The Auditory Steady State Response in Individuals with ... · 826 J Am Acad Audiol 18:826–845...

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J Am Acad Audiol 18:826–845 (2007)

*Department of Surgery [Otolaryngology], University of Kentucky College of Medicine Lexington, Kentucky;†Neuroaudiology Lab, Department of Communication Sciences, Department of Otolaryngology, School of Medicine, University ofConnecticut, Storrs, Connecticut

Jennifer B. Shinn, Ph.D., University of Kentucky College of Medicine, Otolaryngology – Chandler Medical Center, B317Kentucky Clinic, Lexington, Kentucky 40536-0284

The Auditory Steady State Response inIndividuals with Neurological Insult of theCentral Auditory Nervous System

Jennifer B. Shinn* Frank E. Musiek†

Abstract

The auditory steady state response (ASSR) has recently gained attentionwith respect to estimates of hearing sensitivity and configuration of hearing loss.The present investigation compared behavioral thresholds to estimated ASSRthresholds in subjects with confirmed CANS lesions to determine if thispopulation can be accurately evaluated with ASSR techniques. Comparisonswere made between the experimental group and a normal control groupmatched for age and hearing sensitivity. ASSR thresholds were obtained forthe carrier frequencies of 500 and 2000 Hz with a 46 Hz modulation rate andcompared to behavioral thresholds. Within and between group comparisonswere made. The control group demonstrated strong correlation between theirbehavioral and estimated ASSR thresholds which significantly contrasted theneurological group. Additionally, individuals with neurological impairment of theCANS exhibited elevated thresholds that were on average 24 dB greater at2000 Hz than their behavioral thresholds. These results suggest that individualswith neurological insult may appear as hearing impaired or having greater hearingloss than is actually present. As a result, the ASSR may demonstrate the potentialto assist in the detection of CANS dysfunction.

Key Words: Auditory steady state response, central auditory nervous system,lesion, brainstem, cortex, auditory processing, electrophysiology

Abbreviations: ABR = auditory brainstem response; AM = amplitudemodulation; APD = auditory processing disorder; ASSR = auditory steadystate response; CANS = central auditory nervous system; CPA = cerebello-pontine angle; DPOAE = distortion product otoacoustic emissions; FM =frequency modulation; IRATE = Index of Relative Approximation of ThresholdEstimates; MLR = middle latency response

Sumario

Las respuestas auditivas de estado estable (ASSR) han ganado atenciónrecientemente con respecto a la estimación de la sensibilidad auditiva y laconfiguración de la pérdida auditiva. La presente investigación comparó losumbrales conductuales con umbrales estimados por ASSR en sujetos con

Human auditory steady state respons-es (ASSRs), also termed “amplitudemodulation following responses,”

were first introduced more than 25 years agowith a number of follow up investigationsshortly thereafter (Campbell, 1977; Hall,1979; Rickards and Clark, 1984; Kuwada etal., 1986). The ASSR is an electrophysiologi-cal neural response of the auditory system tofrequency and/or amplitude modulated tones(Picton et al., 2003). The ASSR is recordedusing the same montage as the auditorybrainstem response (ABR); however, itsrecording and analysis are performed in adifferent manner. The ASSR relies not onlyon precise neural synchrony, but on the abil-ity of the auditory system to phase lock overtime.

First recorded in the visual system(Regan, 1966), steady state evoked potentials(steady state responses) have recentlyreceived considerable attention in the audito-ry sciences. The recent attention is a functionof their ability to objectively determine hear-ing sensitivity through the use of frequencyspecific stimuli in both pediatric and adultpopulations (Cohen, Rickards & Clark, 1991;Chambers and Meyer, 1993; Rance et al.,1995; Cone-Wesson et al., 2002a; Cone-Wesson et al., 2002b; Cone-Wesson et al.,

2002c; Luts & Wouters, 2005; Johnson &Brown, 2005; Scherf et al., 2006;Sturzebecher et al., 2006). The ASSR has fol-lowed a long line of evoked potentials, whichhave been well established, accepted andintegrated into diagnostic audiology. Perhapsthe most widely utilized is the ABR. For thepast 35 years the ABR has demonstratedexcellent validity and reliability in the objec-tive measurement of hearing sensitivity(Hecox and Galambos, 1974; Kileny andMagathan, 1987) and neurodiagnostic audi-ology (Starr and Achor, 1975; Selters andBrackman, 1977; Musiek and Lee, 1995).Specifically, it has been established as both asensitive and reliable tool in the detection ofretrocochlear lesions of the auditory nerveand auditory brainstem pathways. However,the ABR has met with some criticism regard-ing its ability to obtain accurate estimates offrequency specific threshold information. Infact, it has been proposed that ASSRs yieldbetter correlations to behavioral thresholdsthan do low frequency tone-burst ABRs(Cone-Wesson et al., 2002 a). Although theconcept of the ASSR has been around for anextended period of time, its implementationin clinical practice has only recentlyemerged. There are several factors that con-tribute to the rationale for the use of the

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lesiones CANS confirmadas para determinar si esta población podía serevaluada con exactitud por medio de técnicas de ASSR. Las comparacionesse realizaron entre el grupo experimental y un grupo control normal ordenadospor edad y sensibilidad auditiva. Los umbrales de los ASSR se obtuvieron pormedio de frecuencias portadoras de 500 y 2000 Hz, con una tasa de modulaciónde 46 Hz y se compararon con los umbrales conductuales. Se realizaroncomparaciones entre los grupos y dentro de un mismo grupo. El grupo de controlmostró una fuerte correlación entre sus umbrales conductuales y los estimadospor ASSR, que contrastó significativamente con el grupo neurológico.Adicionalmente, los individuos con un trastorno neurológico de CANS exhibieronumbrales elevados que fueron en promedio 24 dB más alto en 2000 Hz quesus umbrales conductuales. Estos resultados sugieren que los individuos conalteraciones neurológicas pueden lucir como alterados auditivamente oteniendo una pérdida auditiva mayor de la realidad. Como resultados, los ASSRpuede demostrar el potencial para ayudar en la detección de la disfunción porCANS.

Palabras Clave: Respuestas auditivas de estado estable, sistema nerviosoauditivo central, lesión, tallo cerebral, corteza, procesamiento auditivo,electrofisiología

Abreviaturas: ABR = respuestas auditivas del tallo cerebral; AM = modulaciónde la amplitud; APD = trastorno de procesamiento auditivo; ASSR = respuestaauditiva de estado estable; CANS = sistema nervioso auditivo central; CPA =ángulo ponto-cerebeloso; DPOAE = emisiones otoacústicas por productos dedistorsión; FM = modulación de la frecuencia; IRATE = Índice de AproximaciónRelativa de Estimado de Umbrales; MLR = respuestas de latencia media

ASSR as opposed to the ABR in clinical prac-tice, specifically in the diagnosis of hearingloss. Unlike the ASSR, traditional ABRmeasurements are obtained using a stimulussuch as a click or tone burst. In contrast, theASSR uses steady state stimuli which do nothave to be turned on and off. This preventsspectral splatter and allows for the use of fre-quency specific stimuli in order to obtain afrequency specific response, especially at thelow frequencies.

