Publications using TDT

Objective: The purpose of this study was to examine working memory for sequences of auditory and visual stimuli in prelingually deafened pediatric cochlear implant users with at least 4 yr of device experience. Design: Two groups of 8- and 9-yr-old children, 45 normal-hearing and 45 hearing-impaired users of cochlear implants, completed a novel working memory task requiring memory for sequences of either visual-spatial cues or visual-spatial cues paired with auditory signals. In each sequence, colored response buttons were illuminated either with or without simultaneous auditory presentation of verbal labels (color-names or digit-names). The child was required to reproduce each sequence by pressing the appropriate buttons on the response box. Sequence length was varied and a measure of memory span corresponding to the longest list length correctly reproduced under each set of presentation conditions was recorded. Additional children completed a modified task that eliminated the visual-spatial light cues but that still required reproduction of auditory color-name sequences using the same response box. Data from 37 pediatric cochlear implant users were collected using this modified task. Results: The cochlear implant group obtained shorter span scores on average than the normal-hearing group, regardless of presentation format. The normal-hearing children also demonstrated a larger "redundancy gain" than children in the cochlear implant group-that is, the normal-hearing group displayed better memory for auditory-plus-lights sequences than for the lights-only sequences. Although the children with cochlear implants did not use the auditory signals as effectively as normal-hearing children when visual-spatial cues were also available, their performance on the modified memory task using only auditory cues showed that some of the children were capable of encoding auditory-only sequences at a level comparable with normal-hearing children. Conclusions: The finding of smaller redundancy gains from the addition of auditory cues to visual-spatial sequences in the cochlear implant group as compared with the normal-hearing group demonstrates differences in encoding or rehearsal strategies between these two groups of children. Differences in memory span between the two groups even on a visual-spatial memory task suggests that atypical working memory development irrespective of input modality may be present in this clinical population.

Alport syndrome is an inherited disorder of type IV collagen with progressive nephropathy, ocular abnormalities, and high-tone sensorineural deafness. In X-linked Alport syndrome, mutations in the COL4A5 gene encoding the alpha5 chain of type IV collagen lead to loss of the alpha3/alpha4/alpha5 network and increased susceptibility of the glomerular basement membrane to long-term damage. The molecular defects that underlie the otopathology in this disease remain poorly understood. We used a canine model of X-linked Alport syndrome to determine the expression of type IV collagen alpha-chains in the inner ear. By 1 month in normal adult dogs, the alpha3, alpha4, and alpha5 chains were co-expressed in a thin continuous line extending along the basilar membrane and the internal and external sulci, with the strongest expression along the lateral aspect of the spiral ligament in the basal turn of the cochlea. Affected dogs showed complete absence of the alpha3/alpha4/alpha5 network. The lateral aspect of the spiral ligament is populated by tension fibroblasts that express alpha-smooth muscle actin and nonmuscle myosin and are postulated to generate radial tension on the basilar membrane via the extracellular matrix for reception of high frequency sound. We propose that in Alport syndrome, the loss of the alpha3/alpha4/alpha5 network eventually weakens the interaction of these cells with their extracellular matrix, resulting in reduced tension on the basilar membrane and the inability to respond to high frequency sounds.

Thyroid hormone receptors are encoded by the TRalpha (NR1A1) and TRbeta (NR1A2) loci. These genes are transcribed into multiple variants whose functions are unclear. Analysis by gene inactivation in mice has provided new insights into the functional complexity of these products. Different strategies designed to modify the TRalpha locus have led to strikingly different phenotypes. In order to analyze the molecular basis for these alterations, we generated mice devoid of all known isoforms produced from the TRalpha locus (TRalpha(0/0)). These mice are viable and exhibit reduced linear growth, bone maturation delay, moderate hypothermia, and reduced thickness of the intestinal mucosa. Compounding TRalpha(0) and TRbeta(-) mutations produces viable TRalpha(0/0)beta(-/-) mice, which display a more severe linear growth reduction and a more profound hypothermia as well as impaired hearing. A striking phenotypic difference is observed between TRalpha(0/0) and the previously described TRalpha(-/-) mice, which retain truncated TRDeltaalpha isoforms arising from a newly described promoter in intron 7. The lethality and severe impairment of the intestinal maturation in TRalpha(-/-) mice are rescued in TRalpha(0/0) animals. We demonstrate that the TRDeltaalpha protein isoforms, which are natural products of the TRalpha locus, are the key determinants of these phenotypical differences. These data reveal the functional importance of the non-T3-binding variants encoded by the TRalpha locus in vertebrate postnatal development and homeostasis.

