neurobiology of (central) auditory processing disorder and language

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CHAPTER 4

NEUROBIOLOGY OF(CENTRAL) AUDITORYPROCESSING DISORDERAND LANGUAGE-BASEDLEARNING DISABILITY

KAREN BANAI AND NINA KRAUS

(Central) auditory processing disorder(abbreviated here APD) is defined as adeficit in the processing of auditoryinformation, despite normal hearingthresholds, that primarily involves theauditory modality (ASHA, 2005; Jerger &Musiek, 2000). This umbrella definitionencompasses a wide variety of perceptualand cognitive manifestations. APD thuscannot be reduced to a single anatomicsite or impaired process in the auditorysystem. The question of whether such a nonspecific definition can really bene-fit research, diagnosis, and treatment notwithstanding, in this chapter we will focus on the physiologic processesthought to underlie the perception ofauditory aspects that fall within the realmof APD. We will review evidence for spe-cific physiologic processes and anatomicsites contributing to normal and abnor-

mal auditory processing. In particular wereview studies of the physiology andanatomy of: (1) auditory temporal pro-cessing, (2) auditory perception in noise,(3) representation and discrimination ofacoustic features and (4) binaural pro-cessing. We also present evidence for (5) training-related neural plasticity ofthese processes where such evidenceexists, focusing on training studies aimedat populations with symptoms of APD.The physiologic processes reviewed herewith their accompanying perceptual cor-relates are summarized in Table 4–1. Toour knowledge, physiologic and anatomicstudies of APD diagnosed populationshave been rare. On the other hand, manystudies have focused on auditory pro-cessing in populations diagnosed withlanguage-based learning disabilities (e.g.,specific language impairment [SLI] and

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Banai K, Kraus N (2006) Neurobiology of (central) auditory processing disorder and language-based learning disability. In: Handbook of Central Auditory Processing Disorder: Volume I: Auditory Neuroscience and Diagnosis, G.D. Chermak, F.E. Musiek (eds), San Diego: Plural Publishing Inc. pp. 89-116.

dyslexia) in which symptoms of APD areoften present. Throughout the chapterwe will use the general term LLD (language-based learning disorder) torefer to this population. The principles

we present here derive, therefore, fromour understanding of the normal audi-tory system as applied to a wide array ofstudies in clinical populations intersect-ing with APD.

90 (CENTRAL) AUDITORY PROCESSING DISORDER

Table 4–1. Auditory Processing Deficits: Perception and Neurophysiology

Perceptual Difficulty Proposed Neurophysiological Correlates

Temporal Processing

Temporal resolution Delayed onset of auditory brainstemresponse (ABR) to speech

Temporal order judgment1 Abnormal cortical representation of soundunder temporal stress

Backward masking detection Delayed ABR wave V in masked conditions

Modulation detection Reduced amplitude aodulation followingresponse (AMFR)

Auditory Perception in Noise

Processing of speech in noise1 Abnormal suppression of otoacousticemissions (OAE), speech-evoked ABR;cortical representation of speech innoise,2 frequency following response(FFR) magnitude.2

Representation and Discrimination of Acoustic Features (Speech and Nonspeech)

Discrimination of acoustic features1 Abnormal cortical representation of sound;immature cortical responses;2 abnormalmismatch negativity response (MMN).2

Speech perception1 Delayed speech-evoked ABR onset;reduced magnitude of the FFR in F1frequency range; abnormal corticallateralization and N1 responses.

Speech discrimination1 Abnormal MMN2 and P3 (not reviewedhere)

Binaural Processing

Sound localization, dichotic Abnormal binaural interaction listening1 components (BIC)

Training Related Plasticity1Improve with training and 2Exhibit training related plasticity in the LLD population

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Temporal Processing

Temporal processing in the auditory sys-tem is defined, broadly, as the ability ofthe auditory system to represent andprocess changes in the acoustic signalthat occur over time (e.g., the temporalenvelope of the signal), and to its abilityto process brief transient acoustic events(e.g., sound onset and consonants). Ade-quate auditory perception requires goodtemporal resolution on the time scale ofmicroseconds for the processing of bin-aural cues, milliseconds for processing oftemporal synchrony, tens of millisecondsfor the processing of speech transientsand voicing information and hundreds ofmilliseconds to seconds for the process-ing of prosodic and suprasegmental cues.In addition, in order to make sense of ourenvironment, the intact auditory systemneeds to be sensitive to the order inwhich acoustic events occur (e.g., “on”vs. “no”) and be able to transitionbetween those time scales and integrateinformation from all the time scales tocreate a unitary auditory percept.Indeed, evidence suggests that encodingof temporal information into a coherentform begins as early as the cochlearnucleus and continues up to the auditorycortex (Frisina, 2001; Griffiths, Uppen-kamp, Johnsrude, Josephs, & Patterson,2001).

The measurement of auditory evokedpotentials provides a window into tem-poral processing, providing informationabout neural timing with fractions of amillisecond precision.Available recordingtechniques enable the study of timingalong the ascending auditory pathwayfrom the XIIIth nerve to the auditory cor-tex and indeed most of our informationon temporal processing in humans comes

from such studies. Additional informa-tion, in particular regarding cortical tem-poral processing comes from studies ofpatients with cortical lesions. However,it should be noted that due to the com-plex pattern of connectivity in the audi-tory pathway (e.g., massive feedbackconnections), and the relative nature ofperception (i.e. its dependence on con-text) it is hard to attribute a specific per-ceptual deficit to a specific anatomiclocation along the pathway without addi-tional information (Eggermont & Ponton,2002; Phillips, 1995).

Temporal Resolution

Of particular interest here is the brain-stem’s response to sound. Transientacoustic events evoke a pattern of volt-age changes in the auditory brainstem.The resulting waveform provides infor-mation about brainstem nuclei along theascending auditory pathway (see Hood,1998; Jacobsen, 1985 for reviews). Con-verging evidence suggests that learning-impaired populations show normal click-evoked auditory brainstem responses(ABR) (Grontved, Walter, & Gronborg,1988a, 1988b; Jerger, Martin, & Jerger,1987; Lauter & Wood, 1993; Mason &Mellor, 1984; McAnally & Stein, 1997;Purdy, Kelly, & Davies, 2002), yet about athird of all individuals diagnosed withlanguage-based learning problems mani-fest reduced temporal synchrony at thelevel of the upper brainstem (i.e., laterallemniscus, inferior colliculus) in responseto speech sounds (Banai, Nicol, Zecker, &Kraus, 2005; Cunningham, Nicol, Zecker,Bradlow, & Kraus, 2001; King, Warrier,Hayes, & Kraus, 2002; Wible, Nicol, &Kraus, 2004) and backward masked sig-nals (Marler & Champlin, 2005).

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The speech-evoked ABR may be con-ceptualized as the neural code of a speechsyllable (reviewed in Johnson, Nicol, &Kraus, 2005).To a consonant-vowel sylla-ble, the onset response (waves V, A) represents the burst onset of a voicedconsonant, whereas later portions likelyrepresent the offset of the onset burst orthe onset of voicing (wave C) and theoffset of the stimulus (wave O). The har-monic portion of the speech stimulusgives rise to the frequency-followingresponse (FFR, waves D, E, and F) (Gal-braith, Arbagey, Branski, Comerci, & Rector, 1995; Krishnan, 2002).The FFR ischaracterized as a series of transient neu-ral events phase locked to the periodicinformation within the stimulus (Marsh

& Worden, 1968; Sohmer & Pratt, 1977).Disruption of either the onset or the FFRis likely to result in impaired representa-tion of important segmental and supraseg-mental information, respectively, withinthe speech sound thus degrading theinput into higher levels of the auditorysystem (Kraus & Nicol, 2005). A charac-teristic brainstem response to the speechsyllable /da/ is shown in Figure 4–1. Likethe familiar click-evoked ABR, speech-evoked ABRs can be obtained from anindividual subject with relative ease, mak-ing it an objective biological marker ofauditory processing (Johnson et al., 2005;Russo, Nicol, Musacchia, & Kraus, 2004).

Using this measure in large groups ofnormal learning children and children


Figure 4–1. Top: Stimulus waveform (amplitude vs. time) of thespeech syllable /da/. The first 10 ms correspond to the consonantportion whereas the larger amplitude portion from 10 to 40 mscorresponds to the vowel portion of the syllable. Bottom: the cor-responding brainstem evoked response (speech-ABR) recordedfrom a typically developing 9-year-old child). Waves V and Amarked on the response waveform correspond to the brainstem’sresponse to the initial portion of the syllable, whereas the FFRcorresponds to the vowel.

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diagnosed with LLD has shown that chil-dren with LLD present abnormalities ofboth the onset response and the mag-nitude of the FFR. King et al. (2002)demonstrated that wave A of the onsetresponse was at least 1 SD delayed in 20of the 54 listeners with LLD they studied,and that these listeners also had delayedwaves C and F.Wible et al. (2004) furtherstudied the differences in brainstemencoding of speech between normallearning and children with LLD. Theyconcluded that children with LLD hadmarkedly shallower slopes of the tran-sition between onset waves V and A,suggesting a more sluggish response inthese children. They also showed thatthe amplitude of the FFR was signifi-cantly reduced among LLD children inthe frequency region corresponding tothe first formant (F1) of the /da/ stimu-lus used. Similarly, Cunningham et al.(2001) demonstrated that the magnitudeof the FFR in response to a stimulus pre-sented in background noise was reducedin a group of LLD children in the F1 fre-quency range. The magnitude of theresponse in the fundamental frequency(F0) range on the other hand was foundto be normal in both quiet (Wible et al.,2004) and noise (Cunningham et al.,2001). Recently, Banai et al. (2005) esti-mated, in the largest sample yet studiedwith speech-ABR, that 30% of childrenwith LLD show onset responses that areabnormal at the 2 SD level when a unify-ing onset score was created based on thelatencies of onset waves V and A, as wellas the duration and slope of the transi-tion between them.

A similar phenomenon was recentlyshown with more simple stimuli. Marlerand Champlin (2005) studied ABR elicitedby tone bursts in a group of childrenwith LLD (specifically diagnosed with

SLI). They reported that even thoughwave V latencies did not differ betweenchildren with normal learning and chil-dren with LLD when tone bursts werepresented alone, wave V of the LLD groupwas significantly delayed when the sametone was presented immediately fol-lowed by a noise burst (backward mask-ing condition). It may be that a similarmechanism underlies abnormal onsetresponses to speech sounds (which arepotentially masked by the steady stateportion of the stimulus) and masked non-speech sounds. Supporting this notion,children with LLD and elevated back-ward masking detection thresholds alsohave abnormal brainstem encoding ofspeech sounds (Johnson, Nicol, Zecker,Wright,& Kraus, 2004).

Neurons in the auditory system,including the auditory brainstem, show a high degree of sensitivity to oxygenshortage during development. A recentstudy of rats who suffered from experi-mentally induced anoxia at birth showedthat one consequence of this oxygenshortage was a degraded click-ABR (Strataet al., 2005). It may be that a similarprocess contributes to abnormal ABRsmeasured to complex sounds in childrenwith LLD. Although click ABR in thesechildren are typically within clinicalnorms, they tend to be delayed (Song et al., 2006). It is therefore possible thatscalp-measured ABR in humans are notsensitive enough to document thisminute effect and that deficits are there-fore observed only in response to morecomplex stimuli.

