Biomedical subjects
Publications and source records attributed to K R Henry.
Forward maskers within two frequency-intensity domains are capable of decreasing (enhancing) CAP latency: one region flanks the low frequency tail, the other flanks the tip/high frequency slope regions of the latency tuning curve (TC). By contrast, amplitude enhancement typically does not flank the high frequency slope region.
Inbred strains of mice have several advantages as models for human noise-induced hearing loss. However, the isogenic nature of inbred lines is very unlike the human condition, and may make this species less valuable as an auditory model. The present experiments start with two mouse genotypes having lifelong normal cochlear functions: The CBA/CaJ and the AUS/sJ inbred strains. These strains and their F1 hybrid offspring were examined for noise-induced elevation of the auditory brainstem response (ABR) threshold. The F1 line had an intermediate degree of loss and the most uniform high frequency cochlear loss. Methylprednisolone was found to protect the F1 from noise-induced losses, whereas naloxone did not.
The mouse has several distinct advantages as an experimental model for human audition. Mice and humans express a similar presbyacusic and ototraumatic pattern. Several genetic mouse models also exist for conditions resembling human auditory disorders, such as otosclerosis. This paper reviews the strains of inbred mice (e.g. the CBA/J) which have recently been used as models for the normal human auditory system, describing their deficiencies. It is suggested that the F1 offspring of CBA/CaJ and AU/SsJ inbred mice would have advantages over existing models.
Inbred strains of laboratory mice have several distinct advantages as models for examining conditions that influence the human auditory system, but the CBA/J mouse which has most often been used as a normal model has recently been found to have several disadvantages. This paper is the first report of the auditory brainstem responses (ABRs) of the F1 offspring of CBA/CaJ and AU/SsJ parents. At midlife, high-frequency ABR thresholds are lower in the F1 than in either parental genotype. Tuning curves obtained by forward masking of the ABR also display heterosis, i.e. they are narrower in the F1 than in either parental strain.
Under restricted frequency and intensity conditions, forward masking can result in the amplitude of the CAP being increased above its unmasked value (Henry, 1991). The present study provides a quantitative analysis of this enhancement effect. In response to forward maskers having the same frequency as the probe stimulus, central frequency (CF) enhancement varies as a function of the level of the forward masker: the lowest masker level at which it can reliably be detected is often well below the visual detection threshold of the CAP generated by the unmasked probe stimulus; the highest masker level at which it can reliably be detected corresponds to approximately 10 dB above the probe stimulus CAP threshold. A second low frequency (LF) enhancement region also exists, encompassing a narrow range of more intense maskers. CF enhancement can double the amplitude of the CAP, whereas LF enhancement is less pronounced. The magnitude of CF enhancement varies as a function of the duration of the forward masker, with longer durations generally increasing the magnitude of the effect. This duration effect, however, interacts with the level of the stimulus. Decreasing the interval between the end of the forward masker and the beginning of the probe increases the magnitude of CF enhancement.
Forward masking can either decrease or increase the response to a subsequent stimulus. In the gerbil, frequency-intensity domains of the maskers that decrease the amplitude of the compound action potential (CAP) can be plotted as the sharply defined CAP tuning curve (TC). Regions were also found over which masking increases (enhances) the amplitude of the CAP. Center-frequency (CF) enhancement domains were found in approximately 2/3 of the animals tested, in response to maskers having frequencies very near that of the probe stimulus, at levels ranging from below the CAP detection threshold to just below the tip threshold of the TC. Approximately 2/3 of the animals showing CF enhancement also displayed low-frequency (LF) enhancement, in response to a domain which borders the low-frequency tail of the TC.
In the gerbil maintained at euthermic (37.5 degrees C) conditions, forward masking produces a compound action potential tuning curve (CAP TC) which is less sensitive but more sharply tuned than that which is generated by simultaneous masking. These differences between forward- and simultaneously-masked CAP TCs are minimized at hypothermic (30 degrees C) conditions. The unmasking effect occurs at both temperatures, suggesting that hypothermia does not exert these changes by eliminating two-tone suppression.
To evaluate the influence of the acoustic context on the latency and amplitude tuning curves (TCs) of cochlear nerve compound action potentials (CAPs), tonal stimuli were generated with a variety of amplitude modulation envelopes. CAPs were produced by intensity increases (onsets) and decreases (offsets) from the low ambient sound level and by intensity changes from a preexisting tonal level. Onset CAPs from ambient levels generated V-shaped TCs. However, when simultaneous masking was used with onset CAPs which were produced by a 5- to 12-dB increase from preexisting levels of approximately 65 dB SPL, TCs were W-shaped and similar in appearance to those produced by simultaneous masking of offset CAPs. The forward masking of this same CAP resulted in a very sharp V-shaped TC. These data suggest that the preadaptation to 10 ms of a moderate level of a tonal stimulus can increase the tuning of ensembles of cochlear neurons to subsequent transient amplitude changes.