Preschoolers and adults were asked to detect a 1000-Hz signal, which was masked by a multitone complex. The frequencies and amplitudes of the components in the complex varied randomly and independently on each presentation. A staircase, cued two-interval, forced-choice procedure disguised as a “listening game” was used to obtain signal thresholds in quiet and in the presence of the multitone maskers. The number of components in the masker was fixed within an experimental condition and varied from 2 to 906 across experimental conditions. Thresholds were also measured with a broadband noise masker. Eight preschool children and eight adults were tested. Although individual differences were large, among both adults and children, there was little difference between the groups in the mean amount of masking produced by the maskers with large numbers of components (400 and 906). There was also a small but significant difference between adults and children in the mean amount of masking produced by the broadband noise. The difference between the groups was much larger with smaller numbers of components. Data obtained from the adults were basically similar to that previously reported [cf. Neff and Green, Percept. Psychophys. 41, 409–415 (1987); Oh and Lutfi, J. Acoust. Soc. Am. 104, 3489–3499 (1998)]: maskers comprised of 10–40 components produced as much as 30 to 60 dB of masking in some, but not all listeners. Those same maskers produced larger amounts of masking (70–83 dB) in many of the preschool children, although, as in the adult group, individual differences were large. The component-relative-entropy (CoRE) model [Lutfi, J. Acoust. Soc. Am. 94, 748–758 (1993)] was used to describe the differences in performance between the children and adults. According to this model the average child appears to integrate information over a larger number of auditory filters than the average adult.

Acoustic behaviors including orientation and social communication depend on neural integration of information across the sound spectrum. In many species, spectral integration is performed by combination-sensitive neurons, responding best when distinct spectral elements in sounds are combined. These are generally considered a feature of information processing in the auditory forebrain. In the mustached bat's inferior colliculus (IC), they are common in frequency representations associated with sonar signals but have not been reported elsewhere in this bat's IC or the IC of other species. We examined the presence of combination-sensitive neurons in frequency representations of the mustached bat's IC not associated with biosonar. Seventy-five single-unit responses were recorded with the best frequencies in 10–23 or 32–47 kHz bands. Twenty-six displayed single excitatory tuning curves in one band with no additional responsiveness to a second signal in another band. The remaining 49 responded to sounds in both 10–23 and 32–47 kHz bands, but response types varied. Sounds in the higher band were usually excitatory, whereas sounds in the lower band either facilitated or inhibited responses to the higher frequency signal. Interactions were usually strongest when the higher and lower frequency stimuli were presented simultaneously, but the strength of interactions varied. Over one-third of the neurons formed a distinct subset; they responded most sensitively to bandpass noise, and all were combination sensitive. We suggest that these combination-sensitive interactions are activated by elements of mustached bat social vocalizations. If so, neuronal integration characterizing analysis of social vocalizations in many species occurs in the IC.

The visual system uses information about the relative depth of contours and surfaces to link and segment elements of visual scenes. The integration of form and depth information was studied in areas V1 and V2 of the alert macaque. Neurons in area V2 used contextual depth information to integrate occluded contours, signal the presence of object boundaries, and segment surfaces: (1) Amodal contour completion occurs when a contour passes behind an occluder. The basis of contour completion, the facilitation of neuronal responses to stimuli located within their receptive fields (RFs) by contextual lines lying outside their RFs, was blocked by orthogonal lines intersecting the contours but was recovered when the orthogonal line was placed in the near depth plane. (2) An illusory contour will modally complete separated elements located across an isoluminant field if the elements are placed in the near depth plane. V2 neurons responded when line segments were placed outside the RF in the near depth plane and a field of uniform luminance covered the RF. (3) Texture elements within a surface will “capture” the perceived depth consistent with the disparity of the surface's boundary, even when given no disparity themselves. V2 neurons responded to the center elements of a grating as if they contained disparity, even though disparity was present only for the grating's end elements located beyond the RF borders. These results, which were more common in V2 than in V1, demonstrate a role for V2 in the three-dimensional representation of surfaces in space.