Taken together with the perceptualdeficits present among individuals withLLD, this combined body of researchsuggests that processing of rapidlychanging spectrally complex informa-tion at the level of the brainstem is one


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likely source of APD. It is anticipatedthat the brainstem response to speechsounds will be incorporated into the clin-ical evaluation of APD (e.g., see BioMAPTM

—Biological Marker of Auditory Process-ing, Bio-logic Systems Corp, Mundelein,IL). Furthermore, as explained in detailin the relevant sections below, brainstemtiming was found to correlate with therobustness of the cortical response innoise (Wible, Nicol, & Kraus, 2005), andthe majority of individuals with abnor-mal cortical detection of rare acousticevents also have delayed speech-evokedABRs (Banai et al., 2005). Thus, deficientbrainstem timing may affect the corticalresponse to sound.

The timing of the N1 evoked responseis sometimes considered an index oftemporal processing at the cortical level.However, as it is optimally evoked witha stimulation rate slower than 2 Hz (Hall,1992), and as the response is probablyless affected by the physical characteris-tics of the stimulus, but rather by itsfunctional significance (Kraus & McGee,1992), it may be more useful to considerit as representing the initial cortical pro-cessing of the auditory signal. Its mani-festations in individuals with LLD are discussed further below under Represen-tation of Acoustic Features.

Encoding of Stimulus TemporalEnvelope

Another measure of auditory encodingof stimulus structure can be obtained byrecording the amplitude modulation fol-lowing response (AMFR). This responseencodes the frequency of the fluctua-tions in the amplitude envelope of anamplitude-modulated (AM) sound. Themagnitude of this response has been

found to be reduced in individuals withdyslexia, meaning they need deeper(larger) signal modulation to detect itspresence compared to controls. Thisphysiologic finding corresponds withbehavioral findings of higher AM detec-tion thresholds (McAnally & Stein, 1997;Menell, McAnally, & Stein, 1999), andsuggests that auditory encoding of signalmodulation difficulties may lead to per-ceptual difficulties in following suchtemporal modulations in speech. For adiscussion of the role of temporal infor-mation in speech see Rosen (1992). TheAMFR has multiple thalamic and corticalgenerators (Herdman et al., 2002; Kuwada,Batra, & Maher, 1986), with subcorticalgenerators probably contributing to theprocessing of fast modulations (>80 Hz)and cortical ones to the processing ofslower (<40 Hz) rates. However, behav-ioral evidence suggests that individualswith dyslexia have similar deficits acrossall modulation rates (Lorenzi, Dumont, &Fullgrabe, 2000; Menell et al., 1999), andthe magnitudes of their AMFR were sim-ilarly reduced across the range from 10 to320 Hz rates (Menell et al., 1999).

Temporal Order/Sequencing ofRapid Acoustic Events

Perceptual organization of sound, such asdetermining temporal order, is typicallythought of as a function of the auditorycortex (see Näätänen, Tervaniemi, Suss-man, Paavilainen, & Winkler, 2001 for re-view). Nagarajan et al. (1999) presentedpoor readers with pairs of brief tones,asking them to determine the order inwhich the tones were presented (high-low; low-high; high-high; low-low, a taskoriginally used by Tallal with a language-impaired population) and recorded their


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evoked magnetic responses to the tonepairs. Poor readers had a normal responseto the first tone, but had a significantlyreduced response to the second onewhen interstimulus interval (ISI) withinthe pair was short (100 or 200 ms), butnot when it was longer (i.e., 500 ms).These neurophysiologic findings wereconsistent with better behavioral per-formance in the long ISI condition.These data suggest that while the basiccortical response in poor readers may beintact, representation of successive sig-nals is impaired. Bishop and McArthur(2004) reported similar results in thepopulation diagnosed with SLI. Theyreported enhanced correlations betweenthe cortical response to a single tone andthe response to tone pairs in individualswith SLI, indicating a less reliable pro-cessing of tone sequences. Bishop andMcArthur suggested that these findingsreflect immature auditory processingamong some individuals with SLI. Simi-larly,Temple et al. (2000) using nonverbalanalogues of a formant transition founda disruption of the neural response tothe transient stimulus in subjects withdyslexia.They showed that an area in theleft prefrontal cortex that became acti-vated among normal readers in responseto a rapidly transient stimulus, but not inresponse to a slower transition, did notshow this increased activation in dyslex-ics in response to rapidly changing stim-uli. Moreover, Poldrack et al. (2001)reported that an area within the left infe-rior frontal cortex (pars triangularis),that is specifically involved in phono-logic processing, also showed changes inactivation that were related to the degreeof compression of a speech signal (i.e.,temporal processing). These findingssuggest that areas that are not typicallyconsidered auditory areas have an impor-

tant role in auditory processing. Yet,since these areas are not sensitive to spe-cific acoustic characteristics, some otherfunctional property must be sharedbetween “simple auditory” and phono-logical processing.

To summarize, populations diagnosedwith LLD such as dyslexia and SLI arecharacterized by abnormalities in severaldifferent aspects of temporal processingas measured by imaging and electrophys-iologic techniques. Importantly, thesepopulations also manifest difficulties inthe perception of temporal information.Some individuals with LLD have difficul-ties in tasks requiring temporal orderjudgments (Cacace, McFarland, Ouimet,Schrieber, & Marro, 2000; Farmer & Klein,1995; Heath, Hogben, & Clark, 1999;Nagarajan et al., 1999; Tallal, 1980; Tallal& Piercy, 1973), detection of amplitudeand frequency modulations in sound(Lorenzi et al., 2000; Menell et al., 1999;Rocheron, Lorenzi, Fullgrabe, & Dumont,2002; Talcott et al., 2003; Witton, Stein,Stoodley, Rosner, & Talcott, 2002) anddetection of backward masked tones(Griffiths, Hill, Bailey, & Snowling, 2003;Marler, Champlin, & Gillam, 2002;Wrightet al., 1997). Overall, it is estimated that30 to 50% of individuals diagnosed withdyslexia also manifest an auditory per-ceptual deficit characteristic of APD(Amitay, Ahissar, & Nelken, 2002; King,Lombardino, Crandell, & Leonard, 2003;Ramus, 2003). It has been suggested,most notably by Tallal and her colleagues,that such a pattern of deficits should leadto difficulties in the representation anddiscrimination of consonants character-ized by brief formant transitions and con-sequently to difficulties in phonologicprocessing and reading which are thehallmarks of dyslexia (Tallal, 1980; Tallal,Miller, & Fitch, 1993). Subsequent studies


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have indeed shown that many individualswith language-based learning problems,have poorer phonemic discrimination(Adlard & Hazan, 1998; Breier, Fletcher,Denton, & Gray, 2004; Breier et al., 2001;Cornelissen, Hansen, Bradley, & Stein,1996; Joanisse, Manis, Keating, & Seiden-berg, 2000; Reed, 1989; Rosen & Manga-nari, 2001; Ziegler, Pech-Georgel, George,Alario, & Lorenzi, 2005) in addition totheir reading and phonologic deficitssuggesting a possible link between tem-poral processing and literacy. Poor dis-crimination is not, however, restrictedonly to rapidly changing consonants, butfound also for vowels (e.g. Putter-Katz et al., 2005; Rosen & Manganari, 2001).Also, it should be noted that speech perception deficits are probably mostlycharacteristic of children with a historyof SLI (Joanisse et al., 2000).

Neurophysiology ofPerception in Noise

A hallmark of APD is unusual difficultiesin speech understanding in noisy envi-ronments (Chermak, Hall, & Musiek,1999; Chermak, Tucker, & Seikel, 2002).Individuals with LLD show abnormalphysiologic responses to sound at thecortical level when it occurs in back-ground noise. Cunningham et al. (2001)investigated cortical and brainstem re-sponses in normal learning children andchildren with LLD in response to speechstimuli in quiet and in noise. Physiologicresponses at both the cortical and brain-stem level did not differ between groupsin ideal listening conditions (i.e., quiet).On the other hand, both cortical andbrainstem responses of children withLLD were significantly reduced when

the same /da/ stimulus was presented innoise. This pattern of neurophysiologicfindings matched the observed patternof perceptual deficits whereby childrenwith LLD had normal discriminationthresholds in quiet, but significantly ele-vated thresholds in noise. Both percep-tion and cortical responses significantlyimproved, however, when the stimuliwere presented in a cue-enhanced “clearspeech” mode. At the brainstem level,cue enhancement improved the timingof the onset response, but had no effecton response magnitude.Wible, Nicol andKraus (2002) showed that repeated pre-sentations of a stimulus in noise resultedin less reliable P1/N1/P2/N2 corticalresponses (i.e., lower correlations be-tween responses to repeated stimuli) ina subset of children with LLD, but not in normal learning children, suggestingthat the LLD system is more sensitive tothe stresses of a noisy listening situation.Warrier, Johnson, Hayes, Nicol and Kraus(2004) found that the correlation betweencortical responses in quiet and noise(i.e., the degree of response degradationby noise), which serves to test the relia-bility of the cortical response in noise,also was severely reduced in about 20%of LD participants tested. Further studiesshowed a strong correlation betweenthe brainstem onset response and thedegree of degradation of cortical correla-tion in noise (Wible et al., 2005) and thatonly the subset of children with LLDwith abnormal brainstem timing arelikely to show severely abnormal corticalresponses in noise (King et al., 2002).Furthermore, only in this group did lis-tening training (i.e., Earobics) result insignificant enhancement of the reliabilityof cortical function in noise (Hayes, War-rier, Nicol, Zecker, & Kraus, 2003; Kinget al., 2002). This abnormal physiology


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coincides with poor perception of speechin noise (Cunningham et al., 2001). Fur-thermore, while children with LLD withboth normal and abnormal brainstemtiming alike also show poor discrimina-tion of speech in quiet listening condi-tions, only among those children withLLD with abnormal brainstem timing didspeech discrimination improve followinglistening training (King et al., 2002). Takentogether, these findings imply that amongchildren with LLD, physiologic process-ing of speech in noise is abnormal atboth the brainstem and cortical levels,and that encoding of speech in noisecan be improved with either trainingor the use of cue enhanced stimuli.

Taking a somewhat different approach,based on evidence linking the medialolivocochlear bundle (MOCB) of thelower brainstem to hearing in noise,Muchnik et al. (2004) objectively testedthe function of the MOCB system in children diagnosed with APD using oto-acoustic emissions (OAE) with and with-out acoustic stimulation of the contralat-eral ear. In the normal population,contalateral stimulation suppresses theOAE (e.g. Collet et al., 1990), probablyreflecting the inhibitory control of theMOCB on the outer hair cells. Muchniket al. (2004) reported that the suppres-sion effect was significantly reduced inthe APD group compared to normal con-trols, characterizing 11 of 15 children inthe APD group. Furthermore, 80% of thechildren with APD in this study exhib-ited severely impaired speech percep-tion in noise. These findings provide evidence for abnormal function of thedescending auditory pathway in APD,and taken together with the cortical andhigher brainstem findings summarizedabove, likely suggest an important top-down effect in APD.

Representation andDiscrimination of Acoustic Features

Information about representation ofsound at the level of the auditory cortexcan be obtained by recording the obliga-tory cortical response to sound (P1/N1/P2/N2), whereas information on deficitsin acoustic discrimination is most com-monly obtained from the mismatch neg-ativity response (MMN) (Näätänen, 1992).The MMN is generated in response to achange in a repetitive sequence of stim-uli, that is, when rare acoustic stimuli arepresented amidst common (standard)stimuli in an oddball paradigm. Undersuch presentation conditions, the braingenerates a negative potential in responseto the rare element, even when the dif-ference between the standard and rarestimuli is barely perceptible. The MMNprobably has several generators includingthe thalamocortical pathway, the auditorycortex, and frontal brain regions (Krauset al., 1994; Rinne, Alho, Ilmoniemi,Virta-nen, & Naatanen, 2000; Sams, Kaukoranta,Hamalainen, & Naatanen, 1991).

