Acoustic Reflexes in Aural Atresia Patients: Evidence of an Intact Efferent System?

OBJECTIVE: To record crossed acoustic reflex thresholds (xART's) postoperatively from patients after surgical repair of unilateral congenital aural atresia (CAA). To seek explanations for when xARTs can and cannot be recorded. We hope to understand the implications for this central auditory reflex despite early afferent deprivation. METHODS: Patients who underwent surgery to correct unilateral CAA at a tertiary academic medical were prospectively enrolled to evaluate for the presence of xART. Preoperative ARTs in the normal (non-atretic) ear, and postoperative ipsilateral ARTs (stimulus in the normal ear) and contralateral ARTs (stimulus in the newly reconstructed atretic ear; record in the normal ear) were measured at 500, 1000, and 2000 Hz. RESULTS: Four of 11 patients with normal ipsilateral reflex thresholds preoperatively demonstrated crossed acoustic reflexes postoperatively (stimulus in reconstructed ear; record from normal ear). Four other patients demonstrated normal ipsilateral thresholds preoperatively but did not have crossed reflexes postoperatively. No reflexes (pre- or postoperatively) could be recorded in 3 patients. Crossed reflex threshold is significantly correlated with the postoperative audiometric threshold. There was no correlation between ipsilateral and contralateral reflex thresholds. CONCLUSION: Crossed acoustic reflexes can be recorded from some but not all postoperative atresia patients, and the thresholds for those reflexes correlate with the postoperative pure tone threshold. The presence of acoustic reflexes implies an intact CN VIII-to-opposite CN VII central reflex arc despite early unilateral sound deprivation.

Congress of Neurological Surgeons Systematic Review and Evidence-Based Guidelines on Intraoperative Cranial Nerve Monitoring in Vestibular Schwannoma Surgery.

Question 1: Does intraoperative facial nerve monitoring during vestibular schwannoma surgery lead to better long-term facial nerve function? Target Population: This recommendation applies to adult patients undergoing vestibular schwannoma surgery regardless of tumor characteristics. Recommendation: Level 3: It is recommended that intraoperative facial nerve monitoring be routinely utilized during vestibular schwannoma surgery to improve long-term facial nerve function. Question 2: Can intraoperative facial nerve monitoring be used to accurately predict favorable long-term facial nerve function after vestibular schwannoma surgery? Target Population: This recommendation applies to adult patients undergoing vestibular schwannoma surgery. Recommendation: Level 3: Intraoperative facial nerve can be used to accurately predict favorable long-term facial nerve function after vestibular schwannoma surgery. Specifically, the presence of favorable testing reliably portends a good long-term facial nerve outcome. However, the absence of favorable testing in the setting of an anatomically intact facial nerve does not reliably predict poor long-term function and therefore cannot be used to direct decision-making regarding the need for early reinnervation procedures. Question 3: Does an anatomically intact facial nerve with poor electromyogram (EMG) electrical responses during intraoperative testing reliably predict poor long-term facial nerve function? Target Population: This recommendation applies to adult patients undergoing vestibular schwannoma surgery. Recommendation: Level 3: Poor intraoperative EMG electrical response of the facial nerve should not be used as a reliable predictor of poor long-term facial nerve function. Question 4: Should intraoperative eighth cranial nerve monitoring be used during vestibular schwannoma surgery? Target Population: This recommendation applies to adult patients undergoing vestibular schwannoma surgery with measurable preoperative hearing levels and tumors smaller than 1.5 cm. Recommendation: Level 3: Intraoperative eighth cranial nerve monitoring should be used during vestibular schwannoma surgery when hearing preservation is attempted. Question 5: Is direct monitoring of the eighth cranial nerve superior to the use of far-field auditory brain stem responses? Target Population: This recommendation applies to adult patients undergoing vestibular schwannoma surgery with measurable preoperative hearing levels and tumors smaller than 1.5 cm. Recommendation: Level 3: There is insufficient evidence to make a definitive recommendation. The full guideline can be found at: https://www.cns.org/guidelines/guidelines-manage-ment-patients-vestibular-schwannoma/chapter_4.

