rob van der willigen

Q ui ckTi me™ and a TI FF (LZW) decompressor are needed to see thi s pi cture.

Rob van der WilligenRob van der Willigen

http://www.mbfys.ru.nl/staff/r.vanderwilligen/CNP04/COLLEGES/2008/P5/http://www.mbfys.ru.nl/staff/r.vanderwilligen/CNP04/COLLEGES/2008/P5/AudPerc_2008_P5_Anatomy_Physiology_V1.pptAudPerc_2008_P5_Anatomy_Physiology_V1.ppt

Auditory PerceptionAuditory Perception

Q ui ckTi me™ and a TI FF (LZW) decompressor are needed to see thi s pi cture. General Outline P4 General Outline P4

P4: Auditory Perception

- Cochlear Mechanotransduction

- Physiology of the Auditory Nerve

P5: Auditory Perception


Sensory Coding and Transduction

Cochlear Mechanotransduction

Mammalian Auditory Pathway

Recapitulation previous lectures


6 critical steps


Recapitulation previous lectures


Peripheral Auditory Peripheral Auditory SystemSystem


The Organ of Corti mediates mechanotransduction:

The cochlea is filled with a watery liquid, which moves in response to the vibrations coming from the middle ear via the oval window.

As the fluid moves, thousands of hair cells are set in motion, and convert that motion to electrical signals that are communicated via neurotransmitters to many thousands of nerve cells.


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BM

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Cochlear nonlinearityCochlear nonlinearityActive processing of

sound

The response of the BM at location most sensitive for ~ 9 KHz tone (CF).The level of the tone varied from 3 to 80 dB SPL (iso-intensity contours). Figure 3. Vertical lines mark the responses to a tone at either 4.5 or 9 kHz.

BM input-output function for a tone at CF (~9 kHz, solid line) and a tone one octave below (~4.5 kHz) taken from the iso-intensity contour plot.

INPUT level (dB SPL)OU

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CF= 9 kHz

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Frequency [kHz]


Cochlear nonlinearityCochlear nonlinearityHair cell function

IHC: Principal Sensor

Sends frequency-specific information to the brain based on the vibratory pattern of the basilar membrane

OHC: Effector (Cochlear amplifier)

Provides frequency-specific energy to the basilar membrane.

10 m


Cochlear nonlinearityCochlear nonlinearityHair cell

physiology

IHCs are responsible for turning the movement of the basilar membrane into changes in the firing rate of the auditory nerve.

OHCs are anatomically and physiologically quite different from inner hair cells.

OHCs act as tiny motors that amplify the mechanical movement of the basilar membrane.

10 m


1. Nucleus2. Stereocilia3. Cuticular plate4. Radial afferent ending (dendrite of type I neuron)5. Lateral efferent ending6. Medial efferent ending7. Spiral afferent ending (dendrite of type II neuron)

Cochlear nonlinearityCochlear nonlinearityHair cell anatomy

IHC OHC


Cochlear nonlinearityCochlear nonlinearityIHC Innervation

The IHC is synaptically connected to all type I spiral ganglion neurons forming the radial afferent system (blue) going to the cochlear nuclei (CN).

The lateral efferent system (red) arising from small neurons in the ipsilateral lateral superior olivary complex (LSO) brings a feedback control to the IHC/type I afferent synapse.


Cochlear nonlinearityCochlear nonlinearityOHC Innervation

OHC synapses with a few (at least in basal and mid-portions of the cochlea) small endings from type II spiral ganglion neurons, forming the spiral afferent system (green).

In turn, large neurons of the medial efferent system (red), from both sides of the medial superior olivary complex (MSO), form axo-somatic synapses with the OHC.


Cochlear nonlinearityCochlear nonlinearityCochlear

Innervation

type 1

type 2

Inner hair cells: Main source of afferent signal in auditory nerve. (~ 10 afferents per hair cell)

Outer hair cells: Primarily receiving efferent inputs.