Both mammals and birds use the interaural time difference (ITD) for localization of sound in the horizontal plane. They may localize either real or phantom sound sources, when the signal consists of a narrow frequency band. This ambiguity does not occur with broadband signals. A plot of impulse rates or amplitude of excitatory postsynaptic potentials against ITDs (ITD curve) consists of peaks and troughs. In the external nucleus (ICX) of the owl's inferior colliculus, ITD curves show multiple peaks when the signal is narrow-band, such as tones. Of these peaks, one occurs at ITDi, which is independent of frequency, and others at ITDi ± T, where T is the tonal period. The ITD curve of the same neuron shows a large peak (main peak) at ITDi and no or small peaks (side peaks) at ITDi ± T, when the signal is broadband. ITD curves for postsynaptic potentials indicate that ICX neurons integrate the results of binaural cross-correlation in different frequency bands. However, the difference between the main and side peaks is small. ICX neurons further enhance this difference in the process of converting membrane potentials to impulse rates. Inhibition also appears to augment the difference between the main and side peaks.

Recent progress has been made regarding the prevention of hearing loss. However, the complete protection of both hair cells and spiral ganglion neurons, with restored function, has not yet been achieved. It has been shown that spiral ganglion neuronal loss can be prevented by neurotrophin 3 (NT3) and hair cell damage by N- methyl- d -aspartate (NMDA) receptor antagonists. Here we demonstrate that the combined treatment with MK801, a NMDA antagonist, and NT3 protect both cochlear morphology and physiology from injury. Pretreatment with MK801 prevented hearing loss and the dendrites of the spiral ganglion neurons from swelling after noise-induced damage. The acute phase of insult with the aminoglycoside antibiotic amikacin resulted in swollen afferent dendrites beneath the inner hair cells. The chronic phase resulted in complete hair cell loss and near-complete loss of spiral ganglion neurons. This damage caused a near-complete loss of hearing sensitivity as displayed by elevated (>90-dB sound pressure levels) auditory brainstem response thresholds. The treatment of amikacin-exposed animals with MK801 gave only a partial protection of hearing. However, the combined treatment with NT3 and MK801 in the amikacin-comprised ear resulted in improved mean hearing within 20 dB of normal. Furthermore, hair cell loss was prevented in these animals and spiral ganglion neurons were completely protected. These results suggest that the NMDA antagonist MK801 protects against noise-induced excitotoxicity in the cochlea whereas the combined treatment of NT3 and MK801 has a potent effect on preserving both auditory physiology and morphology against aminoglycoside toxicity.

The relationship between sensory sensitivity and reading performance was examined to test the hypothesis that the orthographic and phonological skills engaged in visual word recognition are constrained by the ability to detect dynamic visual and auditory events. A test battery using sensory psychophysics, psychometric tests, and measures of component literacy skills was administered to 32 unselected 10-year-old primary school children. The results suggest that children's sensitivity to both dynamic auditory and visual stimuli are related to their literacy skills. Importantly, after controlling for intelligence and overall reading ability, visual motion sensitivity explained independent variance in orthographic skill but not phonological ability, and auditory FM sensitivity covaried with phonological skill but not orthographic skill. These results support the hypothesis that sensitivity at detecting dynamic stimuli influences normal children's reading skills. Vision and audition separately may affect the ability to extract orthographic and phonological information during reading.

We examined the coding of sound-source location by ensembles of neurons in the auditory cortex. Broadband noise bursts were presented from loudspeakers throughout 360° in the horizontal plane. Sound levels varied from 20 to 40 dB above neural thresholds. We recorded temporal spike patterns simultaneously at 16 recording sites in area A2 of α-chloralose-anesthetized cats. Spike patterns of individual units varied in spike counts and in spike timing as a function of sound-source location. Ensembles of up to 19 units recorded simultaneously demonstrated additional location sensitivity in the form of relative spike counts and relative spike timing among neurons. We used an artificial neural network (ANN) algorithm to recognize ensemble spike patterns and, thereby, to infer the locations of sound sources. The ANN could estimate stimulus locations based on ensemble responses to single-stimulus presentations. Median errors (MEs) averaged 49.2 ± 11.9° (mean ± SD; n = 34; chance level, 90°). The ANN maintained better-than-chance performance even when input spike patterns were expressed as relative spike counts across units (i.e., no information available from absolute spike counts of individual units; ME, 63.0 ± 11.8°) or when spike latencies were represented as time relative to the first spike for each trial (i.e., no external time reference available; ME, 54.3 ± 12.4°). The ANN performance improved monotonically as the sizes of ensemble patterns were increased by combining patterns across the entire unit sample. The performance by ensembles of 128 units approached the level of localization performance of behaving cats.