Diffusion tensor tractography of normal facial and vestibulocochlear nerves.

PURPOSE: Diffusion tensor tractography (DTT) is not adequately reliable for prediction of facial and vestibulocochlear (VII-VIII) nerve locations, especially relative to a vestibular schwannoma (VS). Furthermore, it is often not possible to visualize normal VII-VIII nerves by DTT (visualization rates were 12.5-63.6%). Therefore, DTT post-processing was optimized for normal VII-VIII nerve visualization with and without manual noise elimination. METHODS: DTT examinations of ten patients were evaluated to assess the improvement in performance by modifying seed region of interest (ROI) and fractional anisotropy (FA) threshold. Seed ROI was placed at the porus of the internal auditory meatus, and FA threshold values were either fixed or variable for each patient. DTT visualization of cranial nerves VII-VIII was evaluated and the noise effect was measured. RESULTS: Cranial nerves VII-VIII were visualized in 90% of patients without using manual noise elimination by modifying the seed ROI and FA threshold. The visualization rate with FA threshold of the upper limit in each patient (100%) was significantly higher than that with FA threshold of 0.1 (75%) (p = 0.02). The incidence rate of noise with FA threshold of the upper limit (10%) was not significantly different than the FA threshold of 0.1 (20%) (p = 0.66). CONCLUSION: Seed ROI modification and FA thresholding can improve the visualization of cranial nerve VII-VIII locations in DTT. This technique is promising for its potential to determine the relationship of cranial nerves VII-VIII to VS.

Durability of hearing preservation after microsurgical treatment of vestibular schwannoma using the middle cranial fossa approach.

OBJECT: The middle cranial fossa (MCF) approach is a microsurgical technique described as a primary option in the treatment of small, intracanalicular schwannomas involving the eighth cranial nerve. Excellent rates of complete tumor resection, hearing preservation, preservation of facial nerve function, and low complication rates have been reproduced using this technique. However, the durability of hearing preservation attained using the various treatment options has not been adequately assessed. The purpose of this study was to evaluate the durability of long-term hearing preservation in patients with vestibular schwannoma (VS) treated via the MCF approach. The authors hypothesize that hearing preservation in these patients will prove to be durable years after treatment in a high percentage of cases. METHODS: Retrospective medical chart review was performed in 103 consecutive patients undergoing resection of VS via a modified MCF approach between 1999 and 2008. Patients in whom surgical goals were gross-total resection and hearing preservation were included. Preoperative and postoperative hearing assessment was performed using standard audiometric testing, and classified according to American Academy of Otolaryngology-Head and Neck Surgery (AAO-HNS) guidelines as a primary outcome measure. Outcomes and neurological complications initially, and at 1, 3, and 5 years following operation were analyzed. RESULTS: Initial hearing preservation rates were in keeping with the best previously published results. At initial postoperative audiometric follow-up, of the patients presenting with Class A hearing, 67% remained Class A, 17% were Class B, 1% were Class C, and 15% were Class D. Of patients presenting with Class B hearing, 24% were Class A, 53% remained Class B, 6% were Class C, and 18% were Class D. Of patients presenting with Class C hearing, 100% remained Class C. To assess the durability of hearing preservation in our patients, the authors evaluated hearing function at regular intervals after the initial postoperative audiometric follow-up. Audiometric data were available for 56 patients at 5-year follow-up. Of the 20 patients with Class A hearing at initial postoperative follow-up with 5-year follow-up, 13 (65%) remained Class A, 6 (30%) were Class B, and 1 (5%) was Class C. Of the 12 patients with Class B hearing at initial postoperative follow-up with 5-year follow-up, 4 (33%) were Class A, 4 (33%) remained Class B, and 4 (33%) were Class C. Of the 3 patients with Class C hearing at initial postoperative follow-up with 5-year follow-up, all 3 (100%) remained Class C. CONCLUSIONS: A majority of patients with preserved hearing following the MCF approach for treatment of VS experience durability of their preserved hearing at 5-year follow-up. The initial AAO-HNS classification was preserved in 13 (65%) of the 20 patients who had Class A hearing at 5 years, and in 8 (67%) of the 12 who had Class B hearing at 5 years. Overall, a decline in AAO-HNS classification was noted in 15% of patients with preserved Class A hearing, and in 33% of those with preserved Class B hearing. Facial nerve function was preserved in 91% of cases. Superior hearing preservation as well as good outcomes in facial nerve function and few serious complications can be accomplished using the MCF approach for resection of small VSs.

