Robert Burkard

The functional anatomy of gaze-evoked tinnitus and sustained lateral gaze

Objective: To identify neural sites associated with gaze-evoked tinnitus (GET), an unusual condition that may follow cerebellar–pontine angle surgery. Methods: The authors examined eight patients with GET and used PET to map the neural sites activated by lateral gaze in them and seven age- and sex-matched control subjects. Results: In patients with GET, tinnitus loudness and pitch increased with lateral gaze and, to a lesser extent, up and down gaze. Evidence for neural activity related to GET was seen in the auditory lateral pontine tegmentum or auditory cortex. GET-associated nystagmus appears to activate the cuneus and cerebellar vermis. These sites were found in addition to an extensive network that included frontal eye fields and other sites in frontal, parietal, and temporal cortex that were activated by lateral gaze in seven control subjects and the patients. The unilateral deafness in patients with GET was associated with expansion of auditory cortical areas responsive to tones delivered to the good ear. In addition to GET, unilateral deafness, end-gaze nystagmus, and facial nerve dysfunction were common. Conclusions: Patients with GET have plastic changes in multiple neural systems that allow neural activity associated with eye movement, including those associated with the neural integrator, to stimulate the auditory system. Anomalous auditory activation is enhanced by the failure of cross-modal inhibition to suppress auditory cortical activity. The time course for the development of GET suggests that it may be due to multiple mechanisms.

Cu/Zn SOD deficiency potentiates hearing loss and cochlear pathology in aged 129,CD-1 mice.

Copper/zinc superoxide dismutase (Cu/Zn SOD) is a first‐line defense against free radical damage in the cochlea and other tissues. To determine whether deficiencies in Cu/Zn SOD increase age‐related hearing loss and cochlear pathology, we collected auditory brainstem responses (ABRs) and determined cochlear hair cell loss in 13‐month‐old 129/CD‐1 mice with (a) no measurable Cu/Zn SOD activity (homozygous knockout mice), (b) 50% reduction of Cu/Zn SOD (heterozygous knockout mice), and (c) normal levels of Cu/Zn SOD (wild‐type mice). ABRs were obtained by using 4‐, 8‐, 16‐, and 32‐kHz tone bursts. Cochleas were harvested immediately after testing, and separate counts were made of inner and outer hair cells. Compared with wild‐type mice, homozygous and heterozygous knockout mice exhibited significant threshold elevations and greater hair cell loss. Phenotypic variability was higher among heterozygous knockout mice than among wild‐type or homozygous knockout mice. Separate groups of wild‐type and homozygous knockout mice were examined for loss of spiral ganglion cells and eighth nerve fibers. At 13 months of age, both wild‐type and knockout mice had significantly fewer nerve fibers than did 2‐month‐old wild‐type mice, with significantly greater loss in aged knockout mice than in aged wild‐type mice. Thirteen‐month‐old knockout mice also had a significant loss of spiral ganglion cells compared with 2‐month‐old wild‐type mice. The results indicate that Cu/Zn SOD deficiencies increase the vulnerability of the cochlea to damage associated with normal aging, presumably through metabolic pathways involving the superoxide radical. J. Comp. Neurol. 413:101–112, 1999.

Brain imaging of the effects of lidocaine on tinnitus

Using a single-blind placebo-controlled design, we mapped lidocaine related changes in neural activity, measured by regional cerebral blood flow (rCBF) with (15)O-H(2)O positron emission tomography. Intravenous lidocaine produced both increases and decreases in the loudness of tinnitus. The change in tinnitus loudness was associated with a statistically significant change in neural activity in the right temporal lobe in auditory association cortex. Decreases in tinnitus loudness resulted in larger changes in rCBF than increases. The unilateral activation pattern associated with tinnitus, in contrast with the bilateral activation produced by a real sound, suggests that tinnitus originates in the central auditory system rather than the cochlea. In addition, generalized lidocaine effects were found in the basal ganglia, thalamus, and a region spanning the Rolandic fissure.

Noise-induced hearing loss in chinchillas pre-treated with glutathione monoethylester and R-PIA.

The protective effects of glutathione monoethylester (GEE) and GEE in combination with R-N6-phenylisopropyladenosine (R-PIA) were evaluated in the chinchilla when exposed to impulse (145 dB pSPL) or continuous (105 dB SPL, 4 kHz OB) noise. Six groups of 10 chinchillas were used as subjects. Before exposure to noise, the subjects were anesthetized, a 30 microl drop of drug was placed on the round window (GEE [50, 100, 150 mM], GEE 50 mM and R-PIA). Forty minutes later the subject was exposed to either impulse or continuous noise. The 50 mM treatment provided significant protection from impulse noise, but not from continuous noise exposure. The combination provided significant protection from both the continuous and impulse noise. In a separate set of experiments, glutathione (GSH) levels were measured in the perilymph. All the drug treatments elevated GSH levels. The results are discussed in terms of antioxidant treatments as a prophylactic measure against noise-induced hearing loss.