Type I neurons (95% of all ganglion cells) have a single ending radially connected to IHCs.Type II small,

unmyelinated neurons spiral basally after entering the organ of Corti and branch to connect about ten OHCs, in the same row.


Cochlear nonlinearityCochlear nonlinearityTotal Cochlear Innervation

Each IHC is innervated by approximately 10 Type-I 8th nerve fibers.

Each Type II 8th nerve fiber synapses with about 10 OHCs but each outer hair cell synapses with several nerve fibers.

There are also approximately 900 efferent fibers (fibers that come into the cochlea from more central locations).

Innervation is both Ipsilateral and Contralateral.


Cochlear nonlinearityCochlear nonlinearityIn Vivo Cochlear

Innervation

Cochlear Innervation by Temporally Regulated Neurotrophin ExpressionThe Journal of Neuroscience, 2001, 21(16):6170–6180


Cochlear nonlinearityCochlear nonlinearityHair cell numbers and life

timeIn the human cochlea, there are 3,500 IHCs and about 12,000 OHCs.

This number is low, when compared to the millions of photo-receptors in the retina or chemo-receptors in the nose! In addition, hair cells share with neurons an inability to proliferate they are differentiated.

Thus, the final number of hair cells is reached very early in development (around 10 weeks of fetal gestation); from this stage on our cochlea can only lose hair cells.


Cochlear nonlinearityCochlear nonlinearityHair cell function

IHC: Principal Sensor

Sends frequency-specific Information to brain based on the vibratory pattern of the basilar membrane

OHC: Effector (Cochlear amplifier)

Provides frequency-specific energy to the basilar membrane..

10 m


Cochlear nonlinearityCochlear nonlinearityFunctional relationship IHC and

OHC


Cochlear nonlinearityCochlear nonlinearity

The response of the healthy mammalian basilar membrane (BM) to sound (1) is sharply tuned,

(2) highly nonlinear, and

(3) compressive.

Damage to the outer hair cells (OHCs) results in changes to all three attributes: in the case of total OHC loss, the response of the BM becomes broadly tuned and linear.Many of the differences in auditory perception and performance between normal-hearing and hearing impaired listeners can be explained in terms of these changes in BM response.

Loss of OHCs affects nonlinearity


Cochlear nonlinearityCochlear nonlinearity

Cochlea is highly compressive:

In the mid-level region a change in input sound pressure of 40 dB (from 40 to 80 dB SPL) leads to a change of slightly less than 10 dB in the velocity of the BM.

A change in velocity by a factor of 10 corresponds to a 20-dB change in response.

This is equivalent to a compression ratio of approximately 5:1, compared to the essentially linear (1:1) relationship between sound pressure and BM velocity in the case of the post mortem cochlea.

GAIN equals Amplitude of motion divided by

Amplitude of stimulus pressure

No nonlinearity post mortem

Basilar-membrane intensity-velocity coding functions for a chinchilla using a tone at the 10 kHz

Rugero et al. Rugero et al. (1997)(1997)


Cochlear nonlinearityCochlear nonlinearityOHC motor driven by Tectorial membrane

OHCs have a unique type of motility. They convert receptor potentials into cell length changes at acoustic frequencies.

The activation of the outer hair cell motor driven by the motion of the tectorial membrane into which the tips of the tallest stereocilia are inserted.

OHCs contract when depolarized (-60 mV)OHC lengthen when hyperpolarized (-70 mV)

A second class of sensory receptors, the outer hair cells couple visco-elastically the reticular lamina to the basilar membrane through their supporting Deiters' cells (yellow).


Cochlear nonlinearityCochlear nonlinearityOHC motor driven by the Tectorial

membrane

A virtuous loop. Sound evoked perturbation of the organ of Corti elicits a motile response from outer hair cells, which feeds back onto the organ of Corti amplifying the basilar membrane motion.