Neurophysiologic intraoperative monitoring of the vestibulocochlear nerve.

Neurosurgical procedures involving the skull base and structures within can pose a significant risk of damage to the brain stem and cranial nerves. This can have life-threatening consequences and/or result in devastating neurologic deficits. Over the past decade, intraoperative neurophysiology has significantly evolved and currently offers a great tool for live monitoring of the integrity of nervous structures. Thus, dysfunction can be identified early and prompt modification of the surgical management or operating conditions, leads to avoidance of permanent structural damage.Along these lines, the vestibulocochlear nerve (CN VIII) and, to a greater extent, the auditory pathways as they pass through the brain stem are especially at risk during cerebelopontine angle (CPA), posterior/middle fossa, or brain stem surgery. CN VIII can be damaged by several mechanisms, from vascular compromise to mechanical injury by stretch, compression, dissection, and heat injury. Additionally, cochlea itself can be significantly damaged during temporal bone drilling, by noise, mechanical destruction, or infarction, and because of rupture, occlusion, or vasospasm of the internal auditory artery.CN VIII monitoring can be successfully achieved by live recording of the function of one of its parts, the cochlear or auditory nerve (AN), using the brain stem auditory evoked potentials (BAEPs), electrocochleography (ECochG), and compound nerve action potentials (CNAPs) of the cochlear nerve.This is a review of these techniques, their principle, applications, methodology, interpretation of the evoked responses, and their change from baseline, within the context of surgical and anesthesia environments, and finally the appropriate management of these changes.

[Linear accelerator radiosurgery for the treatment of vestibular schwannoma]. / Radiocirugia con acelerador lineal en el tratamiento del schwannoma vestibular.

INTRODUCTION AND AIM: Radiosurgery is among the treatment options for patients with vestibular schwannoma. We present the experience in our institution in the treatment of this disease with this technique. PATIENTS AND METHODS: A retrospective study was made including 20 patients (11 women and 9 men; median age: 55.15 years-old) with vestibular schwannoma who received linear accelerator radiosurgery treatment since April 2005 until December 2008. Follow-up period was between 12 and 42 months, considering clinical examination of cranial nerves VII (House-Brackmann scale) and VIII (Gardner-Robertson scale) as well as radiological findings (considering tumor volume). For statistical analysis, the Fisher's exact test and logistic regression test were used. RESULTS: Certain worsening of hearing function was present in 25% of the patients. Five patients had large tumors at the moment of the treatment (equal or larger than 3.5 cm3), from which four deteriorated from headache, unsteady gait, dizziness/vertigo, facial numbness and tinnitus, with statistical significance (p < 0.05). From the first year of treatment on, there was a tumor volume decrease tendency, with no tumor growth in the medium/long term follow-up, achieving a local control rate of 100%. CONCLUSIONS: Radiosurgery has become an alternative in the treatment of patients with vestibular schwannoma of appropriate size, with high safety level, using low radiation doses, low rate of complications and good tumor control rate in the medium term follow-up.

AML1/Runx1 is important for the development of hindbrain cholinergic branchiovisceral motor neurons and selected cranial sensory neurons.