There has been extensive research overthe past decade regarding the clinical utilityof the ASSR in both the pediatric and adultpopulations. It appears that in cases ofcochlear impairment, the ASSR presents as areliable and effective tool in the estimation ofboth sensitivity and configuration of hearingloss for both the pediatric and adult popula-tions (Rance et al, 1995; Cohen et al., 2002 a,b; Rance, 2005) In fact, it has been demon-strated by Rance and colleagues (1995) thatthe greater the degree of hearing impair-ment, the more accurate the estimation ofhearing sensitivity.

ASSR has emerged as a clinical tool in theassessment of hearing sensitivity. Similar tothe ABR, it may have clinical applicationwith respect to the detection and diagnosis ofcentral auditory disorders. Although theASSR has been established as a useful tool inthe detection and diagnosis of hearingimpairment, later in this paper it will beviewed as a possible test for central auditorydysfunction. Before this can happen, severalconsiderations must be taken into account inthe development of diagnostic assessmenttools in this auditory arena. In order for atest to be integrated into the clinical arenafor the detection of central auditory nervoussystem (CANS) and/or neurological lesions, itshould first be evaluated on three popula-tions of subjects (Lusted, 1978). Initially, themeasure should be evaluated on those sub-jects with normal peripheral hearing sensi-tivity who are free of any neurological pathol-ogy in order to obtain normative data.Secondly, a test should be administered onthose subjects who present with peripheralhearing loss. Finally, before a test should beimplemented into clinical use, its sensitivityand specificity should be determined. Thiscan only be accomplished by evaluating testperformance on subjects with known lesionsof the CANS. However, to date, there is apaucity of investigations into the effects of

neurological lesions of the CANS on ASSRresults.

There are some concerns regarding theability of the ASSR to accurately evaluatehearing sensitivity in individuals with neuro-logical compromise of the CANS. Discussionswith manufacturers indicate that in the nearfuture it will be proposed that the ASSR beused in adult populations and a wider rangeof pediatric populations. Specifically, it hasbeen suggested that the ASSR would be auseful tool in institutions such as theVeterans Administration. Additionally, itsuse has been recommended for neonates andinfants who present with high risk for hear-ing loss. Diagnostic evaluations in theseaforementioned populations often becomecomplicated because they are at higher riskthan the “normal” population for neurologicalinvolvement. Presently, it remains unclear asto the effects of neurological lesions on ASSRresults. The primary concern is that perhapsin cases where patients present with neuro-logical pathology that the elevated electro-physiological thresholds noted may not be anaccurate reflection of hearing acuity. Ratherthey may be a result of the inability of a com-promised CANS to phase lock onto the stim-ulus presented, thus mimicking a hearingimpairment which may not be present ormay not be as severe as is reflected on theASSR results. In turn, the ASSR is an evokedpotential generated by neurological mecha-nisms, and involves both brainstem andauditory cortical structures (Kuwada et al.,2002). As a result, the ASSR may demon-strate the potential to assist in the detectionof CANS lesions. Therefore, before the ASSRis further implemented in practice, it is criti-cal that it be evaluated on individuals withneurological involvement.

As the literature has historically suggest-ed, the ASSR has demonstrated a strong abil-ity to accurately predict hearing sensitivityin both pediatric and adult populations(Rance et al, 1995; Cohen et al., 2002 a, b;Rance, 2005). It has been well establishedthat when neurological involvement is pres-ent, traditional electrophysiological testssuch as the ABR and middle latency response(MLR) demonstrate abnormal responses(Starr and Achor, 1975; Musiek and Lee,1995; Musiek et al., 1999; Japaridze,Shakarishvili and Karanishvilie, 2002).Additionally, there have been several investi-gations which have demonstrated that in

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cases of retrocochlear involvement, ABRthresholds correlate poorly with actualbehavioral thresholds (Warren, 1989;Marangos, Schipper and Richter, 1999).Warren (1989) investigated the correlationbetween ABR and pure-tone thresholds inthe pediatric population. He recognized thatthe ABR threshold can be influenced byretrocochlear involvement. Subsequently,Marangos and colleagues (1999) performed alarge scale retrospective study in order toexamine the correlation between ABR andsubjective pure-tone thresholds in cases ofcerebellopontine angle (CPA) tumors. Theyfound that in the control group, there was adiscrepancy between ABR and pure-tonethresholds of approximately 3.6 dB.However, in the cases with CPA tumors, theABR thresholds were significantly elevatedcompared to the pure-tone thresholds, withmean group differential of 31.2 dB. They con-cluded that an ABR threshold discrepancygreater than 30 dB may provide an addition-al indicator of retrocochlear pathology. Thisleads one to consider that similar abnormali-ties may be observed for the ASSR in cases ofa neurological impairment. If this is the case,perhaps the ASSR can be used as a diagnos-tic tool for the detection and differentiation ofneurological lesions of the CANS.

Few studies have investigated the effectsof ASSR in individuals with auditory nerve orCANS impairment. Rance and colleagues(1999, 2002) have examined the ASSR incases of auditory neuropathy. They investi-gated infants and young children who werediagnosed with auditory neuropathy basedon the findings of repeatable cochlear micro-phonic potentials in the presence of absentclick-evoked ABRs. Both behavioral andASSR thresholds were established for allsubjects. This investigation revealed weakcorrelations between behavioral results andASSR thresholds, suggesting that in cases ofneurological insult, the ASSR is unable toaccurately predict hearing sensitivity.

There are two main purposes of this study,both of which were related to the examina-tion of the effect of neurological involvementon the ASSR. The first is to evaluate theimpact of neurological involvement on ASSRresults with respect to their ability to accu-rately and reliably estimate hearing sensitiv-ity. If it is proven that ASSR demonstratesdifficulty determining hearing sensitivity inthe presence of neurological insult, then it

may be that it is a tool that can be used in theassessment of central auditory processingdeficits. Therefore, this study also aimed todetermine whether or not ASSRs could befeasibly utilized in the detection and diagno-sis of lesions of the CANS.

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Twenty-two individuals recruited from theUniversity of Connecticut in Storrs,Connecticut, as well as the National Hospitalfor Neurology and Neurosurgery in London,England, participated in the study. Subjectsranged in age from 18 to 80 years. All sub-jects volunteered for this study and met theInstitutional Review Boards’ criteria for theenrollment of human subjects at theUniversity of Connecticut and the NationalHospital for Neurology and Neurosurgery.

