PET imaging of the normal human auditory system: responses to speech in quiet and in background noise.

The neural mechanisms involved in listening to sentences, and then detecting and verbalizing a specific word are poorly understood, but most likely involve complex neural networks. We used positron emission tomography to identify the areas of the human brain that are activated when young, normal hearing males and females were asked to listen to a sentence and repeat the last word from the Speech in Noise (SPIN) test. Listening conditions were (1) Quiet, (2) Speech, (3) Noise, and (4) SPIN with stimuli presented monaurally to either the left ear or the right ear. The least difficult listening task, Speech, resulted in bilateral activation of superior and middle temporal gyrus and pre-central gyrus. The Noise and SPIN conditions activated many of the same regions as Speech alone plus additional sites within the cerebellum, thalamus and superior/middle frontal gyri. Comparison of the SPIN condition versus Speech revealed additional activation in the right anterior lobe of the cerebellum and right medial frontal gyrus, near the cingulate. None of the left ear-right ear stimulus comparison revealed any significant differences except for the SPIN condition that showed greater activation in the left superior temporal gyrus for stimuli presented to the right ear. No gender differences were observed. These results demonstrate that repeating the last word in a sentence activates mainly auditory and motor areas of the brain when Speech is presented, whereas more difficult tasks, such as SPIN or multi-talker Noise, activate linguistic, attentional, cognitive, working memory, and motor planning areas.

HSV amplicon-mediated neurotrophin-3 expression protects murine spiral ganglion neurons from cisplatin-induced damage.

Ototoxicity is a major dose-limiting side effect of cisplatin (DDP) administration due to its propensity to induce destruction of hair cells and neurons in the auditory system. Previous studies demonstrated that TrkC-expressing spiral ganglion neurons (SGN) are protected from the cytotoxic effects of DDP by localized delivery of the trophic factor neurotrophin-3 (NT-3). Successful in vivo implementation of such a therapy requires the development of an efficient gene delivery vehicle for expression of NT-3 within the cochlea. To this end, we constructed a herpes simplex virus (HSV) amplicon vector that expressed a c-Myc-tagged NT-3 chimera (HSVnt-3myc). Helper virus-free vector stocks were initially evaluated in vitro for their capacity to direct expression of NT-3 mRNA and protein. Transduction of cultured murine cochlear explants with HSVnt-3myc resulted in production of NT-3 mRNA and protein up to 3 ng/ml as measured over a 48-h period in culture supernatants. To determine whether NT-3 overexpression could abrogate DDP toxicity, cochlear explants were transduced with HSVnt-3myc or a murine intestinal alkaline phosphatase-expressing control vector, HSVmiap, and then exposed to cisplatin. HSVnt-3myc-transduced cochlear explants harbored significantly greater numbers of surviving SGNs than those infected with control virus. These data demonstrate that amplicon-mediated NT-3 transduction can attenuate the ototoxic action of DDP on organotypic culture. The potency of NT-3 in protecting spiral ganglion neurons from degeneration suggests that in vivo neurotrophin-based gene therapy may be useful for the prevention and/or treatment of hearing disorders.

Relationships among age-related differences in gap detection and word recognition.

The relationships among age-related differences in gap detection and word recognition in subjects with normal hearing or mild sensorineural hearing loss were explored in two studies. In the first study, gap thresholds were obtained for 40 younger and 40 older subjects. The gaps were carried by 150-ms, modulated, low-pass noise bursts with cutoff frequencies of 1 or 6 kHz. The noise bursts were presented at an overall level of 80 dB SPL in three background conditions. Mean gap thresholds ranged between 2.6 and 7.8 ms for the younger age group and between 3.4 and 10.0 ms for the older group. Mean gap thresholds were significantly larger for the older group in all six conditions. Gap thresholds were not significantly correlated with audiometric thresholds in either age group but the 1-kHz gap thresholds increased with age in the younger group. In the second study, the relationships among gap thresholds, spondee-in-babble thresholds, and audiometric thresholds of 66 subjects were examined. Compared with the older subjects, the younger group recognized the spondees at significantly lower (more difficult) spondee-to-babble ratios. In the younger group, spondee-in-babble thresholds were significantly correlated with gap thresholds in conditions of high-frequency masking. In the older group, spondee-in-babble thresholds, gap thresholds, and audiometric thresholds were not significantly correlated, but the spondee-in-babble thresholds and two audiometric thresholds increased significantly with age. These results demonstrate that significant age-related changes in auditory processing occur throughout adulthood. Specifically, age-related changes in temporal acuity may begin decades earlier than age-related changes in word recognition.