Cochlear nonlinearityCochlear nonlinearityOHC Boost BM vibrations at Vmax

OHCs are proposed to generate positive (cell-body shortening)forces during maximum BM velocity toward scala media (a) and

negative (cell body lengthening) forces during maximum BM velocity toward scala tympani (b)

K. E. Nilsen and I. J. Russell. K. E. Nilsen and I. J. Russell. (2000)(2000)

Scala Mediaa

b Vmax

Vmax

Scala Media

Scala Tympani

Scala Tympani


Cochlear nonlinearityCochlear nonlinearityOHC

Activity

OHC activity:

Increases sensitivity (lowers thresholds)

Increases selectivity (reduces bandwidth of auditory filter)

Produces a non-linear amplitude response

Produce Otoacoustic emissions


Cochlear nonlinearityCochlear nonlinearityNonlinearity is an active

process

From Pickles (1988)

Cochlear Tuning is sharp and the responses are highly nonlinear

Base Apex


Cochlear TransductionCochlear TransductionIHC mechanotransduction



(1) Kinocilia / Stereocilia Linked

(2) Displacement Opens K+ Channels

(3) Depolarization (inward current) Less negative membrane potential→ release of glutamate

(4) K+ flows through cell

(5) Vesicle release in synaptic cleft Glutamate → increase spike rate in auditory nerve

Positive displacement

Depolarization



(1) Kinocilia / Stereocilia Linked

(2) Displacement Closes K+ Channels

(3) Hyperpolarization (outward current) Less positive membrane potential→ inhibits release of glutamate

(4) K+ flows ceases

(5) Decreases spike rate in auditory nerve

Negative displacement

Hyperpolarization


Cochlear nonlinearityCochlear nonlinearityHair cell anatomy


To enhance frequency tuning:

Mechanical resonance of hair bundles: Like a tuning fork, hair bundles near base of cochlea are short and stiff, vibrating at high frequencies; hair bundles near the tip of the cochlea are long and floppy, vibrating at low frequencies.

Electrical resonance of cell membrane potential.




Very fast (responding from 10 Hz – 100 kHz10 sec accuracy).


Cochlear TransductionCochlear TransductionIHC stimulus response relationship

At low frequencies the membrane potential of the IHC follows every cycle of the stimulus (AC response, top).

At high frequencies the membrane potential is unable to follow individual cycles, but instead remains depolarized throughout the duration of the stimulus (DC response, bottom).

At intermediate frequencies the membrane potential exhibits a “mixed” AC + DC response.

Inner hair cells are thus responsible for turning mechanical movement of the basilar membrane into membrane potential changes NOT action potentials.



Reflect s Ca++ entry into the cell.

Motion of the Kinocilia modulates K+ influx, which causes Ca++ influx, but there is also background Ca++ leakage, so vesicles are released even without sound input.

The release rate varies among synaptic terminals, resulting in variation in sensitivity.

The auditory neurons that synapse on the IHC use AMPA receptors and have a very short time constant (~200 μsec).

Vesicle release


Cochlear TransductionCochlear TransductionIHC activity and Action Potentials

Action Potentials are generated in the auditory nerve cells

NOT in the IHCs

and mostly when the basilar membrane moves upward.


Cochlear nonlinearityCochlear nonlinearitynonlinearity is an active

process

Depends on the endolymphatic cochlear batteryFurosemide decreases [K+], stops process.

Not present in post-mortem cochlear preparations (in vitro). Requires metabolic energy.


Stria-Vascularis (dark red area) “battery” maintains the potential difference and powers the active process in a living animal.

SV

ST

SM

Disruption of electrical equilibrium via:

drugsElectrical stimulationblood supply

effects hearing

Cochlear nonlinearityCochlear nonlinearityEndolymphatic cochlear battery

SM Scala mediaST Scala tempanySV Scala vestibuli

Drawing from www.the-Drawing from www.the-cochlea.infocochlea.info

0 mV

0 mV

K+ low

K+ low


Cochlear TransductionCochlear TransductionIHC versus OHC mechanotransduction

Fluid movement bends the hairs of the IHCs.

