P300 and Other Auditory Late Responses

Question 1

When was P300 first identified?

Answer 1

Mid-1960s

Question 2

What are P300s?

Answer 2

A cognitive or discriminatory auditory evoked response
It occurs as a result of higher-level internal brain processing associated with stimulus recognition and novelty
Referred to as a cognitive response or a reflection of attention to a stimulus - endogenous response

Question 3

Why do some researchers argue that the terms exogenous and endogenous are problematic to use to classify AER with cortical generators?

Answer 3

All cortical responses include auditory and cognitive sources that are difficult to entangle
All of these responses are as much affected by attention and meaning as well as the physical stimulus properties

Question 4

Is the P300 a non-sensory specific response?

Answer 4

Yes
It can also be observed with visual and somatosensory stimulation
Can also be seen in gaps of silence in a continuous stimulus

Question 5

Is the P300 essentially an ALR component?

Answer 5

Yes
With an extended time frame and recorded under special stimulus conditions
Observed between 300-310 ms on average (in normal subjects the P300 range is 250 to 400 ms)
*REMEMBER RANGE

Question 6

What are the neural generators for P300?

Answer 6

Complex and poorly understood
Multiple overlapping sites that may be activated simultaneously (especially in the primary auditory cortex, frontal cortex, temporal cortex, temporoparietal association cortex, and multisensory temporal cortical areas) - respond to multiple senses
The P300 is probably generated by other regions such as the hippocampus (where short term memory functions are stored - shrinks with alzhiemers), limbic system, and cingulate gyrus

Question 7

What is the stimulus for P300?

Answer 7

The most common is the “oddball” paradigm
The standard stimulus accounts for about 80% of the total stimuli and the rare or “oddball” stimulus accounts for 20%
The oddball stimulus is presented in a pseudorandom fashion

Question 8

Does background sounds/noise affect the amplitude of the P300?

Answer 8

No

Question 9

How does an increased intensity affect the amplitude of the P300?

Answer 9

Increases

Question 10

What can the infrequent or target stimulus include?

Answer 10

Tonal signals - frequency differences (1000 Hz standard vs 2000 Hz target), intensity differences, duration differences
Speech signals - different phonemes (/ba/ vs /da/), different acoustic characteristics of phonemes (VOT)

Question 11

What are the two components of the P300 with the appropriate stimulus?

Answer 11

P3a and P3b

Question 12

What stimulus do you need to elicit a P3a and P3b?

Answer 12

A three-tone oddball paradigm (standard stimuli, rare target stimuli, rare non-target stimuli)
If the listener is not asked to attend to the rare non-target stimuli, the response obtained is designated as the P3a
The P3b is elicited by the subject attending to the rare target stimuli

Question 13

What is P3a?

Answer 13

Passive
Can occur in response to changes of either the attend or nonattentive stimuli
It is believed to have at least partial neural generators in the frontal lobe
Pre-attention

Question 14

What is P3b?

Answer 14

Active
P3b is only elicited in response to effortful attention
The difference between the target and nontarget stimulus is in the level of expectation (aren’t told about the 3rd random sound - they will notice it but will not pay attention because they were not expecting it to happen)

Question 15

Should you ask the patient to count how much of the infrequent stimulus they hear?

Answer 15

Yes
This will keep them attended to the signal
Tell them you will ask them how many they counted

Question 16

Can you patient fall asleep for the P300?

Answer 16

No

Question 17

Can the standard stimuli be used to elicit the ALR along with the P300 response?

Answer 17

Yes

Question 18

What is the rare non-target stimuli?

Answer 18

It is infrequent but random
Not asking them to pay attention to this

Question 19

When does a target response occur?

Answer 19

When listeners are asked to count for the deviant sound and the nontarget deviant is unexpected
The greater the difference between the standard and nonstandard stimuli, the larger the amplitude of the P3 complex

Question 20

Are P3a and P3b suggested to reflect different neural processes?

