Publications using TDT

Objectives: To assess the importance of 2 variables, transducer tip diameter and resection of the round window (RW) niche, affecting the optimization of the mechanical stimulation of the RW membrane with an active middle ear implant (AMEI). Materials and Methods: Ten temporal bones were prepared with combined atticotomy and facial recess approach to expose the RW. An AMEI stimulated the RW with 2 ball tip diameters (0.5 and 1.0 mm) before and after the resection of the bony rim of the RW niche. The RW drive performance, assessed by stapes velocities using laser Doppler velocimetry, was analyzed in 3 frequency ranges: low (0.25–1 kHz), medium (1–3 kHz) and high (3–8 kHz). Results: Driving the RW produced mean peak stapes velocities (HEV) of 0.305 and 0.255 mm/s/V at 3.03 kHz, respectively, for the 1- and 0.5-mm tips, with the RW niche intact. Niche drilling increased the HEV to 0.73 and 0.832 mm/s/V for the 1- and 0.5-mm tips, respectively. The tip diameter produced no difference in output at low and medium frequencies; however, the 0.5-mm tip was 5 and 6 dB better than the 1-mm tip at high frequencies before and after niche drilling, respectively. Drilling the niche significantly improved the output by 4 dB at high frequencies for the 1-mm tip, and by 6 and 10 dB in the medium- and high-frequency ranges for the 0.5-mm tip. Conclusion: The AMEI was able to successfully drive the RW membrane in cadaveric temporal bones using a classical facial recess approach. Stimulation of the RW membrane with an AMEI without drilling the niche is sufficient for successful hearing outputs. However, the resection of the bony rim of the RW niche significantly improved the RW stimulation at medium and higher frequencies. Drilling the niche enhances the exposure of the RW membrane and facilitates positioning the implant tip.

Changes of ocular dominance in the visual cortex can be induced by visual manipulations during a critical period in early life. However, the role of critical period plasticity in normal development is unknown. Here we show that at the onset of this time window, the preferred orientations of individual cortical cells in the mouse are mismatched through the two eyes and the mismatch decreases and reaches adult levels by the end of the period. Deprivation of visual experience during this period irreversibly blocks the binocular matching of orientation preference, but has no effect in adulthood. The critical period of binocular matching can be delayed by long-term visual deprivation from birth, like that of ocular dominance plasticity. These results demonstrate that activity-dependent changes induced by normal visual experience during the well-studied critical period serve to match eye-specific inputs in the cortex, thus revealing a physiological role for critical period plasticity during normal development.

Neural encoding of pitch in the auditory brainstem is shaped by long-term experience with language. The aim herein was to determine to what extent this experience-dependent effect is specific to a particular language. Analysis of variance of brainstem responses to Mandarin and Thai tones revealed that regardless of language identity, pitch-tracking accuracy of whole tones was higher in the two tone language groups (Chinese, Thai) compared to the non-tone language group (English), and that pitch strength of 40-ms tonal sections was generally more robust in tone relative to non-tone languages. Discriminant analysis of tonal sections, as defined by variation in direction and degree of slope, showed that moderate rising pitch was the most important variable for classifying English, Chinese, and Thai participants into their respective groups. We conclude that language-dependent enhancement of pitch representation transfers to other languages with similar phonological systems. From a neurobiological perspective, these findings suggest that neural mechanisms local to the brainstem are tuned for processing pitch dimensions that are perceptually salient depending upon the melodic patterns of a language.

