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Development ofSound Localization

2How do the neural mechanismssubserving sound localization

develop?

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Overview of the development ofsound localization Gross localization responses are observed soon

after the cochlea begins to function and innewborn humans.

The precision of sound localization improvesbetween birth and 5 years of age.

Localization under complex listening conditionstakes longer to develop.

Experience appears necessary for the formationof auditory spatial maps.

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Overview of this lecture Electrophysiological evidence of development of

binaural hearing mechanisms in humans. Morphological and physiological evidence of

development of binaural hearing mechanisms innonhumans.

Limitations imposed by immature peripheralcoding.

Development of spatial maps and role ofexperience.

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ABR binaural interaction component

McPherson et al. (1989) measured what is called the binaural interaction componentof the ABR. This series of waveforms illustrate how the binaural interactioncomponent is recorded. The top two waveforms are auditory brainstem responsesrecorded to clicks presented to the right ear (top) and the left ear (second from top).The third waveform from the top is the ABR recorded when both ears are stimulatedsimultaneously (binaural response). The monaural responses should representneural responses along the auditory brainstem pathway, including those from somenuclei that are constructed to process interaural differences. But at least someneurons in those nuclei respond more when they are stimulated by both ears, andthat neural response will only be reflected in the binaural ABR. So the differencebetween the sum of the two monaural responses (fourth waveform from top) and thebinaural response represented this extra binaural response (bottom waveform). Thedifference between the summed monaural and the binaural responses in called thebinaural interaction component. McPherson et al measured the BIC in adults and innewborn infants. The results for infants are shown on the right. Although he ABRwaveform is clearly different in the newborn compared the adult, the BIC is quitesimilar, suggesting that binaural processing at the level of the brainstem is working.Given that newborns can tell whether a sound is coming from the left or right, thisisn’t very surprising.McPherson, D. L., Tures, C., & Starr, A. (1989). Binaural interaction of the auditorybrain-stem potentials and middle latency auditory evoked potentials in infants andadults. Electroecepalogr. Clin. Neurophysiol., 74, 124-130.

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MLR binaural interaction component

McPherson et al. also recorded binaural middle latency responses(MLR). The middle latency response is complex, in that it includescomponents that come from the thalamus as well as the reticularformation, which is involved in arousal and regulation of behavioralstate. It can be difficult to record in infants because it is affected bystate and sleep stage. Nonetheless, McPherson et al. were able torecord the response in some newborns, to calculate a BIC in the sameway that they calculated the ABR BIC. Their results are shown here, theadult BIC is at the bottom left, the infant on the bottom right. Infantsshow a BIC in the MLR, but it is different from that seen in adults- itlooks like the polarity of the response is reversed in the infants. So thisresult suggests that the neural mechanism involved in binauralinteractions at this level of the auditory system are immature at birth,but it is not clear exactly how they are immature.

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Binaural responses detectable inmost newborns

Cone-Wesson et al. recorded the binaural interaction components forABR Waves III and V and for the MLR in newborn infants. (ABR - 30 HzHP refers to Wave V recorded with filter settings for MLR.) They usedhigh and low level clicks as well as 500 and 4000 Hz tones to elicitresponses. These researchers found that the majority of newbornsproduced BICs in all conditions.Cone-Wesson, B., Ma, E., Fowler, C.G. (1997). Effect of stimulus leveland frequency on ABR and MLR binaural interaction in humanneonates. Hear. Res., 106, 163-178.

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Newborn binaural responses suggestlimitations on binaural processing

Furst et al. (1990) examined the effect of ITD on ABR binauralinteraction components. In adults they found that one of the waves ofthe BIC that they labeled β was present in adult responses- - shown onthe left here for ITDs of 1 ms and less and that the subject’ s report of afused intracranial image of the clicks matched the ITD at which β wasrecorded. Furst et al. (2004) recorded BICs from the ABR in newborninfants with different ITD. They found that few infants exhibited BICs forITD greater than about .4 msec. This suggests some immaturity of theneural mechanism underlying ITD processing, but all the conditions underwhich the BIC can be recorded in infants, the age at which it becomesmature have not been determined.Furst, M., Bresloff, I., Levine, R. A., Merlob, P. L., & Attias, J. J. (2004).Interaural time coincidence detectors are present at birth: evidencefrom binaural interaction. Hearing Research, 187(1-2), 63-72.FURST M, EYAL S, KORCZYN AD PREDICTION OF BINAURALCLICK LATERALIZATION BY BRAIN-STEM AUDITORY EVOKED-POTENTIALS HEARING RESEARCH 49 (1-3): 347-359 NOV 1990

