Auditory Evoked Potentials

							           Electrophysiology -I
                Chapter 1:
Electric Fields of Synchronous Neural Activity
    Electric Fields of Synchronous Neural
    Activity

 Voltage changes in neocortical nerve cells can be recorded with
  electrodes

 Combined electrical activity recording is called the
  electroencephalogram (EEG)

 EEG changes as a function of brain state and depends on
  electrode location
Frequency Domain Analysis

 Most common strategy for analyzing EEG is signal
  averaging

 Assumes time-locked sequences


 Signal-to-noise ratio is improved by square root of epochs
  averaged
Overview
During stimulation with sound, EEG undergoes
changes in a time-locked fashion in response to sound
changes


These changes are called auditory evoked potentials
(AEPs)


These potentials are averaged: the AEPs add up and
become larger than the background waves (EEG)
Overview
 Time between onset of acoustic change and occurrence of
  peak latency ranges from 1ms to over 500 ms (.5 sec)
 AEPs can be used to obtain thresholds at various audiometric
  frequencies
   Objective testing
   Short-latency is used more for threshold while long-latency is
    used primarily for cognitive processing
 AEPs recorded from the scalp are generated in the cochlea
  (CM,SP,CAP), in the brainstem (ABR), and in the auditory
  cortex (MLR, long latency AEPs)
 AEPs can be classified as either compound action potentials
  or compound postsynaptic potentials
Response to Pure Tones
 Cochlear nerve fibers respond best to specific range of tone freq.
 Response to tone is excitatory (increase in discharge rate above
  the spontaneous)
 Initial response is greater if stimulus is abrupt
 Shorter onset time means less freq. specificity
 Rate of discharge is less important than total number of active
  neurons
Responses to Pure Tones, cont.
 At minimum threshold, a cochlear neuron usually responds to
  only one freq.
 It’s important to remember that AEPs are the activity of
  hundreds of neurons together
 The most commonly used stimulus is the acoustic click
   good synchrony but poor freq. resolution
   Resting Activity
 Most afferent cochlear neurons are spontaneously active


 There is a range of discharge rate from low (<0.5 spikes/sec),
  medium(0.5-18spikes/sec), to high(>18 spikes/sec)

 The most sensitive neurons have high rate of spontaneous discharge


 Spontaneous discharge is most likely from random release of
  neurotransmitter at the hair cell synapse
History
 Hallowell Davis (1896-1992) is called the father of evoked-
  response audiometry, as he was first to use long-latency
  AEPs to estimate hearing thresholds – objective
  audiograms.

 Pauline Davis (Hallowell’s wife) was the first to spot
  repetitive changes in the ongoing EEG (1939). But, until
  signal averaging was introduced they could record only
  ALRs.

 Electrocochleography (ECochG) was established by using
  the works of Portmann, Le Bert, and Aran (1967) in
  combination with the work done by Yoshie and coworkers in
  Tokyo
  History (cont.)
 Jewett and colleagues (1970) are credited with being the first to
  develop auditory brainstem response (ABR) recordings, although
  several researchers from all over the world were working at those
  recordings at that time, including Ernest Moore.

 Selters and Brackmann (1977) published their landmark findings on
  prolonged inter-peak latencies in tumor cases (greater than 1 cm)
  History (cont.)
 Geisler et al., (1958) recorded short-latency cortical evoked
  potentials (now called middle-latency responses, MLR).

 The latency range of MLRs (10-50 ms) overlaps with the
  Postauricular muscle (PAM) potential. This lead to two decades of
  fighting about the true nature of the MLRs. Finally ending when
  Maurice Mendel volunteered to be paralyzed with atropine but, still
  showed MLRs.
                    Classification of AEPs
Exogenus, Mesogenous and Endogenous responses- Harkrider et al., 2001
 Exogenous is often used interchangeably with stimulus-related potentials implying that
  conditions external to the listener (e.g. stimulus intensity or duration) affect exogenous
  potentials. Exogenous AEPs are associated with automatic processing within the CNS.

 Mesogenous AEPs fall somewhere in between exogenous and endogenous as both external and
  internal conditions can affect the response. The division between automatic and controlled
  processing is not as well defined. Functional use of the signal affects response amplitude but is
  not necessary to produce the response. The MLR and 40-Hz response are most often classified
  as mesogenous AEPs.

 Endogenous is often used interchangeably with event-related potential meaning that conditions
  internal to the listener (e.g. attention, vigilance) determine endogenous potentials.
  Endogenous AEPs are related to controlled processing within the CNS potentials (for review,
  see Goldstein and Aldrich, 1999; Picton, 1980).
   Classification of AEPs by latency
 Auditory brainstem response (ABR) peaks denoted by Roman
  numerals; I, II, III, IV, V, VI, VII