Compound action potential tuning curves (CAP TCs) generated by masking the N1 component of the CAP provide a means of assessing the ability of the cochlea to selectively tune to certain stimuli. This paper examines some of the factors which can influence this TC when a moderately intense (i.e. 40-80 dB SPL) probe stimulus is used. At these levels, each of the four corners of the trapezoidal stimulus envelope is capable of generating a CAP. Also, short stimulus rise times can merge the CAPs produced by the first two corners, but this does not appear to have a major effect on the CAP TC. It was shown that the N2 component of the CAP for the first corner of the stimulus is equally capable of producing a well-tuned TC. Another study has shown that, in addition to amplitude decrements, one can use latency increases as a criterion for CAP TCs. We have demonstrated that latency TCs are more finely tuned than amplitude TCs at high levels, especially when the stimulus rise time is short.
Investigating theoretical conditions under which linearly-operating tuned structures produce click-like transient responses to onsets and offsets of trapezoidal tone bursts, we come to the following conclusions: (1) each of the four corners of the trapezoidal tone burst is capable of eliciting such a response; (2) the amplitude of the response and its dependence on the frequency of the modulated tone both depend on the phase of the modulated sinusoid at the time a corner occurs; (3) such responses will arise in structures having sufficiently steep band edges, provided that the frequency of the modulated tone is well outside the pass band of the structure--for a corner in cosine phase, the sustained slope of the low-frequency band edge must be greater than zero and that of the high-frequency band edge must be greater than 12 dB/Oct, for a corner in sine phase the sustained slope of the low-frequency band edge must be greater than 6 dB/Oct and that of the high-frequency band edge must be greater than 18 dB/Oct; (4) they will not arise in response to tone bursts whose frequencies fall within the pass band of the structure; (5) nor will they arise in response to a trapezoidal tone burst of any frequency applied to structures (such as simple microphones or drivers) following second-order dynamics and having both spectral zeros at infinity. We present theoretically derived relationships between the amplitude of transient responses and the tone-burst frequency, not only for the corners of trapezoidal tone bursts, but also for tone bursts of more general shapes. We conclude that, owing to its extraordinarily steep high-frequency rolloff, the filter associated with each cochlear axon is well suited to extracting temporal information from onset or offset singularities in modulated tones whose frequencies are above the characteristic frequency of the filter. Applying the theory to observed onset and offset responses to high-intensity tone bursts in auditory afferents of the Mongolian gerbil, we conclude that some of the responses we observed must have been sculpted in part by cochlear nonlinearities.
One way that discrete acoustic events may be signaled to the central nervous system is through spike synchrony over a subpopulation of cochlear axons. Each of the four corners of a trapezoidally modulated tone burst is such an event. Ordinarily, each corner comprises both an abrupt change in envelope slope and a singularity in the modulated waveform. In this study, in addition to stimuli of this sort, we employed a stimulus waveform in which a corner occurred without a waveform singularity. We obtained masker tuning curves for the CAPs corresponding to both kinds of corners and single-unit responses to both kinds of corners. The results suggest that the subpopulation of cochlear axons excited by the singularity component of a corner is distinct from that excited by the abrupt change in envelope slope.
Action potential (AP) tuning curves (TCs), generated by probe stimuli of 60-65 dB SPL with short rise and decay (r&d) times, are less sensitive (have elevated tip thresholds) and are detuned (the frequency is shifted away from that of the probe stimulus, towards a middle frequency of the audiogram). These effects are more pronounced with forward than with simultaneous masking. TCs generated by masking tonal and narrow band noise stimuli are nearly identical, even though the spectrum is much wider for the noise stimulus. Decreasing r&d time has the same effect on TCs generated from both noise and tonal stimuli, even when it only measurably increases the acoustic splatter of the latter. Detuning appears to be related to a temporal-intensity interaction.
Simultaneous sinusoidal masking of the auditory brain-stem response (ABR) which is generated by the offset of a tone produces a W-shaped masking tuning curve (TC) in the gerbil, rat, mouse, and guinea pig. The probe stimulus offset must be very rapid in most animals. Lesions of the contralateral ear, strychnine blockage of the olivocochlear bundle, or removal of the ipsilateral outer ear do not alter the basic properties of the offset masking TC. Increasing the simultaneous masker duration selectively increases the tuning of the offset masking TC peak. Masking only the latter portions of the probe stimulus does not alter the shape of the offset masking TC.
