Unit 3 - Lecture 1 Flashcards
1
Q
What are some general considerations of using animal models?
A
- Most knowledge is from animal models
- Idea: similar anatomy = similar physiology (ensure by orthologous genes)
- Animals with similar anatomy should have similar outcomes to humans
- Similar functions are reported among species with similar anatomy/genetics
2
Q
What are translational issues?
A
Can animal knowledge really be applied to humans?
3
Q
Why is human research largely limited?
A
Human research is largely limited due to ethical reasons.
4
Q
What animals are typically tested on?
A
Mice, monkeys are too expensive
5
Q
What limitations exist with using animal knowledge to study humans?
A
Difficult to study human specified functions (e.g., speech, language)
6
Q
2 classification of methods in neuroscience
A
- Anatomic/ morphological methods
- Functional methods
7
Q
Anatomic/ morphological methods
A
On structures from gross to fine, to molecules
8
Q
What are two types of functional methods?
A
- Behaviour methods (subjective)
- Objective methods
9
Q
Functional methods - behaviour methods (subjective)
A
- Observation (passive, not interference, natural, lack of control)
- Empirical study (stimuli-responses, designed condition)
10
Q
Functional methods - objective methods
A
- Evoked response (Electrophysiology/optical/magnetic responses)
- Functional imaging
11
Q
Methods for anatomy and structures (microstructures)
A
Microstructures: dissection, staining, microscopy technologies
12
Q
Explain how staining works
A
- Staining to show special materials (histochemical staining,
immunohistochemical (IHC): against proteins w/ antibodies) - Staining uses special chemicals and antibodies which specifically target particular proteins (this lets you observe one thin slice)
- We want staining to only stain one particular anti body
- 3D puts the slice information into whole structures
13
Q
What is a very common chemical to use for staining lipids?
A
Golgi staining with silver nitrate
14
Q
How can you track the pathway using a tracer?
- why is it not easy
A
- It is not easy to track the pathway if the fibers are not distributed in a laminated manner (they are very thin)
- There is a special transportation system to carry the tracer to different places from the site of injection
15
Q
IHC to identify special protein (calpain)
A
- Calpain increase in hair cells by noise exposure
- Calpain is a proteinase that is activated by calcium overload in response to noise
- In normal ear, this protein is very low level. If too much calpain, ear can be destroyed.
16
Q
What 3 things does the nucleobase chain form?
A
- Genetic code
- Ribonucleic acid
- Deoxyribonucleic acid
17
Q
What are 4 methods of molecular biology?
A
- Expression
- Immunohistochemistry
- Structural studies
- Genetic methods
18
Q
Methods of molecular biology - expression
A
- Expression: PCR (Polymerase chain reaction) for mRNA (transcription); Western Blotting for proteins (translation)
- Both methdos need to remove tissue and take out cells (therefore cant observe normal structures)
19
Q
Expression - PCR
A
Used to identify mRNA for certain protein
20
Q
Expression - WB
A
- Method to identify proteins
- The protein contains charge and different sizes
- Spread protein on certain gel, the protein will move in a field of electricity because it contains charge, smaller molecule moves faster, larger moves slowly or not at all)
21
Q
Methods of molecular biology - Immunohistochemistry
- what does it use
- what does it allow you to observe
A
- (IHC), with light microscopy and electron microscopy
- Allows you to observe the molecules in the tissue where they are located (used together with dissection, staining, and microscope)
22
Q
Methods of molecular biology - Structural studies
- What is it good for
- What is a limitation
A
Xray observation provides a good observation of 3D proteins (but there are more modern methods); limitation is that it can only observe fixed proteins, not living tissues
23
Q
Methods of molecular biology - Genetic methods
A
- Gene knockout/in: germ cells and conditional knockout/in somatic cells
- Gene therapy:
- Modulation and editing
- siRNA
- Stem cell transplantation
24
Q
Genetic methods - what is gene knockout?
A
- What is the difference between animals with and without the gene?
- Shows the role of the gene, done to eggs so species is born without gene
25
Genetic methods - what is conditional knockout?
Knock out gene at a particular time
26
Genetic methods - What is gene therapy? What are two types
- Decrease or increase the expression of certain genes
- Modulation and editing
- Stem cell transplantation
27
Gene therapy - Modulation and editing
Can correct particular genes for treatment (needs more research)
28
Gene therapy - Stem cell transplantation
- One cell that can be used with other types of cells
- For regeneration, some cells can be treated in vitro (can be manipulated)
- Has been used with Parkinson’s disease
29
What are some methods suitable to human subjects? (5)
These are limited by invasiveness
- Behaviour studies
- Evoked potential studies
- Functional imaging
- Neural recording during surgery
- Biopsy
30
Human subject methods - Behaviour studies
- Subjective
- Give instructions then see human response
- Non-invasive
31
Human subject methods - Evoked potential studies
- Objective
- Using gross-electrodes that are non-invasive
32
Human subject methods - Functional imagine
- Can observe the functional change of the brain
- No surgeries so not harmful
33
Human subject methods - Biopsy
Very popular method, shows if a particular tissue or organ has a disease
34
____ is the most important single category of functional methods in neuroscience
Electrophysiology
35
Electrophysiology is an ____ method that can be used in humans
Objective
36
What are 3 electrophysiology methods?
1. In viva (done on a living organism)
2. In vitro (done in a lab dish/test tube)
3. Pharmacological methods (in vivo and in vitro can be used in pharmacological studies)
37
Electrophysiology - In viva
- Gross electrode vs microelectrode (multi units vs single unit)
- Near field vs far field
- Acute vs chronic
38
Electrophysiology - In vitro
- Patch clamp, whole cell clamp
- Taking out the whole piece of the cell
39
Electrodes for recording and stimulation
- At least two electrodes are needed to form a circuit for signal recoding and stimulation (the material must be conductive).