Representation of AcousticFeatures

The ability of the cortex to adequatelyrepresent the acoustic stimulus is criticalto our ability to further process the stim-ulus in functionally significant ways (e.g.,discriminate, categorize, identify). In thedyslexic population, several studies haveshown abnormal N1 responses to non-speech and speech sounds (i.e., pseudo-words and vowels) (Helenius, Salmelin,Richardson, Leinonen, & Lyytinen, 2002);


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nonspeech sounds with temporal orspectral deviance, and syllables differingin voice onset time (VOT) or second for-mant (Moisescu-Yiflach & Pratt, 2005);2000-Hz tone bursts (Pinkerton, Watson,& McClelland, 1989); and consonants andvowels (Putter-Katz et al., 2005). Lessleft-lateralized responses also have beenreported (Heim, Eulitz, & Elbert, 2003),as well as abnormal cerebral asymmetryto speech sounds (Duara et al., 1991;Gross-Glenn et al., 1991; Leonard et al.,2001). Furthermore, it has been sug-gested that the generating sources ofthese potentials within the auditory sys-tem may vary between typically develop-ing children and children with dyslexia(Heim et al., 2003; Heim et al., 2000). Atbirth, N1 responses to consonant-vowelsyllables (/ga/, /ba/, /da/) of children withfamilial risk for dyslexia and SLI are dif-ferent from those of not-at-risk newborns(Guttorm et al., 2001). Furthermore, N1responses to syllables at birth are predic-tive of later development of language andliteracy skills (Espy, Molfese, Molfese,& Modglin, 2004; Molfese, 2000). Latercomponents of the auditory evokedresponse to speech-sounds at birth alsohave been linked to risk for dyslexia andto language and memory development(Guttorm et al., 2005; Guttorm et al.,2001; Molfese & Molfese, 1985, 1997);however, those components may not rep-resent uniquely auditory processing and,therefore are not discussed further here.

Other studies failed to documents dif-ferences in the basic auditory corticalrepresentation between typically devel-oping individuals and individuals withLLD. Thus, in optimal listening condi-tions, the cortical representation of basicacoustic features (N1/P2/N2) in manyindividuals with learning problems maybe intact, even though it is typically

degraded in nonideal situations such asthose involving noisy environment orrapid stimulus rate (Cunningham, Nicol,Zecker, & Kraus, 2000; Nagarajan et al.,1999; Wible et al., 2002).

In the SLI population, evidence sug-gests that the obligatory cortical responsemay be abnormal, at least in some diag-nosed individuals. Neville, Coffey, Hol-comb, and Tallal (1993) reported that N1amplitudes to a pure tone were reducedand N1 latencies delayed only among lan-guage-impaired children with abnormalauditory temporal processing and poorreading. McArthur and Bishop (2004)reported that individuals with SLI hadage inappropriate N1/P2/N2 responsesto tonal stimuli. In a subsequent study, asubgroup of individuals with SLI hadabnormal N1-P2 responses to both non-verbal tonally complex stimuli and tovowels (McArthur & Bishop, 2005).Takentogether, these findings suggest that atleast among some individuals with SLI thelanguage deficit may be related to a moregeneral auditory processing disorder.

To summarize, in subgroups of indi-viduals with LLD the basic cortical rep-resentation of sound, manifested in theN1/P2 evoked response may be abnor-mal in response to both speech andnonspeech sounds.

Fine-Grained AuditoryDiscrimination

One hallmark of adequate perception isour ability to discriminate fine acousticdifferences between similar stimuli. Suchfine grained auditory discrimination ofboth speech and nonspeech elements isknown to be impaired among many indi-viduals with LLD (Adlard & Hazan, 1998;Ahissar, Protopapas, Reid, & Merzenich,


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2000;Amitay et al., 2002; Banai & Ahissar,2004; Ben-Yehudah, Banai, & Ahissar,2004; Cacace et al., 2000; De Weirdt, 1988;Fischer & Hartnegg, 2004; France et al.,2002; McAnally & Stein, 1996; Mengler,Hogben, Michie, & Bishop, 2005; Walker,Shinn, Cranford, Givens, & Holbert, 2002).Physiologically, the MMN has been usedto characterize discrimination at thepreattentive level. MMN responses ariseto a rare acoustic event occurring amidstfrequent ones and index a detection ofchange in either acoustic feature (e.g.,frequency) or complex sound pattern(e.g., order of sounds in a sequence).MMNs often are also conceptualized asindices of sensory or perceptual memory(see Näätänen et al., 2001 for review).Corresponding to perceptual deficitspresent in various clinical populations,MMNs are also attenuated in thesegroups, as discussed below.Yet, it shouldbe noted that, because MMN responsescurrently can only be reliably quantifiedat the group level (Dalebout & Fox,2001; McGee, Kraus, & Nicol, 1997), andthus are a useful tool for the study ofauditory processing in predefined groups,they are ill-suited for use as a diagnostictool at the individual level.

Discrimination of Speech Sounds

Children with learning and reading prob-lems often exhibit difficulties behaviorallydiscriminating minimal pairs of speechsounds (e.g., /da/ vs. /ga/). Reduced orabsent MMN responses to these con-trasts also often have been documentedin individuals with various learning prob-lems, suggesting that impaired physio-logic processing at a preattentive, pre-conscious level may account for poorperception. Kraus et al. (1996) showedthat children with LLD and children with

attention problems had reduced MMNs,especially when they had difficultiesdisciminating the /da/-/ga/ contrast used.In contrast, the same children had no difficulties perceiving a /ba/-/wa/ pair,and correspondingly had normal MMNsto this contrast. Similar findings werereported by Schulte-Korne, Deimel, Bart-ling, and Remschmidt (1998; 2001). Mau-rer, Bucher, Brem, and Brandeis (2003)studied the MMN response in childrenwith familial risk for dyslexia comparedto those of control children using a stan-dard /ba/ and two deviants—/ta/ and/da/. They found that early positive mis-match responses (MMR) and late MMNresponses were attenuated for the at-riskgroup. Children at risk had enhancedMMRs and reduced MMNs. Similar find-ings were obtained in a group of 6-month-old babies at risk for dyslexia(Leppanen et al., 2002).

More recently, researchers have lookedat MMN in predefined subgroups of indi-viduals with language-learning problems.Banai et al. (2005) compared MMNs inresponse to a deviant /da/ syllable in indi-viduals with LD and normal and abnor-mal brainstem timing to the same speechsyllable. MMN onsets were delayed in thelatter group. Furthermore, individualswith abnormal brainstem timing weremore likely to exhibit reduced MMNmagnitude than individuals with normalbrainstem timing. Lachmann, Berti, Kujala,and Schroger (2005) compared MMNsbetween diagnostic subgroups of dyslexiacomparing subjects with deficits in non-word reading to those with deficits incommon (frequent) word reading. Theyfound that abnormal MMNs were charac-teristic of dyslexics with difficulties inreading frequent words, but not in thosewith difficulties specific to nonwordreading. This was true for both a speech


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(/ba/ vs. /da/) and a nonspeech (700 vs.770 Hz) contrast. On the other hand,both dyslexic groups in this study hadreduced N2 responses for both stimulusconditions. Similarly, in the populationdiagnosed with SLI, MMNs were absentin response to vowel deviants (/a/ stan-dard, /i/ deviant) (Shafer, Morr, Datta,Kurtzberg, & Schwartz, 2005), yet whenindividual data were examined, no rela-tionship was found between MMN andbehavioral discrimination of the samespeech contrast.

Discrimination of AcousticFeatures (Frequency, Duration)

Because APD is associated with nonlin-guistic deficits, and because a variety ofnonverbal discrimination deficits havebeen observed in the LLD population, areview of the physiology of nonverbaldiscrimination deficits is relevant. Bal-deweg, Richardson, Watkins, Foale, andGruzelier (1999) recorded abnormalMMN responses to changes in frequency,but not to changes in the duration of astandard tone, a finding that coincideswith the many reports of abnormal fre-quency discrimination in dyslexia (e.g.,Ahissar et al., 2000; Baldeweg et al.,1999; Ben-Yehudah et al., 2004; McAnally& Stein, 1996). Similar findings werereported for at-risk 6-month-old infantsand kindergarten children (Leppanenet al., 2002; Maurer et al., 2003, respec-tively) and for a subgroup of dyslexicswith difficulties in frequent word read-ing (Lachmann et al., 2005). In contrast,other groups have reported that MMNsto frequency deviants did not differbetween dyslexic and control subjects(Kujala, Belitz, Tervaniemi, & Naatanen,2003; Schulte-Korne et al., 1998). Becausethe frequency difference in Kujala et al.’s

(2003) study was 250 Hz, as opposed to50 to 70 Hz in studies that did report agroup difference, it is possible that groupdifferences emerge only when stimulusdifferences are smaller.

Abnormal MMNs typically are attrib-uted to abnormal function of the auditorycortex; however, observed behavioral defi-cits likely involve an interaction betweenthe physical characteristics of the stimu-lus and the required cognitive operation.Thus, Johnsrude, Penhune, and Zatorre,(2000) reported that patients with surgi-cal excision of either the left or the rightHeschl’s gyrus (auditory cortex) couldstill adequately discriminate pitch, butpatients with right hemisphere excisionscould no longer discriminate the direc-tion of pitch change (up or down) eventhough they could readily discriminatethe two sounds as different. Similar find-ings were observed in the dyslexic pop-ulation where the degree of deficit in fre-quency discrimination also depends onthe type of discrimination required (Banai& Ahissar, 2006; France et al., 2002).

Backward Masking

One manifestation of abnormal temporalacuity in children with language prob-lems is increased detection thresholdsfor backward masked signals (Wrightet al., 1997). It has been suggested thatfor some children with LLD, difficultiesin discrimination of consonant-vowel syl-lables arise from a masking effect of thesteady-state vowel and the brief initialconsonant (Tallal, Merzenich, Miller, &Jenkins, 1998). As explained above (seeTemporal Processing), this perceptualdeficit may be related to abnormal pro-cessing of backward masked signals atthe level of the brainstem (Marler &Champlin, 2005). Another physiologic


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correlate of elevated backward maskingthresholds is found, however, at the cortical level. Children with SLI exhibitdelayed and smaller MMNs to backwardmasked signals (Marler et al., 2002). Sim-ilarly, in a group of participants withdyslexia, Kujala et al. (2003) found abnor-mal MMNs in response to sound orderreversal within a tone pair when the pairwas followed (i.e., backward masked) byan additional tone, but not when the pairwas preceded by one (i.e., forwardmasked). In this study, no differences in MMN amplitude were observed to asimple frequency deviant or to an orderreversal in a nonmasked condition asmentioned above.

The relationships between the MMNand brainstem abnormalities are not clear.Although in many cases deficits co-occurat both levels (Banai et al., 2005; Marler& Champlin, 2005), the causal directionis still not known. If one assumes thatbasic sensation is intact among childrenwith LLD as evident from their basicallynormal responses to click-evoked ABR,their elevated backward masking thresh-olds may be attributed to an impairmentof sensory memory (i.e., impaired corticaldiscrimination of sensory traces) (Kujalaet al., 2003; Marler et al., 2002) or toother top-down influences.