Conductive hearing loss, produced by otitis media with effusion, is widespread in young children. However, little is known about its short- or long-term effects on hearing or the brain. To study the consequences of a conductive loss for the perception and processing of sounds, we plugged the left ear canal of ferrets for 7–15 months during either infancy or adulthood. Before or during plugging, the ferrets were trained to perform a binaural task requiring the detection of a 500 Hz tone, positioned 90° to the right, that was masked by two sources of broad-band noise. In one condition (“control”), both noise sources were 90° right and, in the second condition (“bilateral”), one noise source was moved to 90° left. Normal ferrets showed binaural unmasking: tone detection thresholds were lower (mean 10.1 dB) for the bilateral condition than for the control condition. Both groups of ear-plugged ferrets had reduced unmasking; the mean residual unmasking was 2.3 dB for the infant and 0.7 dB for the adult ear-plugged animals. After unplugging, unmasking increased in both groups (infant, 7.1 dB; adult, 6.9 dB) but not to normal levels. Repeated testing during the 22 months after unplugging revealed a gradual return to normal levels of unmasking. These results show that a unilateral conductive hearing loss, in either infancy or adulthood, impairs binaural hearing both during and after the hearing loss. They show scant evidence for adaptation to the plug and demonstrate a recovery from the impairment that occurs over a period of several months after restoration of normal peripheral function.

The electrophysiological and neurochemical characteristics of the nondopaminergic nigrostriatal (NO-DA) cells and their functional response to the degeneration of dopaminergic nigrostriatal (DA) cells were studied. Three different criteria were used to identify NO-DA cells: (1) antidromic response to striatal stimulation with an electrophysiological behavior (firing rate, interspike interval variability, and conduction velocity) different from that of DA cells; (2) retrograde labeling after striatal injection of HRP but showing immunonegativity for DA cell markers (tyrosine hydroxylase, calretinin, calbindin-D28k, and cholecystokinin); and (3) resistance to neurotoxic effect of 6-hydroxydomine (6-OHDA). Our results showed that under normal conditions, 5–8% of nigrostriatal neurons are immunoreactive for GABA, glutamic acid decarboxylase, and parvalbumin, markers of GABAergic neurons, a percentage that reached 81–84% after 6-OHDA injection. Electrophysiologically, NO-DA cells showed a behavior similar to that found in other nigral GABAergic (nigrothalamic) cells. In addition, the 6-OHDA degeneration of DA cells induced a modification of their electrophysiological pattern similar to that found in GABAergic nigrothalamic neurons. Taken together, the present data indicate the existence of a small GABAergic nigrostriatal pathway and suggest their involvement in the pathophysiology of Parkinson’s disease.

Basilar-membrane responses to clicks were measured, using laser velocimetry, at a site of the chinchilla cochlea located about 3.5 mm from the oval window (characteristic frequency or CF: typically 8–10 kHz). They consisted of relatively undamped oscillations with instantaneous frequency that increased rapidly (time constant: 200 μs) from a few kHz to CF. Such frequency modulation was evident regardless of stimulus level and was also present post-mortem. Responses grew linearly at low stimulus levels, but exhibited a compressive nonlinearity at higher levels. Velocity-intensity functions were almost linear near response onset but became nonlinear within 100 μs. Slopes could be as low as 0.1–0.2 dB/dB at later times. Hence, the response envelopes became increasingly skewed at higher stimulus levels, with their center of gravity shifting to earlier times. The phases of near-CF response components changed by nearly 180 degrees as a function of time. At high stimulus levels, this generated cancellation notches and phase jumps in the frequency spectra. With increases in click level, sharpness of tuning deteriorated and the spectral maximum shifted to lower frequencies. Response phases also changed as a function of increasing stimulus intensity, exhibiting relative lags and leads at frequencies somewhat lower and higher than CF, respectively. In most respects, the magnitude and phase frequency spectra of responses to clicks closely resembled those of responses to tones. Post-mortem responses were similar to in vivo responses to very intense clicks.