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ConclusionBinaural evoked potentials have not

been well described in humaninfants

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Morphological andphysiological evidence ofbinaural development in

nonhumansWhat limits binaural processing

during development?

The question, as before, is whether it is the acoustics, peripheralcoding, or neural development that limits sound localization duringdevelopment. I studies of nonhumans, as in the BIC ABR studies, theacoustics are irrelevant as the stimuli are presented under earphonesand the acoustics are controlled.For a number of years, researchers who studied auditory neuraldevelopment argued that the brainstem neural structures involved insound localization were pretty much formed and ready to function assoon as the ear could give them some input.

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Lateral superior olive: IID circuit

Remember that the circuit involved in the earliest stage of interauralintensity difference processing involves bilateral projections from bushycells in the anteroventral cochlear nucleus (AVCN) to the lateralsuperior olive (LSO). The contralateral AVCN projects to the medialnucleus of the trapezoid body (MNTB) and MNTB projects to the LSO,providing inhibit input to LSO neurons, while the ipsilateral AVCNprojects directly to the LSO, providing an excitatory input. So LSOneurons respond when the sound is more intense at the ipsilateral ear.Brugge and his colleagues investigated the anatomy and physiology ofthis pathway in newborn kittens-- right at the time when the cochlea firststarts to function, a few days before intense sounds can evoke acochlear response. The picture they provided of the structure of theAVCN-MNTB-LSO circuit is shown at the bottom of the slide. The endbulbs of held on the AVCN neurons aren’t as well developed, and theconnections between neurons are not as extensive, but the circuit isthere.

Blatchley, B. J., & Brugge, J. F. (1990). Sensitivity to binaural intensityand phase difference cues in kitten inferior colliculus. J Neurophysiol,64(2), 582-597.Brugge, J. F. (1983). Development of the lower brainstem auditorynuclei. In R. Romand (Ed.), Developments of Auditory and VestibularSystems (pp. 89-120). New York: Academic Press.

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Medial superior olive: ITD circuit

A similar situation holds for the circuit involved in calculating interauraltime differences. Here, AVCN bushy cells project bilaterally to theneurons of the medial superior olive, and while inputs from either earleads to a response in the MSO neurons, these neurons respond bestwhen they receive simultaneous inputs from the two ears. Thestructures in newborns are shown at the bottom of the picture. Theconnections aren’t as extensive as in the adult, but the circuit is there.

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Responses of LSO neurons to IID

This story of remarkably mature interaural processing continues withconsideration of the responses of LSO and MSO neurons. This figureshows the response of single neurons to interaural intensity differences.The response is plotted along the y-axis as a function of the IID (on thex-axis). The response in an adult cat is shown in the x;s, a 13-day-oldkitten is shown in the unfilled symbols. In both cases, the neuronresponds best to an IID just over 0 dB, and the response goes down asthe IID deviates from that value. If anything, the kitten’s response ismore finely tuned than the adult's.

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Responses of MSO neurons to ITD

These are responses of MSO neurons to interaural phase differences(in π radians, so zero means no phase or time differences and 1.0would be 1Xπ, so the sound in the two ears is completely out of phase(time difference equal to half the period), and at 2π, they’re back inphase. The symbols are the same as in the last slide. These neuronsseem to respond best to a a phase difference that slightly favors theipsilateral ear, and again, the response of the kitten neuron is verysimilar to the response of the adult neuron.

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Normalized spike rate?

Notice that in both of these figures, the response of the neurons isplotted as “normalized spike rate”. What that means is that the spikerate is expressed as a percentage of the maximum spike rate of thatneuron. Why is that important?