The mechanisms that regulate the acquisition of distinctive neuronal traits in the developing nervous system are poorly defined. It is shown here that the mammalian runt-related gene Runx1 is expressed in selected populations of postmitotic neurons of the embryonic central and peripheral nervous systems. These include cholinergic branchial and visceral motor neurons in the hindbrain, restricted populations of somatic motor neurons of the median and lateral motor columns in the spinal cord, as well as nociceptive and mechanoreceptor neurons in trigeminal and vestibulocochlear ganglia. In mouse embryos lacking Runx1 activity, hindbrain branchiovisceral motor neuron precursors of the cholinergic lineage are correctly specified but then fail to progress to a more differentiated state and undergo increased cell death, resulting in a neuronal loss in the mantle layer. In contrast, the development of cholinergic somatic motor neurons is unaffected. Runx1 inactivation also leads to a loss of selected sensory neurons in trigeminal and vestibulocochlear ganglia. These findings uncover previously unrecognized roles for Runx1 in the regulation of mammalian neuronal subtype development.

Steroid-dependent auditory plasticity leads to adaptive coupling of sender and receiver.

For seasonally breeding vertebrates, reproductive cycling is often coupled with changes in vocalizations that function in courtship and territoriality. Less is known about changes in auditory sensitivity to those vocalizations. Here, we show that nonreproductive female midshipman fish treated with either testosterone or 17beta-estradiol exhibit an increase in the degree of temporal encoding of the frequency content of male vocalizations by the inner ear that mimics the reproductive female's auditory phenotype. This sensory plasticity provides an adaptable mechanism that enhances coupling between sender and receiver in vocal communication.

Morphological study on the rootlets comprising the root of the intermediate nerve.

The number and arising sites of the rootlet comprising the intermediate nerve root were investigated in 100 sides of human brains. The arising sites of the rootlets were the pons halfway between the facial and vestibulocochlear nerves (31.9%), the arising portion of the vestibulocochlear nerve on the pons (28.8%) and the stem of the vestibulocochlear nerve (15.9%). The number of roots varied from one to five, with the most common being one root (58%). The number of rootlets per root also varied from one to five. Most of the roots had one rootlet (63%), while 2% of the roots had five rootlets. The variation of the arising sites of the intermediate nerve rootlets and its clinical significance were also discussed.

Distribution of Fos labeling in the inferior olive following transient blockade of the VIIIth cranial nerve.

The sodium channel blocker, tetrodotoxin (TTX), is an effective tool for blockade of action potentials in neurons. Unilateral transtympanic administration of 3 mM TTX produced behavioral symptoms paralleling those previously reported following unilateral vestibular ablation. Behavioral symptoms were evident as early as 15 min post-TTX. Fos immunocytochemistry revealed an initial bilateral distribution of Fos in the inferior olive (IO) followed by an almost exclusively unilateral distribution of Fos. By 1 h, Fos was predominantly localized in subdivisions of the IO contralateral to TTX treatment. Fos labeling in the IO was most pronounced at 2- and 6-h survival times and was localized in the contralateral IOA, IOB, IOC, IOBe, and IOK subdivisions and bilaterally in the IOM and IODM. Other regions of the brainstem including the vestibular nuclei, prepositus hypoglossi, dorsal paragigantocellular reticular nucleus, nucleus of the tractus solitarius and locus coeruleus also exhibited altered patterns of Fos labeling following TTX. The finding that Fos activity in the IO is initially bilateral and then rapidly becomes unilateral has not been reported for the traditional vestibular ablation models and may be unique to the TTX model. In addition, since altered Fos activity is readily detected in the IO at time-points prior to detectable changes in Fos in the central vestibular complex it is possible that the IO is particularly sensitive to events precipitated by unilateral vestibular disturbance.

Petrosal presigmoid approach to the petro-clival and anterior cerebellopontine region (extended retrolabyrinthine, transtentorial approach).