 Middle latency response (MLR) are indicated by Po, Na, Pa, Nb,
  and Pb

 Auditory late response (ALR) are indicated by P1, N1, P2, and
  N2.
  Short Latency AEPs
 Latencies of less than 10 ms and the shortest responses are the
  cochlear potentials
   CM and SP
   Generated by hair cells
 CM largely generated by outer hair cells, while the SP is
  generated by inner hair cells
 These help determine if hearing loss occurs at the level of the
  hair cells or higher up
  CAP and ABR
 Dominant neural representatives of the short-latency AEPs
  originate from neural structures peripheral to the auditory
  midbrain
 CAP and ABR little affected by sleep or sedation
   Best results come from patients in either state
 Main use is to obtain threshold information and in differential
  diagnosis of vestibular schwannomas and Meniere’s disease
MLRs and ALRs
 Latencies range from 10-50 ms (but recording is from 0-50 ms)
 Longer-latency MLR responses are affected by sleep and are
  difficult to measure under sedation
 Long-latency AEPs comprise every component with latency above
  50 ms
   Further subdivisions to determine what caused the response to occur
    (i.e. stimulus vs. task)
 Time boundary:
   MLRs and long-latency AEPs border at 50 ms
   Also functions to separate components affected by attention and those
    that are not
Mismatch Negativity (MMN)
 Formed by responses following an unexpected sound, such as
  an infrequent tone of 1000 Hz among a series of more
  frequent tones of 110 Hz
   MMN is also called the deviant or oddball sound
 MMN reflects neural information in the brain that allows
  behavioral detection of a difference in two sounds
   If the subject is required to press a button or count the deviant
    tones, an additional positive peak will occur at a latency of 300
    ms
   The N400 can be elicited later when a word at the end of a
    sentence is perceived as semantically wrong
Classification by Source
 Can be made on the basis of what type of electrical activity
  generated by nerve cells contributes to the AEPs
 When neuron not activated, the potential is -70 mV (the
  resting potential)
 Transient signals can depolarize neurons, called the excitatory
  postsynaptic potential
   Changes are measured by electrodes placed close to a cell
   Depolarizations are small, so many have to occur synchronously for the
    electrodes to measure the changes
 Nerve cells produce slow localized membrane voltage changes
  (postsynaptic potentials) and fast voltage changes (action
  potentials or spikes)
  Synchronous Activity in Spatially
  Aligned Structures
 If large number of neurons are activated at the same time, then changes
  in membrane and action potential firing rates occur together across
  neurons.

 The corresponding currents add up in phase and become so large they
  can be detected at the scalp

 Only structures with spatial alignment of neurons with the same
  orientation of their current-producing parts produce far-field potentials

 Action potentials are produced in axons.
   Spatially aligned axons can produce far-field potentials
 If all axons from a group of cells are oriented in a parallel fashion
  (as in a nerve),they form a nerve that can produce far-field
  potentials

 Auditory nerve is made up of about 30,000 parallel nerve fibers


 When activated by a transient sound a compound action
  potential (CAP) is produced
 ABRs
 A typical ABR has a sequence of up to 7 vertex positive
  waves with negative valleys between
 Wave peaks are typically labeled with Roman numerals
 Wave I & II are the compound action potentials of the
  auditory nerve (N1 and N2)
 Peaks with numbers from wave III up to and including
  wave V likely are generated sequentially in the auditory
  brainstem
    ABR Recording
 Typically, the recording of ABR is done in a way that slow activity
  (below 100Hz) is filtered out. This is the activity that is composed of
  PSPs (but also of muscle potentials)
 Synchronous activity and a spatial alignment determine the amplitude
  of the various AEP components:
    The more fibers that are simultaneously active, the larger the
     amplitude
 Higher stimulus levels typically activate more fibers and produce
  larger AEP amplitudes
 Another factor is the change in surrounding tissue resistance
    The largest response amplitudes are found for the most abrupt and
     largest changes in resistance
AEPs of Cortical Origin
 There is a tonotopic map, where the CF is systematically
  mapped along the cortical surface
 The sites of depolarization are called sinks, because of the
  inward current of positive ions
 The sites where the current leaves the dendrites is called a
  source
 Amplitude of Cortical AEPs
 If voltage is spread out over larger surface then amplitude
  is reduced

 Cancellations from opposing polarity contributions can
  also reduce amplitude

 Peak overlap can also affect amplitude
  Latencies of Cortical Periods
 The cochlear traveling wave delay amounts to approx 2
  periods of the tone and becomes important for LF
  components
   The delay is .5 ms for 4 kHz but reaches 4 ms for 500 Hz
 The time it takes for neural activity to go from cochlea to
  cortex
   Includes synaptic delays (6 synapses with a delay of 1-2 ms each)
    and neural conduction delays
   Adds up to 17 ms for the Na component of the MLR, considered
    the first sign of cortical activity
   Latencies of Cortical Periods
 The latencies of the MLRs go up in steps of 10-15 ms
 These latencies become understandable if one assumes
  buildup times for the PSPs (about 4 ms) and slow
  intracortical neural conduction (1 m/s)
 After Pb and P1, the latency differences between subsequent
  peaks are too long to be the result of large conduction delays
  and a single synaptic delay
 A solution is by neural activity looping around in
  reverberant circuits in cortex and thalamus and
  synchronizing about every 50-100 ms
   Latency of Cortical Potentials
 Cochlear traveling wave delay amounts to 2 periods of the
  tone. (Exp: delay for 4KHz is 1/4000 X 2 = 0.5ms)

 Time it takes for neural activity to go from cochlea to
  cortex (includes six synaptic delays of 1-2 ms each and
  neural conduction delays)

 Buildup times for postsynaptic potentials(about 4ms) and
  slow intracortical neural conduction (1m/s)
The 10-20 international electrode system