Publications using TDT

The aim of the study was to evaluate quantitatively ictal and interictal phonophobia in episodic migraine (EM). We included subjects with EM and age- and gender-matched controls. Sound stimuli were pure tones at frequencies of 1000, 4000 and 8000 Hz. Sound aversion thresholds (SATs) were determined as the minimal sound intensity perceived as unpleasant or painful. Migraineurs were examined both between and during attacks. We compared interictal SATs in migraineurs with those in controls. We also compared ictal and interictal SATs in migraineurs. Sixty migraineurs and 52 controls were included. Interictal mean SAT of migraineurs, averaged for the three frequencies, was significantly lower than that of controls [90.4 (0.8) dB vs. 105.9 (1.1) dB, respectively, P < 0.0001]. In migraineurs, mean ictal SAT, averaged for the three frequencies, was significantly lower than interictal SAT [76.0 (0.9) dB vs. 91.0 (0.8) dB, respectively, P < 0.0001]. Patients with EM exhibit increased sound aversion between attacks that is further augmented during an acute attack.

The strength of the medial olivocochlear (OC) reflex is routinely assayed by measuring suppression of ipsilateral responses such as otoacoustic emissions (OAEs) by a brief contralateral noise, e.g., (Berlin, C.I., Hood, L.J., Cecola, P., Jackson, D.F., Szabo, P. 1993. Does type I afferent dysfunction reveal itself through lack of efferent suppression. Hear. Res. 65, 40-50). Here, we show in anesthetized guinea pigs, that the magnitude of OC-mediated suppression of ipsilateral cochlear responses (i.e., compound actions potentials (CAPs), distortion product (DP) OAEs and round-window noise) slowly builds over 2-3 min during a sustained contralateral noise. The magnitude of this build-up suppression was largest at low ipsilateral stimulus intensities, as seen for suppression measured at contra-noise onset. However, as a function of stimulus frequency, build-up suppression magnitude was complementary to onset suppression, i.e., largest at the lowest and highest frequencies tested. Both build-up and onset suppression were eliminated by cutting the OC bundle. In contrast to "slow effects" of shock-evoked medial OC activity (Sridhar, T.S., Liberman, M.C., Brown, M.C., Sewell, W.F. 1995. A novel cholinergic "slow effect" of efferent stimulation on cochlear potentials in the guinea pig. J. Neurosci. 15, 3667-3678), which are mediated by slow intracellular changes in Ca concentration in OHCs, build-up effects of contralateral noise are immediately extinguished upon OC bundle transection and are likely mediated by central modulation of the response rates in MOC fibers due to the sustained noise. Results suggest that conventional tests of OC reflex strength may underestimate its magnitude in noisy environments.

The detection of an intensity increment in a longer duration sinusoid or pedestal is often used as a measure of intensity resolution, but the decision processes underlying this measure are poorly understood. Thresholds were obtained for detection of an increment in a 370-ms, 4-kHz pedestal in quiet or in noise to determine the relative contributions of background noise level and pedestal level, the effect of increment duration, and the effect of different noise spectra. Increment detection thresholds expressed in units of ΔL[10 log(1+ΔI/I)] decreased as pedestal levels increased. At low pedestal levels, increment detection was limited by the masking effect of the noise and was similar across noise conditions for pedestals of equal sensation level. At high pedestal levels, the noise had no effect and increment detection was determined by the pedestal level in dB SPL (sound pressure level). Increment detection improved with increasing increment duration and was altered less by a noise band above the pedestal/increment frequency than by a broadband noise that produced equal masking at the pedestal/increment frequency. The quadratic-compression model described by Neely and Jesteadt [(2005). Acta Acust. Acust. 91, 980–991] provided a better approximation to the data than a model based on excitation patterns.

Objectives: The objective of this study was to evaluate the efficacy of a word-based auditory-training procedure for use with older adults who have impaired hearing. The emphasis during training and assessment is placed on words with a high frequency of occurrence in American English. Design: In this study, a repeated-measures group design was used with each of the two groups of participants to evaluate the effects of the word-based training regimen. One group comprised 20 young adults with normal hearing and the other consisted of 16 older adults with impaired hearing. The group of young adults was not included for the purpose of between-group comparisons. Rather, it was included to demonstrate the efficacy of the training regimen, should efficacy fail to be demonstrated in the group of older adults, and to estimate the magnitude of the benefits that could be achieved in younger listeners. Results: Significant improvements were observed in the group means for each of five measures of post-training assessment. Pretraining and post-training performance assessments were all based on the open-set recognition of speech in a fluctuating speech-like background noise. Assessment measures ranged from recognition of trained words and phrases produced by talkers heard during training to the recognition of untrained sentences produced by a talker not encountered during training. In addition to these group data, analysis of individual data via 95% critical differences for each assessment measure revealed that 75 to 80% of the older adults demonstrated significant improvements on most or all of the post-training measures. Conclusions: The word-based auditory-training program examined here, one based on words having a high frequency of occurrence in American English, has been demonstrated to be efficacious in older adults with impaired hearing. Training on frequent words and frequent phrases generalized to sentences constructed from frequently occurring words whether spoken by talkers heard during training or by a novel talker.