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Immature neurons don’t respondmuch

It’s important because the base maximum spike rate is very different inan immature animal than in a mature animal. The graph on the leftillustrates the response of auditory nerve fibers in cats of different ages,as a function of sound intensity, from the Walsh and McGee paper.There is a progressive increase in the maximum response rate withage. The rate at which the spike rate increases as the intensityincreases gets steeper with age as well. The graph on the right showsthe slope of these spike rate-intensity function sin the auditory nerveand in the cochlear nucleus as a function of age. Over the early weeksof postnatal life, there is a progressive increase in hat slope in both theauditory nerve and the cochlear nucleus.

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Immature LSO provides lessinformation about IID

Sanes and Rubel (1998) took a different look at the development of theLSO response. The graph here shows the actual spike rate of LSOneurons of kittens and adult cats. If you look at how much kitten andadult cat LSO neurons are responding as the IID changes, you see thatthe kitten neurons have a very limited range of response compared tothe adult. The table puts some numbers on this. Dynamic range refersto the range of IIDs over which the average neuron responses. It isbigger in adult cats tan it is in 15-16 or 13-14 day old kittens. If youcalculate how much the spike rate changes for each 1 dB change in IID(“IID resolution” in the table), the number is smaller in the kittens than inthe adult cats. So the kitten brain ahs much less information telling itthat the position of a sound source has changed.

Sanes, D. H., & Walsh, E. J. (1998). The development of centralauditory function. In E. W. Rubel, R. R. Fay & A. N. Popper (Eds.),Development of the auditory system (pp. 271-314). New York: SpringerVerlag.Sanes, D. H., & Rubel, E. W. (1988). The functional ontogeny ofinhibition and excitation in the gerbil auditory brain stem. J Neurosci, 8,682-700.Sanes, D. H., & Rubel, E. W. (1988). The ontogeny of inhibition andexcitation in the gerbil lateral superior olive. J. Neurosci., 8(2), 682-700.

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Range of IIDs eliciting a responseincreases with age.

Sanes and Rubel also noted that the range of IIDs to which neurons inthe LSO responded also increased as the cats got older. The neuronsin the kitten LSO were all tuned to a narrow range of negative(ipsilateral ear higher intensity) IIDs, while adult LSO neuronsresponded to IIDs across the entire range. This suggests again that IIDprocessing is not mature at this time, and at least part of the problem isthe dynamic range of the auditory neurons that provide the input toLSO.

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Immature phase locking will leadto poor ITD processing

We know that the MSO has to have well phase-locked inputs from thetwo ears to be able to calculate ITDs on a µsecond scale. Although wedon’t have good data on this, it is clear that if the the precision of phaselocking is increasing over the early weeks of the cat’s life, then the MSOis not going to be able to do a very good job of providing informationabout the precise ITD.

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Conclusions re: interaural cue calculationin the immature auditory system The circuits used in calculating interaural

differences are in place when the cochleastarts to function.

The immature responses of neurons thatprovide input to the superior olive limitinteraural cue calculation.

The neurons of the superior olive may alsobe immature, independent of their inputs.

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Forming a map of auditory spaceITD 30 µsIID 4 dBSpectral shapeIntensity -5 dB

20 degrees visual angle in azimuth5 degrees visual angle in elevation.6 meters away

ITD -10 µsIID -2 dBSpectral shapeIntensity -6 dB

-10 degrees visual angle in azimuth- 5 degrees visual angle in elevation.6 meters away

The idea of a map of auditory space is really the idea that everyposition in space has associated with it an array of sensorycharacteristics: auditory, visual, somatosensory, olfactory (not sureabout taste…), vestibular and kinesthetic. In other words, if I hear asound with certain interaural differences, a certain spectral shape, witha certain intensity, then I know that if I point my eyes to a positionspecified in terms of the visual field, I will see something there. Similarlyif I reach my arm out at a particular angle, I will feel something there--and so on. And somewhere in the brain there is a sort of look up tablewith entries for every position in space.