Discrimination of Tonal Patterns

MMN responses can be elicited not onlyin response to a single-feature deviant,but also in response to deviations intonal pattern or order. Several studiesfound abnormal MMNs in individualswith dyslexia in response to pattern devi-ations (Kujala et al., 2000; Kujala &Naatanen, 2001; Schulte-Korne, Deimel,Bartling, & Remschmidt, 1999). Schulte-Korne et al. (1999) reported reduced

MMN among individuals with dyslexia inresponse to a violation of a sound pat-tern (i.e., the relative duration of two ofthe components in the pattern). Similarly,Kujala et al. (2000) reported reducedMMNs in a dyslexic group in response torare tone sequences, but normal MMNsin response to rare tone pairs.

Summary

Available data imply that fine discrim-ination of small differences in acousticfeatures characterizes a subgroup of in-dividuals diagnosed with LLD. BecauseMMNs are abnormal in response to bothspeech and nonspeech stimuli, thesefindings suggest that, when present,auditory discrimination deficits maybeof a general nature and probably notrestricted to one type of stimulus. Futurework will reveal if there are specificacoustic aspects, common to both speechand nonspeech signals that are deficientlyperceived. For recent reviews of studieslinking these auditory event related poten-tials (ERPs) to language-based learningproblems see Lyytinen et al. (2005) andHeim and Keil (2004).

Binaural Processing

Binaural interaction is considered espe-cially relevant to the diagnosis of APD,as binaural processing is thought tounderlie deficits in both sound localiza-tion and listening in noise. Indeed,administration of behavioral tasks requir-ing the presence of binaural interactionis recommended in the report of theConsensus Conference on the Diagnosisof Auditory Processing Disorders (Jerger


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& Musiek, 2000). A physiologic measureof binaural interaction can be obtainedfrom the binaural interaction component(BIC) of the brainstem evoked response.The BIC is computed as the differencebetween the sum of the responses tomonaural stimulation and the responseto binaural stimulation (Dobie & Berlin,1979).The BIC may serve as an objectivemeasure of binaural processing. SeeChapter 11 in volume 1 of this Hand-book for discussion of clinical measuresof binaural interaction.

Children suspected of or diagnosedwith APD showed a different BIC patterncompared to normal children (Delb,Strauss, Hohenberg, & Plinkert, 2003;Gopal & Pierel, 1999). However, becausethe amplitude and latency of the BIC israther variable in the normal populationand highly variable in the APD popula-tion, Delb et al. (2003) concluded thatthe BIC is of limited diagnostic value,especially given the time commitment toobtain the three sets of measurementsrequired for its calculation.

Consistent with the presence ofdeficit in binaural processing, deficits inaccurate perception that require integra-tion of information from both ears suchas sound localization and dichotic listen-ing (Amitay et al., 2002; Ben-Artzi, Fos-tick, & Babkoff, 2005; Edwards et al.,2004) have been found, but little isknown about the biological correlates ofthese deficits in the LLD population. Therole of the auditory brainstem in binau-ral processing has been demonstrated ina rare case of a patient with a unilaterallesion of the inferior colliculus. In thispatient, sound localization was impairedbehaviorally and wave V of the ABR wasdelayed when evoked by stimulation ofthe contralateral ear (Litovsky, Fligor, &Tramo, 2002).

(How) Can Training HelpIndividuals with Auditory

Processing Deficits?

Research on the outcomes of trainingaimed specifically at groups diagnosedwith APD is limited, yet available dataindicate that difficulties in speech per-ception in noise can be alleviated bytraining. Putter-Katz et al. (2002) studieda group of 20 children diagnosed withAPD. All trained children had normalaudiometric thresholds, good wordrecognition in ideal listening conditions,and normal click-ABR. Their most com-mon complaint was difficulty under-standing speech in noisy environments(e.g., the classroom).The children partic-ipated in 13 to 15 weekly remediationsessions over a period of 4 months. Atthe same time, classroom modificationswere recommended and implemented.The goal of the remediation sessions wasto improve auditory processing abilitiesin noisy environments. The sessionsincluded listening comprehension activ-ities in the presence of noise and com-peting stimuli and tasks of selective anddivided attention. Noise levels or degreeof stimulus competition increased pro-gressively throughout the course of the program. In addition, children werecoached in the use of compensatorystrategies such as speech-reading andmetacognitive awareness. In addition,the use of FM devices was demonstratedand tried by the participants. At the endof the program, significant improvementsin processing speech in noise and under-standing competing sentences (dichoticlistening) were documented.Furthermore,parents and teachers reported improvedlistening behavior at home and in theclassroom following training.


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Another approach to training is basedon commercially available computer-based listening training programs such asFast ForWord® (FFW) (Merzenich et al.,1996; Tallal et al., 1996) and Earobics®

(Diehl, 1999). These programs havegained increasing popularity in the yearsfollowing the reports of improved speechperception, language comprehension,and phonologic processing (Habib et al.,2002; Merzenich et al., 1996; Tallal et al.,1996). Despite differences between theprograms, both emphasize improvingspeech perception and phonologic pro-cessing through the use of acousticallymodified speech and an adaptive trainingregimen. The rationale behind thisapproach is that in cases of severe tem-poral processing deficits, children (mostnotably with SLI) are not able to distin-guish naturally produced speech sounds,but may be able to tell apart larger, artifi-cially enhanced temporal differences(Tallal et al., 1996). Following improve-ment, these enhancements are reduced,with the expectation that by the end of training the child will learn to ade-quately discriminate natural speech. Inaddition, these programs include mod-ules with specific training on phonologicawareness, following oral instructions,and other tasks aimed at increasing theability of the trainee to process language.

Although the benefits of such pro-grams, compared with ”traditional class-room instruction,” seem obvious, inde-pendent assessments of their successhave been rare. Several recent studiesquestion training-related gains in readingand reading related skills (Agnew, Dorn,& Eden, 2004; Hook, Macaruso, & Jones,2001), despite gains in nonverbal audi-tory discrimination (Agnew et al., 2004).In a randomized controlled trial, Cohenet al. (2005) compared outcome meas-

ures in children with severe SLI, all ofwhom continued their regular speechand language therapy in school, who par-ticipated either in home-based therapywith FFW or received home-based inter-vention using computer–based activitiesthat did not employ modified speech.A third group received no additionalintervention and served as the control.They found that each group made gainsin language scores; however, FFW train-ing resulted in gains in language skillsthat were no greater than that of theother computer intervention or the reg-ular, school-based speech and languagetherapy.

In contrast to the disappointing gainsin reading and reading-related skillsreported in the Cohen et al. study, sev-eral studies have shown that commerciallistening training may result in normal-ization of cortical function in childrenwith LLD. Hayes Warrier, Nicol, Zecker,and Kraus (2003) have shown that corti-cal responses in quiet of LLD childrentrained with Earobics exhibited an accel-erated pattern of maturation followingtraining and that their cortical responsesin noise were enhanced and becamemore resilient to the degrading effects ofbackground noise. Warrier et al. (2004)found that the correlation between cor-tical responses in noise and in quietincreased following training, again sug-gesting increased reliability of corticalprocessing in noise following training.Moreover, Russo, Nicol, Zecker, Hayes,and Kraus (2005) showed that the FFRportion of the brainstem response tospeech became more resilient to noisefollowing training and that the magni-tude of change was highly correlatedwith the degree of cortical change. Thetransient component of the speech-ABRappears to be unaffected by training


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(Hayes et al., 2003; Russo, Nicol, Zecker,Hayes, & Kraus, 2005). Following FFWtraining, Temple et al. (2003) foundincreased activation in the left temporalparietal cortex and most notably in pre-frontal cortex. Taken together, these stud-ies suggest that training serves to normal-ize brain function in trained children,although it does not necessarily resultin immediate literacy-related changes.Yet, it is reasonable to hypothesize thatnormalized physiologic function may bea precondition to behavioral changes.

Both Earobics and FFW have beencriticized for the modest improvementsin literacy related skills, which are typi-cally stated as the reason for undertakingtraining. Remediation of LLD and APDremain, to date, an enormous challenge.Conventional phonologic-based interven-tion to reading problems does not alwaysresult in improved reading (Rivers &Lombardino, 1988), and in many casesreading remains abnormally slow (Wise,Ring, & Olson, 1999, 2000). Availabledata suggest that no single remediation issuccessful in all children with a variety ofauditory-language disorders.

Another type of training that mayenhance phonologic processing in nor-mal learning children is training on thediscrimination of a wide array of phone-mic contrasts (Moore, Rosenberg, & Cole-man, 2005). An intriguing outcome ofthe Moore et al. study is that the literacy-related improvements were observed in the face of little or no improvementon the trained task. Although this type oftraining may be effective in the LLD pop-ulation as well, it should be noted thatthe pattern of training-related gains (i.e.,nonspecific generalization) likely reflectplasticity of higher order mechanisms(auditory attention, auditory memory)

rather than low-level sensory mecha-nisms (see Ahissar, 2001).

Moreover, because APD is associatedwith an auditory deficit that is not nec-essarily language-specific, it may beworthwhile referring to studies of non-verbal auditory training. In the generalpopulation, discrimination of many acous-tic cues (e.g., pitch, duration) substan-tially improves with practice (Amitay,Hawkey, & Moore, 2005; Ari-Even Roth,Amir, Alaluf, Buchsenspanner, & Kishon-Rabin, 2003; Delhommeau, Micheyl, &Jouvent, 2005; Delhommeau, Micheyl,Jouvent, & Collet, 2002; Demany, 1985;Demany & Semal, 2002; Goldstone, 1998;Irvine, Martin, Klimkeit, & Smith, 2000;Wright, 2001; Wright et al., 1997) andtraining is accompanied by plastic neuralchanges in both humans (Atienza, Can-tero, & Dominguez-Marin, 2002; Gottselig,Brandeis, Hofer-Tinguely, Borbely, &Achermann, 2004; Jancke, Gaab, Wusten-berg, Scheich, & Heinze, 2001; Menning,Roberts, & Pantev, 2000) and other pri-mates (E.Ahissar et al., 1992; Bao, Chang,Davis, Gobeske, & Merzenich, 2003;Beitel, Schreiner, Cheung, Wang, & Mer-zenich, 2003; Recanzone, Schreiner, &Merzenich, 1993), attesting to the plas-ticity of central auditory processing evenin adulthood.

Studies of learning-impaired popula-tions have been less common, but find-ings point to the potential of nonverbalauditory training. Kujala et al. (2001)trained 7-year-old children with readingimpairment on an auditory-visual patternmatching task. Children heard a series ofnonverbal sound patterns varying inpitch, duration, and intensity and wereasked to match them to correspondingvisual patterns. This training resulted in significant improvements in reading


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accuracy and speed and in a significantincrease in the MMN response to tone-order reversals. Schaffler, Sonntag, Hart-negg, and Fischer (2004) trained a largegroup of dyslexic listeners on an array of five auditory tasks (i.e., intensity andfrequency discrimination, gap detection,temporal order judgments, and lateraliza-tion). Up to 80% of trained individualsimproved on any given task, reachingage-matched control levels.These percep-tual gains were accompanied by significantimprovements in phonemic discrimina-tion and spelling. Preliminary evidencesuggests that similar training on a widearray of auditory discrimination tasks ina group of teenagers with severe dyslexiaaccompanied by additional learning prob-lems also resulted in improved speechperception and verbal working memory(Banai & Ahissar, 2003).

