Behavioral Studies of the Olivocochlear Efferent System Learning to Listen in Noise

ORIGINAL ARTICLE Behavioral Studies of the Olivocochlear Efferent System Learning to Listen in Noise

Bradford J. May, PhD; Jennifer Budelis; John K. Niparko, MD

Background: Olivocochlear (OC) neurons make up an Results: As predicted by the hypothesized function of efferent, descending auditory system that returns sound OC feedback systems, the lesioned cats exhibited sig- representations to the inner ear soon after they have en- nificantly elevated thresholds only when tested in back- tered the brain. Efferent inputs into the cochlea modu- ground noise. This initially poor performance returned late outer hair cell activity to improve the neural encod- to normal values after long-term exposure to the testing ing of auditory signals in background noise. Based on this procedure. physiological evidence, loss of efferent feedback is expected to degrade perception in noise. Attempts to con- firm this prediction with long-term audiological assess- Conclusions: The results of our animal studies support ments have met with mixed results. the OC enhancement of sound localization behavior in background noise. Also, our behavioral observations Objective: To isolate procedural factors that may di- suggest the acquisition of alternate listening strategies minish the demonstration of long-term OC deficits in lis- that allowed lesioned cats to minimize the functional tening tasks. consequences of their auditory deficits by attending more closely to remaining directional cues. These Design: Operant conditioning procedures were used to learned compensatory behaviors were encouraged by train domestic cats to signal a change in the location of our present experimental design, which incorporated an auditory stimulus by responding on a lever. The small- long-term training under consistent stimulus condi- est detectable change in location was measured by ma- tions. These findings point out the potential limitations nipulating the distance between speakers under quiet con- of the highly routine audiological procedures that have ditions and in the presence of background noise. been used to assess the impact of OC feedback on Functional consequences of efferent feedback were evalu- human hearing. ated by comparing the sound localization thresholds of OC-lesioned cats with normal controls. Arch Otolaryngol Head Neck Surg. 2004;130:660-664

HE PERIPHERAL AUDITORY system, which links the superior olivary system distributes the complex to the cochlea.1 These efferent physical dimensions of an projections constitute a reflex arc that has acoustic stimulus across the capacity to modify the neural repre- large populations of neu- sentations of sound at the earliest stages rons.T The extraction of elemental percep- of auditory processing (Figure 1A). Al- tual attributes, such as loudness, pitch, and though 2 separate OC systems are im- location, from this highly encoded repre- plied by anatomical differences between sentation demands intensive neural com- efferent neurons in the medial and lateral putations that involve no less than 9 sub- brainstem,2 current physiological descrip- cortical nuclei. Information does not tions are limited to medial OC (MOC) neu- simply ascend the processing levels of the rons.3,4 The present study investigated the central auditory system. Within each behavioral consequences of MOC influ- nucleus, ascending representations are ences that are inferred from these physi- From the Department of transformed by descending influences from ological results. Otolaryngology–Head and Neck Surgery, The Johns higher-order neurons to emphasize the Olivocochlear projections termi- Hopkins University, Baltimore, specific parameters that characterize a nate within the cochlear nucleus and in- Md. The authors have no sound. ner ear (Figure 1B). The MOC fibers in- relevant financial interest in The most widely studied efferent au- fluence cochlear sensitivity and frequency this article. ditory pathway is the olivocochlear (OC) tuning by altering the sound-driven elec-