- Two electrodes creates a loop to allow the current to pass
- A grounding electrode provides a pathway to reduce noise
- Isolation is needed, only tip is exposed to tissue.
- Also dependent on the diameter (spatial selectivity)
40
Explain gross electrodes (7)
- Thick, and low impedance
- Tough
- Poor spatial resolution
- Far-field recording
- Noninvasive (but can also be used invasively, but micro electrode cannot be noninvasive)
- Responses from many neurons
- Depends on synchronized activity
41
Explain microelectrodes (7)
- Thin, high impedance (high level noise)
- Fragile
- Good spatial resolution
- Invasive
- Near-field recording (micro electrode wont work in far-field because of the low impedance that is needed for gross electrodes)
- Single unit responses
- Need surgery to place electrode close to the target,
42
Voltage clamp: breakthrough for action potential
- Axon from Giant Squid provides the best sample for the study of voltage clamp: to study the feature of ion channels at different membrane potential (axon is 1mm which allows investigation of membrane/action potential)
- In generation of action potential, the permeability of ion channels are changed with both time and membrane potential. In order to identify the contribution of the two factors, voltage clamp fix the membrane potential to see the change with time. (We cannot freeze time!)
43
Explain the patch clamp
- Patch clamp: voltage clamp on small patch
- Patch is small, allow the study of ion channel properties (single ion channel if patch is really small) cell is sucked into the pipe in order to tear of a small piece.
- This allows us to understand how a particular ion channel works (in vitro study)
44
Functional Features of Individual Neurons (4)
1. Functional units (neurons and circuits)
2. Single neuron activities are the foundation of signal coding
3. Must be recorded separately (single unit study)
4. By microelectrodes
45
Explain single unit studies
Single unit study forms the foundation of neuroscience (very time consuming, need to repeat hundreds of times)
46
How are acoustic signals are coded in neural behaviour? (3)
- By rate change
- By phase locking (temporal pattern)
- By place (tonotopic map in auditory pathway)
47
What are 2 ways to record timeline in experiment?
1. Acute
2. Chronic
48
Explain acute recording
- Recording over several hours
- Under anesthesia to make animal stabilized
- Difficulty to hold electrode in position
- Suitable for microelectrode recording of single neurons
49
Explain chronic recording
- Using implanted electrodes
- Can be gross and microelectrodes
- Can be recorded from awake animals
- Long-lasting, allow more manipulation over time
50
What are two types of single unit recording?
1. Single channels
2. Multi-channels
51
Explain single channel single unit recording
- Recording activities of one neuron at a time
- Very time consuming
- Can be combined with dye injection to verify neurons with certain response pattern
52
Explain multi-channel single unit recording
- Recoding activities of many neurons that may be connected via circuits
- Allow exploring of neural circuits and the mechanism of signal processing
- Can be done using acute and implantable electrodes.
53
What are 7 changes from peripheral (low level) to central station (high level, cortex)?
1. Increased number of neurons (SGNs increase in the cortex)
2. Increased versatility
3. Slower working speed (due to synaptic delay, temporal resolution goes down)
4. More complicated circuits, allowing detailed processing
5. Specified processing combined with high level of integration (seen in high levels)
6. More place coding (more functional features are related with place coding)
7. Responses are modulated by many factors—inconsistent response to the same stimuli (sleep, attention, activities, etc)
54
Central neurons and signal processing
- Relay neurons and inter neurons
- Principle pathway and local circuits
- Excitation and inhibition
- Membrane property variation
55
Excitation and inhibition doesn’t exist in the ____
Peripheral
56
Relay neurons deliver single across different ____, inter neurons are ____
Stimuli (long distance), local
57
Integration of Auditory Function (what are the 3 types)
- Integrate information from single unit studies
- Example in intensity coding of auditory nerve
- Longitude integration (along pathway: ascending and descending innervation)
- Transverse integration: ex: integration across different frequency channels for speech coding
- Cross-modality integration
58
EEG tests ____ brain activity
Spontaneous
59
Explain EEG
- Electroencephalography: only largely synchronized brain rhythm can be demonstrated
- Spontaneous brain activity
- Can occur with or without stimulation (always brain activity happen)
60
Evoked potential is ____ to stimuli
Time locked
61
Explain time locking
- You know when the response will happen after the stimulation
- Due ton consistency of the time lock, the EVPs can be picked up from large noise by time averaging.
- Detection of such small signal depends on phase/time locking
62
What is time averaging?
- Time averaging = we can do thousands of sweeps so over time
- You are averaging the response (because every sweep you get a response)
- Noise is random at all times, the noise cancels out each sweep (this is why time averaging works)
- Gets the peak to stand out
63
What does AER stand for?
Auditory evoked response
64
What are 5 ways to categorize AER?
1. Labelled by latency
2. Labelled by stimulus
3. Labelled as exogenous or endogenous
4. Labelled by the distance between the electrode and the generator
5. Labelled by generator
65
1. Labelled by latency
- The most common method of categorization
- Early, middle, and later latency
66
Explain short latency (5)
Shorter the latency...
- Lower the generators in ascending pathway, therefore smaller in amplitude
- Deeper in location
- Smaller in number of neurons
- More transient for synchrony required
- Less influenced by sleep
67
ABR has ____ latency, which means it is ____.
Short, low in the ascending pathway
68
Why is the shortest latency response the smallest amplitude? Where is it located?
The shortest latency response is smallest amplitude because the structure is deeply inside the brainstem (far away from the electrode that is bring used to measure)
69
Long latency = ____. Where does it directly come from?
Bigger amplitude (Directly from the cortex)
70
Short latency response can also be called a ____.
Transient response
71
2. When something is labelled by stimulus it can either be ____ or ____.
Transient, sustained
72
Transient: signals vs. response
- Signal: quick change of signal with time, better transient at onset and offset than other signals (transient = quick change)
- Responses: those rely on the transient feature of signals, e.g., CAP in EcochG, ABR etc.