The effect of broadband noise on the human brainstem auditory evoked response. I. Rate and intensity effects

A series of experiments investigated the effects of continuous broadband noise (ipsilateral) on wave V of the click-evoked brainstem auditory evoked response (BAER). In general, a broadband noise masker increases the latency and decreases the amplitude of wave V. Varying both click and noise intensity, it was found that noise levels above about 40 dB SPL increase the latency and decrease the amplitude of wave V, regardless of click intensity. The effects of noise on wave V amplitude appear constant across click intensity, whereas the effects of a constant noise level on wave V latency decrease at higher click intensities. Both masking and adaptation increase wave V latency, but their combined effects are occlusive: rate-induced wave V latency shift decreases in the presence of continuous broadband noise. The clinical and theoretical implications of these findings are discussed.

A comparison of maximum length and Legendre sequences for the derivation of brain-stem auditory-evoked responses at rapid rates of stimulation.

Experiments were performed in which brain-stem auditory-evoked responses (BAERs) were elicited by two types of pseudorandom pulse trains: maximum length sequences (MLS) and Legendre sequences (LGS). In experiment 1, each pulse sequence was presented at 50 dB nHL with minimum pulse intervals varying from 1 to 10 ms. Wave V latency increased and wave V amplitude decreased with decreasing minimum pulse intervals, with no significant effect of the type of sequence (MLS vs LGS), and no significant interaction between sequence and minimum pulse interval in terms of wave V amplitude or latency. In a second experiment, the minimum pulse interval was held constant at 4 ms, while MLS and LGS levels were varied from 20 to 60 dB nHL. With increasing click intensity, there is a decrease in wave V latency and an increase in wave V amplitude. There was no significant effect of type of sequence (LGS vs MLS) or interaction between type of sequence and stimulus intensity for wave V amplitude or latency. Despite the obvious violation of the assumptions (linearity and stationarity) underlying the application of maximum length sequence analysis and Legendre sequence analysis, both techniques produced reliable responses remarkably similar in morphology to evoked responses obtained by conventional averaging. The results of these experiments support the possibility that analysis methods based on pseudorandom pulse sequences may prove more efficient in data collection and provide a more thorough description of the electrophysiologic behavior of the auditory system compared to conventional averaging.

Stimulus dependencies of the gerbil brain‐stem auditory‐evoked response (BAER). I: Effects of click level, rate, and polarity

Three experiments evaluating the effects of various stimulus manipulations on the click-evoked gerbil brain-stem auditory-evoked response (BAER) are reported. In experiment 1, click polarity and level were covaried. With increasing click level, there is a parallel decrease in the latency of the first five BAER peaks (i-v) and an increase in BAER peak amplitudes. Mean wave i amplitude was greater for rarefaction than condensation clicks at high click levels; mean wave v amplitude was greater for condensation clicks at higher click levels. Experiment 2 covaried click rate and polarity. The latency of the BAER peaks increased with increasing click repetition rate. This rate-dependent latency increase was greater for the later BAER peaks, resulting in an increase in the i-v interval with increasing click rate. As rate increased, the amplitudes of waves i and v decreased monotonically, whereas the amplitudes of waves ii-iv were largely uninfluenced by click rate. As in experiment 1, mean wave i amplitude was greater for rarefaction clicks, whereas mean wave v amplitude was greater for condensation clicks. The magnitude of these polarity dependencies on waves i and v amplitude decreased with increasing click rate. Experiment 3 evaluated the effects of click polarity on BAERs to high-intensity (100 dB pSPL) clicks presented at a rate of 10 Hz. In eight of ten gerbils evaluated, wave i amplitude was greater to rarefaction clicks, and, in all ten animals, wave v amplitude was greater to condensation clicks. The effects of click level and rate on BAER peak amplitudes, latencies, and interwave intervals are reminiscent of stimulus dependencies reported for the human BAER. The effects of click polarity on the amplitudes of waves i and v of the gerbil BAER have also been reported for the human BAER.

