1 Q551 Brain and Cognition Cognitive Neuroscience “If the brain were simple enough to understand, we would be too stupid to understand it”
Transcript of Week 3 Lecture Notes
1
Q551 Brain and Cognition
Cognitive Neuroscience
“If the brain were simple enough to understand, we would be too stupid to understand it”
2
Brain and Cognition Week 3
Gross Brain Anatomy and PhysiologySynaptic transmissionEEG/MEG/PET/fMRI
3
The Chemical Synapse
4
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).
5
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.
6
Excitatory Effects of Neurotransmitters
EPSP = ExcitatoryPost-SynapticPotential
7
Inhibitory Effects of Neurotransmitters
IPSP = InhibitoryPost-SynapticPotential
8
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.
9
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).
10
Integration of Synaptic Inputs
Distal and proximal synaptic inputs:
11
Learning and Plasticity
We will return to these topics in a future week
12
13
14
Anatomy-Exterior View
15
Anatomy-Major Structures
16
Anatomy-Interior View
17
Anatomy-Four Lobes
18
Anatomy-Major Areas
Four Lobes:
• Frontal Lobe
• Parietal Lobe
• Temporal Lobe
• Occipital Lobe
• Thalamus
• Cerebellum
19
Anatomy-Association Corti
20
Major Areas- Speech Pathways
21
Cortical Anatomy
Representation of Imaging Data Sets:- 3-D based- Surface based
Broca’s Area
Motor Cortex
Visual Cortex
Auditory Cortex
gyrus
sulcus
22
Cortical Anatomy
The macaque monkey cortex - unfolded.
Felleman and Van Essen, 1991.
23
Cortical Anatomy
24
“Brain Flattening”
25Source: Marty Sereno, UCSD
26Source: Marty Sereno, UCSD
27
“Brain Averaging”
28
Standardized Brain Atlas
29
Methods of Cognitive Neuroscience
Neurobiology:NeuroanatomyNeurophysiology
Neuroimaging TechniquesPETMRI/fMRIEEGMEG
Evidence from DysfunctionLesionsDiseases of the CNS
Cognitive Psychology
Computational Approaches
30
Methods of Cognitive Neuroscience
31
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
32
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)
33
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.
34
A New Method…Transcranial Magnetic Stimulation (TMS)
35
EEG
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).
36
EEG
Standard placements of electrodes on the human scalp: A, auricle; C, central; F, frontal; Fp, frontal pole; O, occipital; P, parietal; T, temporal.
37
EEG
38
EEG
39
EEG
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.
40
The Electroencephalogram
A simple circuit to generate rhythmic activity
41
The Electroencephalogram
Two ways of generating synchronicity:
a) pacemaker; b) mutual coordination
1600 oscillators (excitatory cells)
un-coordinated coordinated
42
EEG
EEG potentials are good indicators of global brain state. They often display rhythmic patterns at characteristic frequencies
43
EEGEEG suffers from poor current source localization and the “inverse problem”
44
EEG
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).
45
EEGPower spectrum:
46
EEG - ERP
ERP’s are obtained after averaging EEG signals obtained over multiple trials (trials are aligned by stimulus onset).
47
MEGThe MEG laboratory
Images courtesy of CTF Systems Inc.
48
MEGMeasures changes in magnetic fields that accompany electrical activity.
49
MEG
An example (auditory task):
50
51
52
53
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.
1 2 3
Viktor Jirsa (FAU): http://www.ccs.fau.edu/~jirsa/Imaging.html
54
Sensing Techniques-Cat Scans
55
Sensing Techniques-Cat Scans
56
Sensing Techniques-Cat Scans
• Cat Scans use x-rays to show structures
• Really precise maps
• Hard to determine functions
57
PET
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.
58
Sensing Techniques-PETRadioactive element decays, gives off positron
Positron moves a short distance and gives off two gamma rays in opposite directions
59
Sensing Techniques-PET
60
PET Scans
Eyes Closed White Light Complex Scene
61
PET Scans
EpisodicTask
SemanticTask
Difference
62
PET Scans
63
PET
64
PET - Examples
In cognitive studies, a subtraction paradigm is often used.
65
PET - Examples
Another example of control and taskstates, and of averaging over subjects:
Marc Raichle
66
PET - Examples
M. Raichle(a) Passive viewing of nouns; (b) Hearing of nouns; (c ) Spoken nouns minus viewed or heard nouns; (d) Generating verbs.
67
PET - Examples
M. Raichle
68
PET - Examples
M. Raichle
PET images taken at different times, e.g. during learning, can be compared.
69
PET - ExamplesPET images are pretty to look at ...
… and can be combined with other imaging modalities, here MRI.
70
Functional Magnetic Resonance Imaging
Typical MRI Scanner
71
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
72
PET - MRI in Comparison
73
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)
74
fMRI Method
75
MRI Scans
76
MRI Scans
77
fMRI - Examples
78
Stimulus: “checkerboard pattern”V1 responsesJezzard/Friston 1994
79
80
fMRI High-Resolution Mapping
Kim et al., 2000
BOLD fMRI in cat cortex (level of area 18)
81
fMRI High-Resolution Mapping
Kim et al., 2000
82
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.
83
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.
84
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
