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A genetic screen for mutations that disrupt an auditory response in Drosophila melanogaster.

Hearing is one of the last sensory modalities to be subjected to genetic analysis in Drosophila melanogaster. We describe a behavioral assay for auditory function involving courtship among groups of males triggered by the pulse component of the courtship song. In a mutagenesis screen for mutations that disrupt the auditory response, we have recovered 15 mutations that either reduce or abolish this response. Mutant audiograms indicate that seven mutants reduced the amplitude of the response at all intensities. Another seven abolished the response altogether. The other mutant, 5L3, responded only at high sound intensities, indicating that the threshold was shifted in this mutant. Six mutants were characterized in greater detail. 5L3 had a general courtship defect; courtship of females by 5L3 males also was affected strongly. 5P1 males courted females normally but had reduced success at copulation. 5P1 and 5N18 showed a significant decrement in olfactory response, indicating that the defects in these mutations are not specific to the auditory pathway. Two other mutants, 5M8 and 5N30, produced amotile sperm although in 5N30 this phenotype was genetically separable from the auditory phenotype. Finally, a new adult circling behavior phenotype, the pirouette phenotype, associated with massive neurodegeneration in the brain, was discovered in two mutants, 5G10 and 5N18. This study provides the basis for a genetic and molecular dissection of auditory mechanosensation and auditory behavior.

Animals↗

Plasticity in the neural coding of auditory space in the mammalian brain.

Sound localization relies on the neural processing of monaural and binaural spatial cues that arise from the way sounds interact with the head and external ears. Neurophysiological studies of animals raised with abnormal sensory inputs show that the map of auditory space in the superior colliculus is shaped during development by both auditory and visual experience. An example of this plasticity is provided by monaural occlusion during infancy, which leads to compensatory changes in auditory spatial tuning that tend to preserve the alignment between the neural representations of visual and auditory space. Adaptive changes also take place in sound localization behavior, as demonstrated by the fact that ferrets raised and tested with one ear plugged learn to localize as accurately as control animals. In both cases, these adjustments may involve greater use of monaural spectral cues provided by the other ear. Although plasticity in the auditory space map seems to be restricted to development, adult ferrets show some recovery of sound localization behavior after long-term monaural occlusion. The capacity for behavioral adaptation is, however, task dependent, because auditory spatial acuity and binaural unmasking (a measure of the spatial contribution to the "cocktail party effect") are permanently impaired by chronically plugging one ear, both in infancy but especially in adulthood. Experience-induced plasticity allows the neural circuitry underlying sound localization to be customized to individual characteristics, such as the size and shape of the head and ears, and to compensate for natural conductive hearing losses, including those associated with middle ear disease in infancy.

Adaptation, Physiological↗

Acute study on the efficacy and safety of an auditory brainstem prosthesis.

Patients with profound binaural sensorineural hearing loss can be treated with cochlear implantation. In recent years, patients who have lost the integrity of the auditory nerve between the spiral ganglion and the cochlear nucleus in the brainstem, and cannot benefit from a cochlear implant, have reported auditory sensations following direct stimulation of the cochlear nucleus with an auditory brainstem prosthesis. To examine the safety and efficacy of such a prosthesis, the cochlear nuclei of guinea-pigs were acutely implanted and stimulated unilaterally with bipolar surface electrodes using the parameters of human implants. The activation of the central auditory pathway by the prosthesis was demonstrated using the 2-deoxyglucose technique. There was broad 2-deoxyglucose labelling in the ipsilateral cochlear nucleus and bilaterally in the inferior colliculi, indicating unusual stimulation of the ipsilateral ascending pathway. Histological examination was performed on all cochlear nuclei. The volumes of cochlear nuclei and the neuron sizes and density in the cochlear nuclei were analysed with three-dimensional reconstruction techniques, and comparisons were made between the stimulated and unstimulated sides. No histological difference, either by direct visual observation or by statistical comparisons, was observed between the stimulated cochlear nuclei and the control sides. These results suggest that in the acute case the auditory brainstem prostheses can safely and effectively activate the auditory pathway in guinea-pigs.

Acoustic Stimulation↗

Effects of same-modality interference on immediate serial recall of auditory and visual information.

