Auditory Long Latency Evoked

Potentials

Presenter: Niraj KumarModerator: Ms Rashmi Bhat 1

CONTENTS

1. Introduction2. Generators3. Recording parameters4. Factors affecting5. Protocol6. Clinical utility7. References

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INTRODUCTION

• It is event-related potentials (ERPs) occurring 50 to 300 ms following stimulus onset;

namely, the P1-N1-P2 complex.

• These auditory evoked potentials are brain responses that are evoked by the presentation of auditory stimuli and processed in or near the auditory cortex, and they are therefore referred to as cortical auditory evoked potentials (CAEPs).

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• the P1-N1-P2 complex is traditionally considered to be comprised of slow components (50-300 ms).

• ERPs can also be classified as sensory evoked, processing contingent or movement related.

• Sensory-evoked components are obligatory, exogenous potentials, meaning their amplitudes and latencies are primarily determined by physical and temporal characteristics of the stimulus, such as intensity or frequency.

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• P1, N1 and P2 are considered to be sensory-evoked potentials.

• The P1-N1-P2 complex while composed of sensory-evoked components is not purely sensory. It is affected by attention and can be modified by auditory training.

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Historical Overview:

• The LLR was actually the first auditory electrical response to be recorded from CNS.

• P1-N1-P2 complex was discovered in 1939 by P.A. Davis, who described changes in the electroencephalogram (EEG) in response to sound in EEG as ‘K-complex.

• As electric computers and signal averaging become available in some of the premiere auditory research labs in the early 1960s, a proliferation of studies of ALLR as “an accurate obj. method of evaluating auditory acuity in man”

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• By the second half of the 1960s development of instrumentation of specifically for clinical measurement of late auditory potentials was reported in the scientific literature.

• Davis designed a device called HAVOC (histogram, average, and ogive computer) and coupled it to GATES (generators of acoustic transients) and a system of amplifying and filtering the incoming EEG.

• With the help of these combination of equipment high quality waveform were recorded.

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• Historically, brief stimuli such as clicks and tone bursts have been used to evoked the P1-N1-P2 complex.

• However these responses can also be elicited by changes in an ongoing sound such as intensity and frequency modulation of a sustained tone or in response to acoustic changes in ongoing, more complex sounds, such as speech (Martin, Lee, and Kurtzberg)

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COMPONENTS AND GENERATORS OF LLR

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Components:The P1-N1-P2 Complex:The P1-N1-P2 Complex:

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• P1, N1 and P2 are typically recorded together, at least in adults; When elicited together, the response is referred to as the P1-N1-P2 complex.

• N2 might or might not be present even in Normal's, so not much importance is given for that.

• The specific latencies and amplitudes of each peak depend on the acoustic characteristics of the incoming sound and on subject factors.

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• P1, the first major component of the P1-N1-P2 complex, is a vertex-positive voltage deflection that often occurs between 55 to 80 ms. after sound onset.

• P1 is usually small in amplitude in adults (typically

<2 uv) but is large in young children and may dominate their response.

• Generators of P1 have traditionally been identified in the primary auditory cortex and specifically Heschl’s gyrus.

• P1 is typically largest when measured by electrodes over midline central to lateral central scalp regions. 14

• Generation of P1 may actually be more complex than early studies suggest, and additional regions that may contribute to this response, including the hippocampus, planum temporale, and lateral temporal cortex have been identified.

• Recent work has also focused attention on the importance of neocortical areas to P1.

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• N1 appears as a negative peak that often occurs between 90 to 110 ms after sound onset.

• N1 latency can be longer in some cases, depending on the duration and complexity of the signals used to evoke the response.

• N1 follows P1 and precedes P2.

• Compared to P1, N1 is relatively large in amplitude in adults (typically 2-5 uv, depending on stimulus parameters).

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• In young children, however, N1 generators may be immature and therefore the response absent, particularly if stimuli are presented rapidly.

• N1 is known to have multiple generations in the primary and secondary auditory cortex and is therefore described as having at least three components.

• The first is fronto-central negativity (N11) that is

generated by bilateral vertical dipoles in or near the auditory cortex in the superior portion of the temporal lobe and is largest when measured by electrodes near the vertex.

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• It is thought that this component may reflect attention to sound arrival, the reading out of sensory information from the auditory cortex, or the formation of a sensory memory of the sound stimulus in the auditory cortex

• The second component is known as the T complex.

• It is a positive wave occurring approximately 100 ms after sound onset, followed by a negative wave occurring approximately 150 ms after sound onset.

