Lateralization of virtual sound sources with a binaural cochlear-implant sound coding strategy inspired by the medial olivocochlear reflex.

Many users of bilateral cochlear implants (BiCIs) localize sound sources less accurately than do people with normal hearing. This may be partly due to using two independently functioning CIs with fixed compression, which distorts and/or reduces interaural level differences (ILDs). Here, we investigate the potential benefits of using binaurally coupled, dynamic compression inspired by the medial olivocochlear reflex; an approach termed "the MOC strategy" (Lopez-Poveda et al., 2016, Ear Hear 37:e138-e148). Twelve BiCI users were asked to localize wideband (125-6000 Hz) noise tokens in a virtual horizontal plane. Stimuli were processed through a standard (STD) sound processing strategy (i.e., involving two independently functioning sound processors with fixed compression) and three different implementations of the MOC strategy: one with fast (MOC1) and two with slower contralateral control of compression (MOC2 and MOC3). The MOC1 and MOC2 strategies had effectively greater inhibition in the higher than in the lower frequency channels, while the MOC3 strategy had slightly greater inhibition in the lower than in the higher frequency channels. Localization was most accurate with the MOC1 strategy, presumably because it provided the largest and less ambiguous ILDs. The angle error improved slightly from 25.3° with the STD strategy to 22.7° with the MOC1 strategy. The improvement in localization ability over the STD strategy disappeared when the contralateral control of compression was made slower, presumably because stimuli were too short (200 ms) for the slower contralateral inhibition to enhance ILDs. Results suggest that some MOC implementations hold promise for improving not only speech-in-noise intelligibility, as shown elsewhere, but also sound source lateralization.

Decreased perception of high frequency sound in severe obstructive sleep apnea.

Obstructive sleep apnea (OSA) is characterized by recurrent episodes of upper airway obstruction during sleep, which is manifested by apnea or hypopnea. Decreased blood oxygen saturation, changes in heart rate, fluctuations in brain perfusion, changes in intracranial pressure, snoring and vibration are factors that may potentially affect hearing in patients with OSA. The aim of the present study was to test the hypothesis that hearing is affected in OSA. 43 males aged 34-74 years (mean 48.2) with suspected sleep-disordered breathing without other comorbidity or medication that may affect sleep or hearing were included. Nocturnal polysomnography, pure tone audiometry (PTA), transient evoked otoacoustic emissions (TEOAE) and brainstem auditory evoked potentials (BAEP) were evaluated. The severity of OSA was indicated by the number of apneas and hypopneas per hour of sleep (apnoe/hypopnoe index - AHI). OSA (AHI>/=5) was detected in 28 patients by polysomnography. Mild OSA (AHI 5-15) was confirmed in 11 patients, severe OSA (AHI>/=30) in 17 patients. Simple snoring (AHI<5) was diagnosed in 15 males. In patients suffering from severe OSA, tone audiometry demonstrated higher auditory threshold at frequencies of 4000 and 8000 Hz than in patients with AHI<15 (p<0.005). Auditory threshold values correlated with age in all groups. At a frequency of 8000 Hz, auditory threshold additionally correlated with BMI, AHI, oxygen desaturation index and decreased oxygen saturation. No differences were detected in TEOAE and BAEP between subjects with OSA and snoring. PTA and TEOAE decreased with increasing age. The present results show decreased perception of high frequency sound in severe OSA.

Renexin as a rescue regimen for noise-induced hearing loss.

Renexin, a compound of cilostazol and ginkgo biloba extract, has been reported to produce neuroprotective effects through antioxidant, antiplatelet, and vasodilatory mechanisms. This study was designed to investigate the protective effects of renexin on hearing, the organ of Corti (OC), and medial olivocochlear efferents against noise-induced damage. C57BL/6 mice were exposed to 110 dB SPL white noise for 60 min and then randomly divided into three groups: high- and low-dose renexin-treated groups and noise only group. Renexin were administered for 7 days: 90 mg/kg to the low-dose, and 180 mg/kg to the high-dose groups. All mice, including the controls underwent hearing tests on postnoise day 8 and were killed for cochlear harvest. We compared the hearing thresholds and morphology of the OC and cochlear efferents across the groups. The renexin-treated groups recovered from the immediate threshold shifts in a dose-dependent manner, while the noise group showed a permanent hearing loss. The renexin-treated ears demonstrated less degeneration of the OC. The diameters of the efferent terminals labeled with α-synuclein were preserved in the high-dose renexin-treated group. In the western blot assay of the cochlear homogenates, the treated groups displayed stronger expressions of α-synuclein than the noise and control groups, which may indicate that noise-induced enhanced activity of the cochlear efferent system was protected by renexin. Our results suggest that pharmacologic treatment with renexin is hopeful to reduce or prevent noise-induced hearing loss as a rescue regimen after noise exposure.