Two studies investigated the effects of same-modality interference on the immediate serial recall of auditorily and visually presented stimuli. Typically, research in which this task is used has been conducted in quiet rooms, excluding auditory information that is extraneous to the auditorily presented stimuli. However, visual information such as background items clearly within the subject's view have not been excluded during visual presentation. Therefore, in both the present studies, the authors used procedures that eliminated extra-list visual interference and introduced extra-list auditory interference. When same-modality interference was eliminated, weak visual recency effects were found, but they were smaller than those that were generated by auditorily presented items. Further, mid-list and end-of-list recall of visually presented stimuli was unaffected by the amount of interfering visual information. On the other hand, the introduction of auditory interference increased mid-list recall of auditory stimuli. The results of Experiment 2 showed that the mid-list effect occurred with a moderate, but not with a minimal or maximal, level of auditory interference, indicating that moderate amounts of auditory interference had an alerting effect that is not present in typical visual interference.

Acoustic Stimulation↗

Visual and auditory information as determinants of primacy effects.

Recent research has demonstrated that auditory and visual information have similar mnemonic properties. The relative influence of verbal, auditory, and visual stimulus materials on the primacy effect in free recall was studied. Significant primacy effects were obtained when either verbal or auditory-input stimuli were presented. However, primacy effects were suppressed when pictorial materials were used, principally because of elevation of recall for midlist and later elements. Instructions to use visual mental imagery at encoding suppressed primacy effects for verbal materials, but not for auditory materials, indicating that although auditory information processing is probably similar to phonological processing within working memory, auditory processing may share cognitive resources with visuospatial processing. Results are shown to be predictable and interpretable within the item-specific/relational information distinction of Hunt and Einstein (e.g., 1981), and within the working-memory theory of Baddeley (e.g., 1986).

Adolescent↗

Stimulus-dependent central processing of auditory stimuli: a PET study.

Positron emission tomography (PET) was used to investigate the neural systems involved in the central processing of different auditory stimuli. Noise, pure tone and pure-tone pulses, music and speech were presented monaurally. O-15-water PET scans were obtained in relation to these stimulations presented to five normal hearing and healthy subjects. All stimuli were related to a basic scan in silence. Processing of simple auditory stimuli, such as pure tones and noise, predominantly activate the left transverse temporal gyrus (Brodmann area [BA] 41), whereas sounds with discontinued acoustic patterns, such as pure-tone pulse trains, activated parts of the auditory association area in the superior temporal gyri (BA 42) in both hemispheres. Moreover, sounds with complex spectral, intensity, and temporal structures (words, speech, music) activated spatially even more extensive associative auditory areas in both hemispheres (BA 21, 22). PET has revealed a remarkable potential to investigate early central auditory processing, and has provided evidence of the coexistence of functionally linked, but individually active parallel and serial auditory networks.

Acoustic Impedance Tests↗

Optical mapping of neural responses and their gamma-aminobutyric acid-ergic inhibitory effects in the auditory brainstem of early postnatal mice.

gamma-Aminobutyric acid (GABA)ergic neurons play important tropic and modulatory roles in the auditory pathway, especially in the early stage between postnatal Days 0 and 5. The effects of GABA and GABAa receptor antagonist were observed in this experimental study. Numerous histological and electrophysiological studies have been performed on the contribution of GABA to the auditory pathway; however, the spatio-temporal patterns of excitatory propagation and the relationships between GABA receptor and excitatory propagation have yet to be reported. Using an optical recording technique and a voltage-sensitive dye, the spatio-temporal patterns of excitatory propagation were observed in the auditory brainstem slices of early postnatal mice. A bath containing 50 microM GABA was applied, which largely inhibited the excitatory activities along the vestibulocochlear pathway. Bicuculline methiodide (BMI), a competitive antagonist against GABAa receptor, partially reversed the effects of GABA on the optical signals. Bath application of BMI alone helped to facilitate the depolarization course and its effect was apparent as an enlargement of the depolarized region from the cochlear nucleus and vestibular nucleus to some adjacent brainstem nuclei, as well as enhancing the amplitude of changes in the optical signals. The experimental results seem to suggest that GABAa receptors are widely distributed in an early postnatal auditory brainstem. GABA exhibited a greater modulating effect in the adjacent brainstem nuclei, which are involved in complex information processes, than that observed in the modulating primary auditory pathway. In the present experiment, significant GABAergic contributions to the optical recordings in the auditory brainstem were observed.