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• The T complex is generated by a radial source in the secondary auditory cortex within the superior temporal gyrus and is therefore largest when measured by electrodes over mid temporal scalp regions.

• While it has been proposed that the T complex may involve a simple inversion of the N11 component. .

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• The third component is a negativity occurring approximately 100 ms after sound onset that is best recorded near the vertex using long inter-stimulus intervals.

• The generator of the component is unknown, and it may not be specific to sound.

• In general recorded from electrodes in midline central scalp locations.

• For this reason, it is wise to include electrodes over lateral temporal sites to optimally pick up contributions from the secondary auditory cortex.

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• P2 is a positive waveform that occurs approximately 180 ms after sound onset.

• It is relatively large in amplitude in adults (approx. 2-5 uv or more) but may be absent in young children.

• P2 is not as well understood as the P1 and N1 components, but it appears to have generators in multiple auditory areas including the primary auditory cortex, the secondary cortex and the mescencephalic reticular activating system.

• It has been hypothesized that P2 (or at least the magnetic version P2m) is generated from multiple sources, with a center of activity near Heschl’s gyrus.

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• P2 is best recorded using electrodes over midline central scalp regions.

• As with N1, P2 does not appear to be a unitary potential, meaning that it is likely that there are several component generation processes occurring in the time-frame of P2, these components may be different for different age groups and subject states.

• P2 latencies are consistently reported to be

delayed in older adults.

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Component Classification Generators

LLR P60

(P1)

(a) Exogenous

(b) Late potential

(c) Long latency evoked

potential

- Late thalamic projections into Auditory cortex

- Specific sensory system

N 100 (N1) (a) Exogenous

(b) Late potential

(c) Long latency RESP

-Supra temporal auditory cortex

-Non specific poly sensory system

P160 (P2) (a) Exogenous

(b) Late potential

-Lateral-frontal supra temporal auditory cortex

P200 (N2) (a) endogenous

(b) Late potential

(c) Long latency

-Supra temporal auditory cortex

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P300 - Endogenous

- Cognitive response

-Hippocampus & Frontal lobe

N400 Endogenous -Multiple parallel and sequential generators in the

cortex

P500 Endogenous -Multiple parallel and sequential generators in the

cortex

T-Complex Exogenous -Posterior temporal lobe

CNV Endogenous -Thalamic nuclei midbrain (Redicular formation)

Processing

negativity

Endogenous -Auditory cortex

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RECORDING PARAMETER USED for THRESHOLD ESTIMATION

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Recording parameters for supra threshold applications

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Summary of recording parameters for supra threshold applications

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Recording Factors:• The P1-N1-P2 complex and threshold estimation.

• Clinical judgment should be used to determine the most efficient response testing, it is often wise first to obtain thresholds for a high frequency in each ear and a low frequency in each ear and subsequently to fill in other frequencies provided the patient remains quiet, alert, and cooperative.

• It is not always necessary to begin testing at high intensities (e.g. 80 dBpeSPL), and it may be more efficient to begin with stimuli of low to moderate intensity (e.g. 20-40 dB peSPL).

• If a response is present at low intensities, it is not necessary to test at higher intensities.

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Factor Affecting

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FACTORS AFFECTINGStimulus Factors•While it is possible to obtain P1-N1-P2 using a variety of stimuli, including clicks, tone bursts, complex sounds, and speech, much of the parametric literature has focused on click and/or tone burst stimuli.

•It is likely that many of the same principles will hold for complex stimuli such as speech, however, there might also be complex interactions among the various acoustic parameters contained within the speech signal that affect the neural detection and processing of the speech signal differently than simple stimuli.

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Type of stimulus:

•Tonal stimulus: tonal stimulus have been typically used to elicit ALR (Davis, Bowers, &Hirsh,1968)

•Amplitudes for the N1 and P2 components of the ALR are larger, and latencies longer for low frequency tonal signal in comparison to high frequency signal (Alain, Woods, & Covarrubias, 1997; Jacobson et al., 1992; Sugg & Polich,1995)

•Some components of ALR (e.g., p100 & N250) show larger amplitudes and shorter latency for complex tones than for single frequency tonal stimuli.

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Speech:

• Speech stimulus are quiet efficient in eliciting the ALR.