(REPRINTED) ARCH OTOLARYNGOL HEAD NECK SURG/ VOL 130, MAY 2004 WWW.ARCHOTO.COM 660

©2004 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 09/25/2021 tromotile responses of outer hair cells.5 This mecha- nism for automatic gain control may protect the ear from A damaging sounds and also enhance hearing in back- Brain 6-8 ground noise. Because outer hair cells play a pivotal Ear role in MOC feedback, common forms of sensorineural hearing loss compromise not only ascending auditory rep- Olivary Complex resentations but also the principal effectors of the descending OC system. It is possible to manipulate OC neurons indepen- Cochlea dently of the ascending auditory pathways because efferent axons follow a separate course through the brain- B Cochlea stem and into the cochlea. In most animal studies, the OC fibers are exposed along the floor of the fourth ventricle (Figure 2A), where the neurons may be acti- vated by electrical stimulation or silenced by surgical le- 9,10 Afferent sions. These interventions most effectively address the Axons extensively crossed pathway of the MOC system. Outer On exiting the lateral brainstem, OC axons enter the Hair Cells 11 Inner cochlea via the inferior branch of the vestibular nerve. Efferent Hair Cells This anatomical detail has important clinical implica- Axons tions. When the vestibular nerve is sectioned to allevi- Figure 1. The reflex arc of medial olivocochlear neurons. A, The auditory ate intractable balance disorders, patients maintain af- brainstem of the cat in frontal section. Sound representations from the ear ferent function but lose all efferent feedback to the affected ascend to the olivary complex via the ventral afferent pathway and project ear (Figure 2B). back to the ear via the dorsal efferent pathway. B, Cross-sectional view of the inner ear. The major ascending afferent pathway arises from inner hair cells. Previous clinical studies have attempted to associ- Descending medial olivocochlear projections terminate on outer hair cells. 12-14 ate OC lesions with a unique pattern of hearing loss. Adapted from Hearing Research (Liberman MC. Effects of chronic cochlear These audiological assessments have investigated tone de-differentiation on auditory-nerve response. Hear Res. 1990;49:209-224) detection, intensity and frequency discrimination, ©1990, with permission from Elsevier. loudness adaptation, frequency selectivity, and spatial lateralization. Although an emphasis has been placed on stimulus conditions that maximize OC influences A in physiological preparations,14 demonstrations of auditory deficits in patient populations have been SC equivocal. IC Electrical Stimulation CBL Brainstem Lesions Based on clinical outcomes, it was hypothesized that Fourth conventional audiological procedures may fail to assess Ventricle OC function. To test this hypothesis, an animal behav- Lesion Crossed Site ior study was conducted to evaluate the effects of bilat- CN eral OC lesions on the sound localization behaviors of Uncrossed AN domestic cats. As predicted by previous behavioral and VN LSO physiological results, lesioned cats showed poor perfor- MSO mance when directional acuity was measured in the presence of continuous background noise. Initially robust per- Vestibular Nerve Section ceptual deficits diminished after repeated testing under B constant stimulus conditions. These findings suggest that Figure 2. Functional manipulations of the olivocochlear pathways. A, Most low-uncertainty audiological procedures may obscure the laboratory studies involve electrical stimulation or surgical lesions along the functional significance of efferent feedback by promot- floor of the fourth ventricle. Brainstem lesions are most effective if they are ing compensatory listening strategies. made bilaterally. B, Vestibular nerve (VN) sections eliminate olivocochlear projections in route to the ear. AN, auditory nerve; CBL, cerebellum; CN, cochlear nucleus; IC, inferior colliculus; LSO, lateral superior olive; MSO, METHODS medial superior olive; SC, superior colliculus. Adapted from Hearing Research (Liberman MC. Effects of chronic cochlear de-differentiation on All surgical and behavioral procedures were approved by the auditory-nerve response. Hear Res. 1990;49:209-224) ©1990, with permission from Elsevier. Institutional Animal Care and Use Committee of The Johns Hop- kins School of Medicine, Baltimore, Md. Detailed descriptions of training methods for sound localization testing in cats are tained clean ears, good general health, and normal adult weights provided in previous publications.15,16 for the course of experiments. Experiments were performed on 6 adult male cats. The cats Experimental trials were designed to test the subject’s were individually caged and fed a restricted diet of dry chow. ability to detect changes in the elevation of a sound source in The feeding regimen was supplemented by liquefied meat paste quiet and in background noise. The cats were trained to that served as rewards for correct responses during behavioral release a response lever when auditory stimuli shifted from a testing sessions. Cats showed a strong appetite for meat paste reference speaker directly in front of the subject (0° elevation) and only moderate food deprivation was needed to motivate to a randomly selected comparison speaker at a higher eleva- subjects to work continuously for hourly sessions. Each cat main- tion in the median plane. After correct releases, a peristaltic