Finally, preliminary findings regardingthe positive outcomes of music trainingare worth mentioning. Overy (2003)studied the effects of musical training ineight children with dyslexia. Childrentrained on a series of musical games de-signed to emphasize timing and rhythmskills for 20 minutes per session, threetimes a week for 15 weeks in small groupsimproved significantly on rapid auditoryprocessing, rhythm copying, phonologicprocessing, and spelling tests (althoughnot on reading) compared to a 15-weekpretraining waiting period.

Taken together with Moore et al.’s(2005) findings and with recent studieson the effects of prolonged musicalexperience on cognition (see Schellen-berg, 2005) and verbal memory in bothadults (Chan, Ho, & Cheung, 1998) andchildren (Ho, Cheung, & Chan, 2003),it seems that auditory training affectsclusters of processes rather than the

encoding of specific types of stimuli.Importantly, these studies seem to sug-gest that effects of intensive training arenot limited solely to the specific stimulipracticed, but rather extend to affectwider systems of the brain, based onfunctional relationships with the trainedprocesses, as would be suggested by the-ories regarding the hierarchy of percep-tual processing (Hochstein & Ahissar,2002). (See Chapter 4 in Volume II of thisHandbook for additional review of theliterature on auditory training and its useas treatment for APD.)

Summary

The findings reviewed in this chapter linkdifferent perceptual and cognitive mani-festations of APD in the LLD populationto different physiologic processes, asbriefly summarized here. (1) Difficultiesin temporal processing are linked to delaysin neural timing at both the auditory brain-stem and cortex, in response to speechand nonspeech sounds. (2) Abnormalperception and cortical representationof speech in noise similarly are linkedwith potential sources of deficit, as lowas the brainstem. Furthermore, in individ-uals with LLD, cortical processing is moresusceptible to the degrading effects ofbackground noise compared to the nor-mal population. (3) Discrimination defi-cits for both speech and nonspeechsounds are linked with abnormal corticalprocessing of fine stimulus differences(MMN). Furthermore, auditory corticalprocessing in infancy is predictive oflater development of language and cog-nitive skills. (4) Little is known about thebiological basis of abnormal binaural


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processing in LLD, although reducedbinaural components, probably originat-ing at the brainstem have been recordedin children with APD. (5) Listening train-ing (with modified speech stimuli) hasbeen shown to be effective in normaliz-ing cortical function in children withLLD. Furthermore, training was found toimprove the resilience of auditory path-way activity to noise at both brainstemand cortical levels. Additional research isrequired to create training regimens withsizeable effects on language and literacyand to determine who are the subgroupsof LDs that are most aided by training.

APD is heterogeneous in nature. Dif-ferent types of APD are present amongsubgroups of populations diagnosed withlanguage-based learning problems, mani-festing deficits spanning a wide range ofstimuli (pure tones to speech syllables),and processing time frames (fractions ofmilliseconds to seconds). Although thecausal relationships between the pres-ence of an APD and the linguistic andcognitive deficits which form the crux oflearning disabilities are still poorlyunderstood, it is clear that in many cases(estimates range from 30 to 50% of diag-nosed individuals) the presence of APDmay serve as a marker of a language orlearning problem. On the other hand,data on cases of APD without accompa-nying language or cognitive deficits arerare, possibly because individuals withan isolated deficit in one auditory pro-cess are not likely to detect it unlesstested. Indeed, available perceptual dataindicate that in the general populationdifferent auditory abilities are not corre-lated, whereas in the LLD population sig-nificant correlations exist (Banai & Ahissar,2004). This suggests that, although spo-radic symptoms of APD are in somecases present in the normal population,

they are unlikely to be diagnosed with-out the presence of additional pathologyin the language or cognitive domain.

In addition to the variability in percep-tual processing in the LLD population,the varied evoked response findings indi-cate that even among individuals withLLD with APD symptoms it is impossibleto point to a single abnormal physiologicprocess. Thus, LLD subgroups exhibitabnormal processing at different levelsof the auditory system, spanning thebrainstem, the auditory cortex, or both.Additionally, individuals with LLD exhibitabnormal processing in areas outsidewhat are considered classic auditory areas,such as prefrontal regions. In addition tothe common bottom-up explanation forthe role of auditory processing in literacy,a top-down account is thus also likely.Thus, it is possible that a deficient high-level process (e.g., attention, workingmemory) is manifested in literacy andlanguage problems and in auditory pro-cessing deficits through feedback con-nections from higher to lower areas. Itmay be that these abnormalities, in turn,are accompanied by different behavioralmanifestation of APD. Recent findings inanimal models demonstrate how high-level influences shape auditory processingand plasticity (Fritz, Elhilali & Shamma,2005; Polley, Steinberg & Merzenich,2006). Thus, abnormal processing at thelevel of the lower and upper brainstemmay be linked to difficulties in percep-tion in noise, whereas cortical deficitsmay be more indicative of subtle discrim-ination deficits. Further research in well-defined groups is required to lend furthersupport for this assertion.

In terms of etiology, numerous envi-ronmental and genetic mechanisms, aswell as the interaction between geneticsand environment, likely account for this


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large spectra of behavioral and physio-logic findings. For example, followingboth a short period of anoxia and in-duced cortical microgyria (small corticallesions), rats show evidence of abnormalauditory processing as well as deficientsound-evoked brainstem timing (Clark,Rosen, Tallal, & Fitch, 2000; Fitch, Tallal,Brown, Galaburda, & Rosen, 1994; Strataet al., 2005), reminiscent of temporal-processing deficits in persons with LLD.Although the functional significance ofAPD to the development of language andcognitive abilities and ultimately to suc-cess in school is still poorly understood,data from developmental studies cer-tainly suggest a predictive link betweenauditory processing and later cognitivedevelopment.

Early diagnosis and treatment of audi-tory processing deficits is of potentialimportance in easing future learningproblems and improving language devel-opment among children with LLD withAPD-related symptoms. In recent years,several biological markers of auditoryprocessing, literacy, and language havebeen proposed. These markers includedelayed brainstem timing in response tospeech syllables (see Johnson et al.,2005, for review) and a differential pat-tern of the cortical evoked response tospeech syllables in newborns (see Lyyti-nen et al., 2005, for review). In the clinic,using these markers in addition to avail-able test batteries can help inform thediagnosis and treatment recommenda-tions of APD. Further studies are requiredto elucidate the relationships betweenthese markers and behavioral diagnosticmeasures of APD, as well as their appli-cability to different subgroups and in dif-ferent developmental stages. In addition,future research should look at possibleseparate markers, corresponding to the

various APD observed, rather than a sin-gle universal marker. This biologicallybased approach may ultimately lead toimproved understanding of a variety ofclinical conditions that are still insuffi-ciently understood.

Finally, because the preconsciousencoding of sound at the cortical andsubcortical levels and the perception ofmany acoustic features can be enhancedwith training, auditory training regimensare promising tools for the ameliorationof APD. However, in order for training tofulfill an important role in remediation,further research is required to create op-timal training regimens for children andclinical populations; better understandthe relationships between the behavioraloutcomes of training and neural plastic-ity; and develop training procedures thatwill optimize the outcome in terms ofgeneralization and transfer of learning.

References

Adlard,A., & Hazan,V. (1998). Speech percep-tion in children with specific reading dif-ficulties (dyslexia). Quarterly Journal ofExperimental Psychology A, 51, 153–177.

Agnew, J. A., Dorn, C., & Eden, G. F. (2004).Effect of intensive training on auditoryprocessing and reading skills. Brain andLanguage, 88(1), 21–25.

Ahissar, E., Vaadia, E., Ahissar, M., Bergman,H., Arieli, A., & Abeles, M. (1992). Depen-dence of cortical plasticity on correlatedactivity of single neurons and on behavioralcontext. Science, 257(5075), 1412–1415.

Ahissar, M. (2001). Perceptual training: a toolfor both modifying the brain and exploringit. Proceedings of the National Academyof Science, USA, 98(21), 11842–11843.

Ahissar, M., Protopapas, A., Reid, M., & Mer-zenich, M. M. (2000). Auditory processing


04_MusiekV1_89-116 8/4/06 11:41 AM Page 107

Karen

Inserted Text

BioMAP;

parallels reading abilities in adults. Pro-ceedings of the National Academy of Sci-ence USA, 97(12), 6832–6837.

Amitay, S., Ahissar, M., & Nelken, I. (2002).Auditory processing deficits in readingdisabled adults. Journal of the Associa-tion of Research in Otolaryngology, 3(3),302–320.

Amitay, S., Hawkey, D. J., & Moore, D. R.(2005). Auditory frequency discriminationlearning is affected by stimulus variability.Perception and Psychophysics, 67(4),691–698.

Ari-Even Roth, D., Amir, O., Alaluf, L., Buch-senspanner, S., & Kishon-Rabin, L. (2003).The effect of training on frequency dis-crimination: generalization to untrainedfrequencies and to the untrained ear. Jour-nal of Basic Clinical Physiology andPharmacology, 14(2), 137–150.

ASHA. (2005). (Central) auditory processingdisorders—the role of the audiologist.Rockville, MD: Author.

Atienza, M., Cantero, J. L., & Dominguez-Marin, E. (2002). The time course of neu-ral changes underlying auditory percep-tual learning. Learning and Memory,9(3), 138–150.

Baldeweg, T., Richardson, A., Watkins, S.,Foale, C., & Gruzelier, J. (1999). Impairedauditory frequency discrimination indyslexia detected with mismatch evokedpotentials. Annals of Neurology, 45(4),495–503.

Banai, K., & Ahissar, M. (2003). Perceptualtraining generalizes to verbal workingmemory. Neural Plasticity, 10(3), 182.

Banai, K., & Ahissar, M. (2004). Poor fre-quency discrimination probes dyslexicswith particularly impaired working mem-ory. Audiology and Neuro-Otology, 9(6),328–340.

Banai, K., & Ahissar, M. (2006). Auditory pro-cessing deficits in dyslexia: task or stimu-lus related? Cerebral Cortex. Publishedonline Jan 11 2006.

Banai, K., Nicol, T., Zecker, S. G., & Kraus, N.(2005). Brainstem timing: implications for

cortical processing and literacy. Journalof Neuroscience, 25(43), 9850–9857.

Bao, S., Chang, E. F., Davis, J. D., Gobeske, K.T., & Merzenich, M. M. (2003). Progressivedegradation and subsequent refinement ofacoustic representations in the adult audi-tory cortex. Journal of Neuroscience,23(34), 10765–10775.

Beitel, R. E., Schreiner, C. E., Cheung, S. W.,Wang, X., & Merzenich, M. M. (2003).Reward-dependent plasticity in the pri-mary auditory cortex of adult monkeystrained to discriminate temporally modu-lated signals. Proceedings of the NationalAcademy of Science, USA, 100(19),11070–11075.

Ben-Artzi, E., Fostick, L., & Babkoff, H. (2005).Deficits in temporal-order judgments indyslexia: evidence from diotic stimuli dif-fering spectrally and from dichotic stimulidiffering only by perceived location. Neu-ropsychologia, 43(5), 714–723.

Ben-Yehudah, G., Banai, K., & Ahissar, M.(2004). Patterns of deficit in auditory tem-poral processing among dyslexic adults.NeuroReport, 15(4), 627–631.

Bishop, D. V., & McArthur, G. M. (2004).Immature cortical responses to auditorystimuli in specific language impairment:Evidence from ERPs to rapid tone se-quences. Developmental Science, 7(4),F11–18.