• Amplitude of the N1 to P2 complex is larger speech sounds than for single freq. tonal stimuli, but latency values for the N1 and P1 are usually earlier for tonal versus speech stimuli (Ceponiene et al., 2001)

• Natural vowel sounds generate ALR components (N1 and later waves) that are detected with considerably larger amplitude from the left hemisphere, whereas tonal stimuli produce symmetrical brain activity (Szymanski., 1999)

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Intensity:

•P1-N1-P2 amplitude increases with stimulus intensity in an essentially linear manner, though the amplitude-intensity function may saturate at intensities exceeding approximately 70 dB normal hearing level (nHL), particularly when short ISIs are used.

•Amplitude of the N1 and P2 wave does increase in parallel for low and moderate levels.

•For higher signal levels, how ever, P2 amplitude continues to increase while amplitude of N1 decreases( Adler & Adler., 1989)

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• Frequency:

• As stimulus frequencies increases, amplitude of the complex decreases even when loudness is controlled. Latencies increase as frequency decreases particularly when high stimulus intensities are used.

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• Rate and ISI:• P1-N1-P2 amplitude increases as the rate of

stimulus presentation decreases until the ISI is approximately 10 seconds.

• At low stimulus intensities, amplitudes asymptote or level off at shorter ISIs, while at high stimulus intensities, amplitude increases continue to occur even beyond ISIs of 10 seconds.

• The most pronounced effect of longer ISI times is within 1 to 6 seconds.

• There is little change in latency as stimulus rate changes.

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• Stimulus Duration:

• Amplitude increase as stimulus duration increases up to approximately 30 to 50 ms but decreases when rise and fall times exceed 50 ms

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• Ears:

• Amplitudes are larger for binaural than monaural stimuli. Latencies are similar for monaural and binaural stimuli however, N1 shows shorter latency when recorded contra laterally than ipsilaterally.

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Number of Stimuli:

•Response amplitude decreases as the number of stimuli presented increases.

•This effect is maximal over approximately the first five stimuli presented and is most likely due to neural refractoriness.

•This effect is stimulus specific, because if a new sound is introduced. N1 amplitude increases by an amount proportional to the magnitude of stimulus change.

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Subject Factors:Subject State:•Unlike the auditory brainstem response, the P1-N1-P2 complex can be affected by subject state. For example, attending or ignoring a competing audio signal can increase N1 and P2 amplitudes, particularly for low intensity sounds.

•Morphology is also dramatically affected by sleep, but in a complex manner.

•The N1 component may be attenuated in sleep, and an additional negativity emerges at approximately 300 ms. Changes in morphology vary as a function of sleep state.

•These sleep-related changes in morphology can significantly increase the variability of the response. For this reason, P1-N1-P2 is typically recorded while subjects are awake.

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Maturation and Aging:

•The morphology of the P1-N1-P2 complex is affected by maturation. The complex changes dramatically over the first 2 years of life.

•The complex begins as a large P1 wave is followed by a broad, slow negativity occurring near 200 to 250 ms after the onset of the sound.

•A P1-N1-P2 complex similar to that of adults is not seen until approximately 9 to 10 years of age unless stimuli are presented at a very slow rate.

•Refractory changes occurring between the ages of 6 and 18 years of age can affect waveform morphology.

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• Responses recorded at midline central electrode sites, reflecting contributions from primary auditory cortex, mature more rapidly than those from lateral temporal sites, which reflect maturation of secondary auditory cortex.

• These potentials continue to mature until the second decade of life and then change again with old age. Prolonged N1 and P2 latencies and amplitude changes have been reported in aging adults.

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• ALR latency decreases and amplitude increases as a function of age during childhood, up until about age 10 years (Weitman, Fishbin & Graziani, 1965; Whiteman & Graziani, 1968).

• Some investigators have described the latency increase and also amplitude decrease, with advanced age (Callaway, Halliday, 1973; Goodlin et al. 1978; Roth & Kopell, 1980).

• James et al. (1997) examined maturational changes in spectro-temporal features of central and lateral N1 components of the auditory evoked potential to tone stimuli presented with a long stimulus onset asynchrony.

Peak latencies of both components decreased with age.

Peak amplitude also decreased with age consequently, the difference between the lateral N1 and the central N1 amplitude also decreased with age.

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• Deepa (1997) studied the age related change in ALLR. The LLR waveforms achieved at 70, 50 and 30 dBnHL.

was significant difference between children and adults for all the peak latency and for amplitude.

There was no significant difference between males and females for adult and children.

There was a significant difference only in N1 peak latency 7-8 years group, P2 latency between 8-9 years group and P2 latency between 7-9 years of age group.