Cochlear implants stimulate the auditory nerve with amplitude-modulated (AM) electric pulse trains. Pulse rates >2,000 pulses per second (pps) have been hypothesized to enhance transmission of temporal information. Recent studies, however, have shown that higher pulse rates impair phase locking to sinusoidal AM in the auditory cortex and impair perceptual modulation detection. Here, we investigated the effects of high pulse rates on the temporal acuity of transmission of pulse trains to the auditory cortex. In anesthetized guinea pigs, signal-detection analysis was used to measure the thresholds for detection of gaps in pulse trains at rates of 254, 1,017, and 4,069 pps and in acoustic noise. Gap-detection thresholds decreased by an order of magnitude with increases in pulse rate from 254 to 4,069 pps. Such a pulse-rate dependence would likely influence speech reception through clinical speech processors. To elucidate the neural mechanisms of gap detection, we measured recovery from forward masking after a 196.6-ms pulse train. Recovery from masking was faster at higher carrier pulse rates and masking increased linearly with current level. We fit the data with a dual-exponential recovery function, consistent with a peripheral and a more central process. High-rate pulse trains evoked less central masking, possibly due to adaptation of the response in the auditory nerve. Neither gap detection nor forward masking varied with cortical depth, indicating that these processes are likely subcortical. These results indicate that gap detection and modulation detection are mediated by two separate neural mechanisms.

Our knowledge of age-related changes in auditory processing in the central auditory system is limited, unlike the changes in the peripheral hearing organs which are more extensively studied. This study aims to further understanding of temporal processing in aging using non-invasive electrophysiological measurements in a rat model system. Amplitude modulation following responses (AMFRs) were assessed using sinusoidally amplitude modulated (SAM) tones presented to aged (92- to 95-weeks old) and young (9- to 12-weeks old) Fischer-344 rats. The modulation frequency and sound level were systematically varied, and the SAM stimuli were also presented simultaneously with wideband background noise at various levels. The overall shapes and cutoff frequencies of the AMFR temporal modulation transfer functions (tMTFs) were similar between young and aged animals. The fast Fourier transform (FFT) amplitudes of the aged animals were similar to the young in the 181-512 Hz modulation frequency range, but were significantly lower at most modulation frequencies above and below. There were no significant age-related differences in the nature of growth or FFT amplitudes with change in sound level at 256 and 1024 Hz modulation frequencies. The AMFR amplitudes were also not correlated with the ABR wave I or wave III amplitudes elicited for broadband click stimuli presented at the same sound level suggesting that sustained AMFR provide complementary information to phasic ABR responses. The FFT amplitudes varied significantly between young and aged animals for SAM stimuli in the presence of background noise, depending on the modulation frequency used and signal to noise ratio. The results show that the representation of temporally modulated stimuli is similar between young and aged animals in quiet listening conditions, but diverges substantially with the addition of background noise. This is consistent with a decrease in inhibition causing altered temporal processing with age.

Attending and responding to sound location generates increased activity in parietal cortex which may index auditory spatial working memory and/or goal-directed action. Here, we used an n-back task (Experiment 1) and an adaptation paradigm (Experiment 2) to distinguish memory-related activity from that associated with goal-directed action. In Experiment 1, participants indicated, in separate blocks of trials, whether the incoming stimulus was presented at the same location as in the previous trial (1-back) or two trials ago (2-back). Prior to a block of trials, participants were told to use their left or right index finger. Accuracy and reaction times were worse for the 2-back than for the 1-back condition. The analysis of functional magnetic resonance imaging data revealed greater sustained task-related activity in the inferior parietal lobule (IPL) and superior frontal sulcus during 2-back than 1-back after accounting for response-related activity elicited by the targets. Target detection and response execution were also associated with enhanced activity in the IPL bilaterally, though the activation was anterior to that associated with sustained task-related activity. In Experiment 2, we used an event-related design in which participants listened (no response required) to trials that comprised four sounds presented either at the same location or at four different locations. We found larger IPL activation for changes in sound location than for sounds presented at the same location. The IPL activation overlapped with that observed during the auditory spatial working memory task. Together, these results provide converging evidence supporting the role of parietal cortex in auditory spatial working memory which can be dissociated from response selection and execution.