Answer 20

Yes
Due to difference in scalp topography and cortical sources

Question 21

Is P300 polysensory?

Answer 21

Yes
Responds to more than just auditory stimuli

Question 22

Does memory storage play a part?

Answer 22

Yes
In identifying P3b
Need to remember the standard stimulus to distinguish between that and the target stimulus
P3a doesn’t really use memory storage because you are not attending to that sound

Question 23

What is the spectral energy for P300 responses?

Answer 23

1-15 Hz (quick, rapid onset signals are not ideal)

Question 24

What are the other recording parameters for P300?

Answer 24

Epoch = 500+ ms
Rate < 1.1/sec
Filter bandpass = 0.5-1 to 100 Hz
Stimulus = oddball paradigm
Polarity = alternating (not an important parameter)
Intensity = 70 dB nHL or less
Electrode montage = noninverting Cz or Fz; Fpz = ground

Question 25

Do the frequencies used in the standard and deviant stimuli appear to make a difference in the generation of P300?

Answer 25

No Common to use 2000 Hz tone burst (frequent) and 500 Hz tone burst (infrequent)

Question 26

What is the amplitude of P3 responses?

Answer 26

About 10 to 20 microvolts

Question 27

Are P3s also describes in terms of latency and amplitude?

Answer 27

Yes But amplitude is more sensitive

Question 28

How do you calculate P300 latency?

Answer 28

Made in ms from the response onset to the peak of the P300 wave Unlike the waveforms for earlier latency responses including ABR, P300 is often broad and characterized by multiple positive peaks Latency is determined for the midpoint of the wave

Question 29

Is there great individual variability for P300 latency?

Answer 29

Yes, related to stimulus parameters, task difficulty, and subject factors such as age, alertness, attention, and cognitive status

Question 30

What are P300 abnormalities?

Answer 30

Often reported in terms of decreased latency, reduced amplitude, and abnormal or absent waveforms

Question 31

What are some factors that affect the P300?

Answer 31

Age (neuromaturation) - will not see a good P300 before 6 Drugs that affect the CNS (depressants suppress the P300, stimulants have variable effects) Disease conditions Attention

Question 32

How does P300 change due to neuromaturation?

Answer 32

From early school age to adolescents, P300 latency decreases, amplitude increases, and morphology improves The relationship between age and latency has been reported as a change in latency of ~ 20 ms from 5 to 13 years (for every age increase, your latency decreases by about 20 ms) It is difficult to measures from infants and children because of attention issues and artifacts Younger children may have a different scalp distribution (due to fontanels) and morphology P300 becomes adult-like by about 15 years The P300 is recorded less reliably with advancing age (slight increase in latency of about 1 to 2 ms/year)

Question 33

Does attention significantly affect the P300 response?

Answer 33

Yes, it is an endogenous response Affected by the listener's ability to attend to the oddball stimulus Absence of a P3 response may be due to the individual's inattention to the rare stimulus rather than their ability to process sounds Absence of P300 when alertness is not questionable may be evidence of higher-level CANS dysfunction such as dementia The P3a can be elicited without the listener actively attending to the oddball non-target stimulus

Question 34

How do drugs affect P300?

Answer 34

Anesthetic drugs produce different effects on different ALRs (some can affect latency and others amplitude) Sedatives and tranquilizers can also affect ALRs and P300 Drugs that product a central suppression of brain activity will significantly influence and usually diminish the ALRs and P300 Acute alcohol intoxication can decrease the amplitude of ALR and P300 responses (alcohol is a depressant of the CNS - inhibit the inhibition and excitation is left)

Question 35

What is the P300 like in alcoholics?

Answer 35

Studies over the past few decades have found that the amplitude of the P300 and P3a and P3b are significantly lower in alcoholics than non-alcoholics (even when not drinking) This decreased amplitude is noted for both auditory and visual tasks and are more pronounced for visual tasks The decrease in P300 amplitude is more pronounced for male alcoholics In several studies with Native American participants, the decrease in the P300 amplitude also has been reported for children of alcoholics who themselves have yet to become alcoholics - indicating a possible predisposition to alcoholism

Question 36

Is the P300 polysensory?