- Example: click evoked ABR (click is the stimuli which is a transient signal, ABR is also transient)
73
Why do we need transient?
- Smaller amplitude due to deeper location and smaller amount of neurons
- Larger difference between electrode and target, therefore we need the neurons working together
- Short duration resulting in stronger requirement for synchronization
74
____ is the most transient auditory evoked response
ABR
75
Only see transient signal at the ____ and ____ of tone burst. Therefore ____ is the most transient.
onset, offset, click
76
A transient ____ is needed to produce a transient ____.
Signal, response
77
Why does ABR require a transient stimulus?
1. Early response generated from deeper structure (spatial attenuation)
2. Early response generated from smaller number of neurons.
3. Action potential of early response has shorter duration, therefore require better synchronization.
78
Transient vs frequency selectivity
- Transient: signal with short duration, sharp on and off
- Abrupt on and off causes frequency splattering, therefore poor frequency selectivity
- The more transient the stimulus is, the less frequency selective you will have (a very quick onset and offset means there is more chance for splattering)
79
What is a method for compromising splattering?
Short duration tone with time windows
80
Short duration means ____.
Broad band
81
____ are more frequency selective than a click because they ____.
Tone bursts, don’t splatter as much
82
Explain a click
- what is it (range)
- what is below
- where is synchronization best
- Broad spectrum signal, further limited by transducer (speaker or earphone) but still broad, up limit: ~4-5 kHz
- Evoke below 5 kHz, spread at high intensity
- Synchronization better in high F at basal end due to high speed of traveling wave
83
Why is a click a broadband signal?
- A click is a broadband signal because it is so short in duration and quickly changes with time
- Therefore, a click is going to have poor frequency selectivity
84
Explain a click by a 0.1ms pulse
- what is the half power point
- what are the main contributors of ABR?
- what intensity is a cochlear excited at below 5 kHz?
- 0.1 ms pulse is the click that we use (the cut off frequency is at 5 kHz = half power point)
- Between 0 – 5 is the main contributors of the ABR (3kHz – 5 Khz) = better synchronization
- At low to moderate intensity, cochlea is excited below 5kHz
85
Major contributor to ABR is ____ region
2-5 kHz
86
Using clicks for ABR will give you the best ____.
Frequency region
87
Sustained response or steady-state response
- Example: 40 Hz response
- Repeated click presented at a rate of 40 Hz (doesn't depend on transient, but periodicity)
- Or any signal with periodicity of 40 Hz, such as AM
- You can have a signal with a frequency of 4000 Hz, but you can amplitude modulate it so the periodicity is 40 Hz
88
What are event-related potentials?
Related to the circumstances under which they are elicited rather than to the physical properties of the signals
89
What is ASSR?
- what frequencies and where is the generator
- Auditory steady state response
- ASSR at higher frequency: generator moves to brainstem
- ASSR = a clinical method to record sustained response
90
Why does ERP happen?
It is not entirely clear, it may be related to internal brain activities
91
steady-state potential is not a response to the ____ of the signal, but to ____.
transient feature, periodicity
92
What is the advantage for a 40 Hz event related response?
Big amplitude, better frequency selectivity (due to long duration of stimuli)
93
What is the disadvantage for a 40 Hz event related response?
- Unknown generator, not reliable in children, influenced by sleep (consciousness)
94
How 40 Hz ASR added up?
If stimuli have periodicity of 40 Hz (25 ms interval), the peaks will add up (the stimuli will match the interval and enhance the signal)
95
ASSR signals
- carriers
- what does it tell us
- what produces periodicity
- signal energy
- Carriers: could be tone, narrow/wide band noise
- ASSR tell the function of region of carrier frequency (CF)
- Amplitude modulation to produce periodicity: modulation frequency (MF)
- Signal energy: mainly at CF, two sidebands: CF+/-MF
96
For ASSR use a long-lasting signal with a periodicity of ____
40 Hz
97
The carrier could be 4000 Hz or anything, but need to modulate it at ____ for it to work
40 Hz
98
Long-lasting signal create better ____.
Frequency selectivity
99
ASSR is able to tell the function of the frequency region of the ____.
Carrier frequency
100
Signal energy is mainly distributed around the ____
Carrier frequency (two side bands is the modulation frequency around the carrier frequency)
101
What is the source of a 40 Hz tone come from?
Midbrain and above
102
What is the source of an 80 Hz tone come from?
Brainstem
103
Explain the source of higher frequencies (3)
- More from peripheral (lower level)
- Smaller amplitude
- Less influenced by sleep
104
Explain the modulation frequency
- what is it
- what does it impact
- what if our modulation frequency is high
- The modulation frequency is the rate at which the amplitude of the carrier tone fluctuates over time (the 40Hz tone)
- Where the steady state responses are generated depends on the modulated frequency
- The higher the modulation frequency, the more contribution from the auditory peripheral (but less neurons here for get a smaller amplitude); so it’s a tradeoff
105
Need to be awake in ____ so difficult for infants
ASSR
106
3. Labelled as Exogenous or endogenous
- what processing does each use
- what are examples of each
Exogenous
- Depend on the physical features of the stimulus (SLR, MLR, N1-P2, LLR)
- Only bottom up processing
Endogeneous
- Perceptual; depends on the context no physical features (P300 and other cognitive components)
- Top down and bottom up processing
107
What is P300?
Occurs 300 seconds after the stimulus
108
Mismatch negativity (MMN) - 6
- Event Related Potential, but not cognitive
- Elicited by discriminable changes in signal
- No attention is needed
- But based upon memory train established by preceding (standard) stimulus
- Odd-ball paradigm
- Not endogenous, it belongs to middle latency
109
What is the oddball paradigm?