Subjects were divided into two groups of11 subjects. The first group of subjects, iden-tified as the control group, was composed ofindividuals who were matched to a neurolog-ical group for age and behavioral hearingsensitivity. These individuals were free oflearning disabilities, otologic disorder or neu-rological involvement based on their reportedhistories. Individuals in the control groupwere matched for age to within 10 years ofthe neurological group. Hearing sensitivitywas symmetrical between ears for each sub-ject with pure-tone thresholds within 10 dBacross the frequencies of 500 through 4000Hz. Subjects were individually matchedbased on their pure-tone average (PTA) forthe frequencies of 500 and 2000 Hz (the fre-quencies evaluated for the estimated ASSRthresholds). They were required to demon-strate hearing sensitivity within ± 10 dB HLof the PTA for each ear.

The second, or the neurological group, wascomprised of subjects with lesions of theCANS. Subjects in the neurological groupconsisted of individuals with confirmedbrainstem, sub-cortical and/or corticallesions (Table 1). The neurological group wasdefined as having lesions within but not lim-ited to the CANS. These lesions were delin-eated using the anatomical boundaries setforth by Galaburda and Sanides (1980). Eachsubject underwent either a T1 or T2 weight-ed Magnetic Resonance Imaging (MRI) studywhich was interpreted by both neurologists


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and radiologists. Neurological subjects wereincluded regardless of level of hearing acuity.A detailed description of the neurologicalsubjects can be found in Table 1.

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All subjects demonstrated a normal oto-scopic examination as defined by non-occlud-ing cerumen, no tympanic membrane dullnessand an obvious cone of light. Mean values andstandard deviations for the two groups forages and PTA’s are shown in Table 2.

Prior to participating in the experimentalprotocols, each subject was asked to report ontheir audiologic, otologic and neurologic histo-ries. Any control subject who reported arecent history of otologic pathology (withinone year) or positive neurological history wasexcluded from the study. Handedness was notconsidered as an inclusion/exclusion factor.

The GSI Audera™ system, used for thisstudy, has two default protocols which can beused on the adult population. The use ofthese protocols allows for the assessment oftwo different regions of the CANS and twodifferent subject states. The protocol utilizedin the present investigation is referred to bymanufacturers of the GSI Audera™ as the“Awake” protocol. For the purposes of the

present investigation, the “Awake” protocolwill be referred to as the low rate protocol.This specific protocol was designed to be usedwith awake adults older than 10 years of age.It has a fixed modulation frequency of 46 Hzregardless of the frequency tested, thus like-ly eliciting a response from the auditory cor-tex. Stimuli used in this protocol were sinu-soidal in nature and used a combined ampli-tude modulation (AM) of 100% and frequen-cy modulation (FM) of 10% of the carrier fre-quency. The intensity of the stimuli is dis-cussed in the procedures. The noise criterion,or sensitivity, was set to -134.7 dBV, where-140.4 is equal to 0.1 microvolts.

In order to understand the test proce-dures, a basic knowledge of response typeswhich can be obtained via the GSI Audera™is necessary. Three response types: 1) phaselocked, 2) random and 3) noise are possible. Aphase locked response is indicative of aresponse above the subject’s threshold ofhearing. The phase locked response occurswhen the probability curve reaches 97%(p <.03). In order for this to occur, there mustbe a response which is recognizable above theongoing EEG activity. In contrast, a randomresponse is one in which the response doesnot reach probability thresholds and theRMS value, and the response does not exceed


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Table 1. Description of neurological subjects’ site of lesion and disorder.

Subject Site of Lesion Disorder

1 Pons Infarct

2 Pons Infarct

3 Pons Infarct

4 Pons Unknown

5 Temporal Lobe Internal Capsule Infarct

6 Internal Capsule Infarct

7 Striatocapsular Infarct

8 Insula Infarct

9 Capsulo-Thalamus Infarct

10 Internal Capsule Infarct

11 Parietal - Temporal Parietal Junction Tumor

Table 2. Means and standard deviations (in parentheses) for age, thresholds (in dB HL) at 500 Hz and2000 Hz, and PTAs.

Group Age 500 Hz 2000 Hz PTA Left Ear PTA Right Ear

Control 54.91 10.2 17.9 14.1 14.1(15.3) (10.9) (15.8) (12.1) (14.7)

Neurological 53.7 12.5 24.3 18.4 18.4(15.9) (7.9) (15.5) (10.1) (8.9)

the noise threshold limits. In other words,inadequate phase locking occurs. This is con-sidered to be a “no response.” It is thereforeassumed that the subject is unable to physio-logically detect that particular intensity andfrequency. Finally, a noise response is whenthe ASSR does not reach probability thresh-olds and the RMS value exceeds the noisethresholds limits. This may be the result ofexcessive internal or external noise activity.

All testing was completed in a sound-treated room or quiet listening environmentin order to reduce ambient noise levels.Subjects underwent conventional audiomet-ric evaluations using TDH 49 supra-auralheadphones. All subjects were administereda full audiometric evaluation using conven-tional clinical procedures. Normal hearingsensitivity was defined as audiometricthresholds ≤ 25 dB HL bilaterally. Pure-toneair-conduction thresholds were establishedusing a modified Hughson Westlake tech-nique. Thresholds for the octave frequenciesfrom 250 and 8000 Hz were established usinga calibrated GSI 61™ audiometer. Subjectswho demonstrated hearing thresholdsgreater than 20 dB HL between the frequen-cies of 2000 and 4000 Hz and 4000 and 8000Hz were evaluated at the inter-octave fre-quencies of 3000 and/or 6000 Hz, respective-ly. Subjects with air-conduction thresholdsgreater than 15 dB also underwent bone-con-duction testing to rule out conductiveinvolvement. Any subject who presented withan air-bone gap greater than 15 dB HL wasexcluded from the study.

Distortion Product Otoacoustic Emissions(DPOAEs) were performed on both groups ofsubjects to assess outer hair cell integrity.DPOAEs were recorded using the GSI™ 60system. The two primary stimulus tonesused to obtain the responses were 70 dB SPLwith an f2/f1 ratio of 1.2 across the frequen-cies tested. A total of 5 octaves (1000 to 5000Hz) were tested with obtaining 3 points peroctave, resulting in a total of 15 DPOAEs.Normative values were those based onDartmouth Hitchcock Medical center norms(Musiek and Baran, 1997). The internaldefault criterion was set for a maximum of150 frames. DPOAEs were repeated toinsure test-retest reliability. Results wererequired to be consistent with pure-toneaudiometric results (i.e., present in cases ofnormal peripheral hearing sensitivity, andabnormal in cases of hearing loss).

The GSI Audera™ was used as the labora-tory instrumentation for the present study toobtain and analyze ASSR responses. It waschosen due to the significant body of researchbehind its development and its widespreadclinical use. Subjects were seated in a reclin-ing chair in a comfortable position. The skinwas prepared for electrode placement bycleaning the electrode site with Nuprep™skin gel and an alcohol pad. Snap electrodeswere placed on the subject with the non-inverting electrode placed on the high fore-head (Fz), the inverting electrodes at eachmastoid (A1, A2). An electrode at the midforehead served as the ground. Impedanceswere maintained at less than 10 kilo-ohmsacross the electrode array for all subjects andconditions. The stimuli were deliveredthrough TIP-50 insert earphones which wereplaced snugly in the ear canal of each subject.