Characteristics associated with marginal hearing loss and subjective well-being among a sample of older adults.

The influence of marginal hearing loss on subjective well-being was studied in order to assess the audiological rehabilitation needs of older individuals. Behavioral and audiological data were obtained from 40 subjects 61-81 years of age. Group A included 20 subjects with normal audiometric thresholds. Group B included 20 subjects with mild-to-moderate degrees of high-frequency hearing loss. Each subject completed a hearing loss screening survey, an Assistive Technology Device Predisposition Assessment (ATD PA) and a Profile of Hearing Aid Performance (PHAP). The PHAP and hearing loss screen were adequate assessments of self-reported hearing loss, as was the subjective rating of hearing section of the ATD PA. People with high-frequency marginal hearing loss reported on the ATD PA less satisfaction with their independence, reduced emotional well-being, and more limitation from their hearing loss than those with normal hearing. It is concluded that marginal degrees of hearing loss in older persons can influence subjective well-being, which suggests the importance of a renewed emphasis on audiological rehabilitation for this population.

Speech recognition in noise and presbycusis: relations to possible neural mechanisms.

This study is part of ongoing efforts to characterize and determine the neural bases of presbycusis. These efforts utilize humans and animals in sets of overlapping hypotheses and experiments. Here, 50 young adult and elderly subjects, with normal audiometric thresholds or high-frequency hearing loss, were presented three types of linguistic materials at suprathreshold levels to determine speech recognition performance in noise. The study sought to determine how peripheral and central auditory system dysfunctions might be implicated in the speech recognition problems of elderly humans. There were four main findings. (1) Peripheral auditory nervous system pathologies, manifested as reduced sensitivity for speech-frequency pure tones and speech materials, contribute to elevated speech reception thresholds in quiet, and to reduced speech recognition in noise. (2) Good cognitive ability was demonstrated in the old subjects who took advantage of supportive context as well or better than young subjects, strongly indicating that the cortical portions of the speech/language nervous system did not account for the speech understanding dysfunctions of the old subjects. (3) When audibility and cognitive functioning were not affected, the demonstrated speech-recognition in-noise dysfunction remained in old subjects. This implicates auditory brainstem or auditory cortex temporal-resolution dysfunctions in accounting for the observed differences in speech processing. (4) Performance differences between young and elderly subjects with elevated thresholds illustrate the effects of age plus hearing loss and thereby implicate both peripheral and central dysfunctions in presbycusics. This is because the differences in performance between young and elderly subjects with normal peripheral sensitivity identified a central auditory dysfunction.

The effects of signal frequency and absolute bandwidth on gap detection in noise.

Whether temporal resolution in noisebursts is primarily determined by the highest frequency component in the signal or its absolute bandwidth remains unclear. In this study, the absolute bandwidths and upper cutoff frequencies of signal noisebursts were varied across broad frequency ranges, several times greater than previously jointly studied. The purpose was to determine how each independently affects detection, taking into consideration that bandwidth effects at one signal frequency might be very different from bandwidth effects at another. Gap detection thresholds were obtained for five subjects with normal hearing in a 2 IFC paradigm. Signals were noisebursts whose bandwidths and upper cutoff frequencies varied among 1, 2, 4, 8, and 12 kHz. Their duration was 150 ms and they were presented at an overall level of 75 dB SPL above a 45 dB SPL white noise floor. The largest mean gap detection threshold, 6.98 ms, was obtained for a noiseburst with a bandwidth of 1 kHz and upper cutoff frequency of 12 kHz. The smallest mean gap detection threshold, 2.22 ms, was found with a bandwidth and upper cutoff frequency of 12 kHz. Significant interactions were found to exist between absolute bandwidth and upper cutoff frequency. Although gap detection thresholds generally decreased with increasing signal frequency and bandwidth, the pattern was complex. When the absolute bandwidth was at least one-half the upper cutoff frequency then upper cutoff frequency and not bandwidth determined gap sensitivity; but when the absolute bandwidth was less than one-half of the upper frequency, then both determined gap thresholds.(ABSTRACT TRUNCATED AT 250 WORDS)