Breier, J. I., Fletcher, J. M., Denton, C., & Gray,L. C. (2004). Categorical perception ofspeech stimuli in children at risk for read-ing difficulty. Journal of ExperimentalChild Psychology, 88(2), 152–170.

Breier, J. I., Gray, L., Fletcher, J. M., Diehl, R.L., Klaas, P., Foorman, B. R., et al. (2001).Perception of voice and tone onset timecontinua in children with dyslexia withand without attention deficit/hyperactivitydisorder. Journal of Experimental ChildPsychology, 80(3), 245–270.

Cacace, A. T., McFarland, D. J., Ouimet, J. R.,Schrieber, E. J., & Marro, P. (2000). Tempo-ral processing deficits in remediation-resistant reading-impaired children. Audi-ology and Neuro-Otology, 5(2), 83–97.


04_MusiekV1_89-116 8/4/06 11:41 AM Page 108

Chan, A. S., Ho,Y. C., & Cheung, M. C. (1998).Music training improves verbal memory.Nature, 396(6707), 128.

Chermak, G. D., Hall, J. W., 3rd, & Musiek, F.E. (1999). Differential diagnosis and man-agement of central auditory processingdisorder and attention deficit hyperactivitydisorder. Journal of the American Acad-emy of Audiology, 10(6), 289–303.

Chermak, G. D., Tucker, E., & Seikel, J. A.(2002). Behavioral characteristics of audi-tory processing disorder and attention-deficit hyperactivity disorder: predomi-nantly inattentive type. Journal of theAmerican Academy of Audiology, 13(6),332–338.

Clark, M. G., Rosen, G. D., Tallal, P., & Fitch, R.H. (2000). Impaired processing of com-plex auditory stimuli in rats with inducedcerebrocortical microgyria: An animalmodel of developmental language disabil-ities. Journal of Cognitive Neuroscience,12(5), 828–839.

Cohen, W., Hodson, A., O’Hare, A., Boyle, J.,Durrani, T., McCartney, E., et al. (2005).Effects of computer-based interventionthrough acoustically modified speech(Fast ForWord) in severe mixed receptive-expressive language impairment: Out-comes from a randomized controlled trial.Journal of Speech, Language and Hear-ing Research, 48(3), 715–729.

Collet, L., Kemp, D. T., Veuillet, E., Duclaux,R., Moulin, A., & Morgon, A. (1990). Effectof contralateral auditory stimuli on activecochlear micro-mechanical properties inhuman subjects. Hearing Research,43(2–3), 251–261.

Cornelissen, P. L., Hansen, P. C., Bradley, L., &Stein, J. F. (1996). Analysis of perceptualconfusions between nine sets of conso-nant-vowel sounds in normal and dyslexicadults. Cognition, 59(3), 275–306.

Cunningham, J., Nicol, T., Zecker, S., & Kraus,N. (2000). Speech-evoked neurophysio-logic responses in children with learningproblems: development and behavioralcorrelates of perception. Ear and Hear-ing, 21(6), 554–568.

Cunningham, J., Nicol, T., Zecker, S. G., Brad-low, A., & Kraus, N. (2001). Neurobiologicresponses to speech in noise in childrenwith learning problems: deficits and strate-gies for improvement. Clinical Neuro-physiology, 112(5), 758–767.

Dalebout, S. D., & Fox, L. G. (2001). Reliabilityof the mismatch negativity in the responsesof individual listeners. Journal of theAmerican Academy of Audiology, 12(5),245–253.

De Weirdt, W. (1988). Speech perception andfrequency discrimination in good andpoor readers. Applied Psycholinguistics,9, 163–183.

Delb, W., Strauss, D. J., Hohenberg, G., &Plinkert, P. K. (2003). The binaural inter-action component (BIC) in children withcentral auditory processing disorders(CAPD). International Journal of Audiol-ogy, 42(7), 401–412.

Delhommeau, K., Micheyl, C., & Jouvent, R.(2005). Generalization of frequency dis-crimination learning across frequenciesand ears: Implications for underlying neu-ral mechanisms in humans. Journal of theAssociation of Research in Otolaryngol-ogy, 6(2), 171–179.

Delhommeau, K., Micheyl, C., Jouvent, R., &Collet, L. (2002). Transfer of learningacross durations and ears in auditory fre-quency discrimination. Perception andPsychophysics, 64(3), 426–436.

Demany, L. (1985). Perceptual learning in fre-quency discrimination. Journal of theAcoustical Society of America, 78(3),1118–1120.

Demany, L., & Semal, C. (2002). Learning toperceive pitch differences. Journal of theAcoustical Society of America, 111(3),1377–1388.

Diehl, S. (1999). Listen and learn? A softwarereview of Earobics(R). Language, Speech,and Hearing Services in Schools, 30,108–116.

Dobie, R. A., & Berlin, C. I. (1979). Binauralinteraction in brainstem-evoked responses.Archives of Otolaryngology, 105(7),391–398.


04_MusiekV1_89-116 8/4/06 11:41 AM Page 109

Duara, R., Kushch,A., Gross-Glenn, K., Barker,W. W., Jallad, B., Pascal, S., et al. (1991).Neuroanatomic differences between dys-lexic and normal readers on magnetic res-onance imaging scans. Archives of Neu-rology, 48(4), 410–416.

Edwards, V. T., Giaschi, D. E., Dougherty, R. F.,Edgell, D., Bjornson, B. H., Lyons, C., et al.(2004). Psychophysical indexes of temporalprocessing abnormalities in children withdevelopmental dyslexia. DevelopmentalNeuropsychology, 25(3), 321–354.

Eggermont, J. J., & Ponton, C. W. (2002). Theneurophysiology of auditory perception:from single units to evoked potentials.Audiology and Neuro-Otology,7(2),71–99.

Espy, K. A., Molfese, D. L., Molfese, V. J., &Modglin, A. (2004). Development of audi-tory event-related potentials in young children and relations to word-level read-ing abilities at age 8 years. Annals ofDyslexia, 54(1), 9–38.

Farmer, M. E., & Klein, R. M. (1995). The evi-dence for a temporal processing deficitlinked to dyslexia: A review. PsychonomicBulletin and Review, 2, 460–493.

Fischer, B., & Hartnegg, K. (2004). On thedevelopment of low-level auditory dis-crimination and deficits in dyslexia.Dyslexia, 10(2), 105–118.

Fitch, R. H., Tallal, P., Brown, C. P., Galaburda,A. M., & Rosen, G. D. (1994). Inducedmicrogyria and auditory temporal process-ing in rats: a model for language impair-ment? Cerebral Cortex, 4(3), 260–270.

France, S. J., Rosner, B. S., Hansen, P. C.,Calvin, C., Talcott, J. B., Richardson, A. J.,et al. (2002). Auditory frequency discrimi-nation in adult developmental dyslexics.Perception and Psychophysics, 64(2),169–179.

Frisina, R. D. (2001). Subcortical neural codingmechanisms for auditory temporal process-ing. Hearing Research, 158(1–2), 1–27.

Fritz, J. Elhilali, M., & Shamma S. (2005).Active listening: task-dependent plasticityof spectrotemporal receptive fields in pri-mary auditory cortex. Hearing Research,206, 159–176.

Galbraith, G. C., Arbagey, P. W., Branski, R.,Comerci, N., & Rector, P. M. (1995). Intel-ligible speech encoded in the humanbrain stem frequency-following response.NeuroReport, 6(17), 2363–2367.

Goldstone, R. L. (1998). Perceptual learning.Annual Review of Psychology, 49,585–612.

Gopal, K. V., & Pierel, K. (1999). Binauralinteraction component in children at riskfor central auditory processing disorders.Scandinavian Audiology, 28(2), 77–84.

Gottselig, J. M., Brandeis, D., Hofer-Tinguely,G., Borbely, A. A., & Achermann, P. (2004).Human central auditory plasticity associ-ated with tone sequence learning. Learn-ing and Memory, 11(2), 162–171.

Griffiths, T. D., Uppenkamp, S., Johnsrude, I.,Josephs, O., & Patterson, R. D. (2001).Encoding of the temporal regularity ofsound in the human brainstem. NatureNeuroscience, 4(6), 633–637.

Griffiths,Y. M., Hill, N. I., Bailey, P. J., & Snowl-ing, M. J. (2003). Auditory temporal orderdiscrimination and backward recognitionmasking in adults with dyslexia. Journalof Speech, Language and HearingResearch, 46(6), 1352–1366.

Grontved, A., Walter, B., & Gronborg, A.(1988a). Auditory brain stem responses indyslexic and normal children. A prospec-tive clinical investigation. ScandinavianAudiology, 17(1), 53–54.

Grontved, A., Walter, B., & Gronborg, A.(1988b). Normal ABR’s in dyslexic chil-dren. Acta Otolaryngologica Supplement,449, 171–173.

Gross-Glenn, K., Duara, R., Barker, W. W.,Loewenstein, D., Chang, J.Y.,Yoshii, F., et al.(1991). Positron emission tomographicstudies during serial word-reading by nor-mal and dyslexic adults. Journal of Clini-cal and Experimental Neuropsychology,13(4), 531–544.

Guttorm, T. K., Leppanen, P. H., Poikkeus, A.M., Eklund, K. M., Lyytinen, P., & Lyytinen,H. (2005). Brain event-related potentials(ERPs) measured at birth predict later lan-guage development in children with and


04_MusiekV1_89-116 8/4/06 11:41 AM Page 110

without familial risk for dyslexia. Cortex,41(3), 291–303.

Guttorm,T. K., Leppanen, P. H.T., Richardson,U., & Lyytinen, H. (2001). Event-relatedpotentials and consonant differentiationin newborns with familial risk for dys-lexia. Journal of Learning Disabilities,34(6), 534–544.

Habib, M., Rey, V., Daffaure, V., Camps, R.,Espesser, R., Joly-Pottuz, B., et al. (2002).Phonological training in children with dys-lexia using temporally modified speech:a three-step pilot investigation. Interna-tional Journal of Language and Commu-nication Disorders, 37(3), 289–308.

Hall, J. W. (1992). Handbook of auditoryevoked responses. Needham Heights,Mass: Allyn & Bacon.

Hayes, E. A., Warrier, C. M., Nicol, T. G.,Zecker, S. G., & Kraus, N. (2003). Neuralplasticity following auditory training inchildren with learning problems. ClinicalNeurophysiology, 114(4), 673–684.

Heath, S. M., Hogben, J. H., & Clark, C. D.(1999). Auditory temporal processing indisabled readers with and without orallanguage delay. Journal of Child Psychol-ogy and Psychiatry, 40(4), 637–647.

Heim, S., Eulitz, C., & Elbert,T. (2003).Alteredhemispheric asymmetry of auditory P100min dyslexia. European Journal of Neuro-science, 17(8), 1715–1722.

Heim, S., Eulitz, C., Kaufmann, J., Fuchter, I.,Pantev, C., Lamprecht-Dinnesen, A., et al.(2000). Atypical organisation of the audi-tory cortex in dyslexia as revealed by MEG.Neuropsychologia, 38(13), 1749–1759.

Heim, S., & Keil, A. (2004). Large-scale neuralcorrelates of developmental dyslexia.European Child and Adolescent Psychia-try, 13(3), 125–140.

Helenius, P., Salmelin, R., Richardson, U.,Leinonen, S., & Lyytinen, H. (2002).Abnor-mal auditory cortical activation in dyslexia100 msec after speech onset. Journal ofCognitive Neuroscience, 14(4), 603–617.