Animals↗

Acetylcholinesterase staining in human auditory and language cortices: regional variation of structural features.

Cholinergic innervation of the cerebral neocortex arises from the basal forebrain and projects to all cortical regions. Acetylcholinesterase (AChE), the enzyme responsible for deactivating acetylcholine, is found within both cholinergic axons arising from the basal forebrain and a subgroup of pyramidal cells in layers III and V of the cerebral cortex. This pattern of staining varies with cortical location and may contribute uniquely to cortical microcircuitry within functionally distinct regions. To explore this issue further, we examined the pattern of AChE staining within auditory, auditory association, and putative language regions of whole, postmortem human brains. The density and distribution of acetylcholine-containing axons and pyramidal cells vary systematically as a function of auditory processing level. Within primary auditory regions AChE-containing axons are dense and pyramidal cells are largely absent. Adjacent cortical regions show a decrease in the density of AChE-containing axons and an increase in AChE-containing pyramidal cells. The posterior auditory and language regions contain a relatively high density of AChE-containing pyramidal cells and AChE-containing axons. Although right and left posterior temporal regions are functionally asymmetrical, there is no apparent asymmetry in the general pattern of AChE staining between homologous regions of the two hemispheres. Thus, the pattern of AChE staining covaries with processing level in the hierarchy of auditory cortical regions, but does not vary between the functionally distinct right and left posterior regions. An asymmetry in the size of layer III AChE-rich pyramidal cells was present within a number of cortical regions. Large AChE-rich pyramidal cells of layer III were consistently greater in size in the left hemisphere as compared to the right. Asymmetry in layer III pyramidal cell size was not restricted to language-associated regions, and could potentially have a variety of etiologies including structural, connectional, and activational differences between the left and right hemisphere.

Acetylcholinesterase↗

Distributed auditory cortical representations are modified when non-musicians are trained at pitch discrimination with 40 Hz amplitude modulated tones.

Several functional brain attributes reflecting neocortical activity have been found to be enhanced in musicians compared to non-musicians. Included are the N1m evoked magnetic field, P2 and right-hemispheric N1c auditory evoked potentials, and the source waveform of the magnetically recorded 40 Hz auditory steady state response (SSR). We investigated whether these functional brain attributes measured by EEG are sensitive to neuroplastic remodeling in non-musician subjects. Adult non-musicians were trained for 15 sessions to discriminate small changes in the carrier frequency of 40 Hz amplitude modulated pure tones. P2 and N1c auditory evoked potentials were separated from the SSR by signal processing and found to localize to spatially differentiable sources in the secondary auditory cortex (A2). Training enhanced the P2 bilaterally and the N1c in the right hemisphere where auditory neurons may be specialized for processing of spectral information. The SSR localized to sources in the region of Heschl's gyrus in primary auditory cortex (A1). The amplitude of the SSR (assessed by bivariate T2 in 100 ms moving windows) was not augmented by training although the phase of the response was modified for the trained stimuli. The P2 and N1c enhancements observed here and reported previously in musicians may reflect new tunings on A2 neurons whose establishment and expression are gated by input converging from other regions of the brain. The SSR localizing to A1 was more resistant to remodeling, suggesting that its amplitude enhancement in musicians may be an intrinsic marker for musical skill or an early experience effect.

Acoustic Stimulation↗

FMRI evidence for activation of multiple cortical regions in the primary auditory cortex of deaf subjects users of multichannel cochlear implants.

To investigate the activation of the auditory cortex by fMRI, three deaf subjects users of the Ineraid cochlear implant participated in our study. Possible interference between fMRI acquisition and the implanted electrodes was controlled and safe experimental conditions were obtained. For each subject, electrical stimuli were applied on different intracochlear electrodes, in monopolar mode. Stimulation of each electrode was actually producing auditory sensations of different pitches, as demonstrated by psychophysical pitch-ranking measurements in the same subjects. Because deaf subjects did not hear scanner noise, the data were collected in 'silent background' conditions, i.e. as a result of pure auditory sensations. Functional maps showed activation of the primary auditory cortex, predominantly in the left hemisphere. Stimulation of each different intracochlear electrode revealed different clusters of activation. After cluster grouping, at least three regions have been identified in the auditory cortex of each subject, and comparisons with previous architectonic and functional studies are proposed. However, a tonotopic organization could not be clearly identified within each region. These arguments, obtained without interference with unwanted scanner noise, plead in favor of a functional subdivision of the primary auditory cortex into multiple cortical regions in cochlear implant users.