When I talked about the effects of experience on the development ofsound localization, I suggested that a lack of binaural experience mightdisrupt the formation of this map. I want to talk briefly about somestudies describing how this process might occur. To understand this,you need to think about the problem.

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The auditory system is laid out byfrequency and calculates auditory space

Auditory sceneIntensity XFrequency X Timerepresentation inthe ear

Calculatedspatialrepresentation inthe brain

20, -10, .6

22, -7, .6

-10, -20, .6

20, -20, .4

buzzhum

clickring

Neuralcomputation ofauditory space

The cochlea is organized by frequency (tonotopic organization). Tworeceptors (hair cells) that are close together in the cochlea respond tofrequencies that are close together. The output of the cochlea isorganized by frequency and this organization is maintained throughoutthe auditory pathway. The auditory system has neural circuits that takethe output of the cochlea and compute the locations of sound sourcesin space.

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The visual system is laid outspatially

ViewSpatialrepresentation onretina

Retinotopicrepresentation inthe brain

20, -10, .6

22, -7, .6

-10, -20, .6

20, -20, .4

The visual system is different. The sensory surface--the retina--isspatially organized. In other words, two receptors that are near to eachother in the retina respond to light in places in space that are closetogether. This retinotopic, spatial, organization is maintained throughoutthe visual pathway. Some computation is necessary, of course:Because the retina is 2 dimensional, and space is 3 dimensional, thebrain still has to figure out the distance dimension, but at least the 2dimensions are evident in the retinal image.

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Visual and auditory spatial representationsare superimposed

Scene

Spatialrepresentation onretina

Multimodalspatialrepresentation inthe brain

20, -10, .6

22, -7, .6

-10, -20, .6

20, -20, .4

buzz

humring

click

Intensity XFrequency XTimerepresentationin the ear

Spatial representation in auditory pathway

Some place in the brain, these two spatial representations aresuperimposed. The auditory system processes the sound, the visualsystem processes the light, and then somewhere in the brain, we findneurons that respond to places in space, whether the input from thatplace is sound or light. We say that representation is multimodalbecause it coordinates information from multiple modalities. Onestructure in which we find such a representation of space is in thesuperior colliculus. Physiological studies of the superior colliculusdemonstrate that normal visual and auditory experience is necessaryfor the spatial map to develop normally.

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Normal development of SCresponse in guinea pigs

Azimuthal plane

Neurons respond tosounds in theselocations

This slide shows how the spatial map in the superior colliculus (SC) develops in guinea pigs. Aguinea pig’s gestation period is 68-69 days. Guinea pigs begin to hear prenatally. In terms of thecochlear response, a newborn guinea pig is similar to a 20-day-old kitten. So at this age, theresponse threshold at the level of the auditory nerve is pretty much like that of an adult.The figures at the right of this slide represent the auditory responses of neurons in the SC of 1-11 day-old guinea pigs (top) and adult guinea pigs (bottom). The big circles at the right of thefigure represent the SC (anterior up, lateral to the right), and each dot is the location of oneneuron that Withington-Wray et al. (1990) recorded from. Each of the smaller circles is arepresentation of the responses of one neuron and the letter next to the circle matches thatneuron with the position labeled with the same letter in the schematic of the SC. The small circleis a representation of the azimuthal plane (the horizontal plane that passes through your ears).The figure within the circle outlines the positions in azimuth, in sound field, that that neuronwould respond to. So, for example, the neuron labeled A was near the anterior end of SC and itresponded to sounds that were located around 0º azimuth, The neuron labeled B was a littlemore posterior in SC than the one labeled A, and it responded to sounds that were located alittle to the left of 0º azimuth. So notice two things: Each neuron has a limited section of auditoryspace to which it will respond and As you move from the anterior end of SC to the posterior end,the region to which the neuron responds shifts progressively counterclockwise. Notice that theneuron labeled G is the most posterior neuron and it responds to sounds at 180º azimuth.The responses of 1-11-day old guinea pigs shown at the top of the figure show neither of thesecharacteristics. First, they all respond to sounds over rather large, unselective regions ofauditory space. Second, as you move from the anterior end of SC to the posterior end, you don’tsee a systematic shift in the locations to which the neurons will respond.Withington-Wray et al. studied the development of the responses of these neurons andmanipulated both auditory and visual experience to determine how experience influenced SCdevelopment.They either raised the animals in the dark, so that they had no visual experience orthey raised the animals with constant omnidirectional noise.