Gingko biloba extracts protect auditory hair cells from cisplatin-induced ototoxicity by inhibiting perturbation of gap junctional intercellular communication.

Gap junctional intercellular communication (GJIC) may play an important role in the hearing process. Cisplatin is an anticancer drug that causes hearing loss and Gingko biloba extracts (EGb 761) have been used as an antioxidant and enhancer for GJIC. The purpose of this study was to examine the efficiency of EGb 761 in protecting against cisplatin-induced apoptosis and disturbance of GJIC. House Ear Institute-Organ of Corti 1 auditory cells were cultured and treated with cisplatin (50 µM) and EGb (300 µg/ml) for 24h, and then analyzed by immunocytochemistry (Annexin V/propidium iodide) and Western blots. GJIC was evaluated by scrape-loading dye transfer (SLDT). Basal turn organ of Corti (oC) explants from neonatal (p3) rats were exposed to cisplatin (1-10 µM) and EGb (50-400 µg/ml). The number of intact hair cells was counted by co-labeling with phalloidin and MyoVIIa. EGb prevented cisplatin-induced apoptosis in immunostaining and decreased caspase 3 and poly-ADP-ribose polymerase bands, which were increased in cisplatin-treated cells in Western blots. EGb prevented abnormal intracellular locations of connexin (Cx) 26, 30, 31, and 43 in cells treated with cisplatin and increased quantities of Cx bands. EGb also prevented cisplatin-induced disturbance of GJIC in SLDT. In oC explants, EGb significantly prevented hair cell damage induced by cisplatin. In animal studies, EGb significantly prevented cisplatin-induced hearing loss across 16 and 32 kHz. These results show that cisplatin induces ototoxicity including hearing loss as well as down-regulation of GJIC and inhibition of Cxs in auditory cells. EGb prevents hearing loss in cisplatin-treated rats by inhibiting down-regulation of Cx expression and GJIC. The disturbance of GJIC or Cx expression may be one of the important mechanisms of cisplatin-induced ototoxicity.

Electrophysiological monitoring of hearing function during cochlear perilymphatic perfusions.

CONCLUSION: The cochlear perilymphatic perfusion produces, by itself, significant effects in the cochlear physiology that could be associated with the surgical procedure. These effects need to be well characterized to allow a reliable quantification of the effects of the experimental agent being tested. OBJECTIVES: The study focused on the accurate description of the electrophysiological effects on the cochlear potential recordings of perilymphatic perfusions. METHODS: Two successive cochlear perilymphatic perfusions were carried out. The first used artificial perilymph. The second used artificial perilymph alone or a kainic acid (KA) solution in artificial perilymph. The compound action potential of the auditory nerve (CAP-AN) was recorded: (1) before the first perfusion, (2) after the first perfusion and (3) after the second perfusion, and compared between groups. RESULTS: The first intracochlear perfusion with artificial perilymph produced significant effects in the CAP-AN that could be related to the surgical procedure. These effects were analysed separately from the effects produced by the KA. In particular, the KA administered intracochlearly produced a significant increase in the latency and a decrease in the amplitude of the CAP-AN N1 wave compared with the controls that were perfused twice with artificial perilymph.

Viral vector tropism for supporting cells in the developing murine cochlea.