Adult↗

Functional organization of ferret auditory cortex.

We characterized the functional organization of different fields within the auditory cortex of anaesthetized ferrets. As previously reported, the primary auditory cortex, A1, and the anterior auditory field, AAF, are located on the middle ectosylvian gyrus. These areas exhibited a similar tonotopic organization, with high frequencies represented at the dorsal tip of the gyrus and low frequencies more ventrally, but differed in that AAF neurons had shorter response latencies than those in A1. On the basis of differences in frequency selectivity, temporal response properties and thresholds, we identified four more, previously undescribed fields. Two of these are located on the posterior ectosylvian gyrus and were tonotopically organized. Neurons in these areas responded robustly to tones, but had longer latencies, more sustained responses and a higher incidence of non-monotonic rate-level functions than those in the primary fields. Two further auditory fields, which were not tonotopically organized, were found on the anterior ectosylvian gyrus. Neurons in the more dorsal anterior area gave short-latency, transient responses to tones and were generally broadly tuned with a preference for high (>8 kHz) frequencies. Neurons in the other anterior area were frequently unresponsive to tones, but often responded vigorously to broadband noise. The presence of both tonotopic and non-tonotopic auditory cortical fields indicates that the organization of ferret auditory cortex is comparable to that seen in other mammals.

Acoustic Stimulation↗

High-frequency components of auditory evoked potentials are detected in responsive but not in unconscious patients.

BACKGROUND: The dose-dependent suppression of midlatency auditory evoked potentials by general anesthetics has been proposed to measure depth of anesthesia. In this study, perioperatively recorded midlatency auditory evoked potentials were analyzed in a time-frequency space to identify significant changes induced by general anesthesia. METHODS: Perioperatively recorded auditory evoked potentials of 19 patients, recorded at varying levels of anesthesia, were submitted to a multiscale analysis using the wavelet analysis. Energy contents of the signal were calculated in frequency bands 0-57.1 Hz, 57.1-114.3 Hz, 114.3-228.6 Hz, and 228.6-457.1 Hz. A Friedman test and a Dunn multiple comparisons test were performed to identify significant differences. RESULTS: Statistical evaluation showed a highly significant decrease of the wavelet energies for the frequency bands 57.1-114.3 Hz (P < 0.0001), 114.3-228.6 Hz (P < 0.0001), and 228.6-457.1 Hz (P < 0.0001) for the measuring points representing deep general anesthesia. This decrease is accompanied by a decrease in the wavelet energy of the frequency band 0-57.1 Hz of no statistical significance (P = 0.021) (level of significance set to P = 0.01). The changes are most prominent in the poststimulus interval between 10 and 30 ms. CONCLUSIONS: This study describes the presence of high-frequency components of the auditory evoked potential. The amount of these components is higher during responsiveness when compared to unconsciousness. Temporal localization of the high-frequency components within the auditory evoked potential shows that they represent a response to the auditory stimulus. Further studies are required to identify the source of these high-frequency components.

Acoustic Stimulation↗

Electrophysiologic abnormalities of auditory and visual information processing in patients with traumatic brain injury.

OBJECTIVE: Through both auditory and visual modalities, we sought to explore the efficacy of event-related potentials in detecting residual cognitive impairments in patients with traumatic brain injury (TBI). DESIGN: Control subjects and TBI patients with favorable recovery were recruited. Pure tone and primary color discrimination tasks were utilized to elicit auditory and visual event-related potentials, respectively. All subjects were instructed to push a response button when they detected the target stimuli. Both behavioral and electrophysiologic responses were obtained simultaneously. We analyzed the event-related potential waveforms and examined the differences in amplitude, latency, behavioral reaction time, and response accuracy. RESULTS: A total of 11 TBI patients and 11 control subjects were tested. Results showed that (1) TBI patients had significantly lower P300 amplitude in both auditory (11.2 vs. 22. 7 microV) and visual (11.6 vs. 20.9 microV) domains, (2) TBI patients had significantly longer P300 latency in both auditory (355 vs. 294 msecs) and visual (376 vs. 341 msecs) modalities, and (3) although there was no significant difference in response accuracy (97.7%vs. 100%), reaction time for both auditory and visual tasks were significantly longer in TBI patients (auditory, 404 vs. 277 msecs; visual, 397 vs. 346 msecs). CONCLUSION: Although TBI patients with good recovery showed similar response accuracy when compared with control subjects, they demonstrated significantly poorer performance in both electrophysiologic and behavioral responses. Diminished amplitudes and prolonged latencies in P300 responses indicate impaired organization and categorization of incoming sensory information; prolonged behavioral reaction times suggest slowing in the response execution process. Clinical and theoretical implications and goals for continued research are discussed.