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Effects of visual and auditoryexperience on spatial maps

Withington-Wray et al. studied the development of the responses ofthese neurons and manipulated both auditory and visual experience todetermine how experience influenced SC development.They eitherraised the animals in the dark, so that they had no visual experience orthey raised the animals with constant omnidirectional noise.

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Effects of abnormal auditoryexperience on spatial maps

These are the responses of neurons in the SC of animals who heardomnidirectional noise from birth on. Notice that they respond to a broadrange of locations and that their “best direction” (if you can call it that) isnot predicted by their location within SC.Withington-Wray, D. J., Binns, K. E., Dhanjal, S. S., Brickley, S. G., &Keating, M. J. (1990). The maturation of the superior collicular map ofauditory space in the guinea pig is disrupted by developmental auditorydeprivation. Eur J Neurosci, 2, 693-703.Withington-Wray, D. J., Binns, K. E., & Keating, M. J. (1990). A four-dayperiod of bimodality auditory and visual experience is sufficient topermit normal emergence of the map of auditory space in the guineapig superior colliculus. Neurosci Lett, 116, 280-286.Withington-Wray, D. J., Binns, K. E., & Keating, M. J. (1990). Thedevelopmental emergence of a map of auditory space in the superiorcolliculus of the guinea pig. Brain Res Dev Brain Res, 51, 225-236.Withington-Wray, D. J., Binns, K. E., Dhanjal, S. S., Brickley, S. G., &Keating, M. J. (1990). The maturation of the superior collicular map ofauditory space in the guinea pig is disrupted by developmental visualdeprivation. Eur J Neurosci, 2, 682-692.

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Effects of dark rearing on spatialmaps

These figures show the effect of dark rearing on the auditory spatialresponses of neurons in the SC. Each graph plots the location of anindividual neuron in the SC as a function of its “best direction” response(the angle in azimuth at which that neuron responds the best). Theresults for normally reared 35-57-day-old guinea pigs are in therightmost figure. As you move through the SC the angle at which theneuron responds best shifts systematically from 0º azimuth to 180ºazimuth. The results for 1-15-day-old normally reared animals areshown in the leftmost graph. These are like the results in the last slide.As you move through the SC, there is no systematic change in aneuron’s best direction. The results for animals reared in the dark areshown in the middle panel. These animals are between 35 and 57 daysof age, and like immature animals, they do not show a systematicspatiotopic organization.

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Brief normal exposure is sufficientfor normal spatial maps

Withington-Wray et al. looked at groups of animals who were eitherdark reared or noise reared, except for brief periods--about 4 days long-- at different ages. And they found that only 4 days of normal visual andauditory inputs were enough to produce normal spatial maps, as longas the exposure was between 26 and 30 days.

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Spectral as well as interaural cuesare important

These figures show the effects of removing an animals pinna--preventing them from getting the spectral cues that allow us todistinguish front from back and locations in elevation. In these graphsposition in the left hemifield is plotted as negative angles, while those inthe right hemifield are shown in positive angles. The right SC respondsto sounds (and sights) in the left hemifield. The normal organization ofthe SC responses to s sound are shown in the top left graph. As theposition of the neuron in SC moves toward the posterior end of SC, thebest direction shifts from 0º to 180º in azimuth. Animals who have hadboth pinnas removed early in life have SC units that respond to soundsall over the place-- both hemifields even. If you remove the pinnas of anadult animal, the neurons lose their ability to figure out the direction, butthey all still respond to sounds in the left hemifield. Similarly, if the leftpinna is removed, units in the SC on both sides of the brain tend to onlyrespond to sounds in the left hemifield. Schnupp JWH, King AJ, Carlile SAltered spectral localization cues disrupt the development of theauditory space map in the superior colliculus of the ferretJOURNAL OF NEUROPHYSIOLOGY 79 (2): 1053-1069 FEB 1998

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Abnormal experience can produceunusual neural responses.