- what does it measure
- explain the components
- A way to measure mismatch negativity (but also used with endogenous)
- 1st stimuli is regular, common, and occurs more frequently
- 2nd stimuli is rare, and occurs less frequently
- Overall ration is 7:1 (S1 appears more often than S2)
110
Explain the oddball paradigm for mismatch negativity
- what is the process
- what can you determine from this
- Standard: 1000 Hz
- Odd: 1000 Hz +
- When the difference between the standard f and odd f is small, the response is largely overlapped, hardly a difference (not picking up odd stimulus)
- As the odd stimulus goes away from the standard, the responses are different (mismatch negativety)
- Not endogenous (so don’t need to be paying attention, your brain just notices the different response)
- Can determined frequency discrimination threshold (how small does the mismatch negativety have to be to notice a difference)
111
What is the difference between ignoring and attending to the stimuli?
- what are 3 components of endogenous
- when do you see P300
- Endogenous response: longer latency, require attention, related to perception
- P3 does not exist in response to the frequent signal
- We don't see the P3 signal when ignoring the signal
- They actually need to pay attention (if they weren’t paying attention wouldn’t see the P300)
112
Explain the oddball paradigm using words
- Stimuli: sentences with different endings.
- Normal ending: frequent stimuli
- Illogical ending: odd stimuli (R stimulus)
- Perception: understanding the sentences.
- This shows the importance of context
- The weirder that it gets, the response gets bigger (your brain is expecting one thing and you receive something else)
113
4. Labelled by the distance between the electrode and the generator
- explain both
Near-field
- Electrodes close to generator
- Used when monitoring: (1) in surgery room, (2) in combination with far-field recording for localization of generator, (3) behaviour of a single neuron
Far-field
- Electrodes far away from generator
- Used as non-invasive method
114
In most cases, clinical application is ____
Far-field
115
____ is typically invasive so not commonly used in clinic
Near-field
116
5. Labelled by generator
- ECochG
- ABR
- Cortical response/potentials
ECochG: response from cochlea
ABR: auditory brainstem response
Cortical responses/potentials: from cortex (P300)
117
Neural activity and electric field: 2-source and 1-sink in current
- Neurons generate APs which propagate along axons
- Potential difference changes with distance
- The voltage difference goes down with distance
- When excitation happens, it establishes electrodes with the positive side and negative side
- Electric field can be mimicked by 2 poles (one positive and one negative)
118
Explain the dipole electric field in volume conductor
- The dashed lines and solid lines are orthogonal to each other (the voltage is the same along any line)
- This is the electric field the neurons are creating with two poles
- The current between the 2 poles is conducted in volume conductors (not line conductors like daily life)
- Current can go across any dashed line between the two poles
- In order to record the neruons electrical field we have to place the electrode in the same iso-potential line as the two poles (otherwise you wont be able to record the potentials)
- This is why in ABR electrodes are places in a particular location coming from this idea
119
Explain how amplitude changes with distance (in regards to near field and far field)
- Near field: larger amplitude, larger change if distance change
- Far field: smaller amplitude, small change with distance
- If you move electrode across x-axis will get a big amplitude of signal when close to the generator
- Near vs far field looks at amplitude and change with distance
120
Effect of electrode position
- Far field recording yields poor spatial selectivity and smaller amplitude
- Near field recording we see two peaks (better spatial selectivity)
121
Effect of neural structure (open field vs. closed field)
Open field
- Structures are arranged in a regulated orientation
- The response can be spatially added up
- Can use far-field
Closed field
- Arranged randomly
- Can't be easily added up
- Can't measure using far-field
122
Neural activities in closed field cannot be recorded in ____
Far-field
123
Electrocochleography (ECochG)
- when does it mature
- what does it contain
- First group of AER studied
- Mature immediately after birth (in humans, in mice takes 2 weeks)
- Contain receptor potentials from hair cells
- SP (summating potential), CM (cochlear microphonics)
- Neural response—CAP (compound action potentials)
124
ECochG by clicks - How can we get rid of CM and show SP?
- SP is not shown because of filter setting. Eliminating CM by averaging with alternating polarity
- To get rid of the CM, do alternating averaging
- SP is a direct current potential (it can be seen by a click, but more easily with tone bursts)
125
ECochG by tone bursts
1. N1 N2 = ____
2. CAP and CM are ____ because they are alternating in phase
3. CM and SP come from hair cells, both are ____
4. CAP = happens at ____
1. CAP
2. Alternating current (AC)
3. Receptor potentials
4. Onset and offset (because APs are synchronized)
126
Basic feature of CM (6)
- what does it mimic
- does it have latency
- what is it generated by
- what does it reflect
- is it useful
- can it be contaminated
- Mimic sound wave—can be eliminated by alternating averaging (in alternating average, signal is presented in opposite polarity in every following stimulation, adding the response will cancel the CM)
- No latency (except the time for sound travels from speaker to cochlea)
- Generated mainly by OHCs
- Reflect the function of MET
- Least useful in clinic
- Easily contaminated by electro-magnetic artifacts from transducer
127
As soon as the sound stimulates the HCs, ____ happens
CM
128
CM can contaminate the response, so need to get rid of it by ____
Alternating the average (flipping polarity)
129
How to identify artifacts in CM testing? (4)
- Look at the latency (CM only has latency from speaker into the cochlea, but the artifact would have no latency at all)
- Artifacts increases linearly with sound level, but CM saturated at high sound level
- Artifacts have no time delay
- Close sound pathway will reduce CM but not artifacts
130
Basic feature of SP
- what is it
- what is it contributed from
- what doest it vary in (5)
- how is it recorded
- Appears as baseline shift in response to sound (how the whole response has moved down)
- Contributed from IHCs, OHCs and probably neurons (multiple generators)
- Varied in amplitude, polarity with sound intensity, level and duration, as well as electrode location (most variable response)
- Recorded from extracochlear electrode, SP is likely to be negative (similar polarity as CAP), but can also be positive if stimulation frequency is very high.