Gene-based therapeutics are being developed as novel treatments for genetic hearing loss. One roadblock to effective gene therapy is the identification of vectors which will safely deliver therapeutics to targeted cells. The cellular heterogeneity that exists within the cochlea makes viral tropism a vital consideration for effective inner ear gene therapy. There are compelling reasons to identify a viral vector with tropism for organ of Corti supporting cells. Supporting cells are the primary expression site of connexin 26 gap junction proteins that are mutated in the most common form of congenital genetic deafness (DFNB1). Supporting cells are also primary targets for inducing hair cell regeneration. Since many genetic forms of deafness are congenital it is necessary to administer gene transfer-based therapeutics prior to the onset of significant hearing loss. We have used transuterine microinjection of the fetal murine otocyst to investigate viral tropism in the developing inner ear. For the first time we have characterized viral tropism for supporting cells following in utero delivery to their progenitors. We report the inner ear tropism and potential ototoxicity of three previously untested vectors: early-generation adenovirus (Ad5.CMV.GFP), advanced-generation adenovirus (Adf.11D) and bovine adeno-associated virus (BAAV.CMV.GFP). Adenovirus showed robust tropism for organ of Corti supporting cells throughout the cochlea but induced increased ABR thresholds indicating ototoxicity. BAAV also showed tropism for organ of Corti supporting cells, with preferential transduction toward the cochlear apex. Additionally, BAAV readily transduced spiral ganglion neurons. Importantly, the BAAV-injected ears exhibited normal hearing at 5 weeks of age when compared to non-injected ears. Our results support the use of BAAV for safe and efficient targeting of supporting cell progenitors in the developing murine inner ear.

Effects of restricted basilar papillar lesions and hair cell regeneration on auditory forebrain frequency organization in adult European starlings.

The frequency organization of neurons in the forebrain Field L complex (FLC) of adult starlings was investigated to determine the effects of hair cell (HC) destruction in the basal portion of the basilar papilla (BP) and of subsequent HC regeneration. Conventional microelectrode mapping techniques were used in normal starlings and in lesioned starlings either 2 d or 6-10 weeks after aminoglycoside treatment. Histological examination of the BP and recordings of auditory brainstem evoked responses confirmed massive loss of HCs in the basal portion of the BP and hearing losses at frequencies >2 kHz in starlings tested 2 d after aminoglycoside treatment. In these birds, all neurons in the region of the FLC in which characteristic frequencies (CFs) normally increase from 2 to 6 kHz had CF in the range of 2-4 kHz. The significantly elevated thresholds of responses in this region of altered tonotopic organization indicated that they were the residue of prelesion responses and did not reflect CNS plasticity. In the long-term recovery birds, there was histological evidence of substantial HC regeneration. The tonotopic organization of the high-frequency region of the FLC did not differ from that in normal starlings, but the mean threshold at CF in this frequency range was intermediate between the values in the normal and lesioned short-recovery groups. The recovery of normal tonotopicity indicates considerable stability of the topography of neuronal connections in the avian auditory system, but the residual loss of sensitivity suggests deficiencies in high-frequency HC function.

Chronic depolarization enhances the trophic effects of brain-derived neurotrophic factor in rescuing auditory neurons following a sensorineural hearing loss.

The development and maintenance of spiral ganglion neurons (SGNs) appears to be supported by both neural activity and neurotrophins. Removal of this support leads to their gradual degeneration. Here, we examined whether the exogenous delivery of the neurotrophin brain-derived neurotrophic factor (BDNF) in concert with electrical stimulation (ES) provides a greater protective effect than delivery of BDNF alone in vivo. The left cochlea of profoundly deafened guinea pigs was implanted with an electrode array and drug-delivery system. BDNF or artificial perilymph (AP) was delivered continuously for 28 days. ES induced neural activity in two cohorts (BDNF/ES and AP/ES), and control animals received BDNF or AP without ES (BDNF/- and AP/-). The right cochleae of the animals served as deafened untreated controls. Electrically evoked auditory brainstem responses (EABRs) were recorded immediately following surgery and at completion of the drug-delivery period. AP/ES and AP/- cohorts showed an increase in EABR threshold over the implantation period, whereas both BDNF cohorts exhibited a reduction in threshold (P < 0.001, t-test). Changes in neural sensitivity were complemented by significant differences in both SGN survival and soma area. BDNF cohorts demonstrated a significant trophic or survival advantage and larger soma area compared with AP-treated and deafened control cochleae; this advantage was greatest in the base of the cochlea. ES significantly enhanced the survival effects of BDNF throughout the majority of the cochlea (P < 0.05, Bonferroni's t-test), although there was no evidence of trophic support provided by ES alone. Cotreatment of SGNs with BDNF and ES provides a substantial functional and trophic advantage; this treatment may have important implications for neural prostheses.