Traditionally time perception has been considered the product of a central, generic, cognitive mechanism. However, evidence is emerging for a distributive system with modality-specific sensory components (Morrone et al., 2005; Johnston et al., 2006). Here we show that fast contrast adaptation, which can be observed in the retina, induces a change in apparent duration. The perceived duration of a subsecond interval containing a 50% luminance contrast drifting pattern is compressed when it follows a high (90%) as compared to a low (10%) contrast interval. The duration effect cannot be attributed to changes in latency at onset relative to offset, can be dissociated from the effect of contrast context on apparent speed or apparent contrast per se and it occurs in a retinocentric frame of reference. The temporal compression is limited to high drift temporal frequencies (≥10 Hz) and is not observed for equiluminant chromatic stimuli. This pattern of results indicates a major role for the magnocellular pathway in the neural encoding and representation of visual time.

The phase of ongoing theta (4-8 Hz) and alpha (8-12 Hz) electrophysiological oscillations is coupled to high gamma (80-150 Hz) amplitude, which suggests that low-frequency oscillations modulate local cortical activity. While this phase-amplitude coupling (PAC) has been demonstrated in a variety of tasks and cortical regions, it has not been shown whether task demands differentially affect the regional distribution of the preferred low-frequency coupling to high gamma. To address this issue we investigated multiple-rhythm theta/alpha to high gamma PAC in two subjects with implanted subdural electrocorticographic grids. We show that high gamma amplitude couples to the theta and alpha troughs and demonstrate that, during visual tasks, alpha/high gamma coupling preferentially increases in visual cortical regions. These results suggest that low-frequency phase to high-frequency amplitude coupling is modulated by behavioral task and may reflect a mechanism for selection between communicating neuronal networks.

Previous studies by our lab and others have established a role for medial areas of the prefrontal cortex (mPFC) in the top-down control of action during simple reaction-time (RT) tasks. However, the neural circuits that allow mPFC to influence activity in the motor system have remained unclear. In the present study, we used a combination of tract-tracing and reversible inactivation methods to examine the role of a motor-related area in the rat frontal cortex, called the rostral forelimb area (RFA), in the top-down control of action. Neural tracing studies involved used electrical microstimulation to identify RFA and injections of biotinylated dextran amines (BDA) to map out connections of RFA with other parts of the frontal cortex. Connections were found between RFA and mPFC, the agranular insular cortex, and the primary motor cortex. Reversible inactivations using muscimol infusions into RFA increased response times and eliminated delay-dependent speeding, but did not increase premature responding. These results are markedly different from what is obtained when muscimol is infused into mPFC, which leads to excessive premature responding and a reduction of RTs to stimuli at short delays (Narayanan et al., 2006). We also tested animals during the RT task after inactivating the agranular insular cortex, which contains neurons that projects to and receives from RFA and mPFC, and found no effects on RT performance. Together, these studies suggest that RFA is a premotor region in the rat frontal cortex that competes with mPFC to control action selection. We suggest that RFA controls the threshold that is used to initiate responding and generates prepotent excitation over responding that is crucial for temporal preparation.

Descending projections from sensory areas of the cerebral cortex are among the largest pathways in the brain, suggesting that they are important for subcortical processing. Although corticofugal inputs have been shown to modulate neuronal responses in the thalamus and midbrain, the behavioral importance of these changes remains unknown. In the auditory system, one of the major descending pathways is from cortical layer V pyramidal cells to the inferior colliculus in the midbrain. We examined the role of these neurons in experience-dependent recalibration of sound localization in adult ferrets by selectively killing the neurons using chromophore-targeted laser photolysis. When provided with appropriate training, animals normally relearn to localize sound accurately after altering the spatial cues available by reversibly occluding one ear. However, this ability was lost after eliminating corticocollicular neurons, whereas normal sound-localization accuracy was unaffected. The integrity of this descending pathway is therefore critical for learning-induced localization plasticity.

Acoustic communication involves both the generation and the detection of a signal. In the coqui frog ( Eleutherodactylus coqui ), it is known that the spectral contents of its calls systematically change with altitude above sea level. Here, distortion product otoacoustic emissions are used to assess the frequency range over which the inner ear is sensitive. It is found that both the spectral contents of the calls and the inner-ear sensitivity change in a similar fashion along an altitudinal gradient. As a result, the call frequencies and the auditory tuning are closely matched at all altitudes. We suggest that the animal's body size determines the frequency particulars of the call apparatus and the inner ear.