Herdman, A.T., Lins, O.,Van Roon, P., Stapells,D. R., Scherg, M., & Picton, T. W. (2002).Intracerebral sources of human auditory

steady-state responses. Brain Topography,15(2), 69–86.

Ho,Y. C., Cheung, M. C., & Chan, A. S. (2003).Music training improves verbal but notvisual memory: cross-sectional and longi-tudinal explorations in children. Neuro-psychology, 17(3), 439–450.

Hochstein, S., & Ahissar, M. (2002).View fromthe top: hierarchies and reverse hierar-chies in the visual system. Neuron, 36(5),791–804.

Hood, L. J. (1998). Clinical applications ofthe auditory brainstem response. SanDiego, CA: Singular Publishing Group, Inc.

Hook, P. E., Macaruso, P., & Jones, S. (2001).Efficacy of Fast ForWord training on facil-itating acquisition of reading skills by chil-dren with reading difficulties—A longitu-dinal study. Annals of Dyslexia, 51,75–96.

Irvine, D. R., Martin, R. L., Klimkeit, E., &Smith, R. (2000). Specificity of perceptuallearning in a frequency discriminationtask. Journal of the Acoustical Society ofAmerica, 108(6), 2964–2968.

Jacobsen, J. (1985). The auditory brainstemresponse. San Diego, CA: College-Hill Press.

Jancke, L., Gaab, N., Wustenberg, T., Scheich,H., & Heinze, H. J. (2001). Short-term func-tional plasticity in the human auditorycortex: An fMRI study. Brain ResearchCognitive Brain Research, 12(3), 479–485.

Jerger, J., & Musiek, F. (2000). Report of theConsensus Conference on the Diagnosisof Auditory Processing Disorders in School-Aged Children. Journal of the AmericanAcademy of Audiology, 11(9), 467–474.

Jerger, S., Martin, R. C., & Jerger, J. (1987).Specific auditory perceptual dysfunctionin a learning disabled child. Ear andHearing, 8(2), 78–86.

Joanisse, M. F., Manis, F. R., Keating, P., & Sei-denberg, M. S. (2000). Language deficits indyslexic children: speech perception,phonology, and morphology. Journal ofExperimental Child Psychology, 77(1),30–60.

Johnson, K. L., Nicol, T. G., & Kraus, N.(2005). Brain stem response to speech: A


04_MusiekV1_89-116 8/4/06 11:41 AM Page 111

biological marker of auditory processing.Ear and Hearing, 26(5), 424–434.

Johnson, K.L., Nicol, T. G., Zecker, S. G.,Wright, B. A., & Kraus, N. (2004). Brain-stem timing in learning impaired childrenwith excessive auditory backward masking[Abstract]. Association for Research inOtolaryngology, 27, 118.

Johnsrude, I. S., Penhune, V. B., & Zatorre, R.J. (2000). Functional specificity in theright human auditory cortex for per-ceiving pitch direction. Brain, 123(Pt. 1),155–163.

King, C., Warrier, C. M., Hayes, E., & Kraus, N.(2002). Deficits in auditory brainstempathway encoding of speech sounds inchildren with learning problems. Neuro-science Letters, 319(2), 111–115.

King, W. M., Lombardino, L. J., Crandell, C. C.,& Leonard, C. M. (2003). Comorbid audi-tory processing disorder in developmen-tal dyslexia. Ear and Hearing, 24(5),448–456.

Kraus, N., & McGee, T. (1992). Electrophysi-ology of the human auditory system. In A.Poppler & R Fay (Eds.), The mammalianauditory system (Vol. II, pp. 335–404).New York: Springer Verlag.

Kraus, N., McGee, T., Carrell, T., King, C.,Littman, T., & Nicol, T. (1994). Discrimina-tion of speech-like contrasts in the audi-tory thalamus and cortex. Journal of theAcoustical Society of America, 96(5, Pt. 1),2758–2768.

Kraus, N., & Nicol, T. (2005). Brainstem ori-gins for cortical “what” and “where” path-ways in the auditory system. Trends inNeurosciences, 28(4), 176–181.

Krishnan,A. (2002). Human frequency-follow-ing responses: representation of steady-state synthetic vowels. Hearing Research,166(1–2), 192–201.

Kujala, T., Belitz, S., Tervaniemi, M., & Naata-nen, R. (2003). Auditory sensory memorydisorder in dyslexic adults as indexed bythe mismatch negativity. European Journalof Neuroscience, 17(6), 1323–1327.

Kujala,T., Karma, K., Ceponiene, R., Belitz, S.,Turkkila, P., Tervaniemi, M., et al. (2001).

Plastic neural changes and reading im-provement caused by audiovisual trainingin reading-impaired children. Proceedingsof the National Academy of Science, USA,98(18), 10509–10514.

Kujala, T., Myllyviita, K., Tervaniemi, M., Alho,K., Kallio, J., & Naatanen, R. (2000). Basicauditory dysfunction in dyslexia as demon-strated by brain activity measurements.Psychophysiology, 37(2), 262–266.

Kujala, T., & Naatanen, R. (2001). The mis-match negativity in evaluating centralauditory dysfunction in dyslexia. Neuro-science and Biobehavioral Reviews,25(6), 535–543.

Kuwada, S., Batra, R., & Maher, V. L. (1986).Scalp potentials of normal and hearing-impaired subjects in response to sinu-soidally amplitude-modulated tones. Hear-ing Research, 21(2), 179–192.

Lachmann, T., Berti, S., Kujala, T., & Schroger,E. (2005). Diagnostic subgroups of devel-opmental dyslexia have different deficits inneural processing of tones and phonemes.International Journal of Psychophysiol-ogy, 56(2), 105–120.

Lauter, J. L., & Wood, S. B. (1993). Auditory-brainstem synchronicity in dyslexia meas-ured using the REPs/ABR protocol. Annalsof the New York Academy of Science,682, 377–379.

Leonard, C. M., Eckert, M. A., Lombardino, L.J., Oakland, T., Kranzler, J., Mohr, C. M.,et al. (2001). Anatomical risk factors forphonological dyslexia. Cerebral Cortex,11(2), 148–157.

Leppanen, P. H., Richardson, U., Pihko, E.,Eklund, K. M., Guttorm,T. K.,Aro, M., et al.(2002). Brain responses to changes inspeech sound durations differ betweeninfants with and without familial risk fordyslexia. Developmental Neuropsychology,22(1), 407–422.

Litovsky, R. Y., Fligor, B. J., & Tramo, M. J.(2002). Functional role of the human infe-rior colliculus in binaural hearing. Hear-ing Research, 165(1–2), 177–188.

Lorenzi, C., Dumont, A., & Fullgrabe, C.(2000). Use of temporal envelope cues by


04_MusiekV1_89-116 8/4/06 11:41 AM Page 112

children with developmental dyslexia.Journal of Speech, Language and Hear-ing Research, 43(6), 1367–1379.

Lyytinen, H., Guttorm, T. K., Huttunen, T.,Hamalainen, J., Leppanen, P. H. T., Vesteri-nen, M., et al. (2005). Psychophysiology ofdevelopmental dyslexia: A review of find-ings including studies of children at riskfor dyslexia. Journal of Neurolinguistics,18(2), 167–195.

Marler, J. A., & Champlin, C. A. (2005). Sen-sory processing of backward-masking sig-nals in children with language-learningimpairment as assessed with the auditorybrainstem response. Journal of Speech,Language and Hearing Research, 48(1),189–203.

Marler, J. A., Champlin, C. A., & Gillam, R. B.(2002). Auditory memory for backwardmasking signals in children with languageimpairment. Psychophysiology, 39(6),767–780.

Marsh, J. T., & Worden, F. G. (1968). Soundevoked frequency-following responses inthe central auditory pathway. Laryngo-scope, 78(7), 1149–1163.

Mason, S. M., & Mellor, D. H. (1984). Brain-stem, middle latency and late corticalevoked potentials in children with speechand language disorders. Electroencephalo-graphy and Clinical Neurophysiology,59(4), 297–309.

Maurer, U., Bucher, K., Brem, S., & Brandeis,D. (2003). Altered responses to tone andphoneme mismatch in kindergartners atfamilial dyslexia risk. NeuroReport, 14(17),2245–2250.

McAnally, K. I., & Stein, J. F. (1996). Auditorytemporal coding in dyslexia. Philosophi-cal Transactions of the Royal Society ofLondon, B Biological Sciences, 263,961–965.

McAnally, K. I., & Stein, J. F. (1997). Scalppotentials evoked by amplitude-modulatedtones in dyslexia. Journal of Speech, Lan-guage and Hearing Research, 40(4),939–945.

McArthur, G. M., & Bishop, D. V. (2005).Speech and non-speech processing in peo-

ple with specific language impairment: abehavioral and electrophysiologic study.Brain and Language, 94(3), 260–273.

McArthur, G. M., & Bishop, D. V. M. (2004).Which people with specific languageimpairment have auditory processingdeficits? Cognitive Neuropsychology,21(1), 79–94.

McGee, T., Kraus, N., & Nicol, T. (1997). Is itreally a mismatch negativity? An assessmentof methods for determining responsevalidity in individual subjects. Electroen-cephalography and Clinical Neurophysi-ology, 104(4), 359–368.

Menell, P., McAnally, K. I., & Stein, J. F. (1999).Psychophysical sensitivity and physiologicresponse to amplitude modulation inadult dyslexic listeners. Journal of Speech,Language and Hearing Research, 42(4),797–803.

Mengler, E. D., Hogben, J. H., Michie, P., &Bishop, D. V. (2005). Poor frequency dis-crimination is related to oral language dis-order in children: A psychoacoustic study.Dyslexia, 11(3), 155–173.

Menning, H., Roberts, L. E., & Pantev, C.(2000). Plastic changes in the auditorycortex induced by intensive frequencydiscrimination training. NeuroReport,11(4), 817–822.

Merzenich, M. M., Jenkins,W. M., Johnston, P.,Schreiner, C., Miller, S. L., & Tallal, P. (1996).Temporal processing deficits of language-learning impaired children ameliorated bytraining. Science, 271(5245), 77–81.

Moisescu-Yiflach, T., & Pratt, H. (2005). Audi-tory event related potentials and sourcecurrent density estimation in phonologic/auditory dyslexics. Clinical Neurophysiol-ogy, 116(11), 2632–2647.

Molfese, D. L. (2000). Predicting dyslexia at 8years of age using neonatal brain responses.Brain and Language, 72(3), 238–245.

Molfese, D. L., & Molfese, V. J. (1985). Electro-physiologic indices of auditory discrimina-tion in newborn infants:The bases for pre-dicting later language development?Infant Behavior and Development, 8(2),197–211.


04_MusiekV1_89-116 8/4/06 11:41 AM Page 113

Molfese, D. L., & Molfese,V. J. (1997). Discrim-ination of language skills at five years ofage using event-related potentials recordedat birth. Developmental Neuropsychology,13(2), 135–156.

Moore, D. R., Rosenberg, J. F., & Coleman,J. S. (2005). Discrimination training ofphonemic contrasts enhances phonologi-cal processing in mainstream school chil-dren. Brain and Language, 94(1), 72–85.

Muchnik, C., Ari-Even Roth, D., Othman-Jebara, R., Putter-Katz, H., Shabtai, E. L., &Hildesheimer, M. (2004). Reduced medialolivocochlear bundle system function inchildren with auditory processing disor-ders. Audiology and Neuro-Otology, 9(2),107–114.