[Diagnosis of endolymphatic hydrops using low frequency modulated distortion product otoacoustic emissions]. / Diagnostik des endolymphatischen Hydrops mit tieftonmodulierten DPOAE.

BACKGROUND: The low frequency modulation of distortion product otoacoustic emissions (DPOAEs) is an objective audiometric method that appears to be a useful tool for the diagnosis of endolymphatic hydrops (EH), e.g. in patients with Menière's disease, or in those who present only some of the symptoms of the disease. METHOD: Low-frequency modulated DPOAEs were registered in 20 patients with unilateral Menière's disease (13 women and 7 men, aged 40-66 years) and were compared to a control group matched in age and gender. As a diagnostic parameter, the 'modulation index' MI=1/2 MS/DM was used (MS or modulation span, being the difference between the maximal and the minimal DPOAE-amplitude, and DM, being the mean of the suppressed stationary DPOAE-amplitude). RESULTS: In the patients with unilateral Menière's disease, MI was lower than in the control group. This difference was highly significant. In 56% of the patients' contralateral ears MI was lower than the cut off-value and significantly lower than in the control group, but did not differ significantly from the patients' ipsilateral ears. CONCLUSION: The registration of low-frequency modulated DPOAEs is comparable to the generally applied transtympanic electrocochleography in its diagnostic validity. The method is fast and non-invasive and could be applied to monitor the course of the disease.

The effects of the amplitude distribution of equal energy exposures on noise-induced hearing loss: the kurtosis metric.

Seventeen groups of chinchillas with 11 to 16 animals/group (sigmaN = 207) were exposed for 5 days to either a Gaussian (G) noise or 1 of 16 different non-Gaussian (non-G) noises at 100 dB(A) SPL. All exposures had the same total energy and approximately the same flat spectrum but their statistical properties were varied to yield a series of exposure conditions that varied across a continuum from G through various non-G conditions to pure impact noise exposures. The non-G character of the noise was produced by inserting high level transients (impacts or noise bursts) into the otherwise G noise. The peak SPL of the transients, their bandwidth, and the intertransient intervals were varied, as was the rms level of the G noise. The statistical metric, kurtosis (beta), computed on the unfiltered noise beta(t), was varied 3 < or = beta(t) < or = 105. Brainstem auditory evoked responses were used to estimate hearing thresholds and surface preparation histology was used to determine sensory cell loss. Trauma, as measured by asymptotic and permanent threshold shifts (ATS, PTS) and by sensory cell loss, was greater for all of the non-G exposure conditions. Permanent effects of the exposures increased as beta(t) increased and reached an asymptote at beta(t) approximately 40. For beta(t) > 40 varying the interval or peak histograms did not alter the level of trauma, suggesting that, in the chinchilla model, for beta(t) > 40 an energy metric may be effective in evaluating the potential of non-G noise environments to produce hearing loss. Reducing the probability of a transient occurring could reduce the permanent effects of the non-G exposures. These results lend support to those standards documents that use an energy metric for gauging the hazard of exposure but only after applying a "correction factor" when high level transients are present. Computing beta on the filtered noise signal [beta(f)] provides a frequency specific metric for the non-G noises that is correlated with the additional frequency specific outer hair cell loss produced by the non-G noise. The data from the abundant and varied exposure conditions show that the kurtosis of the amplitude distribution of a noise environment is an important variable in determining the hazards to hearing posed by non-Gaussian noise environments.

A model for prelingual deafness, the congenitally deaf white cat--population statistics and degenerative changes.

Cochlear implantation in congenitally deaf children leads to electrical stimulation of an entirely naive central auditory system. In this case, processes of central auditory maturation are induced by the electric stimuli. For the study of these processes the deaf white cat (DWC) appears to be an appropriate model. However, a knowledge of the basic data of these animals is necessary before such a model may be used. This paper presents these data and is one of a series of publications concerning congenital deafness in children and cochlear implantation. In our strain 72% of the animals are totally deaf as judged by the absence of any brain stem evoked potentials at click intensities up to 120 dB SPL peak equivalent. Primarily, there is a degeneration of the entire organ of Corti during the first postnatal weeks. An absence of acoustically evoked brain stem responses in the early postnatal weeks shows that DWCs probably never have any hearing experience. Months after the degeneration of the organ of Corti, the spiral ganglion starts to degenerate from the midportion of the cochlea. However, even in adult cats (2 years), a sufficient number of functionally intact auditory afferents remain, which are suitable for electrical cochlear stimulation.