Intradural tumours affecting the clivus may be divided into three categories depending the area primarily involved by tumour. The second area extends from the spheno-occipital synchondrosis to the level of the jugular foramina. This area is best approached through the petrosal approach and suited for patients with serviceable hearing on the side of the lesion. 35 cases having skull base lesions were operated by the Skull Base Surgery Group of Ege University Medical Faculty between October 1993 and December 1997. 8 out of 35 cases having the intradural tumours affecting the petroclival and anterior cerebellopontine region, the petrosal presigmoid approach was performed in 4 patients. As hearing was absent in another 4 patients, the translabyrinthine route was coupled a the petrosal craniotomy (transtemporal approach). The aim of this article is to highlight the definitions, indications, hints and pitfalls of the approach from the otoneurological point of view.

Acoustic evoked response following transection of the eighth nerve in the rat.

OBJECT: The auditory brainstem response (ABR) is the most widely used means of intra-operative monitoring of the integrity of the auditory nerve and brainstem pathways during surgery in the cerebellopontine angle (CPA). Reliability of this and other electrophysiological techniques has been questioned because of persisting potentials in direct nerve recordings despite complete eighth nerve section. The study was designed to assess the extent to which an acoustic evoked response persists after the cochlear nerve is lesioned in the CPA of the adult rat. METHODS: The eighth nerve was exposed microsurgically via a lateral suboccipital approach without damage to surrounding structures. The auditory brainstem response to monaurally presented click stimuli was recorded using needle electrodes and a bandpass of 10 to 5000 Hz. FINDINGS: Complete sharp sectioning of the nerve in the CPA resulted in immediate disappearance of brainstem-generated potentials but persistence of a large primary, vertex-positive wave in all but one case. This response was also abolished in recordings three days later and after emptying the inner ear canal. Provided that the cochlea remained intact, two weeks later a single, vertex-positive potential in the latency range of wave Ia of the ABR reappeared, reaching its peak amplitude six weeks after sectioning of the nerve. CONCLUSIONS: The short-latency electrical potential recorded following damage of the eighth nerve in the cerebellopontine angle can be mistaken for an indication that nerve function is still preserved. The evoked injury potential is probably the major contributor to this potential that resembles wave I of the ABR. Monitoring of functional auditory integrity must neither be limited to early components of the ABR, nor to the electrocochleogram (EcoG) and the peripheral compound nerve action potential (CNAP), respectively.

Trks and p75 genes are differentially expressed in the inner ear of human embryos. What may Trks and p75 null mutant mice suggest on human development?

Recent work has shown the expression of Neurotrophins low (p75) and high affinity (Trk's A, B, and C) receptors in the developing inner ear sensory neurons of chick and mouse. Likewise the biological significance of such receptor expression was demonstrated by using both Trks and Neurotrophins null mutant mice. The present study was conducted to determine the expression of Trks and p75 proteins in the human inner ear throughout development. Hence to assess the potential role of Neurotrophins in the development of auditory and vestibular specific innervation in man. In other words, we intend to address the issue whether or not what null mutant mice for Trks and p75 have revealed on inner ear development may be relevant for human embryos. Fifty-two inner ears and their cochleovestibular ganglions (CVG) from human embryos and fetuses, ranging from 5 to 24 weeks of pregnancy were analyzed. Both Western blot and immunocytochemistry on frozen sections were used as complementary procedures. Quantitative Western blot studies revealed that Trk-B and C immunoreactivity (IR) appeared by embryonic week 5 in CVG neurons, increased at high levels between embryonic weeks 7 and 12, and later on, in 15 week-old specimens and older began to decrease to minimal levels. Trk-A IR was detected at just moderate levels during 5 and 7 weeks reflecting the presence of NGF high affinity receptors only at these earlier developmental ages. The p75 IR was detected at high degrees in the early stage of the 5th week and at abundant levels in all studied inner ears from the 7th to the 24th pregnancy week. These Western blot observations were corroborated by immunocytochemistry on frozen sections, which also revealed a major distribution of both p75 and Trks on neuronal bodies while p75 appears localized on supporting cells. Our findings reveal a tight correlation between p75 and Trks expression throughout human development and specific inner ear developmental events, such as target-dependent neuronal cell death and afferent hair cells innervation. That kind of association of p75 and Trks temporal pattern with distinctive steps in inner ear developmental schedule, is a feature shared between human embryos and other mammals, such as mouse. Based on the present results and considering them together with the reported phenotype of p75 and Trks null mutant mice, we hypothesize that p75 and Trk receptors, as well as, their binding Neurotrophins may be essential in human inner ear development. Accordingly, they may be required molecules for sensory epitheliums innervation and target-dependent neuronal cell death, during embryogenesis and even early postnatal life, in man.