Näätänen, R. (1992). Attention and brainfunction. Hillsdale, NJ: Lawrence Erlbaum.

Näätänen, R., Tervaniemi, M., Sussman, E.,Paavilainen, P., & Winkler, I. (2001). “Prim-itive intelligence” in the auditory cortex.Trends in Neurosciences, 24(5), 283–288.

Nagarajan, S., Mahncke, H., Salz, T., Tallal, P.,Roberts, T., & Merzenich, M. M. (1999).Cortical auditory signal processing in poorreaders. Proceedings of the National Acad-emy of Science USA, 96(11), 6483–6488.

Neville, H. J., Coffey, S. A., Holcomb, P. J., &Tallal, P. (1993). The neurobiology of sen-sory and language processing in language-impaired children. Journal of CognitiveNeuroscience, 5(2), 235–253.

Overy, K. (2003). Dyslexia and music. Fromtiming deficits to musical intervention.Annals of the New York Academy of Sci-ence, 999, 497–505.

Phillips, D. P. (1995). Central auditory pro-cessing: a view from auditory neuro-science. American Journal of Otology,16(3), 338–352.

Pinkerton, F., Watson, D. R., & McClelland, R.J. (1989). A neurophysiological study ofchildren with reading, writing and spellingdifficulties. Developmental Medicine andChild Neurology, 31(5), 569–581.

Poldrack, R. A., Temple, E., Protopapas, A.,Nagarajan, S.,Tallal, P., Merzenich, M., et al.(2001). Relations between the neural

bases of dynamic auditory processing andphonological processing: evidence fromfMRI. Journal of Cognitive Neuroscience,13(5), 687–697.

Polley, D. B., Steinberg, E.E., & Merzenich, M.M. (2006). Perceptual learning directsauditory cortical map reorganizationthrough top-down influences. Journal ofNeuroscience, 26, 4970–4982.

Purdy, S. C., Kelly,A. S., & Davies, M. G. (2002).Auditory brainstem response, middlelatency response, and late cortical evokedpotentials in children with learning dis-abilities. Journal of the American Acad-emy of Audiology, 13(7), 367–382.

Putter-Katz, H., Adi-Ben Said, L., Feldman, I.,Miran, D., Kushnir, D., Muchnik, C., et al.(2002). Treatment and evaluation indicesof auditory processing disorders. Semi-nars in Hearing, 23(4), 357–364.

Putter-Katz, H., Kishon-Rabin, L., Sachartov,E., Shabtai, E. L., Sadeh, M., Weiz, R., et al.(2005). Cortical activity of children withdyslexia during natural speech processing:evidence of auditory processing deficiency.Journal of Basic Clinical Physiology andPharmacology, 16(2–3), 157–171.

Ramus, F. (2003). Developmental dyslexia:specific phonological deficit or generalsensorimotor dysfunction? Current Opin-ion in Neurobiology, 13(2), 212–218.

Recanzone, G. H., Schreiner, C. E., &Merzenich, M. M. (1993). Plasticity in thefrequency representation of primary audi-tory cortex following discrimination train-ing in adult owl monkeys. Journal of Neu-roscience, 13(1), 87–103.

Reed, M. A. (1989). Speech perception andthe discrimination of brief auditory cuesin reading disabled children. Journal ofExperimental Child Psychology, 48(2),270–292.

Rinne, T., Alho, K., Ilmoniemi, R. J., Virtanen,J., & Naatanen, R. (2000). Separate timebehaviors of the temporal and frontal mis-match negativity sources. Neuroimage,12(1), 14–19.

Rivers, K. O., & Lombardino, L. J. (1998). Gen-eralization of early metalinguistic skills in


04_MusiekV1_89-116 8/4/06 11:41 AM Page 114

a phonological decoding study with first-graders at risk for reading failure. Interna-tional Journal of Language and Commu-nication Disorders, 33, 369–391.

Rocheron, I., Lorenzi, C., Fullgrabe, C., &Dumont, A. (2002). Temporal envelopeperception in dyslexic children. Neuro-Report, 13(13), 1683–1687.

Rosen, S. (1992). Temporal information inspeech: acoustic, auditory and linguisticaspects. Philosophical Transactions ofthe Royal Society of London, B BiologicalSciences, 336(1278), 367–373.

Rosen, S., & Manganari, E. (2001). Is there arelationship between speech and non-speech auditory processing in childrenwith dyslexia? Journal of Speech, Lan-guage and Hearing Research, 44(4),720–736.

Russo, N., Nicol, T., Musacchia, G., & Kraus,N. (2004). Brainstem responses to speechsyllables. Clinical Neurophysiology,115(9), 2021–2030.

Russo, N., Nicol, T. G., Zecker, S. G., Hayes, E.A., & Kraus, N. (2005). Auditory trainingimproves neural timing in the humanbrainstem. Behavioral Brain Research,156(1), 95–103.

Sams, M., Kaukoranta, E., Hamalainen, M.,& Naatanen, R. (1991). Cortical activityelicited by changes in auditory stimuli: dif-ferent sources for the magnetic N100m andmismatch responses. Psychophysiology,28(1), 21–29.

Schaffler, T., Sonntag, J., Hartnegg, K., & Fis-cher, B. (2004). The effect of practice onlow-level auditory discrimination, phono-logical skills, and spelling in dyslexia.Dyslexia, 10(2), 119–130.

Schellenberg, E. G. (2005). Music and cogni-tive abilities. Current Directions in Psy-chological Science, 14(6), 317–320.

Schulte-Korne, G., Deimel, W., Bartling, J., &Remschmidt, H. (1998). Auditory process-ing and dyslexia: evidence for a specificspeech processing deficit. NeuroReport,9(2), 337–340.

Schulte-Korne, G., Deimel, W., Bartling, J., &Remschmidt, H. (1999). Pre-attentive pro-

cessing of auditory patterns in dyslexichuman subjects. Neuroscience Letters,276(1), 41–44.

Schulte-Korne, G., Deimel, W., Bartling, J., &Remschmidt, H. (2001). Speech perceptiondeficit in dyslexic adults as measured bymismatch negativity (MMN). InternationalJournal of Psychophysiology, 40(1), 77–87.

Shafer, V. L., Morr, M. L., Datta, H., Kurtzberg,D., & Schwartz, R. G. (2005). Neurophysi-ological indexes of speech processingdeficits in children with specific languageimpairment. Journal of Cognitive Neuro-science, 17(7), 1168–1180.

Sohmer, H., & Pratt, H. (1977). Identificationand separation of acoustic frequency fol-lowing responses (FFRS) in man. Electro-encephalography and Clinical Neuro-physiology, 42(4), 493–500.

Song, J., Banai, K., Russo N. M., & Kraus, N.(2006). On the relationship betweenspeech- and nonspeech-evoked auditorybrainstem responses. Audiology andNeuro-Otology, 11(4), 233–241.

Strata, F., Deipolyi, A. R., Bonham, B. H.,Chang, E. F., Liu, R. C., Nakahara, H., et al.(2005). Perinatal anoxia degrades auditorysystem function in rats. Proceedings of the National Academy of Science USA,102(52), 19156–19161.

Talcott, J. B., Gram, A., Van Ingelghem, M.,Witton, C., Stein, J. F., & Toennessen, F. E.(2003). Impaired sensitivity to dynamicstimuli in poor readers of a regular orthog-raphy. Brain and Language, 87(2),259–266.

Tallal, P. (1980).Auditory temporal perception,phonics, and reading disabilities in children.Brain and Language, 9, 182–198.

Tallal, P., Merzenich, M. M., Miller, S., & Jenk-ins, W. (1998). Language learning impair-ments: integrating basic science, technol-ogy, and remediation. Experimental BrainResearch, 123(1–2), 210–219.

Tallal, P., Miller, S., & Fitch, R. H. (1993).Neurobiological basis of speech: a case forthe preeminence of temporal processing.Annals of the New York Academy of Sci-ence, 682, 27–47.


04_MusiekV1_89-116 8/4/06 11:41 AM Page 115

Tallal, P., Miller, S. L., Bedi, G., Byma, G.,Wang,X., Nagarajan, S. S., et al. (1996). Languagecomprehension in language-learning im-paired children improved with acousticallymodified speech. Science, 271(5245),81–84.

Tallal, P., & Piercy, M. (1973). Defects of non-verbal auditory perception in childrenwith developmental aphasia. Nature,241(5390), 468–469.

Temple, E., Deutsch, G. K., Poldrack, R. A.,Miller, S. L.,Tallal, P., Merzenich, M. M., et al.(2003). Neural deficits in children withdyslexia ameliorated by behavioral reme-diation: evidence from functional MRI.Proceedings of the National Academy ofScience USA, 100(5), 2860–2865.

Temple, E., Poldrack, R. A., Protopapas, A.,Nagarajan, S., Salz, T., Tallal, P., et al.(2000). Disruption of the neural responseto rapid acoustic stimuli in dyslexia: evi-dence from functional MRI. Proceedingsof the National Academy of Science USA,97(25), 13907–13912.

Walker, M. M., Shinn, J. B., Cranford, J. L.,Givens, G. D., & Holbert, D. (2002). Audi-tory temporal processing performance ofyoung adults with reading disorders. Jour-nal of Speech, Language and HearingResearch, 45(3), 598–605.

Warrier, C. M., Johnson, K. L., Hayes, E. A.,Nicol, T., & Kraus, N. (2004). Learningimpaired children exhibit timing deficitsand training-related improvements in audi-tory cortical responses to speech in noise.Experimental Brain Research, 157(4),431–441.

Wible, B., Nicol,T., & Kraus, N. (2002).Abnor-mal neural encoding of repeated speechstimuli in noise in children with learningproblems. Clinical Neurophysiology,113(4), 485–494.

Wible, B., Nicol, T., & Kraus, N. (2004). Atyp-ical brainstem representation of onset andformant structure of speech sounds inchildren with language-based learningproblems. Biological Psychology, 67(3),299–317.

Wible, B., Nicol, T., & Kraus, N. (2005). Cor-relation between brainstem and corticalauditory processes in normal and language-impaired children. Brain, 128(Pt. 2),417–423.

Wise, B. W., Ring, J., & Olson, R. K. (1999).Training phonological awareness with andwithout explicit attention to articulation.Journal of Experimental Child Psychol-ogy, 72(4), 271–304.

Wise, B. W., Ring, J., & Olson, R. K. (2000).Individual differences in gains from com-puter-assisted remedial reading. Journalof Experimental Child Psychology, 77(3),197–235.

Witton, C., Stein, J. F., Stoodley, C. J., Rosner,B. S., & Talcott, J. B. (2002). Separate influ-ences of acoustic AM and FM sensitivityon the phonological decoding skills ofimpaired and normal readers. Journal ofCognitive Neuroscience, 14(6), 866–874.

Wright, B. A. (2001). Why and how we studyhuman learning on basic auditory tasks.Audiology and Neuro-Otology, 6(4),207–210.

Wright, B. A., Lombardino, L. J., King, W. M.,Puranik, C. S., Leonard, C. M., & Merzenich,M. M. (1997). Deficits in auditory temporaland spectral resolution in language-impairedchildren. Nature, 387(6629), 176–178.

Ziegler, J. C., Pech-Georgel, C., George, F.,Alario, F. X., & Lorenzi, C. (2005). Deficitsin speech perception predict languagelearning impairment. Proceedings of theNational Academy of Science USA,102(39), 14110–14115.


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neurobiology of (central) auditory processing disorder and language

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