Tectorial membrane shearing (b) moves the tallest stereocilia that are inserted in the tectorial membrane.



The OHCs are depolarized in the same way as the IHCs

When an OHC depolarizes, the entire cell contracts and shortens, thereby literally pulling the basilar membrane towards the cell, because the OHCs are affixed to thebasilar membrane through the supporting Deiter cells

This phenomenon, which is known as electromotility, causes the OHCs to actively feed mechanical energy back into the system!

Electromotility it is powered by a specialized protein (Prestin), lodged in the OHCs’

membrane


The Auditory NerveThe Auditory NerveAnatomy

Neural information from inner hair cells: carried by cochlear division of the VIII Cranial Nerve, 30,000 myelinated fibers in Humans (cats have 50,000).

The auditory nerve is formed by the axons of spiral ganglion cells, of which there are two types .

Type I neurons have myelinated cell bodies and innervate IHCs. In humans, each IHC forms synaptic terminals with about 10 Type I fibers.

Type II neurons are unmyelinated and innervate many OHCs longitudinally distributed along the cochlea.

Both types of neurons project to the cochlear nucleus, albeit to different types of cells.

Type I neurons form the vast majority of the AN population (95% in cats). All existing physiological data are from Type I neurons.


The Auditory NerveThe Auditory NerveFunction

The auditory nerve conveys information about sound from the ear to the brain, which decodes this information to control behavior.

Data on responses of the auditory nerve to sound are useful both to infer the processing performed by the ear, and to assess the brain’s performance in various perceptual tasks against that of an ideal observer operating on auditory-nerve information.


The Auditory NerveThe Auditory NerveSpontaneous rate / All-or-none potentials

Depolarizing currents exceeding a threshold produce a large, “all-or-none” action potential which travels along the axon without attenuation.


The Auditory NerveThe Auditory NerveStatistical analysis of neural

dischargesHistograms:

Because neural discharges (action potential or "spikes") occur at discrete, punctuate instants in time, histograms are used to analyze and display the temporal discharge patterns. Histograms estimate the distribution of spike times along a temporal dimension which is divided into small time intervals or "bins". http://web.mit.edu/hst.723/www/Labs/LabANF.htm


The Auditory NerveThe Auditory Nerve

Raster plot.

A single occurrence of an action potential (spike) is represented by a single dot as a function of time after stimulus onset.

Representing firing rates

Post-stimulus histogram (PSTH).

A count of the average number of spikes in each bin (10 ms in this case) following stimulus presentation, and normalization to the number of presentations and the bin size, produces the normalized PSTH.

Normalization gives the firing rate (or probability per unit time of firing ) as a function of time. http://mulab.physiol.upenn.edu/analysis.html#Introduction



Raster plot.

A single occurrence of an action potential (spike) is represented by a single dot as a function of time after stimulus onset.

Representing firing rates

Post-stimulus histogram (PSTH).

A count of the average number of spikes in each bin (10 ms in this case) following stimulus presentation, and normalization to the number of presentations and the bin size, produces the normalized PSTH.

Normalization gives the firing rate (or probability per unit time of firing ) as a function of time.


The Auditory NerveThe Auditory NerveSpontaneous firing

(Kiang et al., 1965)


The Auditory NerveThe Auditory NerveTime Coding

Spike train of spontaneous activity of a single nerve fiber and 5 tonal responses

(Kiang et al., 1965)

PSTH of the spike train. Notice the adaptation after ~20 msec.

Adaptation improves sensitivity to transients, can adjust sensitivity to preserve dynamic range of stimulus-response.

Post-stimulus time histogram


The Auditory NerveThe Auditory NerveTime Coding: Phase locking

In response to low-frequency (< 5 kHz) pure tones, spike discharges tend to occur at a particular phase within the stimulus cycle.

However, spikes do not always occur on every cycle, i.e. there can be 2, 3, or more cycles between consecutive spikes.

Phase locking can be quantified using period histograms (PSTH), which display the distribution of spikes within a stimulus cycle.