131
Basic features of CAP
- where are peaks from
- where does someone think N2 is from
- how is it recorded
- what is it dominated by
- N1 from dendrites of SGNs, latency ~1 ms (first negative peak)
- N2 from axons of SGNs, latency ~ 2 ms (second negative peak)
- Someone thinks that N2 from CN neurons.
- Recorded extrocochlearly, CAP is dominated by SGNs of basal turn—due to better synchrony
- CAP is dominated by ANFs with high SR.
132
If we record outside of the cochlea, it is dominated by SGNs of the ____
Basal turn (better synchronization)
133
What can you determine by looking at the SP/CAP ratio? (4)
- Meniere's disease/endolymphatic hydrops, by measuring SP/CAP ratio
- Identify wave I in ABR
- Monitoring hearing function in surgery
- Diagnosis of auditory neuropathy
134
Need synchrony to see CAP, and no synchrony can mean ____
Auditory neuropathy
135
ABR (Auditory Brainstem Response) (6)
- what response
- what latency
- sleep?
- when developed
- generators
- what is it used for?
- Transient responses—require higher level of synchronization
- Short latencies (<12 ms)
- Not influenced by sleep
- Quick and well documented after-birth development
- Clear generators
- Main form of hearing testing for babies that refer on their hearing screening
136
Combination of near-field and far-field recording to identify generators for ABR
- longest pathway
- shortest pathway
- Shortest pathway: SGN-CN-IC
- Longest pathway: SGN-CN-MNTB-SOC-LL-IC
- Therefore, one peak may result from multiple nuclei.
- Far field first to get wave 1, 2, 3, 4, 5 (so you know the times these happen and with the near field recording you can see what records what)
137
Identification of the Neural Generators - 3 methods
Methods
1. Simultaneous near-field and far-field recording
2. Lesion experiment
3. Three dimensional recording
As you get up into the brainstem (wave 3, 4, 5 is more complex)
- Wave 1 = auditory nerve
- Wave 2 = cochlear nucleus
- The others are more complex
138
What is a lesion experiment?
Lesion a certain generator to see which peak disappears
139
What is 3 dimensional recording?
Can see how the response changes by different placement of electrodes
140
Certain wave peak may have ____ because the complexity of auditory pathway
Multiple generators
141
AMLR—Auditory Middle Latency Response (6)
- what is the latency
- generators
- when is it developed
- is it contaminated
- sleep?
- what does it have better?
- Latencies: 12-50 ms
- Generators: not clear/multiple sources for each peak (less clear cause higher up in the pathway)
- Later development. not available at birth (need 14 mo. to see clearly, not mature until 7yrs)
- Easily contaminated by muscle movement (a tense neck can ruin your middle latency response)
- Influenced by sleep (be awake)
- Better frequency selectivity—steady state response
142
Any response longer than a short latency response is ____
Influenced by sleep
143
ALR—Auditory Later Response (6)
- what is the latency
- what is it made up of
- sleep
- generators
- amplitude size
- what does it need
- Latencies: 50-250 ms (long latency response)
- Multiple components
- Influenced by sleep
- Unclear generators
- Big amplitude (more amount of neurons)
- But need longer stimulus interval
144
Application of AER in Auditory Assessment (5) - what do you need for long latency tests in humans
- Long-latency response provides better frequency selectivity
- Need cooperation from subject
- Only for mature subjects
- Big variation (as compared to small latency)
- ABR is still used most, but need improvement
145
What is not an AER?
EEG (you don't need a stimulus)
146
Categorization of imaging methods (4)
CT: computerized tomography (based upon X-ray)
PET: positron emission tomography (on radiation)
MRI/fMRI: magnetic resonant tomography
Multiphoton Microscopy
147
What imaging techniques are morphological?
CT and MRI
148
What imaging techniques are functional?
PET and fMRI
149
Is multiphoton microscopy morphological or functional?
Both
150
What imaging techniques are being used in clinics? What one is still being researched?
CT, PET, and MRI/fMRI are used in clinics
Multiphoton microscopy is still being researched
151
Explain X-ray and radiography
- Radio beam and absorption (Different tissue has different absorption rate)
- Standard x-ray: source-subject-film
152
What is one step ahead of x-ray? explain what CT uses
- CT scan is one step ahead of x-ray (it is more focused and looks at single layers at a time, less broad)
- CT: laminography based upon rotation of source and detector, laminography at multiple planes produces polytomography
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Explain CT scan (6)
- what does it do
- what are images shown by
- how is the image reconstructed
- what has low contrast
- what is it best for
- Scanning with focused beam on thin layer of tissue
- Show image according to absorption
- Reconstruction by computer software
- High spatial resolution
- Contrast across different soft tissue is low (as compared to MRI)
- Best for bony structure
154
Explain how a CT scan is set up
- A collimator is a device that narrows a beam of particles or waves.
- The source and detector both rotate around the body (one layer at a time before moving to the next layer)
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Contrast-Enhancement in X-ray and CT: why is it done? what are 3 methods?
Contrast-enhancement is done to increase absorption and to show soft tissues with CT better.
3 methods are
- Inject substance into body space and blood
- Iodinated compounds
- Air injection: pneuomoencephalography
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Acoustic neuroma is shown in CT scan by ____
Enhancer
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Explain MRI
- how are atoms aligned
- how are atoms excited
- what do different tissues show
- what is MRI better for
- Atoms are aligned by external magnetic field
- And excited by radio impulse at Larmor fre to high energy status
- Different tissue, different signals-->images
- Better resolution for soft tissues
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Explain what the protons are doing at the start of an MRI (4)
- Each atom contains a small magnetic field
- The magnetic field in each atom is randomized in term of direction, therefore you will not see the magnetic force because they cancel each other spatially
- An MRI applies a strong magnetic field, which pushes the individual atoms into the same direction (alignment)
- When alignment happens, the magnetic field can be formed
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Explain the radio frequency used in MRI
- A signal of radio frequency (RF) at the Larmor Frequency of each nucleus (or the natural frequency) pushes the proton in the nucleus out of alignment: high energy status
- The energy of driving magnetic field is absorbed at Larmor frequency.