[Auditory evoked potentials from brain stem determined in acoustic nerve neurinomas]. / Badanie wywolanych potencjalów sluchowych z pnia mózgu (PSPW) w przypadkach nerwiaków nerwu sluchowego.

An analysis of the studies of Brain Stem Electric Response Audiometry of patients operated on Bachaumont Clinic or in Cochin hospital in Paris, because of acoustic neurinoma, was carried out. The studies comprised 88 patients divided into groups according to the size of tumour. A group of small intrameatal tumours, a group of up to 2 cm tumours, a group of between 2 and 3 cm tumours and a group of above 3 cm tumours. A control group of examined patients consisted of 20 persons with one-side acoustic impairment or two-side impairment but predominant on one side and patients with one-side tinnitus or two-side tinnitus but predominant on one side. Examinations of these patients made with CT and NMR did not show presence of acoustic neurinoma. BERA's tests did not show a response in case of 22 patients with acoustic neurinoma. In 71% of cases BERA's tests showed an extrahelix type, for which in 50% of cases a prolonged latency on the side of the tumour was found. In 4% of cases Brain Stem Electric Response Audiometry gave results within normal range both with respect to morphology and latency time of each wave. A slight correlation between the size of tumour and type of BERA change was found.

A stochastic model of the electrically stimulated auditory nerve: single-pulse response.

Most models of neural response to electrical stimulation, such as the Hodgkin-Huxley equations, are deterministic, despite significant physiological evidence for the existence of stochastic activity. For instance, the range of discharge probabilities measured in response to single electrical pulses cannot be explained at all by deterministic models. Furthermore, there is growing evidence that the stochastic component of auditory nerve response to electrical stimulation may be fundamental to functionally significant physiological and psychophysical phenomena. In this paper we present a simple and computationally efficient stochastic model of single-fiber response to single biphasic electrical pulses, based on a deterministic threshold model of action potential generation. Comparisons with physiological data from cat auditory nerve fibers are made, and it is shown that the stochastic model predicts discharge probabilities measured in response to single biphasic pulses more accurately than does the equivalent deterministic model. In addition, physiological data show an increase in stochastic activity with increasing pulse width of anodic/cathodic biphasic pulses, a phenomenon not present for monophasic stimuli. These and other data from the auditory nerve are then used to develop a population model of the total auditory nerve, where each fiber is described by the single-fiber model.

Advances in monitoring of seventh and eighth cranial nerve function during posterior fossa surgery.