Before electrophysiological recordingswere initiated, behavioral thresholds for theASSR stimuli were established using thesame modified Hughson-Westlake procedure(see below) as used for the pure-tone testing.Subjects were presented with and responseswere obtained for the steady state stimuligenerated by the Audera™ for the octave fre-quencies of 500, 1000, 2000 and 4000 Hz.Stimuli were presented for approximately 0.5to 1 second. Subjects were asked to indicateeither verbally or manually when theydetected a tone. The threshold was consid-ered to be the lowest intensity level at whicha response was detected for 3 out of 5 pre-sentations.

All ASSR testing was pseudo-randomizedbetween ears and across order of test presen-tation. This was accomplished by counter-balancing the order of protocol, by ear pres-entation and frequency presentation.Additionally, all subjects were awakethroughout the entire test session.

ASSR thresholds were determined at thefrequencies of 500 and 2000 Hz using a 97%response criterion. These frequencies werechosen because they provided both a low fre-quency and high frequency measurement.Additionally, they reflected those frequenciesgenerally tested when tone-burst ABRs areimplemented. Threshold testing was initiat-ed at 50 dB HL. Stimuli intensity were eitherincreased or decreased depending on thepresence or absence of a response. If aresponse was present, the intensity level wasdecreased by 20 dB HL; if it was absent it


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was increased 10 dB HL. Once phase lockedand random responses were recorded within10 dB HL of each other, the final stimuluswas presented at 5 dB HL above the highestrandom response and 5 dB HL below the low-est phase locked response. The electrophysio-logical threshold was considered to be thelowest level at which a phase locked responsecould be recorded. In addition, the estimatedthreshold was also determined. The estimat-ed threshold is based on an algorithm thatprovides the predicted behavioral thresholdswhich are extrapolated from the ASSR elec-trophysiological threshold data. The extrapo-lated algorithm was derived from researchconducted at the University of MelbourneSchool of Audiology (Rance et al., 1995).

Following data collection, the Index ofRelative Approximation ThresholdEstimates (IRATE) was calculated. TheIRATE was calculated by determining thedifference between the pure-tone audiomet-ric thresholds and the estimated ASSRthresholds at both 500 and 2000 Hz. In otherwords, the equation would be: IRATE =[Thresholdbehavioral -Thresholdestimated ASSR]500

or 2000 Hz. This index was designed to evalu-ate how closely the estimated ASSR thresh-olds correlated to the actual behavioral pure-tone audiometric thresholds.

The methodology for the present investi-gation was developed in order to providemeasures to determine the ability of ASSR toaccurately and reliably estimate hearing sen-sitivity in individuals with lesions of theCANS. As will be discussed later, the meas-urements were designed in order to deter-mine correlations between behavioral andestimated ASSR thresholds, the strength of anew index (IRATE), as well as the sensitivityand specificity of the ASSR in cases of CANScompromise.

RREESSUULLTTSS

Pearson product-moment correlationswere performed to evaluate the relation-

ship between the behavioral audiometricthresholds as reflected on the pure-toneaudiogram and the estimated ASSR thresh-old (both in dB HL). Note that the pure-toneaudiometric thresholds were utilized toreflect what the authors believe the generalpopulation of audiologists would use for com-parative purposes. Table 3 provides the cor-relation coefficient comparisons between thetwo groups for each ear at both 500 and 2000Hz, along with their associated significancevalues. Results for the control group demon-strated that there was a strong and statisti-cally significant (p < 0.01) positive correlationbetween the pure-tone audiometric thresh-olds and the estimated ASSR thresholds atboth 500 and 2000 Hz for each ear. However,the analysis for the neurological grouprevealed poor and statistically non-signifi-cant correlations for the same comparisons.These results suggest that control subjectsexhibited a good relationship between theirpure-tone (behavioral) thresholds and theirestimated ASSR thresholds, whereas theneurological subjects demonstrated a poorrelationship between the same measures.Moreover, the data shows that the size of thecorrelations noted for the control group com-parisons were in general approximatelytwice those of the neurological group.

Figures 1a, b provide individual datapoints to demonstrate the correlationsbetween the behavioral pure-tone thresholdsand the ASSR-estimated thresholds.Interestingly, as shown in other studies, aninspection of the individual subject data sug-gests that control subjects with greaterdegrees of hearing loss may demonstrate acloser relationship between their behavioraland estimated ASSR thresholds than thecontrol group. The neurological group did notdemonstrate this same trend. Rather, withgreater degrees of hearing loss, the behav-ioral thresholds appear to exhibit poorer cor-relations with the estimated ASSR thresh-olds.

The IRATE index was designed to deter-


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Table 3. Correlations between behavioral and estimated ASSR thresholds for each group. Note that *indicates statistical significance beyond the .01 level.

Left Ear Right Ear

500 Hz 2000 Hz 500 Hz 2000 Hz

Control .74 .80 .75 .77*p = .009 *p = .003 *p = .008 *p = .006

Neurological .30 .57 .43 .30p = .365 p = .066 p = .182 p = .369

mine the difference between the actualbehavioral threshold as obtained by a pure-tone audiometric evaluation (behavioral) andthe estimated ASSR threshold at two fre-quencies (500 Hz and at 2000 Hz). Figure 2provides the descriptive data with respect tothe behavioral and estimated ASSR thresh-olds at these test frequencies. As a reminder,the IRATE is an absolute value, which isused to provide a measure of the accuracy ofthe estimated ASSR threshold when com-pared to the actual pure-tone threshold. Themean value was calculated by obtaining theaverage difference in threshold measuresderived by the two test procedures (pure-tone

and ASSR) for each ear at 500 and 2000 Hz.The analysis was performed in this mannerbecause no clear laterality effect has been deter-mined for the ASSR (Herdman et al., 2002).

Statistical analysis using independentsample t-tests demonstrated that there wasnot a significant difference for the IRATEindex between the means of the two groupsat 500 Hz. However, at 2000 Hz, the controlgroup exhibited an IRATE index of only 11.8dB HL, whereas the neurological group pre-sented with an IRATE index of almost 23.9dB HL. This yielded a mean difference of 12.1dB HL between the two groups. The resultssuggest that the estimated ASSR thresholds


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FFiigguurree 11.. Comparisons between behavioral versus estimated ASSR thresholds for the left (filled) and right (open)ears at both 500 Hz (diamonds) and 2000 Hz (circles). Measurements were made in dB HL. Comparisons were madefor both the normal control (upper panel) and neurological group (lower panel). The diagonal line represents a per-fect correlation in each of the two panels.

for patients with neurological damage willtend to overestimate the severity of a co-mor-bid hearing loss at 2000 Hz. For example, if asubject with CANS compromise presentswith a mild hearing loss on pure-tone testing,it is likely that his/her estimated ASSRthreshold testing would indicate the presenceof a moderate hearing loss.