With perfect phase locking, the period histogram would be an impulse.

Period histograms of AN fibers for low-frequency pure tones are nearly sinusoidal at near-threshold level, and become more peaky at moderate and high levels.

See Evans, E. (1975). The cochlear nerve and cochlear nucleus. In D. N. WD Keidel (Ed.), Handbook of Sensory Physiology (pp. 1-109). Heidelberg: Springer.



Alternatively, phase locking can be visualized from interspike interval histograms (ISIH).

This analysis is appealing from the viewpoint of central auditoryprocessing because, unlike period histograms, it does not require an absolute time reference locked to each stimulus cycle.



Alternatively, phase locking can be visualized from interspike interval histograms (ISIH).

Here, phase locking shows up as modes at integer multiples of the stimulus period, i.e. at 1/f, 2/f, 3/f, etc for a pure tone of frequency f.

This analysis is appealing from the viewpoint of central auditoryprocessing because, unlike period histograms, it does not require an absolute time reference locked to each stimulus cycle.

See Evans, E. (1975). The cochlear nerve and cochlear nucleus. In D. N. WD Keidel (Ed.), Handbook of Sensory Physiology (pp. 1-109). Heidelberg: Springer.



Synchrony coding:

For very low-frequency pure tones, period histograms can show severe deviations from a sinusoidal waveform, with sometimes two peaks per cycle (“peak splitting”).

Period histograms for higher frequency tones show less distortion. The synchronization index (vector strength) is a measure of the degree of phase locking varying for 0 for a flat period histogram (no phase locking) to 1 for a pulsatile histogram (perfect phase locking).

Synchronization index falls rapidly with frequency for pure tones above 1 kHz. Above 5-6 kHz, the synchronization index reaches the noise floor of the measurements.

There is no absolute upper frequency limit to phase locking. See Johnson, D. H. (1980). The relationship between spike rate and synchrony in responses of auditory-nerve fibers to single tones. J. Acoust. Soc. Am., 68(4), 1115-1122.


The Auditory NerveThe Auditory NerveTime Coding: CF

See Evans, E. (1975). The cochlear nerve and cochlear nucleus. Handbook of Sensory Physiology (pp. 1-109). Heidelberg: Springer.

Each vertical bar represents one spike (action potential) recorded from an AN fiber in response to a pure tone swept in frequency at different intensities.

Spike discharges occur in all conditions: There is spontaneous activity.

For low intensities, discharge rate increases above spontaneous only for a narrow range of frequencies.


The Auditory NerveThe Auditory NerveTime Coding: CF

As intensity increases, so does the range of frequencies to which the fiber responds.

The outline of the response area (red) represents the pure tone tuning curve or frequency threshold curve.

The frequency for which threshold in dB is minimum is the characteristic frequency (CF).

RECEPTIVE FIELD

See Evans, E. (1975). The cochlear nerve and cochlear nucleus. Handbook of Sensory Physiology (pp. 1-109). Heidelberg: Springer.


The Auditory NerveThe Auditory NerveCF curve versus iso-intensity

contours


The Auditory NerveThe Auditory NerveTime Coding: CF, IHC are critical

Outer hair cell destruction decreases the sensitivity and broadens the tuningof auditory nerve fibers.

Tuning curves show the threshold for response in an auditory nerve fiber as a function of frequency

Kanamycin is a drug which can produce a specific lesion of outer hair cells, leaving inner hair cells normal.


Place Theory:

Place of maximum vibration along basilar membrane.

Tuning curves (or FTC=Frequency Threshold Curve)

Tuning curves measured by finding the pure tone amplitude that produces a criterion response in an 8th nerve fiber.

Tuning curves for four different fibers (A-D) are shown.

The Auditory NerveThe Auditory NerveTime Coding


The Auditory NerveThe Auditory NerveTime Coding: Summary

Responses of individual AN fibers to differentfrequencies are related to their place along the cochlear partition (Basilar menbrane).

