Henry J. Michalewski

Transient deafness due to temperature-sensitive auditory neuropathy

Objective: To define mechanisms accounting for transient deafness in three children(two siblings, ages 3 and 6, and an unrelated child, age 15) when they become febrile. Design: Audiometric tests (pure‐tone audiometry, speech and sentence comprehension), tympanometry, middle ear muscle reflex thresholds, otoacoustic emissions (OAEs), and electrophysiological methods (auditory brain stem responses [ABRs], sensory evoked potentials, peripheral nerve conduction velocities) were used to test the children when they were afebrile and febrile. Results: ABRs, when afebrile, were abnormal with a profound delay of the IV‐V and absence of waves I‐III. The ABR in one of the children, tested when febrile, showed no ABR components. Measures of cochlear receptor function using OAEs were normal in both febrile and afebrile states. Cochlear microphonic potentials were present in the three children, and a summating potential was likely present in two. When afebrile, there was a mild threshold elevation for all frequencies in the 15‐yr‐old and a mild elevation of thresholds for just low frequencies in the two siblings. Speech comprehension in quiet was normal but impaired in noise. One of the siblings tested when febrile had a profound elevation (>80 dB) of pure‐tone thresholds and speech comprehension was absent. Acoustic reflexes subserving middle ear muscles and olivocochlear bundle were absent when febrile and when afebrile. No other peripheral or cranial nerve abnormalities were found in any of the children. Sensory nerve action potentials from median nerve in one of the children showed no abnormalities on warming of the hand to 39°C. Conclusion: These children have an auditory neuropathy manifested by a disorder of auditory nerve function in the presence of normal cochlear outer hair cell functions. They develop a conduction block of the auditory nerves when their core body temperature rises due, most likely, to a demyelinating disorder of the auditory nerve. The auditory neuropathy in the two affected siblings is likely to be inherited as a recessive disorder.

Latency variability and temporal interrelationships of the auditory event-related potentials (N1, P2, N2, and P3) in normal subjects.

Peak latency variation and the temporal interrelationships of the auditory event-related potential were investigated in 12 normal adults (ages 28-42). Measures of variation were based on both conventional averages and single trials. Estimates of N1, P2, N2 and P3 latencies were made on a trial-by-trial basis to target stimuli recorded from Fz, Cz and Pz scalp locations. Results showed that single-trial latency variability of the auditory ERP differed both among the various components and between subjects. Larger standard deviations were measured for the later N2 and P3 components than the earlier N1 and P2 components. Regression analyses between various component latencies indicated a strong covarying relationship between N2 and P3, with N2 accounting for up to 61% of the variance of P3 latency at Pz. Earlier N1 and P2 components added little to the overall prediction of either P3 or N2. For the other components, P2 accounted for 9-16% of the variance of N2, while N1 accounted for approximately 1% of the variance of N2; N1 accounted for 8-10% of the latency variation of P2. The correlations between single-trial peak latencies and RTs were positive but of low magnitude. The highest correlations between peak latency and RT were found for N2 (r = 0.33) and P3 (r = 0.24). The low correlations between the single-trial latencies of N1 and P3 suggest that the processes reflected by these components are independent and support a distinction between the earlier and the later components of the ERP. The close temporal coupling between N2 and P3 suggests that N2 may reflect cognitive properties in common to P3 in stimulus evaluation processes.

Cochlear receptor (microphonic and summating potentials, otoacoustic emissions) and auditory pathway (auditory brain stem potentials) activity in auditory neuropathy.

Objective To define both auditory nerve and cochlear receptor functions in subjects with auditory neuropathy (AN). Design We tested 33 AN subjects (66 ears) and compared them with 21 healthy subjects (28 ears). In AN subjects, the average pure-tone (1, 2, and 4 kHz) threshold loss was 57 dB HL. Click stimuli were used to elicit transient evoked otoacoustic emissions (TEOAEs), cochlear microphonics (CMs), and auditory brain stem responses (ABRs). Both cochlear and ABR potentials were recorded from surface electrodes (vertex-ipsilateral mastoid) using averaging procedures. The amplitudes and latencies of CMs and ABRs and the amplitude of the TEOAEs were analyzed. Results CM amplitudes recorded from normal ears decreased as a function of subject age. CMs recorded from AN subjects fell within the normal age-adjusted range in 60% of the subjects and were >2 SEEs (standard error of estimate) above the age-adjusted normal regression in 40% of the subjects. TEOAEs were absent in 19 (30%) AN ears (bilaterally in eight, and unilaterally in three subjects) and were present in 44 ears. In AN subjects, correlations among CM amplitude, TEOAE amplitude, and pure-tone average thresholds were not significantly related. CM amplitudes were not significantly different whether TEOAEs or ABRs were present or absent. The ABR was present in 21% of AN subjects and consisted of a low-amplitude Wave V without a preceding Wave I. Measures of CM amplitude and PTA hearing loss were not significantly different in those AN ears with a preserved ABR compared with ears with absent ABRs. Summating potentials to transient click stimuli were of small amplitude (<0.1 &mgr;V) and detectable in approximately 50% of the AN and healthy control subjects limiting formal analysis of summating potentials. Conclusions In a significant proportion of AN subjects, we found abnormalities of cochlear receptor function, including elevated CM amplitudes and absence of TEOAEs. These two abnormalities occurred independently of each other. A low amplitude Wave V of the ABR was found in approximately one-fifth of AN subjects, evidence that neural synchrony can be partially preserved in some subjects with this disorder.