- The RF is used in a broad frequency region (contains many different frequencies)
- The Larmor frequency is the natural frequency of each nuclei
- Use a detector to generate the image
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Explain how the protons return from high energy to low energy status
- what happens with T1 and T2
- From high energy status returning to low energy one accomplished with an emission of RF energy (at Larmor frequency)
- Recovery to alignment and the status of losing phase (related to T1 and T2): T1: return to aliment, T2: return to random status without external magnetic field
161
Three status of atoms in magnetic fields (MRI)
- Random (low energy) - natural
- Alignment (forced in phase)
- Irritated (high-energy status)
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In MRI, the emission is picked up by detector and provide information about ____.
Structure
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MRI Image formation
- What is the release of RF specific too?
- How is the RF detected?
- What is the amplitude modulated by?
- How is the image created?
- Release of RF is tissue (nucleus) specific
- RF detected by receiving coils
- Amplitude mapped by Fourier transformation
- Image created by using the signal
- Material jumps back to low energy status to produce images
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MRI T1 and T2-weighted image
- T1: longitudinal (spin-lattice) relaxation time for proton to gain realignment (from high energy status)
- T2: transverse (spin-to-spin) relaxation time for proton to equilibrium value.
- Time durations for T1 and T2 changes with different tissues
- T1>T2 (T2 relaxation is quicker than T1) – T1 is longer than T2 for most tissues (for water both are the same)
- Different structures prefer different images (T1 vs T2)
- In T2 image: water is bright, soft-tissue with fat is dark--Good for showing pathology because most lesions are having water
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For temporal resolution use a ____ weighted image
T2
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What is the main difference between T1 and T2?
T2 relaxation is quicker
167
What does water look like in T1 and T2?
In T1: water is dark
In T2: water is light
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Explain fMRI
- whats it related too?
- what is a common method?
- what does increased brain activity have?
- Related to metabolism and blood flow
- Common method: blood oxygenation level-dependent (BOLD) contrast fMRI
- Increase brain activity—increase deoxyhemoglobin—increase blood flow (2-6 second later), surplus
- Deoxyhemoglobin has greater magnetic susceptibility
- MRI signal represents the ratio which indicates brain activity
- T2-weighted image for quicker imaging (better temporal resolution)
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fMRI - image related to hearing task
- Limitation by the huge scanner noise (>100dB SPL) difficult to get
- Limited by temporal resolution
- Methods to reduce the impact of background noise
- Whatever signal you get will partially come from noise
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Resting status fMRI (rs-fMRI)
- Look for the low frequency vibration of BOLD
- Calculate correlation across different regions
- Strong correlation represents strong connectivity (functional connectivity)
171
One ear stimulation with fMRI
When one ear is stimulated, both sides of the brain are stimulated (shown in PET scan)
172
Explain PET
Radioactive material is injected into blood, stronger signal from area with high blood flow (the brain region that is more active will take more blood supply)
173
PET images for speech perception: strong in ____ side of brain
Left
174
Functional images - the brain area with stronger activity/larger metabolic rate will show ____ signal
Stronger
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Functional methods depend upon areas that are ____ and ____
Oxygenated, deoxygenated
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What does magnetoencephalography measure?
Measures the magnetic field produced by electrophysiological responses
177
What are 2 advantages of magnetoencephalography?
- High time resolution (comparable to EEG, > MRI/PET/CT
- Better spatial resolution than EEG/EP
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Effective ionizing radiation for a PET test is ____ per year.
14 micro-Sievert (mSv)
179
Explain fluorescence microscopy
- what shows the different molecules
- what is the visible wave length
- what absorbs the light
- what is the emitted light different from?
- what 2 things separates the emitted light?
- Fluorescent dyes made highly selective to a molecule of interest (DNR/RNA, protein, lipid), diff. colors for different molecules
- Illuminated by light of a specific wavelength, in visible wavelengths (390-700 nm)
- Absorption of the light by fluorophores, jumping to high-energy state, emitting light when returning back
- The emitted light is different from that of illumination
- The emitted light is separated from the illumination by emission filter and dichroic beamsplitter
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Explain laser confocal scanning microscopy (LCSM) or Confocal microscopy
- why do wide-field fluorescence microscopes have poor resolution?
- how does LCSM work?
- what does it show a better image than?
- Wide-field fluorescence microscopes has poor resolution due to the emitted light from unfocused background
- In LCSM, only one point is illuminated at a time, and pinhole is used to block further from the unwanted area, to increase resolution
- Shows a better image than fluorescence microscopy, but it is still not good enough
181
Limitations of LCSM and advantage
- Visible light is largely scattered and absorbed before it reach a deep target
- Limited the depth upon which the observation can be done.
- Limited the use in vivo.
- Advantage of 2 photon
- Allows visualization of living tissue at depths
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How 2-photon imaging work?
- what does photon absorption do?
- what light is used?
- how close are they applied to each other?
- what is that wave length?
- how is energy released?
- Photon absorptions excite a molecule to higher energy state
- Use infrared light (light that is longer than the wavelength that is visible to us) to reduce absorption and scattering
- The 2-photons are applied within 1 femtosecond of each other
- In this way, the two photons, each with wavelength of 400-500 nm, make the wavelength of excitation to be 800-1000 nm (infrared).
- However, only one photon will release energy at a time, so to present visible light
- Better focus (no out-of-focus light)
183
Single photon images show ____ that are emitted
Multiphoton emits ____ (can be used in living tissue)
large areas, one dot at a time
184
Life imaging of brain
- This is a good tool to investigate brain plasticity (to see how particular material changes over time)
- Used on animals, not humans
185
Methods of Psychological Evaluation (6)
These are methods to determine hearing threshold (sensitivity limen) – softest sounds they can hear, or smallest gap between two sounds they can discriminate...