OBJECTIVE: This study aimed to illustrate some recent advances in intraoperative monitoring of the seventh and eighth cranial nerves (i.e., direct recording of cochlear nerve action potentials [CNAPs] and facial nerve action potentials [FNAPs]). STUDY DESIGN: Reports of representative cases and average postoperative results obtained in subjects submitted to cerebellopontine angle surgical procedures are examined. Results obtained in patients with direct recording techniques are compared with those obtained with the classical monitoring techniques (auditory brain stem response [ABR], electrocochleography [ECoG], facial electromyography [EMG]). SETTING: The study was conducted at an Ear Nose and Throat Department, University of Verona, Verona, Italy. INTERVENTION: Intraoperative monitoring during cerebellopontine angle surgery was performed. RESULTS: Patients monitored with direct audiomonitoring techniques presented better postoperative auditory functions compared to patients monitored with ABR. The FNAP and EMG groups showed FN outcome that did not differ significantly. CONCLUSIONS: Intraoperative monitoring of cranial nerves furnishes a valid tool for identification of neural structures, prevention of damage, understanding of the pathophysiology of damage, and prediction of postoperative function. The fundamental prerequisite for obtaining optimal benefits from monitoring is the use of techniques of direct and continuous electrophysiologic recording with instantaneous feedback to the surgeon, such as CNAPs and FNAPs.

Long-term effects of sectioning the olivocochlear bundle in neonatal cats.

The olivocochlear bundle (OCB) was cut in neonatal cats to evaluate its role in the development of normal cochlear function. Approximately 1 year after deefferentation, acute auditory nerve fiber (ANF) recordings were made from lesioned animals, lesion shams, and normal controls. The degree of deefferentation was quantified via light microscopic evaluation of the density of OCB fascicles in the tunnel of Corti, and selected cases were analyzed via electron microscopy. In the most successful cases, the deefferentation was virtually complete. ANFs from successfully lesioned animals exhibited significant pathophysiology compared with normals and with other animals in which the surgery failed to interrupt the OCB. Thresholds at the characteristic frequency (CF), the frequency at which ANFs are most sensitive, were elevated across the CF range, with maximal effects for CFs in the 10 kHz region. Frequency threshold or tuning curves displayed reduction of tip-to-tail ratios (the difference between CF and low-frequency "tail" thresholds) and decreased sharpness of tuning. These pathological changes are generally associated with outer hair cell (OHC) damage. However, light microscopic histological analysis showed minimal hair cell loss and no significant differences between normal and deefferented groups. Spontaneous discharge rates (SRs) were lower than normal; however, those fibers with the highest SRs remained more sensitive than those with lower SRs. Findings suggest that the interaction between OC efferents and OHCs early in development may be critical for full expression of active mechanical processes.

Additional pharmacological evidence that endogenous ATP modulates cochlear mechanics.

In the cochlea, outer hair cells (OHCs) generate the active cochlear mechanics whereas the supporting cells, such as Deiters' cells and Hensen's cells, may play a role in both the active and passive cochlear mechanics. The presence of receptors for adenosine triphosphate (ATP) on OHCs, Deiters' cells and Hensen's cells indicates that endogenous ATP may have a role in cochlear mechanics. To explore this possibility, the effects of the ATP antagonist, pyridoxal-phosphate-6-azophenyl-2',4'-disulfonic acid (PPADS), were studied in guinea pig both in vitro on isolated OHCs, Deiters' cells, Hensen's cells and pillar cells using the whole-cell configuration of the patch-clamp technique, and in vivo on sound evoked cochlear potentials (cochlear microphonic, CM; summating potential, SP; compound action potential, CAP) and distortion product otoacoustic emissions (DPOAEs) using cochlear perilymphatic perfusion. Results show that PPADS (100 microM) reduced the inward current evoked by 5-10 microM ATP in OHCs, Deiters' cells, Hensen's cells and pillar cells. This effect of PPADS was slow in onset and was slowly reversed to a varying degree in the different cell types. In vivo application of PPADS in increasing concentrations reduced the sound evoked CAP, SP and increased N1 latency starting at about 0.33 mM (SP) and 1 mM (CAP and N1 latency). PPADS (0.33-1 mM) reversibly suppressed the initial value of the quadratic DPOAE and reversed the 'slow decline' in the quadratic DPOAE that occurs during continuous stimulation with moderate level primaries. These results, together with the similar effects of the ATP antagonist suramin reported previously (Skellett et al., 1997), may be evidence that endogenous ATP acting on cells in the organ of Corti alters cochlear mechanics.