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Gender:

•There is some evidence that N1 latencies are shorter and amplitudes larger in women than in men.

•Additionally, amplitude-intensity functions have been reported to be steeper for females than males.

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Handedness:•There was no handedness effect seen for the N1 amplitude, latency of N1 component was shorter for left handed versus right handed subjects.

•P2 amplitude values were smaller in left hand users.

•Handedness was not a factor in N2 amplitude.

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State of arousal and sleep:•Sleep has pronounced effect on LLR

•There are significant but differential changes in the major ALR waves as the person becomes drowsy and falls asleep.

•Progressively diminished amplitude of N1 is seen from wake to sleep state.( Campbell & Colrain, 2002)

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• During the transition to deep sleep P2 amplitude increases (Campbell et al.,1992).

• The over all amplitude of N1 and P2 may remain reasonably stable across sleep stages (de Lugt, Loewy, & Campbell, 1996)

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Attention:•N1 and P2 waves of ALR are altered differentially when the subject is paying close attention to the stimulus or listening for a change in some aspect of the stimulus.

•N1 wave, an increase in attention causes greater amplitude.

•The P2, appears to diminish with increased attention by the subject on the signals (Michie et al., 1993)

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Drugs:•Sedatives: ALR variability is increased.

•Measurement of ALR and P300 responses under sedation is ill advised as validity of the findings may be compromised.

•Opioid analgesic like Morphine, has no apparent effect on ALR or ABR.

•Droperidol produces prolongation of P1 and N1 components by about 10ms and also reduction in amplitude seen.

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• Anesthetic agent: the results across studies are varying greatly.

• Generally concluded that there is little effect on the latency of ALR components, but there might be amplitude reduction seen as anesthesia is given.

• Alcohol: amplitude of ALR is reduced by acute alcohol intoxication.

• Latency of N1 component was seen to be prolonged after alcohol ingestion, where as P2 latency was unchanged( Teo & Ferguson, 1986)

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Applications of CAEPs:

• P1-N1-P2 complex signals the cortical detection of an auditory event, can be reliably recorded in groups and individuals, and is highly sensitive to disorders affecting the central processing of sound.

• Therefore, P1-N1-P2 response are typically used by audiologists to estimate threshold sensitivity, especially in adults; to index changes in neural processing with hearing loss and aural rehabilitation, and to identify underlying biological processing disorders in people with impaired speech understanding.

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• Estimation of hearing threshold• Neurodiagnosis• Selection of amplification• Efficacy of amplification• Neural maturation

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Estimation of Hearing Threshold: • The P1-N1-P2 complex is highly sensitive to hearing

loss and P1-N1-P2 and behavioral thresholds typically fall within approximately 10 dB of each other. Larger discrepancies have been reported, however, this is most likely due to lack of control over subject state.

• The N1 is used in some clinical settings for the assessment of threshold in adult compensation cases and medico-legal patients.

• Similar to the intensity functions for the ABR, N1 latency increases and amplitude decreases as the intensity of the stimulating signal approaches threshold.

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The P1-N1-P2 complex has several advantages over ABR for threshold estimation:

1.It can be elicited by longer-duration, more frequency-specific stimuli than the ABR and thus provides a better estimate of the audiogram.

2.It involves less data collection time because cortical responses are larger in amplitude and thus easier to identify than the ABR.

3.It is mores resistant to electrophysiological noise.

4.It provides a measure of the integrity of the auditory system beyond the brainstem.

5.It can be evoked by complex stimuli, such as speech, and can therefore be used to assess cortical speech detection.

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• It is for these reasons that the P1-N1-P2 complex is considered to be superior to the ABR for threshold estimation.

• Yet in the United States the P1-N1-P2 is rarely used for this purpose, and for the most part has been replaced by the ABR.

• This is likely because the largest population of patients requiring physiological estimates of hearing sensitivity is infants and young children, who need to be sleeping and/or sedated during testing.

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Changes in neural processing with Hg loss and rehabilitation

• One of the more recent applications of CAEPs is monitoring experience-related changes in neural activity.

• Because the central auditory system is plastic, that is, capable of reorganization as a function of deprivation and stimulation, CAEPs have been used to monitor changes in the neural processing of speech in patients with hearing loss and various forms of auditory rehabilitation, such as use of hearing aids,

cochlear implants, and auditory training. 66

Hearing Loss:

• CAEPs have been used to examine changes in the neural processing of speech in simulated and actual hearing loss.