(REPRINTED) ARCH OTOLARYNGOL HEAD NECK SURG/ VOL 130, MAY 2004 WWW.ARCHOTO.COM 661

©2004 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 09/25/2021 Testing in noise began after subjects demonstrated stable A B detection of target stimuli under quiet conditions. Continu- 16 Intact, Quiet 16 Intact, Noise ous broadband noise was presented from a fixed location directly over the subject’s head. The level of the background noise was gradually increased over several sessions to determine the 12 12 maximum tolerable level for subjects with intact OC systems. Elevation

° A noise spectrum level of 15-dB SPL proved to be challenging Natural 8 8 enough to elevate sound localization thresholds without dis- Deficit rupting behavioral stability. Threshold, Olivocochlear influences on sound localization behavior 4 4 were investigated by making brainstem lesions in 3 cats. The objective of the lesion was to transect OC axons as they pass Wi1 Po2 Ba3 Ma4 Co5 Sa6 Wi1 Po2 Ba3 Ma4 Co5 Sa6 beneath the floor of the fourth ventricle (Figure 2A). This route C D is taken by all crossed fibers as well as by a substantial number 16 Lesioned, Quiet 16 Lesioned, Noise of uncrossed MOC fibers. The largely uncrossed lateral OC pathway is spared by this lesioning paradigm. After the cerebellum was elevated to gain access to the fourth ventricle, bilateral in- 12 12 cisions were placed in relation to anatomical landmarks pro- Elevation

° vided by the anterior and posterior cerebellar peduncles. The cuts were oriented in the parasagittal plane at opposite sides 8 8 of the midline (Figure 2A). Threshold,

4 4 RESULTS Wi1 Po2 Ba3 Ma4 Co5 Sa6 Wi1 Po2 Ba3 Ma4 Co5 Sa6 Subject Subject Domestic cats have the acute auditory sense of a noctur- Figure 3. Effects of olivocochlear lesions on sound localization thresholds. nal predator. In addition to their remarkably sensitive A and B, Normal thresholds for 3 intact cats under quiet conditions and in hearing, these animals have excellent spatial acuity. Sound continuous background noise. Cat Sa6 exhibited a natural behavioral deficit localization thresholds thus serve as a practical yet strin- in background noise. C and D, Thresholds for 3 cats with bilateral brainstem lesions. gent test of optimal auditory performance. The 3 intact cats produced thresholds that aver- aged less than 4° under quiet conditions (Figure 3A). pump delivered 1 mL of liquefied food to a spout near the Thresholds increased to 6.7° in continuous background subject’s mouth. noise (Figure 3B). Although noise effects were signifi- Auditory stimuli were noise bursts with a duration of 200 cant (paired t test, PϽ.05), this outcome was predeter- milliseconds and rise and fall times of 10 milliseconds. The noise mined because standard testing conditions were ascer- bursts were synthesized for each presentation using a digital- tained by increasing noise levels until localization deficits to-analog converter with a sampling rate of 100 kHz (RP2; were observed in intact cats. Tucker Davis Technologies, Alachua, Fla). Noise spectrum lev- Olivocochlear lesions exacerbated the disruptive ef- els were randomized from 5- to 15-dB sound pressure level (SPL) to eliminate loudness cues that may have coincided with speaker fects of background noise on sound localization behav- changes. ior. Average thresholds of the 3 lesioned cats more than Sound localization thresholds were derived from re- doubled in relation to normal baselines (Figure 3D). The sponses to an array of comparison speakers in the median plane. statistical difference between lesioned and intact cats was The comparison speaker nearest the reference speaker yielded highly significant (t test, PϽ.005). Despite their pro- low detection rates. The most widely spaced speaker elicited nounced noise deficits, the lesioned cats maintained ex- near-perfect performance. No change from the reference to a cellent directional hearing under quiet conditions (Fig- comparison speaker occurred on 20% of the trials to monitor ure 3C). false-positive responses (ie, guessing). On average, less than The magnitude of sound localization deficits de- 20% of these so-called catch trials elicited false alarms. creased in lesioned cats with prolonged testing. Audi- Threshold was defined as the change in location where response rates reached the signal detection convention d′=1. tory compensation is illustrated by the daily postlesion Signal detection methods provide an unbiased estimate of thresh- thresholds of cat Ba3 (Figure 4). The localization be- old by correcting for false alarm rates. This statistic was calcu- haviors of this representative subject appeared normal ′ lated as follows: d =z(Phit) – z(Pfalse alarm), where z(Phit) is the z under quiet testing conditions. After a stable threshold score for the percentage of hits for a comparison speaker and was obtained in quiet, noise levels were gradually in- z(Pfalse alarm) is the z score for the percentage of false alarms for creased to standard noise conditions (15-dB SPL). Un- catch trials. Because d′ usually does not equal 1 at any of the like the intact cats, who adapted quickly to background comparison speaker locations, the change in elevation at thresh- noise, the lesioned cats required several weeks of addi- old was interpolated from measured values. tional training, smaller incremental changes, and more Reported thresholds were based on combined psycho- repetitive exposures to complete the process of adjust- physical data from a minimum of 10 consecutive testing sessions. To contribute to this summary, daily thresholds could ment. Thresholds in Figure 3C and D reflect the first 10 not deviate by more than 20% from average values or show gen- days of stable performance in quiet and standard noise eral trends toward improving (or deteriorating) performance. conditions for each subject. Also, false alarm rates could not exceed 30% on any day. Trained Cat Ba3 produced stable thresholds in background cats rarely failed to meet the criteria for stability. noise for weeks before developing compensatory listen-