Adult↗

Serial somatosensory and brainstem auditory evoked potentials in monitoring of acute supratentorial mass lesions.

OBJECTIVE: To determine the relevance of serial evoked potentials (brainstem auditory evoked potentials and somatosensory evoked potentials) and clinical parameters (pupillary response and intracranial pressure) in patients with acute supratentorial mass lesions. DESIGN: Prospective case series of comatose patients with acute supratentorial mass lesions. SETTING: Neurocritical care unit of a tertiary care center. PATIENTS: Thirty consecutive patients with the following study inclusion criteria: a) clinical and computed tomography evidence of an acute supratentorial mass lesion; b) implantation of an intracranial pressure monitoring device; and c) a persistent comatose state during the observation period. INTERVENTIONS: Brainstem auditory evoked potentials, somatosensory evoked potentials, intracranial pressure, and pupillary responses were recorded at the time of three particular events: a) immediately after implantation of an epidural intracranial pressure monitoring device; b) during intracranial pressure therapy; and c) at termination of intracranial pressure therapy. Evoked potential results were ranked into three categories: a) normal on both sides; b) abnormal or absent on one side; and c) evoked potentials on both sides abnormal or absent. Spearman's rank correlation was performed to analyze serial recordings. Cross tables were generated to determine the prognostic value of evoked potentials and clinical parameters. Fisher's exact test was applied to calculate statistical significance. MEASUREMENTS AND MAIN RESULTS: Intracranial pressure values correlated with pupillary responses and brainstem auditory evoked potentials during and at the termination of intracranial pressure therapy. Pupillary findings correlated with brainstem auditory evoked potentials only at the time of termination of intracranial pressure therapy. There was no correlation between somatosensory evoked potentials and clinical parameters. Pupillary responses indicated a good or poor recovery during and at the termination of intracranial pressure therapy. Brainstem auditory evoked potentials and intracranial pressure values distinguished between good and poor outcome only at termination of intracranial pressure therapy. Somatosensory evoked potential results did not predict outcome. CONCLUSIONS: Shortly after manifestation of supratentorial mass lesions, the results of evoked potentials and clinical parameters indicate increased intracranial pressure and incipient transtentorial herniation but do not predict sequelae. Our results indicate that after institution of effective therapy, pupillary abnormalities and brainstem auditory evoked potentials serve as valuable prognostic predictors. In contrast, somatosensory evoked potentials reflect neither therapeutic efficacy nor outcome in our patient population.

Acute Disease↗

Impaired brain processing in noise-induced tinnitus patients as measured by auditory and visual event-related potentials.

OBJECTIVES: This study aimed to confirm that the brain processing of auditory stimuli in tinnitus patients is impaired (Attias, Urbach, Gold, & Shemesh, 1993). In addition, possible brain processing dysfunction in response to visual stimuli was assessed. DESIGN: Auditory and visual event-related potentials (ERPs) and reaction times were recorded in response to a standard oddball target detection paradigm. The subjects consisted of 21 noise-induced chronic tinnitus patients and 21 age- and hearing-matched control subjects without tinnitus. RESULTS: The tinnitus patients had significantly prolonged latencies for the auditory nontarget ERP components N1, N2, and P3 and for the auditory target ERP P3 component. The auditory P3 component was also significantly reduced in amplitude for both target and nontarget stimuli for the tinnitus patients. The visual P3 target and nontarget components were similarly significantly prolonged in latency for the tinnitus patients. Reaction times to both target and nontarget stimuli were significantly delayed for the tinnitus patients for both stimulus modalities. CONCLUSIONS: These findings point to a cortical information processing dysfunction in chronic tinnitus patients associated primarily with auditory stimuli. ERPs may provide an objective electrophysiologic tinnitus measure.