Normalexperience

Disparate experience

Researchers have also shown that if inputs in the visual modality areshifted, using prisms, for example, then the auditory map shifts tomatch the visual map. So a neuron that would normally respond best to0º azimuth will respond best to 15º azimuth, if prisms are used to shiftthe visual image 15º the the right. A recent study by Wallace and Steinsuggests that during development, the auditory-visual map is veryplastic. They dark reared kittens, except that every so often they wouldpresent simultaneous visual and auditory stimuli-- the trick was that thevisual stimulus was in one location, while the auditory stimulus camfrom a different location with no visual information associated with it.Some of the results of the study are shown in the graph on the right.The shaded areas represent locations to which neurons in the SCwould respond (receptive fields). The left panel shows auditory (A,green) and visual (V, blue) receptive fields of neurons in a normallyreared animal. The thing to notice is that the two receptive fields mostlyoverlap. The right panel shows the receptive fields of neurons in theanimals who saw and heard things from different placessimultaneously. They have receptive fields, but they have little overlap.So presumably, a cat reared in this way would run away from hismother instead of toward her if she meowed.Wallace MT, Stein BEEarly experience determines how the senses will interactJOURNAL OF NEUROPHYSIOLOGY 97 (1): 921-926 JAN 2007

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Where does experience have its effects?

Scene

Spatialrepresentation onretina

Multimodalspatialrepresentation inthe brain

20, -10, .6

22, -7, .6

-10, -20, .6

20, -20, .4

buzz

humring

click

Intensity XFrequency XTimerepresentationin the ear

Spatial representation in auditory pathway

The measurements I have described have all been in the SC. Thatdoesn’t mean that experience doesn’t affect the stages of processingprior to SC. It is known that the response of the ear isn’t changed inanimals exposed to omnidirectional noise during development, but ITDprocessing in the medial superior olive is affected. Seidl AH, Grothe BDevelopment of sound localization mechanisms in the Mongolian gerbilis shaped by early acoustic experience JOURNAL OFNEUROPHYSIOLOGY 94 (2): 1028-1036 AUG 2005

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Implications: Blind people andsound localization Blind people (and visually deprived guinea

pigs) have same discrimination-type soundlocalization abilities as sighted people.

Interestingly, they are able to localizesound sources by pointing as well assighted people.

Conclusion: Vision isn’t the only sense thatcan define space.

The studies of guinea pigs all show that if you expose adult animals tothe same conditions that affected the spatial map in young animals,adult animals’ spatial maps are not affected. But does that mean thatonce the animal has been visually deprived, he will never be able tolocalize sounds? Various studies show that blind people candiscriminate ITD and IID and spectral differences and distance basedon auditory cues. They can tell if the position of a sound sourcechanges. These results are not surprising-- we know that people withabnormal auditory experience can do these things, even though theycan’t point to the location of a sound source. But Zwiers et al (2001)also showed that blind people can point their nose or their arm to theposition of a sound source as well as sighted people. What thissuggests is that vision isn’t the only sense or system that we use todefine space-- there is somatosensory space and motor/kinestheticspace and coordination of the auditory system with those functioningsystems allows for the development of auditory space.

Pascual-Leone, A., Amedi, A., Fregni, F., Merabet, L. B., & On. (2005).The plastic human brain cortex. [Review]. Annual Review ofNeuroscience, 28, 377-401.

Zwiers, M. P., Van Opstal, A. J., Cruysberg, J. R. M., & Ee. (2001).Two-dimensional sound-localization behavior of early-blind humans.[Article]. Experimental Brain Research, 140(2), 206-222.

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Conclusions Not surprisingly, binaural evoked responses can

be evoked from newborn infants, although themorphology of some responses change with age

Whether binaural interaction or improvements inmonaural coding is responsible for changes inresponse is not clear.

Normal multimodal experience is required for theformation of auditory maps of space.