Spatial and non-spatial sensory information is hypothesized to be evaluated in parallel pathways. In this study, we tested the spatial and non-spatial sensitivity of auditory neurons in the ventrolateral prefrontal cortex (vPFC), a cortical area in the non-spatial pathway. Activity was tested while non-human primates reported changes in an auditory stimulus' spatial or non-spatial features. We found that vPFC neurons were reliably modulated during a non-spatial auditory task but were not modulated during a spatial auditory task. The degree of modulation during the non-spatial task correlated positively with the monkeys' behavioral performance. These results are consistent with the hypotheses that the vPFC is part of a circuit involved in non-spatial auditory processing and that the vPFC plays a functional role in non-spatial auditory cognition.

The role of innate immunity and macrophage recruitment to the inner ear after hair cell injury is a subject where little is known. In this paper, we demonstrate recruitment of monocytes and macrophages to the inner ear after kanamycin. We also examined the effect of fractalkine receptor (CX3CR1) deletion in kanamycin ototoxicity. We observed more functional and structural damage in CX3CR1 null mice compared to wild-type and heterozygous littermates. In order to determine if increased susceptibility to kanamycin resulted from CX3CR1 deletion from cochlear leukocytes, we created bone marrow chimeras by transplanting CX3CR1-null bone marrow into wild-type mice whose native bone marrow was ablated by lethal irradiation. These mice were then treated with kanamycin sulfate. Auditory brainstem responses (ABR), hair cell counts, and numbers of macrophages recruited to the cochlea were recorded in irradiated mice that received either wild-type, CX3CR1 heterozygous, or CX3CR1 knockout bone marrow. A strong correlation was present between numbers of macrophages and hair cell death in recipients transplanted with CX3CR1 null marrow. No correlation between macrophage number and hair cell loss was present in mice transplanted with wild-type or CX3CR1 heterozygous marrow. We suggest that CX3CR1 plays a role in modulating the detrimental effects of cochlear macrophages after kanamycin ototoxicity. Our data point to the possibility that CX3CR1-deficient cochlear macrophages exacerbate kanamycin ototoxicity while CX3CR1-expressing monocytes do not.

Adaptive behavior requires that animals integrate current and past information with their decision-making. One important type of information is auditory-communication signals (i.e., species-specific vocalizations). Here, we tested how rhesus monkeys incorporate the opportunity to listen to different species-specific vocalizations into their decision-making processes. In particular, we tested how monkeys value these vocalizations relative to the opportunity to get a juice reward. To test this hypothesis, monkeys chose one of two targets to get a varying juice reward; at one of those targets, in addition to the juice reward, a vocalization was presented. By titrating the juice amounts at the two targets, we quantified the relationship between the monkeys' juice choices relative to the opportunity to listen to a vocalization. We found that, rhesus were not willing to give up a large juice reward to listen to vocalizations indicating that, relative to a juice reward, listening to vocalizations has a low value.

Responses to tones with frequency < or = 5 kHz were recorded from auditory nerve fibers (ANFs) of anesthetized chinchillas. With increasing stimulus level, discharge rate-frequency functions shift toward higher and lower frequencies, respectively, for ANFs with characteristic frequencies (CFs) lower and higher than approximately 0.9 kHz. With increasing frequency separation from CF, rate-level functions are less steep and/or saturate at lower rates than at CF, indicating a CF-specific nonlinearity. The strength of phase locking has lower high-frequency cutoffs for CFs >4 kHz than for CFs < 3 kHz. Phase-frequency functions of ANFs with CFs lower and higher than approximately 0.9 kHz have inflections, respectively, at frequencies higher and lower than CF. For CFs >2 kHz, the inflections coincide with the tip-tail transitions of threshold tuning curves. ANF responses to CF tones exhibit cumulative phase lags of 1.5 periods for CFs 0.7-3 kHz and lesser amounts for lower CFs. With increases of stimulus level, responses increasingly lag (lead) lower-level responses at frequencies lower (higher) than CF, so that group delays are maximal at, or slightly above, CF. The CF-specific magnitude and phase nonlinearities of ANFs with CFs < 2.5 kHz span their entire response bandwidths. Several properties of ANFs undergo sharp transitions in the cochlear region with CFs 2-5 kHz. Overall, the responses of chinchilla ANFs resemble those in other mammalian species but contrast with available measurements of apical cochlear vibrations in chinchilla, implying that either the latter are flawed or that a nonlinear "second filter" is interposed between vibrations and ANF excitation.