[Effect of variations in middle ear pressure on ruptures of the round window membrane of the inner ear of the guinea pig (Cavia porcellus)]. / Untersuchungen zum Einfluss von Mittelohrdruckschwankungen bei Rupturen der runden Fenstermembran auf das Innenohr des Meerschweinchens (Cavia porcellus).

The electrical activity of the inner ear before and after rupture of the round window membrane was monitored in guinea pigs under different pressure conditions with the aid of electrocochleography. Following studies were conducted weekly over a period of 4 weeks. Findings showed that overpressure below the pressure needed to open the Eustachian tube caused strong temporary functional disturbance of the cochlea, especially at high frequencies. Irreversible changes that were pressure-dependent were observed and occurred mainly at high frequencies. Application of low pressure to the round window membrane caused a functional loss comparable to changes after overpressure. Animals with a predamaged cochlea reacted to overpressure that was below opening pressure of the tube and to corresponding low pressure with a longer lasting functional loss than did animals with an undamaged cochlea.

Modulation of cochlear responses in the guinea pig by low-frequency, phase-shifted maskers following noise trauma.

Low-frequency acoustic biasing using an intensive phase-shifted, low-frequency masker was studied according to its ability to determine disorders of cochlear micromechanics following noise trauma in the guinea pig as animal model. Statistical analyses proved that this technique allowed electrophysiological differentiation of controls versus groups with different degrees of experimentally induced threshold shifts. To substantiate group differences an intensity of at least 70 dB SPL was required for the 52 Hz masker and the difference in relation to the test-tone intensity had to be +/- 10 or +/- 20 dB SPL. The noise-traumatized cochlea could be identified by means of a threshold shift for the 5 microV pseudothreshold, a low modulation span of the compound action potential amplitude (< 25-50 microV frequency dependent), and reduced positive summating potential amplitude with negative non-modulating values within the different measurement phases for 1 and 2 kHz stimulation.

Low-frequency sensorineural loss: clinical evaluation and implications for hearing aid fitting.

Spread of excitation in the cochlea places fundamental limits on the interpretation of audiometric pure-tone hearing loss as a simple map of dysfunction along the cochlear partition, and histologic evidence from human temporal bones will be presented to demonstrate the insensitivity of the audiogram to variations in pathology in the case of low-frequency hearing loss. This article will describe a clinical procedure using simultaneous pure-tone masking to improve upon the localization of cochlear disease, particularly for low-frequency hearing losses, and a model for using the Articulation Index (AI) to develop prognoses for hearing aid performance in these cases, which can then be tested. Fourteen patients with low-frequency hearing loss were divided into two groups based upon threshold shifts caused by a pure-tone masker: those that showed normal low-frequency threshold shifts and those that showed marked shifts at frequencies below the masker, indicating greater loss of function than shown by the unmasked audiogram. Hypothetical audiograms were then generated to model a complete loss of apical function for all patients. Measured speech recognition scores were then compared to AI predictions for the actual and hypothetical audiograms. Best agreement for the patients showing normal masking shifts was between the measured scores and the AI for the actual audiogram, whereas the best agreement for the patients showing marked shifts was with the AI for the hypothetical audiogram. The implications for hearing aid recommendation and fitting in these cases are discussed.

Temporary change of compound action potential amplitude after intense sound exposure.

Intense sound induces a temporary or permanent threshold shift. The aim of this study is to make an experimental model for temporary threshold shift (TTS) using guinea pigs. In this study, two kinds of sound exposure were used for inducing a threshold shift in the guinea pig; one of 110 dB SPL at 10 kHz for 10 min and the other of 120 dB SPL at 10 kHz for 5 min. The former condition produced different levels of reduction in compound action potential (CAP) immediately after sound exposure and different steady levels of CAP amplitude after recovery (within 120 min) in 10 guinea pigs. The latter condition produced a total loss of CAP amplitude immediately after sound exposure in 8 of 9 guinea pigs, and this condition continued for 120 min in 7 of the 9 guinea pigs. Additionally, in 2 of 3 guinea pigs which were exposed the sound of 120 dB SPL at 10 kHz for 5 min, the CAP amplitudes were almost the same as those of control animals 1 day after the exposure. One the basis of these results, we consider the sound of 120 dB SPL at 10 kHz for 5 min to be the optimal intensity and frequency of sound and duration of exposure for producing a TTS in the guinea pig.