Frequency selectivity: Clearest when sounds are very faint.

Threshold Tuning Curve: Map plotting thresholds of a neuron or fiber in response to sine waves with varying frequencies at lowest intensity that will give rise to a response.


The Auditory NerveThe Auditory NerveTime Coding versus Audition

The Place Theory stipulates that frequencies are encoded by activity across the tonotopic array of fibers in the AN, as well as in tonotopic nuclei along the auditory pathway within the brain.

The Timing Theory posits that temporal information conveyed through phase locking provides the dominant cue to frequency information. Upper limit is 5-6 kHz.

Neither the Place nor the Timing Theory can account for all psychophysical data. For example the human hearing range is from 200 up to 20,000 Hz.


The Auditory NerveThe Auditory NerveRate code: The Volley Principle

Because of refractory intervals, no individual fiber can fire with a period equal to that of the input signal. Individual fibers catch a cycle, miss one or more, catch another one, miss a few, etc. The period of the input signal is not preserved on any individual fiber, but it is reflected in the most common interspike interval of a population of fibers.


The Auditory NerveThe Auditory NerveRate code: The Volley Principle

The volley theory is oversimplified since it requires neurons to always firing at the time when the signal amplitude reaches a peak.

This is not the case since the entire hair cell-nerve fiber relationship is probabilistic rather than deterministic.

The point of maximum amplitude is the time when the probability of a pulse is greatest (though not guaranteed).

However, if the fiber is most likely to fire at the amplitude peak, the most common interspike interval (of a population of fibers) will equal the period of the input signal.


The Auditory NerveThe Auditory NerveTime Coding versus Audition

So, we have a Place or Tonotopic Code: Frequency is coded by the place along the BM where 8th N electrical activity is greatest (base=high freq; apex=low freq, etc.)

We also have a Synchrony Code (with the Volley Principle tacked on to make it work even with the limits imposed by refractory intervals) based on the timing of 8th N pulses: Frequency is coded by the interspike interval of a population of fibers (short interspike interval=high freq; long interspike interval=low freq).

Is one of these theories right and the other one wrong? Probably not.

Commonly Held View

~15 to ~400 Hz: Mainly synchrony

~400 to ~5000: Combination of place and synchrony

above ~5000: Only place


The thresholds of auditory nerve fibers vary regularly with low threshold fibers on the pillar side of the inner hair cell and high threshold fibers on the modiolar side.

The low threshold fibers have high spontaneous activity rates, while the high threshold fibers have low spontaneous activity rates.

Spontaneous Activity and Threshold


High spontaneous + low threshold

Low Spontaneous + high threshold

Pillar

Modiolar


The distribution of spontaneous discharge rates (SR) is bimodal, separating AN fibers into two groups.

The high-SR group (SR > 18 spikes/s) forms 60% of the fiber population.

The remaining fibers are further subdivided into a low-SR group (SR < 0.5 sp/s, ~15%) and a medium-SR group (0.5 < SR < 18 sp/s, ~25%).

High-SR fibers form a large synaptic terminal on the “pillar” side of inner hair cells, while low- and medium-SR fibers form smaller terminals on the “modiolar” side.

Spontaneous discharge rate is inversely related to threshold at the CF, high-SR fibers being the most sensitive.

The auditory nerve can be thought of as a two-dimensional array of fibers organized by CF (cochlear place) and sensitivity or threshold (spontaneous rate).

Low-SR fibers are more sharply tuned than high-SR fibers, even though the same inner hair cell is innervated by fibers from both groups. This is consistent with the compressive nonlinearity in basilar-membrane motion.

Spontaneous Activity and Threshold



The Auditory NerveThe Auditory NerveIntensity Information

Rate versus Level Functions

Example of a Low-SR fibers with a high threshold.Data is represented by curve (c) in the right plot.

Curves (a), (b) and (c) are typical of what is observed for neurons with High, Medium and Low SRs, respectively.


The Auditory NerveThe Auditory NerveIntensity Information

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