- Classical methods of limit
- Method of constant stimuli
- Method of adjustment
- Adaptive procedure and derived
- Two-interval forced choice
- Scales of measurement
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Method of Limit or Yes-No Method (for threshold)
- Tester (audiologist) changes stimulus level in discrete steps
- Testee responds: yes/no (or no response)
- Descending series: started well aboce the estimated threshold; check reversal response
- Ascending series: starts well below estimated threshold; check seversal in response
- Calculating averaged of reversals as threshold
- Can be used for both absolute threshold and differentiation threshold
187
How is the method of limit different from finding hearing threshold in clinic?
- The tester is turning down the stimulus level in 2 dB steps
- Much more accurate
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Method of limit for Differential Limen
- Compare between two sounds (is sound 1 or sound 2 louder)
- There will be two transition points (louder to equal, and if the first sound is softer than the second sound)
- Between the 2 transition points the level difference is the ability of discrimination
- To determine the differential limen do averaging of the two transition points
- The larger the difference between the two transition points, discrimination is poor
- 58-53 = 5 which is their differential limen
- They can discriminate within 5 dB (anything between there the subject cant tell there is a difference)
189
What are 2 limitations or bias due to guessing in the method of limit?
Anticipation – the subject predicts change might happen.
- Lower (better) ascending threshold; anticipate the stimulus
- Higher (poorer) descending threshold; anticipates not hearing it
Habituation – no change in response until larger change in stimuli
- Ascending: does not change response from no to yes until threshold exceeds a few trials
- Descending: continues to respond yes after the sound is inaudible
Time consuming because we are trying to be very accurate
190
What does anticipation result in?
Results in a lower/better ascending threshold and a higher descending threshold
191
What technique is used to prevent guessing?
- why does it prevent guessing
- Method of constant stimuli
- Order is random, so subject has no way to guess what will be the next stimuli (could be much louder or much weaker)
- Collect response across many trials to see how many yes responses were presented
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Explain how the method of constant stimuli works?
- Using a fixed set of stimuli (10 or 20 levels)
- The whole set of stimuli is presented in each trial
- Within each trial, the stimuli are presented in random order
- Calculate % correct across many trials
- Draw curve to determine limen (50% response level)
193
Method of constant stimuli example
The whole set consist of 8 levels, totally 50 trials—each stimulus 50 times
194
Step size and accurate estimation
The smaller the steps, the more accurate the estimation
195
Explain how the method of constant stimulation can be used for differential limen
- They are playing the second tone and discriminating which is louder
- Marking how often they say the second tone is louder or quieter
- You can get 50% by guessing, so need to look at differential limen
- 75% determines the differential limen because you can get 50% by guessing
196
Explain why we have to use 75% correct as the threshold for differential limen
- 50% can be obtained by chance (guessing).
- DL is determined at a performance certain value above chance
- DL usually set up at 75% “louder” responses-certain % above chance. – this is used as criteria for threshold
- DL (%) varies: to be more aggressive or conservative
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Method of Adjustment
- what is it
- what is the bias
- Testee controls the signal change (converting point)
- Stimulus is changed continuously not in discrete steps
- Used for testing absolute thresholds and differential limen
- Control dial must be unlabelled to avoid bias
- Bias: perseveration of response/persistence of stimulus
198
Explain perseveration of response
Persistence of the stimulus means that a lower threshold is obtained on a descending run because the subject continues to turn the level
down below threshold as though the sound were still audible
In an ascending trial, the absence of audibility persists so that the subject keeps turning the level up until the true threshold is passed by some amount, which has the opposite effect of raising the measured threshold level.
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Adaptive Procedure
- what does it depend on
- what do you do
- why is it more efficient
- Stimulus presented depends on previous response
- Make changes around threshold (target), not far away
- More efficient method because (1) close to target (2) no need for estimation of target (3) adjustable step size leads to more precision
- Many alternative procedures in practice: e.g. modified method of limit by adaptive procedure
200
What method does the adaptive procedure use?
- Up-Down or staircase method
- Closing in on the threshold
201
Parameter estimation by sequential testing (PEST)
- Adaptive changes in both direction and step size
- As you get closer to the threshold the step sizes are getting smaller
- More efficient (no need for estimation of target, don’t need to have an idea of what their threshold is)
202
Method of Tracking
- what is it an example of?
- what does the subject do?
- Example of the adaptive method
- Subject controls the stimuli, but only the direction (ascending or descending)
- If detected turn it down, if not turn it up
- Fixed rate of change
- Bekesy audiometry (frequency also changes in a fixed rate (not control by subject; subject only controls levels)
203
The principle of adaptive method is that sound level fluctuates around ____
Threshold
204
Bekesy tracking
- what is changed
- how does it work
- what are the trials
- Both frequency and intensity are changed.
- Testee controls only the direction of intensity change (not freq)
- When the sound is audible, tune it down, not audible, tune it up
- Frequency is changed at a fixed rate
- Two different trials with (1) continuous tone, (2) pulsed tone
- Diagnosis mainly based upon the difference between the two trials
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5 types of performance from bekesy tracking
- Type I: normal or CHL (no separation between tones)
- Type II: cochlear HL/SNHL (separation of the two curves at higher frequencies)
- Type III: retrocochlear (much larger separation, auditory neuropathy, the continuous tone drops off because the person is experiencing auditory fatigue)
- Type IV: retro/cochlear (retrocochlear and cochlear pathologies, separation across whole frequency range, but more cochlear loss)
- Type V: pulsed threshold higher than continuous one, seen in non-organic HL
206
Two Alternative/Interval Forced (TAFC) Choice: Method for Difference Limens
- Compare standard tone and probe tone or other alternative comparison (e.g., one interval has noise, the other has noise + signal)
- Threshold must be 75% or higher (because can get 50% by guessing)
- Response modification (variation/size of signal difference between two intervals can be changed)
- Calculate mean
- Variations in procedure regarding this method
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What the % threshold would be if 3IFC
Present 3 intervals and only one will contain the target sound (choose which one has the tone)
- If is 3 intervals forced choice
- The % correctness from guessing is 33%
- The criterion for threshold can be 50%.