(REPRINTED) ARCH OTOLARYNGOL HEAD NECK SURG/ VOL 130, MAY 2004 WWW.ARCHOTO.COM 662

©2004 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 09/25/2021 ing strategies. The daily thresholds shown in Figure 4 focus on sessions during which thresholds decreased from 20 Noise an average of 13.1° to 5.5° in noise. The learning effect Quiet Ͻ was statistically significant (t test, P .001). 15 Elevation

COMMENT ° 10 The present experiments used behavior-based audiological procedures to assess the effects of OC lesions on sound Threshold, localization performance under optimum (quiet) and chal- 5 lenged (noise) conditions. Intact cats showed excellent

spatial acuity in quiet. Normal levels of performance were 0 also noted in subjects with bilateral OC lesions. Based 1234 5 6 7 8 9 10 11 on these observations, it may be assumed that general- Consecutive Sessions ized hearing disorders or motor deficits did not impair Figure 4. Effects of training on the sound localization thresholds of lesioned the ability of lesioned cats to perform the localization task. cat Ba3. Consecutive daily thresholds in noise illustrate the transition from Also, these results suggest a limited role for OC feed- initial deficits to normal performance. These compensatory behaviors were back under quiet listening conditions. observed after weeks of testing in noise. Normal thresholds in quiet were obtained before testing in noise and did not require long-term exposure to The relatively small effects of continuous back- the sound localization task. ground noise on the sound localization thresholds of intact cats support previous interpretations for the OC enhancement of auditory processing in noise.17 The deficits clude intact adjacent frequencies.28 Injury- and use- of cat Sa6 may reflect exceptional natural variations that related cortical reorganizations appear analogous; ie, have been described for the strength of OC feedback in expanded cortical representations have been linked to su- humans and other animals.18,19 Clinical studies have in- perior performance in operant-conditioned discrimina- vestigated this phenomenon by measuring the suppres- tion tasks that require frequency specific behavioral re- sion of otoacoustic emissions by the activity of OC neu- sponse.29 Although the details of the neural reorganizations rons.20-22 Weak efferent suppression is correlated with poor that subserve improved signal detection in noise remain performance in background noise.6,22,23 to be described, the present data suggest that the recov- Lesioned cats exhibited significantly larger local- ery of auditory signal processing after loss of efferent feed- ization deficits in noise than normal controls. These find- back is amenable to similar training effects. ings support correlation studies in humans but do not Our observations in cats with experimentally in- replicate the modest or inconsistent perceptual deficits duced hearing deficits provide a simple, but informa- that are induced by surgical procedures in patients who tive, model for future studies of the complex dynamics have undergone a vestibular neurectomy.12-14 Although between auditory experience and aural rehabilitation. the clinical studies may be criticized because vestibular From this perspective, learning effects that enhance au- nerve sections are often associated with Me´nie`re’s dis- ditory discrimination in OC-lesioned cats represent an ease, lesioning paradigms also yield contradictory re- important step toward the refinement of procedures to sults in animals with normal preoperative hearing.10,24 promote the acquisition of communication skills after The OC lesion was designed to evaluate the function hearing is restored by cochlear implantation or conven- of recurrent connections between the brain and cochlea that tional aids. The question remains, “Do training strate- are thought to preserve the neural encoding of auditory in- gies that succeed within the narrow confines of routine formation in the presence of background noise. Loss of the audiological procedures prepare hearing-impaired lis- OC efferent pathway did not produce the expected, con- teners for less predictable auditory challenges?” To an- sistent loss of sound localization behavior. Rather, consid- swer this question, descriptions of functional recovery erable variability was observed between subjects during must extend beyond controlled laboratory conditions to long-term audiological assessments. Patterns of response the complex and uncertain environments that charac- that slowly returned to normal baseline levels of perfor- terize everyday listening. mance suggest learned compensation in some subjects. In- deed, experimental protocols with prolonged testing tend Submitted for publication January 6, 2004; accepted Janu- to report less robust effects of OC efferent pathway lesion- ary 21, 2004. ing in contrast to short-term assessments, even when simi- This research was funded by grant R01 DC00954 from lar testing procedures are used.25,26 This apparent recov- the National Institute on Deafness and Other Communica- ery of function is not a consequence of incomplete surgical tion Disorders, Bethesda, Md. procedures. Genetically modified mice with no periph- This study was presented at the Ninth Symposium on eral OC function also achieve normal auditory perfor- Cochlear Implants in Children; April 25, 2003; Washing- mance in background noise with sufficient training.27 ton, DC. It is tempting to consider the long-term functional Corresponding author and reprints: Bradford J. May, consequences of OC lesions in terms of central auditory PhD, The Johns Hopkins University, Department of Oto- reorganization following peripheral sensory defects. In laryngology–Head and Neck Surgery, Traylor Bldg, Room cats with restricted cochlear lesions, the frequency se- 505, 720 Rutland Ave, Baltimore, MD 21205 (e-mail: lectivity of the deprived cortical region expands to in- [email protected]).