A Student’s t-test was used to determine ifthere were any statistically significant differ-ences between the normal control and theneurological group at either 500 or 2000 Hz(Figure 3). Results indicate that althoughthere was no significant difference between

the two groups at 500 Hz (p = 0.39), therewas a statistically significant difference at2000 Hz (p = 0.02). This suggests that, formeasurements at 2000 Hz, there was agreater differential between the behavioraland estimated ASSR thresholds for individu-als with neurological impairment of theCANS than for subjects with preserved neu-ral integrity.

In addition, paired t-tests were performedto determine if there were any within groupdifferences between 500 and 2000 Hz.Results indicated that both the neurological-ly impaired (p = 0.02) and the control group


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FFiigguurree 22.. Mean behavioral and estimated thresholds for the control and neurological groups at both 500 and 2000Hz. Error bars represent group standard deviations.

FFiigguurree 33.. Mean IRATE values for both the normal control and neurological groups at 500 and 2000 Hz. Error barsrepresent group standard deviations.

(p = 0.03) showed a statistically significantdifference between these two tested frequen-cies. Finally, paired t-tests were performed todetermine if there were any within group eardifferences for the IRATE at both 500 and2000 Hz. Results indicated that the controlgroup did not demonstrate a statistically sig-nificant ear difference at either 500 Hz (p =0.88) or 2000 Hz (p = 0.84). The neurologicalgroup also failed to demonstrate any signifi-cant ear differences at 500 Hz or (p = 0.16) at2000 Hz (p = 0.40).

Sensitivity and specificity data werederived in order to determine if the ASSRwould be a useful tool in the detection of com-promise associated with lesions of the CANS.Sensitivity and specificity was analyzed forthe IRATE at both 500 and 2000 Hz. Fromthis point forward, the IRATE index calculat-ed at these frequencies will be referred to asthe IRATE500 or IRATE2000 respectively.

Figure 4 presents the sensitivity andspecificity data for the IRATE2000. TheIRATE2000 was the only index for which sen-sitivity and specificity was determined as aresult of the fact that it was the only indexthat yielded statistically significant differentresults. Results were analyzed using both 1and 2 standard deviations around the meanas the cut-off criteria in an attempt to deter-mine which criteria would demonstrate themaximum sensitivity and specificity. The cri-terion used for 1 standard deviation was a 20dB differential between the behavioral andestimated ASSR thresholds, and 2 standarddeviations was considered to be a 28 dB dif-

ferential. Finally, efficiency of the test is the number

of true findings (true positives and true neg-atives) divided by the total number of sub-jects. A high overall efficiency would indicatethat the test is very good at detecting thepresence and absence of a disorder. Resultsfrom data on the 22 subjects indicated thatusing a 1 standard deviation (20 dB) criteri-on resulted in a sensitivity measure of 64%and a specificity rating of 81%. Increasingthe cut-off criteria to 2 standard deviations(28 dB) decreased the sensitivity to 45%;however, the specificity increased to 91%.Test efficiency, or overall accuracy, was alsocalculated. The overall accuracy of the ASSRis found in Figure 5. There was little differ-ence in overall test efficiency between thetwo different cut-off criteria. Overall test effi-ciency for one standard deviation was 73%and for two standard deviations was 68%.The criterion used ranged from the minimumto maximum of the differentials between thebehavioral and estimated ASSR thresholds.This ranged from an IRATE criterion of 0 dBup to 40 dB. The results indicated that thebest combination of sensitivity and specifici-ty measures were achieved when a criterionof 17.5 dB was used as the cut-off betweennormal and abnormal performance. Usingthis value yielded a sensitivity of 64% and aspecificity of 82%, which resulted in essen-tially the same findings as when using onestandard deviation as the cut-off criteria.

The area under the ROC (receiver operat-ing characteristic) curve may be interpreted


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FFiigguurree 44.. Sensitivity (grey) and specificity (black) using the IRATE2000 for both one (top) and two (bottom) stan-dard deviations.

as the likelihood that a disorder will be pres-ent in comparison to the likelihood that itwill be absent. According to Hanley andMcNeil (1984), a ROC area measure fallingbetween 0.7 and 0.9 is associated with a goodtest. Anything greater should be consideredan excellent test and anything less should beconsidered a poor test. The area under theROC curve (Figure 6) was 0.77 for theIRATE2000 which is considered good.However, the area under the ROC curve forthe IRATE500 was poor at only 0.50. Theseresults suggest that the IRATE2000 may pro-vide a means for detecting dysfunction of theCANS.

DDIISSCCUUSSSSIIOONN

PPhhyyssiioollooggiiccaall MMaanniiffeessttaattiioonn ooff NNeeuurraallIInnvvoollvveemmeenntt

Results from the present investigationclearly demonstrate a discrepancy betweenbehavioral tests results and estimated ASSRthresholds in the case of CANS compromise.This phenomenon, however, is not unique tothe present investigation. Rance and col-leagues (1999, 2005) demonstrated theeffects of retrocochlear lesions on the ASSR.This particular study investigated a group ofchildren identified with presumed auditoryneuropathy based on a repeatable cochlearmicrophonic but absent auditory brainstemresponses (ABRs). These subjects were eval-uated both by behavioral and ASSR meas-ures and compared to a control group. Ofnote are the similarities between the work of

Rance and colleagues and the present inves-tigation with respect to both the poor correla-tions, in general, but also to the poorer corre-lations at higher intensities for the neurolog-ical group. Like the study by Rance and col-leagues (1999), the present investigationnoted what visually, although not statistical-ly evaluated, appeared to be poorer correla-tions at high intensities.

The poor correlations for neurological sub-jects found in both studies may be attributedto the lack of neural substrate contributing tothe responses at higher intensity levels.Although the aforementioned and presentstudies utilized different recording parame-ters with respect to both the carrier and mod-


836

FFiigguurree 55.. Overall test efficiency using one (bottom) and two (top) standard deviations.