Auditory temporal processes in normal-hearing individuals and in patients with auditory neuropathy

OBJECTIVE To study objectively auditory temporal processing in a group of normal hearing subjects and in a group of hearing-impaired individuals with auditory neuropathy (AN) using electrophysiological and psychoacoustic methods. METHODS Scalp recorded evoked potentials were measured to brief silent intervals (gaps) varying between 2 and 50ms embedded in continuous noise. Latencies and amplitudes of N100 and P200 were measured and analyzed in two conditions: (1) active, when using a button in response to gaps; (2) passive, listening, but not responding. RESULTS In normal subjects evoked potentials (N100/P200 components) were recorded in response to gaps as short as 5ms in both active and passive conditions. Gap evoked potentials in AN subjects appeared only with prolonged gap durations (10-50ms). There was a close association between gap detection thresholds measured psychoacoustically and electrophysiologically in both normals and in AN subjects. CONCLUSIONS Auditory cortical potentials can provide objective measures of auditory temporal processes. SIGNIFICANCE The combination of electrophysiological and psychoacoustic methods converged to provide useful objective measures for studying auditory cortical temporal processing in normals and hearing-impaired individuals. The procedure used may also provide objective measures of temporal processing for evaluating special populations such as children who may not be able to provide subjective responses.

Auditory averaged evoked potentials and aging: Factors of stimulus, task and topography

The averaged evoked potential to brief tones was compared for 10 young and 10 elderly female subjects. The amplitudes of the sensory components (P1, N1 and P2) were not affected by an infrequent change in pitch of the tones or instructing subjects to count or ignore them; but overall the elderly had a larger P1 and smaller P2 amplitude and a difference in the scalp distribution of P2. Repetition of the tones produced a decrement in these sensory components and a differential one for young and old subjects A slow potential complex consisting of components N2, P3 and SW appeared to changes in tone pitch and became more pronounced when attention was directed to the tones. Overall smaller SPs for oder subjects were interpreted as evidence for a change with age in the cortical representation of the orienting response. Topographical analysis of SPs indicated diminished activity in frontal (Fz) electrodes for elderly persons, suggestive of an enhanced aging process in the frontal cortices.

Sex differences in the amplitudes and latencies of the human auditory brain stem potential

Sex differences in the amplitudes and latencies of the auditory brain stem potential (BAEP) were investigated using 3 levels of intensity and 3 stimulus presentation rates. The females displayed consistently larger BAEPs for waves IV, V, VI, VII than the males. The only latency differences which reached significance over all the intensities and rates occurred for wave V. The females showed significantly shorter wave V latencies than the males. Since hearing losses and individually determined click thresholds were comparable between the two groups tested, the exact sources of the uneven distribution of amplitude and latency effects are in question. Differences in the relative distances of the anatomical generators are considered in accounting for the sex differences. Because the precise origin of the sex differences cannot be stated with certainty at this time, attempts to develop normative data for the BAEP should consider the possible influences of sex differences.

A Dominantly Inherited Progressive Deafness Affecting Distal Auditory Nerve and Hair Cells

We have studied 72 members belonging to a large kindred with a hearing disorder inherited in an autosomal dominant pattern. We used audiological, physiological, and psychoacoustic measures to characterize the hearing disorders. The initial phenotypic features of the hearing loss are of an auditory neuropathy (AN) with abnormal auditory nerve and brainstem responses (ABRs) and normal outer hair cell functions [otoacoustic emissions (OAEs) and cochlear microphonics (CMs)]. Psychoacoustic studies revealed profound abnormalities of auditory temporal processes (gap detection, amplitude modulation detection, speech discrimination) and frequency processes (difference limens) beyond that seen in hearing impairment accompanying cochlear sensory disorders. The hearing loss progresses over 10–20 years to also involve outer hair cells, producing a profound sensorineural hearing loss with absent ABRs and OAEs. Affected family members do not have evidence of other cranial or peripheral neuropathies. There was a marked improvement of auditory functions in three affected family members studied after cochlear implantation with return of electrically evoked auditory brainstem responses (EABRs), auditory temporal processes, and speech recognition. These findings are compatible with a distal auditory nerve disorder affecting one or all of the components in the auditory periphery including terminal auditory nerve dendrites, inner hair cells, and the synapses between inner hair cells and auditory nerve. There is relative sparing of auditory ganglion cells and their axons.