• Martin and colleagues examined N1, MMN (along with P3), and behavioral measures in response to the stimuli /ba/ and /da/ in normally hearing listeners when audibility was reduced using high-pass, low-pass, or broadband noise masking, partially simulating the effects of high-frequency, low frequency, and flat hearing loss, respectively.

• In general, N1 amplitude decreased and latency increased systematically as audibility was reduced. 67

• This finding is consistent with the role of N1 in the cortical detection of sound.

• In contrast, the MMN showed decreasing amplitude and increasing latency changes beginning only when the masking noise affected audibility in the 1000- to 2000- Hz region, which is the spectral region containing the acoustic cues differentiating /ba/ and /da/.

• This finding is consistent with the role of MMN in the cortical discrimination of sound.

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• Similar results have been obtained in individuals with sensorineural hearing loss.

• That is P1-N1-P2 latencies increase and amplitudes decrease in the presence of hearing loss, and MMN latencies increase and amplitudes decrease as behavioral speech discrimination becomes more difficult.

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Hearing Aids:

• ERPs can be reliably recorded in individuals, even when the sound is processed through a hearing aid. Yet to date only a few studies have examined ERPs in patients using hearing aids. In earlier studies, cortical ERPs were recorded in aided versus un-aided conditions in children with varying degrees of hearing loss. These studies showed good agreement with the neural detection and audibility of sound.

• That is, in unaided conditions (subthreshold) the equivalent of the P1-N1-P2 was a clear obligatory P1 response, followed by a prominent negativity (N200-250).

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• Korezak, Kurzberg and Stapells also demonstrated that hearing aids improve the detectability of CAEPs (as well as improving behavioral discrimination performance), particularly for individuals with severe to profound hearing loss.

• Even though most of the subjects with hearing loss showed increased amplitudes, decreased latencies, and improved waveform morphology in the aided conditions, the amount of response change was quite variable across individuals.

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• This variability may be related to the fact that a hearing aid alters the acoustics of a signal, which in turn affects the evoked response pattern.

• Therefore, when sound is processed through a hearing aid, it is necessary to understand what the hearing aid is doing to the signal. Otherwise erroneous conclusions can be drawn from waveform morphology.

• Despite the latency and amplitude changes that can occur with amplification, most subjects with hearing loss tested by Korezak and colleagues still showed longer peak latencies and reduced amplitudes than a normally hearing group.

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Cochlear Implants:• CAEPs can be recorded from individuals with

cochlear implants (Friesen and Tremblay, in press).

• Latencies and amplitudes of N1 and P2 in “good” implant users are similar to those seen in normally hearing adults but are abnormal in “poor” implant users and P2 in particular may be prognostic in terms of separating “good” from “poor” users.

• CAEPs can be recorded in implant users in response to sound presented either electrically (directly to the speech processor) or acoustically (presented via loud-speaker to the implant microphone), however, stimulus-related cochlear implant artifact can sometimes interfere (Martin, in press; Friesen and Tremblay, submitted). 73

Auditory training:

• Even if the central auditory system is capable of processing the signal, the individual’s ability to integrate these new neural response patterns into meaningful perceptual events may vary. For this reason, CAEPs have been used to examine the brain and behavior changes associated with auditory training.

• The objective of auditory training is to improve the perception of acoustic contrasts. In other words, patients are taught to make new perceptual distinctions. When individuals are trained to perceive different sounds, changes in the N1-P2 complex and the MMN have been reported.

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Other Applications:• In addition to hearing loss, CAEPs are being used to

explore the biological processes underlying impaired speech understanding in response to various types of sound and in various populations with communication disorders. In some cases, the motivation is to learn more about the relationship between the brain and behavior.

• Abnormal neural response patterns have been recorded in children with various types of learning problems.

• Older adults with and without hearing loss and individuals with auditory neuropathy or dyssynchrony also show abnormal neural response patterns.

• Because CAEPs reflect experience-related change in neural activity, CAEPs are now being used to examine children with learning problems undergoing speech sound training and other forms of learning such as speech sound segregation and music training.

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Conclusion:Conclusion:

• Cortical auditory evoked potentials (CAEPs) are brain responses generated in or near the auditory cortex that are evoked by the presentation of auditory stimuli.

• The P1-N1-P2 complex signals the arrival of stimulus information to the auditory cortex and the initiation of cortical sound processing.

• Taken together, these CAEPs provide a tool for tapping different stages of neural processing of sound within the auditory system, and current research is exploring exciting applications for the assessment and remediation of hearing loss.

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Thank you….Thank you….

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