This paper concerns the characterization of performance and perceptual learning of somatosensory interval discrimination. The purposes of this study were to define (1) the performance characteristics for interval discrimination in the somatosensory system by naive adult humans, (2) the normal capacities for improvement in somatosensory interval discrimination, and (3) the extent of generalization of interval discrimination learning. In a two-alternative forced choice procedure, subjects were presented with two pairs of vibratory pulses. One pair was separated in time by a fixed base interval; a second pair was separated by a target interval that was always longer than the base interval. Subjects indicated which pair was separated by the target interval. The length of the target interval was varied adaptively to determine discrimination thresholds. After initial determination of naive abilities, subjects were trained for 900 trials per day at base intervals of either 75 or 125 msec for 10–15 d. Significant improvements in thresholds resulted from training. Learning at the trained base interval generalized completely across untrained skin locations on the trained hand and to the corresponding untrained skin location in the contralateral hand. The learning partially generalized to untrained base intervals similar to the trained one, but not to more distant base intervals. Learning with somatosensory stimuli generalized to auditory stimuli presented at comparable base intervals. These results demonstrate temporal specificity in somatosensory interval discrimination learning that generalizes across skin location, hemisphere, and modality.

Mormyrid electric fish have species- and sex-typical electric organ discharges (EODs). One class of tuberous electroreceptors, the knollenorgans, plays a critical role in electric communication; one function is species recognition of EOD waveforms. In this paper, we describe cell types in the knollenorgan central pathway, which appear responsible for analysis of the temporal patterns of spikes encoded by the knollenorgans in response to EOD stimuli. Secondary sensory neurons in the nucleus of the electrosensory lateral line lobe (NELL) act as relays of peripheral responses. They fire a single phase-locked spike to an outside positive-going voltage step. Axons from the NELL project to the toral nucleus exterolateralis pars anterior (ELa). Immediately after they enter the ELa, they send collaterals to terminate on one to three ELa large cells and then continue in a lengthy neuronal pathway that traverses the ELa several times. After a path length of up to 5 mm, the NELL axon terminates on as many as 70 ELa small cells. Thus the large cells appear to be excited first, followed by the small cells, with the intervening length of the axon serving as a delay line. The large cells also respond with phase-locked spikes to voltage steps. Large cell axons extend for ∼1 mm and terminate on several small cells within the ELa. The terminals are known to be GABAergic inputs and are presumed inhibitory. We propose that small cells receive direct inhibition from large cells and delayed excitation from NELL axons. The small cells may act as anti-co-incidence detectors to analyze the temporal structure of the EOD waveform.

Low-frequency cells in the anteroventral cochlear nucleus (AVCN) can be sensitive to changes in the spatiotemporal pattern of discharges across their auditory nerve (AN) inputs (Carney, 1990). This sensitivity suggests that these cells may be tuned to particular spatiotemporal patterns, or features, in the discharge patterns of populations of AN fibers. To evaluate and characterize this sensitivity, we developed a technique whereby the physiological responses of AVCN cells to wide-band noise were analyzed using the simulated response of a population of AN fibers to the same noise stimulus. By averaging the simulated two-dimensional spatiotemporal pattern of AN activity that preceded each AVCN discharge, it was possible to derive a two-dimensional reverse-correlation function that characterized the spatiotemporal tuning of each AVCN cell. The derived spatiotemporal tuning pattern represented a feature in the AN population response that was most likely to precede discharges of the AVCN cell. To test the spatiotemporal tuning characterizations, we used these patterns to predict the responses of cells to noise stimuli statistically independent from the stimuli used to characterize the cells. This technique provides a general tool for the study of any neural system that involves the analysis of spatiotemporal input patterns.

Interaural time and intensity differences (ITD and IID) are processed independently in the owl’s auditory system. This paper examines whether this independence is established in nucleus laminaris (NL), the first site of ITD processing. A plot of discharge rate against time difference (ITD curve) is sinusoidal in NL. The ITDs that produce the peaks are called the most favorable ITDs, and those that produce the troughs are called the least favorable ITDs. IID had little effect on the discharge rates of laminaris neurons for the most and least favorable ITDs. The degree of peak–trough modulation changed slightly with variation in IID. In contrast, IID in tonal stimuli affected the temporal aspect of ITD curves depending on the difference between the stimulus frequency and the neuron’s best frequency (BF). For frequencies below BF, IID caused large and systematic shifts in ITD toward the ear in which the sound was louder, whereas for frequencies above BF, IID caused small shifts in ITD toward the opposite ear. IID had little effect on ITD curves taken with BF or broadband noise. These results can be largely accounted for by the effects of frequency and intensity on the timing of impulses at the level of the cochlear nuclei. Thus, the processing of ITD by NL neurons is independent of IID for behaviorally relevant stimuli, because the timing of impulses is insensitive to sound level when the signal is broadband.