Answer 36

Yes

Question 37

Is the amplitude of the P300 thought to reflect CNS inhibition?

Answer 37

Yes The larger the P300, the greater the inhibition The more irrelevant information that a person is exposed to, the more suppression must occur to respond to relevant information (attending to the relevant information) The low amplitude P300 exhibited by alcoholics indicated less CNS inhibition than controls (may have a harder time suppressing irrelevant stimuli) Researchers have suggested that this lack of inhibition or CNS disinhibition (i.e., hyperexcitability) is involved in predisposition to alcoholism

Question 38

Does fMRI and P300 studies suggest disorganized and inefficient brain functioning in alcoholics?

Answer 38

Yes, in critical areas where P300 originates, including the frontal cortex (executive function), hippocampus (consolidating new memories), and the amygdala (part of the limbic system and responsible for producing and controlling emotional behavior) *all of these areas contribute to selective attention and working memory indicating that alcoholics may have deficits in cognitive function associated with these processes

Question 39

What did they find when the examined AERs in children with learning disabilities and CAPD?

Answer 39

ABR did not appear to be a useful diagnostic tool for the group of LD subjects with suspected CAPD Both AMLR and cortical evoked potentials were sensitive to the suspected CAPD in the children with learning difficulties These results were based on an analysis of group data, however, and relatively few individual children in the LD group showed extremely abnormal results (statistical difference between groups but both groups are ultimately falling in the normal range) Further research is required to establish validated clinical criteria for identifying evoked potential abnormalities in individual children with suspected (C)APD

Question 40

Has P300 been a great interest in the study and diagnosis of Alzheimer's Disease and other dementias?

Answer 40

Yes, because there is not a good biological marker for alzheimers Alzheimer’s patients, with age-adjusted responses show a decrease in both amplitude and latency of P300 not seen in dementia from other causes P300 can identify mild and moderate AD P300 cannot identify severe AD because these patients cannot attend to the stimulus due to the advanced nature of dementia P300 measurements may have the potential for earlier diagnosis of AD and, therefore, better therapy outcomes

Question 41

Can the P300 be a good biological marker for Alzheimers?

Answer 41

Yes It improved after taking an alzheimers drug for a certain period of time P300 became more normal looking

Question 42

Is there a lot of research with schizophrenia and P300?

Answer 42

Yes Probably because the P300 is sensitive to cognitive function and, therefore, responsive to the state of and degenerative course of schizophrenia P300 helped to support that schizophrenia had a biologic basis

Question 43

What are the findings of the P300 for schizophrenia?

Answer 43

They are highly dependent on methodology Typically, the P300 shows decreased amplitude in schizophrenia The P300 also fluctuates as the disease severity fluctuates Decreased amplitude also observed with worsening of symptoms (goes back up when symptoms get better) Increase in amplitude observed after symptoms improve Prolonged P300 latency also has been reported

Question 44

Is there a relationship between P300 and the duration of schizophrenia?

Answer 44

No

Question 45

What were the findings related to type II diabetes and P300?

Answer 45

Those with type II diabetes mellitus with normal hearing had statistically reduced P300 amplitudes and increased latencies (compared to the age and gender matched controls) High blood glucose level immediately prior to testing was found to decrease the P300 amplitude but not the latency

Question 46

What were the findings related to glucose levels and attention and working memory?

Answer 46

Attention and working memory, as represented by P300 amplitude, may deteriorate with an increase in glucose levels Further, the diagnosis of Type II DM in adults may have a negative impact on daily listening skills and attentional abilities based on the P300 response *can have an impact on attention skills, especially if it is not properly managed - could be at risk for dementia later

Question 47

What are N400 and P600 responses?