(REPRINTED) ARCH OTOLARYNGOL HEAD NECK SURG/ VOL 130, MAY 2004 WWW.ARCHOTO.COM 663

©2004 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 09/25/2021 WC, eds. Methods in Comparative Psychoacoustics. Basel, Switzerland: Birkha¨user REFERENCES Verlag; 1995:95-108. 16. Huang AY, May BJ. Spectral cues for sound localization in cats: effects of fre- 1. Rassmussen GL. The olivary peduncle and other fiber projections of the supe- quency domain on minimum audible angles in the median and horizontal planes. rior olivary complex. J Comp Neurol. 1946;99:61-74. J Acoust Soc Am. 1996;100:2341-2348. 2. Warr WB, Guinan JJ Jr. Efferent innervation of the organ of Corti: two separate 17. Kirk EC, Smith DW. Protection from acoustic trauma is not a primary function of systems. Brain Res. 1979;173:152-155. the medial olivocochlear efferent system. J Assoc Res Otolaryngol. 2003;4:445- 3. Liberman MC, Brown MC. Physiology and anatomy of single olivocochlear neu- 465. rons in the cat. Hear Res. 1986;24:17-36. 18. Arnesen AR, Osen KK. Fibre population in the vestibulocochlear anastomosis in 4. Gifford ML, Guinan JJ Jr. Effects of electrical stimulation of medial olivoco- the cat. Acta Otolaryngol. 1984;98:255-269. chlear neurons on ipsilateral and contralateral cochlear responses. Hear Res. 1987; 19. Luebke AE, Foster PK. Variation in inter-animal susceptibility to noise damage is 29:179-194. associated with alpha 9 acetylcholine receptor subunit expression level. J Neu- 5. Dallos P, He DZ, Lin X, Sziklai I, Mehta S, Evans BN. Acetylcholine, outer hair rosci. 2002;22:4241-4247. cell electromotility, and the cochlear amplifier. J Neurosci. 1997;17:2212-2226. 20. Liberman MC, Puria S, Guinan JJ Jr. The ipsilaterally evoked olivocochlear re- 6. Micheyl C, Perrot X, Collet L. Relationship between auditory intensity discrimi- flex causes rapid adaptation of the 2f1-f2 distortion product otoacoustic emis- nation in noise and olivocochlear efferent system activity in humans. Behav Neu- sion. J Acoust Soc Am. 1996;99:3572-3584. rosci. 1997;111:801-807. 21. Giraud AL, Garnier S, Micheyl C, Lina G, Chays A, Chery-Croze S. Auditory ef- 7. Maison SF, Luebke AE, Liberman MC, Zuo J. Efferent protection from acoustic ferents involved in speech-in-noise intelligibility. Neuroreport. 1997;8:1779- injury is mediated via alpha9 nicotinic acetylcholine receptors on outer hair cells. 1783. J Neurosci. 2002;22:10838-10846. 