FFiigguurree 66.. ROC curves for the IRATE index at both 500(solid line) and 2000 Hz (dotted line).

ulation frequencies, the results demonstrat-ed clear similarities. The difference in corre-lations between the experimental groups ismost likely rooted in the electrophysiologicalresponses. They are elevated (poorer) in neu-rological patients in comparison to the actualbehavioral thresholds noted in these sub-jects. If the electrophysiological responsesare elevated, then the estimated responseswould in turn be elevated. The poor correla-tions demonstrated by the neurological groupwere perhaps a result of their need forgreater neural substrate, than what wasavailable, in order to elicit a response.Theoretically, where an individual withstrong neural integrity may require only asmall percentage of neural substrate to elicita phase locked response, the compromisedsystem may require a significantly largerpercentage or area of neural substrate to elic-it a similar response. This is only accom-plished by increasing the level of the stimu-lus. For example, in a normal individual,many nerve fibers fire in response to audito-ry stimuli, even at very low intensity levels(such as at or near threshold). However, ininstances where there is compromise of theCANS, a larger neural area must be recruit-ed in order to elicit the same response that isseen in an individual with a normal auditorysystem. This is accomplished by presentingthe stimuli at a higher intensity level, whichin turn initiates the recruitment of a greaterarea of neural substrate, thus artificially ele-vating the thresholds. In order for a phase-locked response to occur, the intensity mustbe elevated to an intensity level that recruitsenough neural fibers to provide a measurableresponse. This would thus yield the large dis-crepancies observed between behavioral andestimated ASSR thresholds, resulting in theweak correlations.

The poor correlations noted in both studiesmay also be attributed to the poor phasecoherence in subjects with lesions of theCANS. Phase coherence is a statistical meas-ure of phase variance in the analysis ofsteady state responses (Picton et al., 2001).The presence or absence of an ASSR responseis dictated by the phase coherence value.Those phase coherences at or near 1 suggesta strong ASSR response, whereas those near0 indicate poor phase coherence. For exam-ple, if a subject demonstrated a phase coher-ence value of 0.89, this would suggest goodphase locking and, therefore, a high proba-

bility of a response being observed. A phasecoherence value of 0.1, however, suggestsweak phase locking and decreases the likeli-hood of a response being seen. Phase coher-ence is required in order to demonstrate anASSR to a modulated stimulus. If low phasecoherence is present, then no response iselicited. As a result of the neurological com-promise and coincident interruption in neu-ral processing, the experimental group maydemonstrate poor phase coherence even atlevels above their behavioral thresholds.

Poor phase coherence in individuals withspeech perception deficits [a form of an audi-tory processing disorder (APD)] has beendemonstrated in the literature. Ali andJerger (1992) investigated two groups of eld-erly subjects, one of which demonstratedspeech understanding which was consistentwith their degree of hearing sensitivity and asecond that demonstrated speech under-standing which was considerably poorer thanwould be expected given a similar level ofhearing sensitivity. The authors illustratedthat for steady-state evoked responses, phasecoherence although observed for both groups,was significantly poorer in the group withdisproportionate speech understandingscores. Poor speech understanding scoresmay be directly linked to an underlying APD,such as the lack of synchronicity or a tempo-ral processing deficit (Mendelson andRicketts, 2001; Downie et al., 2002).Although the subjects in the neurologicalgroup of the present investigation did notundergo a full auditory processing test bat-tery, many of them expressed difficulty withspeech comprehension based upon theirreported histories. This may be directlylinked to poor phase coherence which couldresult in poor correlations between behav-ioral and electrophysiological thresholds.Although speech perception was not evaluat-ed in the present investigation, temporal pro-cessing was assessed. Speech perceptioncould not be evaluated due to the fact thatsome of the neurological subjects were col-lected in England and were not native speak-ers of American English, or English wasthere second language. This would suggestthat there is perhaps an underlying temporalprocessing deficit (as a result of poor phaselocking) which is likely contributing to theresults of the present investigation.

It is likely that the poor correlationsbetween behavioral thresholds and estimat-


837

ed ASSR thresholds seen in the neurologicalgroup are a result of weak underlying phaselocking of the neurons involved. This may beassociated with abnormal temporal process-ing. If this is indeed the case, a temporal pro-cessing deficit would result in the lack of syn-chronicity and in turn an inability to phaselock. This would thus result in poor correla-tions as seen in the present investigation.The calculation of the differential betweenthe behavioral and ASSR estimated thresh-olds is similar to those described byMarangos and colleagues (1999). The investi-gators in that study concluded that an ABRthreshold discrepancy greater than 30 dBmay provide an additional indicator of retro-cochlear pathology.

Recall, the present study demonstratedthat there was an average of 6.1 dB differen-tial at 500 Hz and an 11.8 dB differential at2000 Hz in the normal group when the behav-ioral thresholds were compared to estimatedASSR thresholds. The neurological group pre-sented with a mean discrepancy of 8.9 dB at500 Hz and nearly a 24 dB discrepancy at2000 Hz. This discrepancy at 2000 Hz is twicethat noted for the control group, and as aresult, it is a statistically significant differ-ence! The present study clearly demonstratedthat for subjects with neurological insult,there was a discrepancy between the behav-ioral and electrophysiologically estimatedthresholds, particularly at high frequencies.Statistical analysis demonstrated a signifi-cant difference at 2000 Hz not only betweengroups, but also within groups when compar-ing frequencies. On the average, the IRATEvalue was significantly smaller at 500 Hzthan at 2000 Hz. This finding is not unique tothe current investigation, as similar findingshave been reported previously in the litera-ture (Cone-Wesson et al., 2002 a). The poorerASSR threshold correlations in the higher fre-quencies for the general population are likelya contributing factor to the significant resultsat 2000 Hz in the present study.

Elevated threshold estimation is notunique to the ASSR and may be more pro-nounced for EPs generated from the auditorycortex. Soliman and colleagues (1993) inves-tigated a large group of patients with epilep-tic seizures using behavioral audiometry, aswell as the MLR and ASSR. MLR recordingsfor 40.7% of their population showed thresh-olds that were elevated over pure-tonethresholds. The elevated thresholds were

attributed to a disturbance in the neuro-transmission of impulses at both the brain-stem and cortical levels. Ineffective neuro-transmission in individuals with neurologi-cal impairment may play a vital role in theinability of the ASSR to accurately and reli-ably predict behavioral thresholds. .

One must also consider that processing ofthe ASSR stimuli is not instantaneous, butthat the processing of the signal must coursethrough the entire auditory system. It hasbeen suggested that phase locking deterio-rates as it ascends the central auditory path-way (Kidd and Weiss, 1990), creating a loss ofsynaptic transmission known as synaptic“jitter” (Blackburn and Sachs, 1989). Phaselocking has also been found to deteriorate asthe frequency increases. This is particularlyevident at or above 2-3 kHz. The combinationof synaptic jitter and the decrement of phaselocking for mid to high frequency tones maycontribute to the present findings of a statis-tically significant IRATE2000 between the twogroups. If, in a healthy neurological system,there is some degree of synaptic degradation,then it follows that an impaired neurologicalsystem will undergo an even greater degreeof degradation by the time the signal reachesthe auditory cortex.