39 – Auditory Temporal Processing during Aging

This chapter presents results of a thematic interdisciplinary approach to characterizing and determining the neural bases of presbycusis. Research audiology, psychoacoustics, behavior and experimental psychology, neuroimaging and neurology, single-cell neurophysiology, neuroanatomy and neurochemistry, and evoked potential neurophysiology contributed to cross-project experiments in humans and animals. By using psychoacoustic and evoked potential neurophysiological paradigms such as forward and backward masking (gaps), interstimulus intervals and rates, and by manipulating naturally occurring pauses and voice-onset times in speech, we were able to gain insights into age-related slowing of central nervous system timing mechanisms. The peripheral auditory system with its extensive bank of filters is responsible for the spectral analysis of simple and complex environmental sounds. Thus, inner ear dysfunction is characterized principally and initially by deficiencies in frequency analysis and sensitivity. In contrast, most sounds, and especially suprathreshold complex sounds such as speech, vary over time. Therefore, measures of temporal resolution that can reflect the integrity of the central auditory system have become especially useful in our research seeking to determine the effects of age, per se, on hearing. Here we present results of our temporal resolution research utilizing human and animal subjects aimed at determining neural sites of hearing loss due to aging. This chapter also reinforces how findings from animal models can assist in understanding the human condition and thus lead to future interventions.

Characteristics of patients with gaze-evoked tinnitus.

Objective The authors describe symptoms and population characteristics in subjects who can modulate the loudness and/or pitch of their tinnitus by eye movements. Study Design Data were obtained by questionnaire. Setting The study was conducted at a university center and a tertiary care center. Patients Respondents had the self-reported ability to modulate their tinnitus with eye movements. Results Ninety-one subjects reported having gaze-evoked tinnitus after posterior fossa surgery involving the eighth nerve. Eighty-seven of them underwent removal of a vestibular schwannoma (acoustic neuroma), two had bilateral eighth nerve tumors (one underwent bilateral tumor removal; the other unilateral tumor removal), one underwent removal of a cholesteatoma, and one underwent removal of a glomus jugulare tumor. Seventeen subjects who had never had posterior fossa surgery reported gaze-evoked tinnitus. Of those with vestibular schwannomas, tumor size ranged from small (<2 cm) to large (>4 cm). The gender distribution was 48.3% male and 51.7% female. In 77% of patients, the gaze-evoked tinnitus was localized to the surgical ear or side of head; 21.8% had bilateral tinnitus that was louder in the surgical ear or side of head. In 86 of 87 subjects, loudness of tinnitus changed with eye movement. Eye movement away from the central (eyes centered) position increased the loudness of tinnitus in all 86 subjects who responded to this question. Seventy-three of 85 (85.9%) patients indicated that pitch changed with eye movement, with pitch increasing in 64/72 (88.9%) of them. Eighty-three of 87 (95.4%) patients reported total loss of hearing in the surgical ear. Seventy of 83 (84.3%) patients reported facial nerve problems immediately after surgery, 52 of 87 (60%) reported persistent facial weakness, and 16 of 87 (18.4%) patients reported persistent double vision. In those 17 subjects with gaze-evoked tinnitus and no posterior fossa surgery, the majority of respondents (14/17, 82.4%) were male. Conclusions Gaze-evoked tinnitus after cerebellar pontine angle surgery is more common than was previously believed. In addition, posterior fossa surgery is not a prerequisite for the development of gaze-evoked tinnitus. It is likely that gaze-evoked tinnitus is a manifestation of functional reorganization. Gaze-evoked tinnitus could result from an unmasking of brain regions that respond to multiple stimulus/response modalities, and/or from anomalous cross-modality interactions, perhaps caused by collateral sprouting.

Auditory brainstem response forward-masking recovery functions in older humans with normal hearing

We investigated the auditory brainstem response (ABR) recovery from forward masking using toneburst maskers and probes. Two subject groups matched for hearing thresholds were evaluated: normal-hearing young adults (21-40 years) and older subjects (63-77 years) with normal audiometric thresholds. Stimuli consisted of 1, 4 and 8 kHz tonebursts, with 2-4 cycle rise/fall time and no plateau. Forward maskers were tonebursts of the same frequency, with a 5 ms rise/fall time and a 20 ms plateau time. Probes were presented at 40 dB above threshold, and the forward masker was adjusted to a level that just eliminated the ABR to the 40 dB sensation level toneburst when the probe onset occurred at masker offset. Forward-masker intervals varied from 2 to 64 ms. ABR wave V latencies were similar for the young and old age groups regardless of toneburst frequency. Under forward-masking conditions, wave V latency was prolonged for the shorter intervals, and recovered to baseline latency by 64 ms. The forward-masker recovery functions were nearly identical for the two age groups for the 1 kHz toneburst. In contrast, there were clear differences in the recovery functions for the two age groups for the 4 and 8 kHz tonebursts. Specifically, the mean latency shift was greater for the aged group for forward-masker intervals of 16 ms or less. The two age groups showed identical latency shifts for longer forward-masker intervals. These data demonstrate prolonged recovery from forward masking in older human subjects. As these subjects had audiometric thresholds within normal limits, one plausible interpretation of this finding is that the prolonged recovery time is a manifestation of an aging effect on the central auditory nervous system rather than the periphery.