A form of processed speech is described that is highly discriminable in a closed-set identification format. The processing renders speech into a set of sinusoidal pulses played synchronously across frequency. The processing and results from several experiments are described. The number and width of frequency analysis channels and tone-pulse duration were variables. In one condition, various proportions of the tones were randomly removed. The processed speech was remarkably resilient to these manipulations. This type of speech may be useful for examining multitalker listening situations in which a high degree of stimulus control is required.

A key function of the auditory system is to provide reliable information about the location of sound sources. Here, we describe how sound location is represented by synaptic input arriving onto pyramidal cells within auditory cortex by combining free-field acoustic stimulation in the frontal azimuthal plane with in vivo whole-cell recordings. We found that subthreshold activity was panoramic in that EPSPs could be evoked from all locations in all cells. Regardless of the sound location that evoked the largest EPSP, we observed a slowing in the EPSP slope along the contralateral–ipsilateral plane that was reflected in a temporal sequence of peak EPSP times. Contralateral sounds evoked EPSPs with earlier peak times and consequently generated action potential firing with shorter latencies than ipsilateral sounds. Thus, whereas spiking probability reflected the region of space evoking the largest EPSP, across the population, synaptic inputs enforced a gradient of spike latency and precision along the horizontal axis. Therefore, within auditory cortex and regardless of preferred location, the time window of synaptic integration reflects sound source location and ensures that spatial acoustic information is represented by relative timings of pyramidal cell output.

The auditory cortex of the cat is composed of 13 distinct fields that have been defined on the basis of anatomy, physiology, and behavior. Although an anatomically based hierarchical processing scheme has been proposed in auditory cortex, few functional studies have examined how these areas influence one another. The purpose of the present study was to examine the bidirectional processing contributions between primary auditory cortex (A1) and the nonprimary posterior auditory field (PAF). Multiunit acute recording techniques in eight mature cats were used to measure neuronal responses to tonal stimuli in A1 or PAF while synaptic activity from PAF or A1 was suppressed with reversible cooling deactivation techniques. Specifically, in four animals, electrophysiological recordings in A1 were conducted before, during, and after deactivation of PAF. Similarly, in the other four animals, PAF activity was measured before, during, and after deactivation of A1. The characteristic frequency, bandwidth, and neuronal threshold were calculated at each receptive field collected and the response strength and response latency measures were calculated from cumulative peristimulus time histograms. Two major changes in PAF response properties were observed during A1 deactivation: a decrease in response strength and a reduction in receptive field bandwidths. In comparison, we did not identify any significant changes in A1 neuronal responses during deactivation of PAF neurons. These findings support proposed models of hierarchal processing in cat auditory cortex.

Overexposure to intense sound can cause temporary or permanent hearing loss. Postexposure recovery of threshold sensitivity has been assumed to indicate reversal of damage to delicate mechano-sensory and neural structures of the inner ear and no persistent or delayed consequences for auditory function. Here, we show, using cochlear functional assays and confocal imaging of the inner ear in mouse, that acoustic overexposures causing moderate, but completely reversible, threshold elevation leave cochlear sensory cells intact, but cause acute loss of afferent nerve terminals and delayed degeneration of the cochlear nerve. Results suggest that noise-induced damage to the ear has progressive consequences that are considerably more widespread than are revealed by conventional threshold testing. This primary neurodegeneration should add to difficulties hearing in noisy environments, and could contribute to tinnitus, hyperacusis, and other perceptual anomalies commonly associated with inner ear damage.