Answer 47

Language related responses Appear specific to language comprehension (responses to specific linguistic stimuli

Question 48

Have N400 and P600 been involved in a lot of research?

Answer 48

No, not from audiology and SLP researchers Just important to understand that the P300 is not the end

Question 49

When is the N400 observed?

Answer 49

In response to semantically inappropriate words He spread warm bread with socks

Question 50

When is the P600 observed?

Answer 50

In response to a syntactically anomalous word in a sentence The boiling water smoke the kitchen

Question 51

What is mismatch negativity (MMN)?

Answer 51

Response first discovered in 1975 It is a small amplitude negative exogenous ALR Response to a negative wave elicited in an oddball paradigm The response can be observed by subtracting the responses to the standard stimuli from those of the deviant (subtract deviant from standard) It occurs in the latency region of around 100 to 300ms

Question 52

What is MMN assumed to detect?

Answer 52

The brain's unconscious detection of a difference (mismatch) process between the sensory inflow created by the deviant stimulus and the memory tract of the standard stimulus It is a pre-attentive stimulus

Question 53

Where are the neural generators of the MMN?

Answer 53

The principle one appears to be located within the supratemporal plane (in or near the primary auditory cortex) Believed to be more midline than generators for other cortical auditory responses (best recorded from midline electrodes) Also may have generators in the frontal lobe and from subcortical regions of the auditory cortex

Question 54

Are MMN responses automatic?

Answer 54

Yes Not confounded by attention and cognition Can be observed even when the listener is not involved in the auditory task – not actively listening (e.g., while reading) Not affected by sleep or attention, and can be recorded during REM sleep

Question 55

What can MMN be seen as?

Answer 55

An enlarged N1 (because it is in the same range) A second large negative peak of N1 Attenuation of the P2 peak

Question 56

What are the most common measured parameters of MMN?

Answer 56

Amplitude and latency MMN amplitude and latency variations are common across and within normal subjects and it may be absent in about half of normal listeners

Question 57

When does the MMN typically present?

Answer 57

Negative deflection beginning at the N1 wave latency (about 100 ms) and then peaking later between 200 and 300 ms

Question 58

What are the recording parameters for MMN?

Answer 58

Same as ALR and P300 The three electrodes are generally enough; one inverting, one non-inverting, and one ground Two electro-oculogram electrodes can be used to monitor eye movements Epoch = 100 to 400 ms Like the ALRs, MMN also has very low frequency energy The subject is generally asked to read during the recording but not pay attention to the stimuli

Question 59

What challenges have limited the use of the MMN?

Answer 59

Development of a test protocol that is brief and reliable (now exists with Eclipse) Enhancement of the signal (MMN) to noise (background electrical activity) ratio for the reliable detection of the MMN wave Proven analysis strategies to statistically assure the presence of a response Improved reliability of MMN recordings in a clinical setting across various patient populations including young children

Question 60

What are the potential clinical applications of MMN?

Answer 60

Processing abilities of cochlear implant patients Study of central auditory function in identifying specific auditory deficits including (C)APD Evaluation of patients who are comatose The aging population Patients with Parkinson’s disease Patients with dementia such as Alzheimer’s disease

Question 61

What limits the clinical application of MMN significantly?

Answer 61

Poor SNR, which makes response detection difficult Inter- and intra-subject variability May not be recorded from all normal adult subjects Technical challenges to reliably interpret a response

Question 62

What produces the clearest MMN responses?

Answer 62

Smaller differences b/w standard and deviant stimulus produces clearest MMN and reduces contamination with other late responses

Question 63

What produces the best P300 responses?

Answer 63

Large differences b/w standards and target stimulus produces largest response amplitudes

Question 64

How do you recognize one channel vs two channel recordings?

Answer 64

Contralateral recordings - wave I is not there due to the attenuation of crossing over Number of recordings - 3 could be one channel Cannot do C3 and C4 or T3 and T4 in a single channel recording