Readiness to respond in a target detection task: pre- and post-stimulus event-related potentials in normal subjects

Brain potentials were recorded from 12 normal subjects engaged in an auditory target detection task (target stimulus probability of 0.2, stimulus rate of 1 every 2 sec) when instructions were (1) to press a response button with the thumb of the dominant hand to each target or (2) to keep a mental count of each target. A pre-stimulus slow negative potential was identified before every stimulus except non-targets immediately after targets. The amplitude of the pre-stimulus negativity was significantly affected by task instructions and was up to 4 times larger during the button press than the mental count condition. In contrast, the amplitudes and latencies of the event-related components (N100, P200, N200 and P300), when slow potentials were removed by filtering, were not different as a function of press or count instructions. The immediately preceding stimulus sequence affected both the amplitude and onset latency of the pre-stimulus negativity; both measures increased as the number of preceding non-targets increased. The amplitude of the pre-stimulus negative shift to targets also increased significantly as RT speed decreased. The major portion of the pre-stimulus negative potential is considered a readiness potential (RP) reflecting preparations to make a motor response. The amplitude of the RP during the target detection task did not significantly lateralize in contrast to the RP accompanying self-paced movements.

Neural and receptor cochlear potentials obtained by transtympanic electrocochleography in auditory neuropathy

OBJECTIVE Transtympanic electrocochleography (ECochG) was recorded bilaterally in children and adults with auditory neuropathy (AN) to evaluate receptor and neural generators. METHODS Test stimuli were clicks from 60 to 120dB p.e. SPL. Measures obtained from eight AN subjects were compared to 16 normally hearing children. RESULTS Receptor cochlear microphonics (CMs) in AN were of normal or enhanced amplitude. Neural compound action potentials (CAPs) and receptor summating potentials (SPs) were identified in five AN ears. ECochG potentials in those ears without CAPs were of negative polarity and of normal or prolonged duration. We used adaptation to rapid stimulus rates to distinguish whether the generators of the negative potentials were of neural or receptor origin. Adaptation in controls resulted in amplitude reduction of CAP twice that of SP without affecting the duration of ECochG potentials. In seven AN ears without CAP and with prolonged negative potential, adaptation was accompanied by reduction of both amplitude and duration of the negative potential to control values consistent with neural generation. In four ears without CAP and with normal duration potentials, adaptation was without effect consistent with receptor generation. In five AN ears with CAP, there was reduction in amplitude of CAP and SP as controls but with a significant decrease in response duration. CONCLUSIONS Three patterns of cochlear potentials were identified in AN: (1) presence of receptor SP without CAP consistent with pre-synaptic disorder of inner hair cells; (2) presence of both SP and CAP consistent with post-synaptic disorder of proximal auditory nerve; (3) presence of prolonged neural potentials without a CAP consistent with post-synaptic disorder of nerve terminals. SIGNIFICANCE Cochlear potential measures may identify pre- and post-synaptic disorders of inner hair cells and auditory nerves in AN.

Frequency Changes in a Continuous Tone: Auditory Cortical Potentials

OBJECTIVE We examined auditory cortical potentials in normal hearing subjects to spectral changes in continuous low and high frequency pure tones. METHODS Cortical potentials were recorded to increments of frequency from continuous 250 or 4000Hz tones. The magnitude of change was random and varied from 0% to 50% above the base frequency. RESULTS Potentials consisted of N100, P200 and a slow negative wave (SN). N100 amplitude, latency and dipole magnitude with frequency increments were significantly greater for low compared to high frequencies. Dipole amplitudes were greater in the right than left hemisphere for both base frequencies. The SN amplitude to frequency changes between 4% and 50% was not significantly related to the magnitude of spectral change. CONCLUSIONS Modulation of N100 amplitude and latency elicited by spectral change is more pronounced with low compared to high frequencies. SIGNIFICANCE These data provide electrophysiological evidence that central processing of spectral changes in the cortex differs for low and high frequencies. Some of these differences may be related to both temporal- and spectral-based coding at the auditory periphery. Central representation of frequency change may be related to the different temporal windows of integration across frequencies.