Demyelination may also contribute to theresults seen in this study. It has been estab-lished that axonal degeneration and demyeli-nation occurs after central nervous systeminjury (Milanov, 1995). This provides aninteresting link to auditory neuropathy. Ithas been suggested that auditory neuropathyresults from demyelination or possible axon-al loss of the auditory nerve (Starr, Pictonand Kim, 2001). This would affect the abilityof the auditory system to fire synchronouslyand at high rates. As indicated by Starr andcolleagues (2003), this would have a directimpact on the auditory system’s ability toprecisely encode temporal cues, and wouldlikely result in impaired speech comprehen-sion and poor gap detection abilities. Starrand colleagues (1991) also indicated that thislack of synchronous firing would also resultin the inability to obtain an ABR. If somedegree of demyelination or axonal loss of theneural substrate is occurring within the cen-tral system as a result of a lesion, it is likelythat this condition may be influencing theability of the neurologically compromisedsubject to demonstrate an accurate and reli-able ASSR. It should be noted that this may


838

not only be true for auditory neuropathy, butalso for other disorders of the central nervoussystem.

As stated above, there are several theoriesand data which may explain the discrepan-cies observed in the present investigation.Further research using both human and ani-mal models has the potential to assist ininvestigating the causes of such discrepantresults. However, it is a result of the differen-tial observed between behavioral and esti-mated ASSR results that the ASSR may actu-ally prove to be a powerful tool in the diagno-sis and detection of lesions of the CANS.

AA DDiiaaggnnoossttiicc IInnddeexx

The present study demonstrates that inthe cases of compromise to the CANS, ASSRdemonstrates weaknesses in its ability toaccurately and reliably determine hearingsensitivity. In particular, the ASSR demon-strate poor correlations between behavioraland estimated ASSR thresholds. However, inlight of this negative finding, the authorspropose the possible use of ASSR in theassessment and diagnosis of individuals withauditory processing disorders. An auditoryprocessing disorder (APD), as defined in theJournal of the American Academy ofAudiology, is as follows:

An APD may be broadly defined as a deficit inthe processing of information that is specific tothe auditory modality. The problem may beexacerbated in unfavorable acoustic environ-ments. It may be associated with difficulties inlistening, speech understanding, languagedevelopment and learning. In its pure form,however, it is conceptualized as a deficit in theprocessing of auditory input. [Jerger andMusiek, 2000, pp 467-468]The assessment of individuals with APD

through behavioral methods has existed formore than 30 years. The use of evoked poten-tials for this purpose is now being imple-mented into clinical test batteries. The ques-tion may be raised as to why neurologicalpatients have been used historically in thedevelopment of central auditory tests.Perhaps the key phrase used in the workingdefinition above as it relates to the presentstudy is the “deficit in the processing of audi-tory input.” Subjects with lesions of the CANSare essentially the only population that canbe used in a clinical investigation. It isknown that subjects with known lesions ofthe CANS will often present with auditory

processing difficulties because key structuresresponsible for proper central auditory func-tion have been compromised. Therefore, bydefinition, they may be labeled as presentingwith an APD in some form.

Additionally, subjects with known lesionsare advantageous to study because today’stechnology allows for the implementation ofadvanced imaging techniques. Researchersare therefore better able to profile APD as itrelates to very specific sites of lesion andstructures involved, making these individu-als ideal subjects to study. Not all individualswho present with APD have discrete lesionsof the CANS as identified by imaging tech-niques. In fact, a majority of the patientsseen clinically are those who present withcentral auditory compromise without suchevident damage. These are often childrenand adults with longstanding difficulties pro-cessing auditory information in spite of thefact that they have “normal” auditory struc-tures, at least as far as can be determined bymodern imaging techniques.

So why investigate subjects with lesions tomake a diagnosis of APD for individuals with-out lesions? Quite simply, the only manner inwhich a central auditory test can be trulyassessed is to first test a group of subjects withknown lesions of the CANS. This serves twopurposes. The first is that it provides us witha better understanding of how lesions of theCANS affect actual test results (Lusted, 1978).Second, it allows clinicians and researchers toobtain sensitivity, specificity and efficiencydata, which help to determine the clinical util-ity of a test. The rationale of the present studywas not only to determine the effects of neuro-logical lesions on the ASSR, but also to probeits ability to be used in a clinical APD test bat-tery. Although some degree of discrepancywould be expected, it is perhaps the degreesize of the discrepancy which should be con-sidered clinically significant.

SSeennssiittiivviittyy aanndd SSppeecciiffiicciittyy

Although the weakness of the ASSR toaccurately and reliably predict auditorythresholds in the presence of neurologicalinsult of the CANS is evident based upon theprevious findings, it was still hoped that per-haps this tool would still have value in itsability to accurately identify cases of possibleCANS involvement. The present study yield-ed sensitivity and specificity measures, of


839

64% and 81% for 1 standard deviation and45% and 91% for 2 standard deviations.Although the sensitivity values are only fairfor both cut-off criteria, the specificity meas-ures for the test using the IRATE2000 arequite good. The ASSR, recorded using a fre-quency modulation of 46 Hz, is believed to begenerated by mechanisms similar to theMLR (Cone-Wesson et al., 2002a). Therefore,associations will be made between the sensi-tivity and specificity of the traditional MLRin comparison to the ASSR at a 46 Hz fre-quency modulation rate.

ROC curves demonstrated the trade-offbetween sensitivity and specificity for vari-ous criteria of the IRATE2000 index. The ROCcurves indicated that the best sensitivity andspecificity measures were obtained using acriterion of 17.5 dB as the cut-off betweennormal and abnormal performance. Usingthis value yielded a sensitivity of 64% and aspecificity of 82%, which were similar to theresults noted above when a one standarddeviation cut-off criteria was applied. Thearea under the ROC curve was 0.769 whichis considered good. There is generally aninverse relationship between the sensitivityand specificity of any diagnostic test. Moreprecisely, as sensitivity is increased, specifici-ty is generally decreased and vice versa(Turner, Robinette and Bauch, 1991).Therefore, in order to increase the sensitivityof this index, the specificity would also becompromised.

The sensitivity of the traditional MLR forthe detection of lesions of the CANS has notbeen extensively investigated. Kraus and col-leagues (1982) studied a group of subjectswith lesions of the CANS and found the sen-sitivity of the MLR to be about 50%. Thehighest sensitivity reported in the literaturethus far was 73.3% for subjects with multiplesclerosis (Celebisoy et al., 1996). Musiek andcolleagues (1999) investigated several meas-ures of the MLR to determine which yieldedthe best sensitivity and specificity measuresfor the detection of lesions of the CANS, sim-ilar to the sensitivity in the present investi-gation. They found that using a contralateralamplitude differential measurement ofgreater than 20% between the two ears pro-vided the best combination of sensitivity andspecificity measures. These findings supportthe consideration of the amplitude of theASSR at supra-threshold response as analternative index.