In previous experiments, it was noted that a cochlear compound action potential (CAP) can be produced by the offset of a tone, provided that the amplitude of the tone is modulated by a trapezoid with slopes that are typically much steeper than required to produce onset responses. Subsequently, such trapezoidal tone bursts with steep slopes were used as probe stimuli in simultaneous and forward masking experiments that were designed to evaluate the tuning characteristics of these offset CAPs. Masker tuning curves (MTCs) were generated by plotting the masker frequency necessary to reduce the amplitude of the offset CAP by 50%. Simultaneous masking of the offset CAP generated a W-shaped MTC, with two sharply tuned tips and one sharply tuned peak. Forward masking generated a sharply tuned V-shaped offset MTC. By contrast, for onset CAPs, both simultaneous and forward masking generated V-shaped MTCs. The very steep stimulus slopes required to produce an offset CAP are likely to generate much more acoustic splatter than the more gradual slopes required to produce an onset CAP, and this may be related to the different shapes of the onset and offset simultaneous MTCs. To explore this possibility, the relationship of the spectral characteristics (determined by fast Fourier transform, or FFT) to the shape of the MTC was studied.(ABSTRACT TRUNCATED AT 250 WORDS)
Dietary restriction was imposed on CBA/J mice, animals which develop presbyacusis late in their lives. Animals restricted for their whole lives, as well as those restricted after midlife, had less presbyacusis than did control mice fed ad libitum. Dietary restriction did not increase the life spans of these mice. Restriction until midlife did not protect from presbyacusis, nor did it increase life span. In this genotype, dietary restriction protects against hearing loss only if it occurs at the age of most rapid decline of cochlear function.
Simultaneous and forward maskers were used to generate 'onset' and 'offset' compound action potential tuning curves (TCs) in the gerbil. The simultaneously masked offset TC, generated in response to a 16 kHz, 65 dB SPL probe stimulus, is W-shaped, with a low frequency tip at 11 kHz, a high frequency tip at 20 kHz, and a peak which occurs at 16 kHz. The 16 kHz forward masked onset TC has a single tip which occurs at 11 kHz. Although it lacks the finely tuned peak and high frequency tip of the stimultaneously masked offset TC, its single tip is more finely tuned than the low frequency tip of the simultaneously masked offset TC. Normalizing these two TCs [(1977) J. Acoust. Soc. Am. 62, 1048-1051] produces a figure which resembles 11 kHz onset TCs with their nonoverlapping regions which are analogs of two-tone suppression (2TS). A similar pattern occurs when probe stimuli at frequencies from 13 to 24 kHz are used to generate offset TCs; i.e., the forward masked offset TC resembles an onset TC and normalizing it to a simultaneously masked offset TC produces areas which resemble analogs of 2TS. Unmasking of the forward masked onset TCs [(1979) Hear, Res. 1, 133-154] produces regions of 2TS which are very similar to those produced by unmasking the forward masked offset TC which is generated by a higher frequency tone. These regions of 2TS for the Offset TC, as determined by unmasking, are very similar to the analogs of 2TS described above.
Action potential tuning curves (TCs) were produced by simultaneous masking of both the onset and offset of tone bursts. Offset TCs are much more sharply tuned than onset TCs when both responses are generated by stimuli at SPLs of 55 to 75 dB. The onset TC tip and the offset TC high frequency tip thresholds accurately reflect increases of the probe SPL, but the low frequency tip and the peak of the offset TC compress this change. With increasing probe SPL, the onset TC and low frequency TC tip (but not the high frequency tip and peak) of the offset TC become progressively detuned.
The LP/J mouse is the only available genetic model for otosclerosis. The otosclerosis-like condition of the LP/J mouse resembles the human condition in several ways, although there are differences in the two species in the most common locus of the dysplastic otic lesions. The mouse model would be more useful if its auditory dysfunction and genetic inheritance could also be compared with the human disease. Matings of the otosclerosis-like LP/J and the normal CBA/J inbred mice were used to generate F1 and backcross generations. The F1 showed neither functional (electrocochleographic) nor anatomical abnormalities, indicating a recessive nature of the mouse genetic disease. This is in contrast to some reports of dominance (with incomplete penetrance) of otosclerosis in humans. No evidence of X-chromosome-linked genetic influence was found in the mouse, in agreement with the human condition. These interpretations were confirmed in tests of the backcross of the F1 to the CBA/J parental genotype (BC). The anatomical and functional abnormalities were present in some of the backcrosses of the F1 to the LP/J parental genotype (BL). A comparison of bone-conducted and air-conducted electrocochleographic responses provided evidence for both conductive and sensorineural losses in the LP/J and BL mice.