Adult↗

Naloxone blockade of (-)pentazocine-induced changes in auditory function.

OBJECTIVE: In a previous report, we found that intravenous (i.v.) (-)pentazocine improved auditory sensitivity and significantly altered compound action potential (CAP) amplitudes. Its sigma (sigma)-receptor-selective optical isomer (+)pentazocine administered at the same dose was without effect, suggesting that the observed auditory neural effects might be mediated by an opioid receptor. To directly test this hypothesis, in the present investigation we attempted to antagonize the auditory neural effects of (-)pentazocine using the pure, nonspecific drug antagonist naloxone. DESIGN: In 25 normal-hearing, male, pigmented chinchillas, amplitude and latency changes in the click-evoked auditory nerve CAP (N1) and cochlear microphonic (CM) were tracked at six stimulus intensities during a baseline period and after the postbaseline administration of the opioid drug agonist (-)pentazocine (16 mg/kg; i.v.). In separate groups of chinchillas, (-)pentazocine was given alone or administered in combination with the standard opioid receptor antagonist naloxone administered at two doses. RESULTS: Robust changes in CAP amplitudes after (-)pentazocine occurred in the absence of measurable alterations in CAP response latencies, CM amplitudes, or blood chemistries and were significantly antagonized when naloxone (5 mg/kg) was added to the i.v. infusion. CONCLUSIONS: The observed blockade clearly indicates that the agonist effects of (-)pentazocine are opioid receptor-mediated and suggests a connection between opioid receptors and auditory neural function. Mechanisms of action and the connection between an opioid modulation of auditory function and stress, hyperacusis, and tinnitus are discussed.

Animals↗

Maturation of human cortical auditory function: differences between normal-hearing children and children with cochlear implants.

OBJECTIVE: We investigated maturation of cortical auditory function in normal-hearing children and in children who receive stimulation of their auditory system through a cochlear implant. DESIGN: As a measure of cortical auditory function, auditory evoked responses (AERs) were recorded from normal-hearing children and adults as well as from children and adults fitted with a cochlear implant. Morphological and latency changes for evoked responses recorded at electrode Cz are reported. RESULTS: For normal-hearing children, there is a gradual evolution of AER features that extends through adolescence, with P1 latency becoming adult-like in the late teens. Latency changes for P1 occur at the same rate for implanted children, but the overall maturation sequence is delayed. By extrapolation from the existing data, the age at which P1 latency becomes adult-like is delayed by approximately 5 yr for the implanted population. Other typical features of the AER, namely N1 and P2, are either delayed in developing or absent in the implanted children. CONCLUSIONS: These preliminary findings suggest both similarities and differences in cortical auditory maturation for normal-hearing and implanted children. For implanted children, the 5 yr delay for maturation of P1 latency roughly corresponds to the average 4.5 yr interval between the onset of deafness and the time of implantation. These findings suggest that during the period of deafness, maturation of cortical auditory function does not progress. However, some, if not all, maturational processes resume after stimulation is reintroduced.

Adult↗

Clinical findings for a group of infants and young children with auditory neuropathy.

OBJECTIVE: To examine the prevalence of auditory neuropathy in a group of infants at risk for hearing impairment and to present an overview of the clinical findings for affected children. DESIGN: Results for 20 subjects who showed repeatable cochlear microphonic potentials in the absence of click-evoked auditory brain stem responses are included in this study. Behavioral and steady state evoked potential thresholds were established in each case. Where possible, otoacoustic emission and speech perception results (unaided and aided) also were obtained. RESULTS: One in 433 (0.23%) of the children in our series had evidence of auditory neuropathy. The audiometric findings for these subjects varied significantly, with behavioral thresholds ranging from normal to profound levels. Discrimination skills were also variable. Approximately half of the subjects showed little understanding, or even awareness, of speech inputs in both the unaided and aided conditions. There were, however, a number of children who could score at significant levels on speech discrimination tasks and who benefited from the provision of amplification. CONCLUSION: The results suggest that auditory neuropathy is more common in the infant population than previously suspected. The effects of neuropathy on auditory function appear to be idiosyncratic, producing significant variations in both the detection and discrimination of auditory signals. As such, the management of children with this disorder must allow for individual differences.

Audiometry, Evoked Response↗