22. Kim DO, Dorn PA, Neely ST, Gorga MP. Adaptation of distortion product oto- 8. Rajan, R. Crossed and uncrossed olivocochlear pathways exacerbate temporary acoustic emission in humans. J Assoc Res Otolaryngol. 2001;2:31-40. shifts in hearing sensitivity after narrow band sound trauma in normal ears of 23. Micheyl C, Collet L. Involvement of the olivocochlear bundle in the detection of animals with unilateral hearing impairment. Audiol Neurootol. 2003;8:250-262. tones in noise. J Acoust Soc Am. 1996;99:1604-1610. 9. Guinan JJ Jr, Gifford ML. Effects of electrical stimulation of efferent olivo- 24. Igarashi M, Cranford JL, Allen EA, Alford BR. Behavioral auditory function after cochlear neurons on cat auditory-nerve fibers, I: rate-level functions. Hear Res. transection of cross olivo-cochlear bundle in the cat, V: pure tone intensity dis- 1988;33:97-113. crimination. Acta Otolaryngol. 1979;87:429-433. 10. May BJ, McQuone SJ. Effects of bilateral olivocochlear lesions on pure-tone in- 25. Dewson JH. Efferent olivocochlear bundle: some relationships to stimulus dis- tensity discrimination in cats. Aud Neurosci. 1995;1:385-400. crimination in noise. J Neurophysiol. 1968;31:122-130. 11. Arnesen RR. Fiber population of the vestibulocochlear anastomosis in humans. 26. Hienz, RD, Stiles P, May BJ. Effects of bilateral olivocochlear lesions on vowel Acta Otolaryngol. 1984;98:501-518. formant discrimination in cats. Hear Res. 1998;116:10-20. 12. Scharf B, Magnan J, Chays A. On the role of the olivocochlear bundle in hearing: 27. May BJ, Prosen CA, Weiss D, Vetter D. Behavioral investigation of some pos- 16 case studies. Hear Res. 1997;103:101-122. sible effects of the central olivocochlear pathways in transgenic mice. Hear Res. 13. Scharf B, Magnan J, Collet L, Ulmer E, Chays A. On the role of the olivocochlear 2002;171:142-157. bundle in hearing: a case study. Hear Res. 1994;75:11-26. 28. Irvine DR. Injury- and use-related plasticity in the adult auditory system. J Com- 14. Zeng FG, Martino KM, Linthicum FH, Soli SD. Auditory perception in vestibular mun Disord. 2000;33:293-311. neurectomy subjects. Hear Res. 2000;142:102-112. 29. Recanzone GH, Schreiner CE, Merzenich MM. Plasticity in the frequency repre- 15. May, BJ, Huang AY, Aleszczyk CM, Hienz RD. Design and conduct of sensory sentation of primary auditory cortex following discrimination training in adult owl experiments for domestic cats. In: Klump GM, Dooling RD, Fay RR, Stebbins monkeys. J Neurosci. 1993;13:87-103.

(REPRINTED) ARCH OTOLARYNGOL HEAD NECK SURG/ VOL 130, MAY 2004 WWW.ARCHOTO.COM 664