The most recent investigation of sensitivi-ty and specificity for EPs compared tradi-tional ABR, MLR and slow cortical responsesin subjects with multiple sclerosis (Japaridze,Shakarishvili and Kevanishvili, 2002). TheMLR demonstrated a sensitivity of 42.5%,similar to the results for the ASSR obtainedin the present study. Additionally, when theMLR was used in conjunction with the ABR,sensitivity increased to 80%. By obtainingthe ASSR at both low (46 Hz) and high (> 80Hz) frequency modulations, it would be rea-sonable to expect that the overall sensitivityin the detection of lesions of the CANS wouldalso increase. The authors acknowledge thefact that few studies have looked at the lowermodulation rates and the present findingsshould not be over-generalized.

Although the sensitivity of the presentstudy was not as strong as had been antici-pated, this measure may have improved witha larger sample size. Additionally, the ASSRmay prove to be more sensitive for brainstemlesions than for sub-cortical or corticallesions. However, the size of the current pop-ulation (four subjects with brainstem lesionsand seven with lesions of the sub-cortex andcortex) did not allow for differential testing inthe present study. As additional confirmedCANS lesions are added to the sample, it isexpected that this investigation will obtain amore accurate indication of the sensitivityand specificity of the ASSR in the detection oflesions of the CANS.

IImmpplliiccaattiioonnss

The results of the present study have sig-nificant implications with respect to the useof ASSR in the screening and diagnosis ofhearing loss for both pediatric and adult pop-ulations. Perhaps the most significant con-cern is the use of ASSR with infants, particu-larly those at risk for neurological insult.Additionally, as the ASSR popularityexpands, so will its use in adult and difficult-to-test populations who are also at risk forneurological compromise.

In 1994, it was documented that neurolog-ical disease or insult accounts for 20% of allhospital admissions (Playford, Crawford andMonro, 1994). Of those, strokes accounted for26% of the diagnoses, followed by degenera-tive diseases at 10%. In 2002 alone, 4.8 mil-lion adults in the United States had experi-enced a stroke at some point in their lifespan


840

(National Center for Health Statistics, 2005);that translated into a prevalence rate of2.4%. Depending on where the site of lesion islocated, many of these individuals mayexhibit auditory deficits.

Perinatal stroke has also become increas-ingly recognized. The current estimates ofperinatal stroke are 1 in 4000 births (Lynchand Nelson, 2001). This rate may also be arti-ficially low as it is acknowledged that perina-tal stroke is often not diagnosed. A majorityof these perinatal strokes involve the middlecerebral artery, which is the primary bloodsupply to the auditory cortex. With such ahigh incidence rate, there is an increasedpossibility of the misdiagnosis of a hearingloss and/or the overestimation of the degreeof hearing loss in newborns and young chil-dren if the hearing status is determined bycurrent ASSR procedures.

Many other pathologies, such ashyperbilirubinemia, perinatal asphyxia,cytomegalovirus and meningitis, alsoplace children at risk for neurologicalimpairment. The Academy of Pediatricsreported that approximately 60% of infantsborn in the United States develop clinicaljaundice. Neonatal hyperbilirubinemia is apathology which may lead to central nervoussystem toxicity and often results in hearingloss related to brainstem dysfunction. Whenit reaches toxic levels, hyperbilirubinemia isknown as “kernicterus.” Kernicterus hasbeen associated with severe neurologicalimpairments and is believed to be responsi-ble for pathologies such as brainstem com-promise (Moller, 2000).

The prevalence of neurological impair-ments in the pediatric population is current-ly not reported. Clinicians, however, have aresponsibility to their patients to be keenlyaware of their neurological status.Additionally, they should understand theeffects of lesions on the CANS for both behav-ioral and electrophysiological test results.The results of the present study, as well asthose from investigators such as Rance andcolleagues (1999), indicate that clinical audi-ologists should be concerned about the accu-racy of the estimated ASSR thresholds inindividuals with neurological compromise ofthe CANS. Additionally, and perhaps moreimportantly, elevated ASSR thresholds mayindicate neurological compromise, in particu-lar in infants with neurological history.

Specifically, the ASSR may overestimate

the degree of hearing impairment for a givenindividual in the presence of an abnormalCANS. For example, a child with a perinatalstroke due to a traumatic birth history mayreceive an electrophysiological evaluation todetermine hearing sensitivity due to a failednewborn hearing screening. If the ASSR isused as the sole screening procedure, thisinfant could be diagnosed with a hearingimpairment that may not be present, or if itis present, it is not as severe as the estimat-ed ASSR thresholds indicate. This type ofneurologic compromise may result not onlyfrom a stroke, but also from conditions affect-ing the neurological system. These mayinclude trauma, seizures and hydrocephalus,as well as hyperbilirubinemia.

As it is currently administered, the ASSRmay not accurately and reliably estimatehearing sensitivity in an adult neurologicalpopulation. This leads one to question itsability to do so in the pediatric population. Itis anticipated that the procedure may havelimited application for use with those infantsand children with neurological compromise.Although this study demonstrated some pos-sible negative implications with respect tothe use of the ASSR in the assessment ofhearing sensitivity in adults with possiblecompromise of the CANS, it may show prom-ise as an objective central auditory test ifadditional modifications to the current proto-cols can be made. It may provide an alterna-tive means for detecting and diagnosing dis-orders of the CANS, such as auditory pro-cessing disorders, temporal processingdeficits and speech perception impairments.

SSuummmmaarryy

The present investigation may be the firstto study the effects of lesions of the CANS onthe ASSR. The current investigation hasdemonstrated some possible negative impli-cations with respect to its ability to accurate-ly and reliably determine ASSR thresholds incases of CANS involvement. However, in spiteof this potential limitation, the ASSR maystill prove to be a highly useful diagnostic toolin the detection of abnormal CANS function-ing in both pediatric and adult populations.Currently, diagnostic measures such as theABR and MLR are used in both thresholdestimation and the diagnosis of CANSinvolvement. The ASSR has the potential toalso be clinically implemented in a similar


841

manner. The ASSR is an attractive tool in the diag-

nosis of possible CANS compromise because itpossessed some diagnostic elements whichare lacking in more mainstream EPs. Theseinclude frequency specificity, modulated stim-ulus and some relative flexibility with respectto the stimulus. Additionally, the ASSR mayprovide a means for electrophysiological cor-relates to psychoacoustic measures such astemporal modulation transfer functions.There are likely many ways in which theASSR could be implemented in the diagnosticarena which have yet to be explored.

The ASSR is currently in its infancy, par-ticularly with respect to its use on popula-tions with retrocochlear pathologies and dis-orders not related to peripheral hearingimpairment. As a result, there are manyavenues which have yet to be investigatedthat deserve attention in the future. Furtherresearch on the ASSR will hopefully yieldpromising results with respect to its use inthe detection of CANS compromise. In addi-tion, it may prove to be a useful tool in deter-mining efficacy of subsequent remediation.

AAcckknnoowwlleeddggmmeennttss.. A special thank you to Drs. DorisEva-Bamiou and Linda Luxon for their significant helpand guidance with subject recruitment.

RREEFFEERREENNCCEESS

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