208
What are the 4 scales of measurement?
- Nominal scales
- Ordinal scales
- Interval scale
- Ratio scales
209
What is a nominal scale?
- The least restrictive
- Assign observations to groups
- Ex: male-female, normal-hearing impaired
- No ordering
210
What is an ordinal scale?
- Rank order of observations (1st, 2nd, etc)
- Does not define the size of difference between the categories
211
What is an interval scale?
- Specify order and distance
- Ordered metric scale (ruler)
212
What is a ratio scale?
- Define distance in ratio instead of absolute unit
- Understand "true zero point" - not actually zero, otherwise the ratio will be indefinitely large (sound level)
- Highest level of scaling (most restrictive)
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Direct Scaling (5)
Ratio
- Ratio estimation (how many times louder)
- Ratio production (make the sound 2 times louder)
Magnitude
- Magnitude estimation (assign a number to a giving sound)
- Magnitude production (match sound to a given number)
Cross-Modality Matching
214
What is the modulus?
- This is the estimation of magnitude (with reference to other stimuli)
- Present at different levels and ask subject how they would compare that sound to the modulus
- A modulus us used so subjects have something to compare
- Trying to quantify how loud something is
- First subject hears sound (modulus) --> then we tell the subject we call this a number 10
- Then present tone at a different level and get them to give a number to that and how it related to the modulus
215
Can the modulus be removed?
- Yes, because it is relative
- Modulus can be removed: absolute magnitude estimation (AME)
216
Magnitude Production
- how to assign numbers (bias)
- Reverse of magnitude estimation
- Subject makes sound level based upon the number that is given
- Can be done with and without modulus (absolute magnitude production (AMP)
- Subject bias: tend not to assign extreme values in magnitude estimation, but to make extreme level adjustments in magnitude production
- A number is given (number 9), and the subject would adjust the sound a produce a sound that is equal to that number
217
Estimation/production without reference to modulus and other stimuli
- where is the bias more true
Bias is especially true at lower sound levels (the separation is close at higher sound levels, but are farther apart at lower sound levels)
218
What is PMB?
- Bias and balancing procedure (PMB—psychological magnitude balance)
- How you balance the bias, accurate representation of a persons loudness sensation
219
Sensitivity vs response proclivity
Sensitivity—real threshold
Proclivity—response bias or uncertainty
220
Proclivity in Psychoacoustic Evaluation - method of limit
- Anticipation
- Habituation
221
Proclivity in Psychoacoustic Evaluation - method of adjustment
Persistence of the stimulus, or perseveration of the response
222
Yes and No: four possible outcomes
Hit = there is a signal and the subject detects
Correct rejection = no signal and subject didn’t hear
Miss = there is a signal but subject fails to detect
False alarm = no signal but subject says there is one
223
Correction for chance success
p(hit)corrected = p(hit) - p (false alarm) / 1 - p (false alarm)
224
If p(hit) = 0.78 and p(false alarm) = 0.17, what is the p(hit)corrected?
0.735
225
A pass is considered...
Not having the disease
226
A fail is considered...
Having the disease (it is bad to have the disease)
227
True failed
False pass
False failed
True pass
- Hit = true failed (TF); subject has the disease and they really do
- Miss = false pass (FP); subject has the disease but results don't show it
- False alarm = false failed (FF); test shows they have the disease, but they actually don't
- Correct rejection = true pass (TP); subject is healthy and the test doesn't show any problem
228
A true fail and a false pass means you are ____.
Impared
229
A false fail and a true pass means you are ____.
Normal/healthy
230
Sensitivity and specificity
Sensitivity = TF/[TF+FP] (% impaired that hit)
- The ability to detect a positive result
Specificity = TP/[TP+FF] (% of normal that pass)
- The ability to detect a negative result
231
A high sensitivity is critical for a ____.
Screening tool
232
A high specificity is critical for terminal ____ tool
Diagnosis
233
What type of test is NBHS?
NBHS is highly sensitive because you don’t want to miss anyone that has hearing loss (more false positives possible) it is screening, then do a diagnostic test to confirm
234
Assumptions of Theory of signal detection (TSD)
- Noise exists: external and internal
- Function changes
- Decision: noise alone (N) or signal-plus-noise (SN)
- Decision axis
- Or magnitude of sensory activation
- Probability
235
How do we make decisions?
- what does a large separation between N and SN mean?
- what does d' represent?
- what does it mean if the curves are largely overlapped?
- what does it mean if there is a large separation between curves?
- Larger the separation between N and SN, and the smaller the σ, the bigger the d’—the measure of sensitivity
- The distance between the response of noise and noise + s are represented by d’
- B shows the cruves largely overlapped, it is harder to make a decision (d’ is smaller)
- A is showing a larger separation so it is easier to make a decision
236
Performance changes with ____ as well as noise
Signal energy
237
Making an internal decision
- 2 ways of bias
Biased by:
(1) Subject knowledge about the chance of signal
(2) Award of correct response (consequence of making different mistakes)
238
____ can influence bias
Instruction
239
What will a good test have?
- A good test will have lower sigma value so a lower difference between the means
- A lower lateral distribution (which makes a larger d’)
240
How to show the quality of signal detection?
- what does it show
- where are each represented?
- How probabilities change with different d’ – shown by ROC curve
- Receiver-operating characteristic—ROC curve
- Show sensitivity and criterion at the same time
- Sensitivity: rep by distance of ROC from the diagonal
- Criterion: particular points along the curve
241
Larger the d’, smaller the ____ when sensitivity is high
False alarm
242
Implication of TSD
- Important for psychoacoustic/neurological experiment
- Design and assumption
- Clear-cut of threshold does not exist
- Outcome depends on methods