Otoacoustic emissions and the categorization of cochlear and retro-cochlear lesions.

There are only some cochlear and retro-cochlear lesions that could be detected using a simple measurement of otoacoustic emissions. A simple description of the various lesions that lead to hearing loss and disruption of emissions is presented, a basis for categorizing cochlear and retro-cochlear lesions is discussed, and the types of clinical symptoms likely to be associated with each type of lesion are outlined.

Early microfilament reorganization in injured auditory epithelia.

Microfilaments (MFs) play an important role in wound healing and other regenerative events. The purpose of this study was to characterize changes in the distribution of MFs in traumatized auditory epithelia and compare these changes between avian (regenerating) and mammalian (nonregenerating) ears. Chicks and guinea pigs were acoustically overstimulated and their auditory epithelia analyzed fluorescence microscopy with phalloidin as a MF-specific marker. Immediately or several hours after overstimulation, we observed a substantial reduction of MFs in stereocilia and the cuticular plate. The circumferential belt of MF which is associated with the adherens junctional complex was constricted in damaged hair cells (HCs) as early as 1 day after the exposure. Concomitant with the junctional constriction, the apical surface area of supporting cells was increased relative to normal, whereas the surface area of HCs was decreased. We conclude the changes in the amount and distribution of MFs which characterize early responses to acoustic damage are similar in avian (regenerating) and mammalian (nonregenerating) auditory epithelia. We hypothesize that changes in MF-mediated tensile forces trigger the process of tissue repair in auditory epithelia in response to insult. In mammals the reorganization of MFs may help maintain the integrity of the reticular lamina and thereby prevent further damage. In contrast, early changes in MFs in chicks may play a role in regulating regenerative tissue responses.

Auditory aspects of seizure in the genetically epilepsy prone rat.

The organ of Corti of Genetically Epilepsy Prone Rats was examined anatomically and electrophysiologically using scanning electron microscopy (SEM) and electrophysiological recording of alternating current cochlear potentials (ACCP) and N1, a volume conductor recording of the primary auditory afferent action potentials. ACCPs for GEPRs with low intensity seizures (Acoustic Response Score (ARS) = 2 or 3) and high intensity seizures (ARS = 9) showed similar impairment in cochlear function. Approximately a 25-35 dB shift in input-output functions was present in GEPRs as compared to controls. SEM revealed several types of possible genetic abnormalities which explain the deficits in cochlear function and could serve as the basis for seizure predisposition in these animals.

Auditory evoked potential alterations induced by pulsed ultrasound.

Diagnostic levels of pulsed ultrasound were applied abdominally over the uteri of pregnant rats for five minutes daily during the first 20 days of gestation. The average energy output of the ultrasound machine at the optimum focal length of the transducer (5.4 cm) was 7.2 mW/sq cm. Postnatal auditory evoked potentials demonstrated a significant alteration in the offspring of the treated animals when compared with similarly treated, but nonexposed controls. This alteration only occurred in the high frequency range. Neither light nor electron microscopy revealed significant morphologic alterations in the cochlear elements of the exposed offspring. Although a cochlear deficit occurred in a range known to be important to the rat's hearing, several issues make this data reassuring to clinicians using diagnostic levels of pulsed ultrasound: the total amount of ultrasound exposure was higher than would be expected with human use, the defect was mild, and the absence of clear-cut morphologic abnormalities may indicate the presence of a minimal, or even reversible, defect.

Critical bandwidth in Menière's disease.

The critical bandwidth in loudness summation was estimated in 20 patients with typical Menière's disease using noise bands centered around 1 kHz. A reduction of the normal loudness difference between broad-band noise and narrow-band noise was present at all except the highest levels. Judged individually, 7 of the 20 patients appeared to have a widened critical band, but in the pooled data the size of the critical band was normal. This was the case in patients with a hearing loss less than 50 dB HL as well as in patients with a hearing loss greater than or equal to 50 dB HL. Expressed in terms of the critical band mechanism as an internal filter system, the single filter appears to have normal bandwidth but the interaction between adjacent filters is defective. The anatomical localisation of this interaction is discussed.