Subject responses were measured for individual narrow-band reproducible stimuli in a low-frequency tone-in-noise detection task. Both N0S0 and N0Sπ conditions were examined. The goal of the experiment was to determine the relative importance of envelope and fine-structure cues. Therefore, chimeric stimuli were generated by recombining envelopes and fine structures from different reproducible stimuli. Detection judgments for noise-alone or tone-plus-noise stimuli that had common envelopes but different fine structures or common fine structures but different envelopes were compared. The results showed similar patterns of responses to stimuli that shared envelopes, indicating the importance of envelope cues; however, fine-structure cues were also shown to be important. The relative weight assigned to envelope and fine-structure cues varied across subjects and across interaural conditions. The results also indicated that envelope and fine-structure information are not processed independently. Implications for monaural and binaural models of masking are discussed.

Lysosomal storage diseases (LSD) are metabolic disorders characterized by accumulation of undegraded material. The mucopolysaccharidoses (MPS) are LSDs defined by the storage of glycosaminoglycans. Previously, we hypothesized that cells affected with LSD have increased energy expenditure for biosynthesis because of deficiencies of raw materials sequestered within the lysosome. Thus, LSDs can be characterized as diseases of deficiency as well as overabundance (lysosomal storage). In this study, metabolite analysis identified deficiencies in simple sugars, nucleotides, and lipids in the livers of MPSI mice. In contrast, most amino acids, amino acid derivatives, dipeptides, and urea were elevated. These data suggest that protein catabolism, perhaps because of increased autophagy, is at least partially fulfilling intermediary metabolism. Thus, maintaining glycosaminoglycan synthesis in the absence of recycled precursors results in major shifts in the energy utilization of the cells. A high fat diet increased simple sugars and some fats and lowered the apparent protein catabolism. Interestingly, autophagy, which is increased in several LSDs, is responsive to dietary intervention and is reduced in MPSVII and MPSI mice fed a high fat diet. Although long term dietary treatment improved body weight in MPSVII mice, it failed to improve life span or retinal function. In addition, the ventricular hypertrophy and proximal aorta dilation observed in MPSVII mice were unchanged by a high fat, simple sugar diet. As the mechanism of this energy imbalance is better understood, a more targeted nutrient approach may yet prove beneficial as an adjunct therapy to traditional approaches.

Background Male field crickets produce pure-tone calling songs to attract females. Receivers are expected to have evolved a "matched filter" in the form of a tuned sensitivity for this frequency. In addition, the peripheral directionality of field crickets is sharply tuned as a result of a pressure difference receiver. We studied both forms of tuning in the same individuals of four species of cricket, where Gryllus bimaculatus and G. campestris are largely allopatric, whereas Teleogryllus oceanicus and T. commodus occur also sympatrically. Results The sharpness of the sensitivity filter is highest for T. commodus , which also exhibits low interindividual variability. Individual receivers may also vary strongly in the best frequency for directional hearing. In G. campestris , such best frequencies occur even at frequencies outside the range of carrier frequencies of males. Contrary to the predictions from the "matched filter hypothesis", in three of the four species the frequency optima of the two involved filters are not matched to each other, and the mismatch can amount to 1.2 kHz. The mean carrier frequency of the male population is between the frequency optima of both filters in three species. Only in T. commodus we found a match between both filters and the male carrier frequency. Conclusion Our results show that a mismatch between the sensitivity and directionality tuning is not uncommon in crickets, and an observed match ( T. commodus ) appears to be the exception rather than the rule. The data suggests that independent variation of both filters is possible. During evolution each sensory task may have been driven by independent constraints, and may have evolved towards its own respective optimum.

This study examined the effects of increased processing load on the closed‐set speech‐identification performance of young and older adults in a one‐talker background. Since the older adults had impaired hearing, speech‐identification performance was measured for spectrally shaped stimuli comparable to those experienced when wearing well‐fit hearing aids. There were three groups of listeners: (1) 19 older adults with high‐frequency sensorineural hearing loss; (2) 10 young adults with normal hearing who were assessed with the same spectrally shaped stimuli as the older adults; (3) 9 young adults with normal hearing who were assessed without spectral shaping and at a poorer target‐to‐competition ratio in an effort to equate overall performance to that of the older adults. In addition to this group factor, there were three within‐participant repeated‐measures independent variables designed to increase the demands on processing for the target and competing speech stimuli. These were: (1) competition meaningfulness (played in forward or reverse direction); (2) gender match between target and competing talkers (same or different gender); and (3) talker uncertainty (either the same target/competition talker pair or one of many such pairs on each trial). These three repeated‐measures independent variables were examined in a 2 × 2 × 2 factorial design. They showed roughly independent and additive effects on speech‐identification such that combinations of these variables decreased performance cumulatively. Older adults performed worse than young adults across the board, but also showed diminished relative improvement as the processing load was decreased. Individual differences in performance among the older adults were also examined.

Achromatic visual information is transferred from the retina to the brain through two parallel channels: ON-center cells carry “white” information and OFF-center cells “black” information (Nelson et al., 1978; Schiller, 1982; Schiller et al., 1986). Responses of ON and OFF retinal and thalamic neurons are approximately equal in magnitude (Krüger and Fischer, 1975; Kremers et al., 1993), but psychophysical studies have shown that humans detect light decrements (black) better and faster than increments (white) (Blackwell, 1946; Short, 1966; Krauskopf, 1980; Whittle, 1986; Bowen et al., 1989; Chan and Tyler, 1992; Kontsevich and Tyler, 1999; Chubb and Nam, 2000; Dannemiller and Stephens, 2001). From recordings of single-cell activity in the macaque monkey's primary visual cortex (V1), we found that black-dominant neurons substantially outnumbered white-dominant neurons in the corticocortical output layers 2/3, but the numbers of black- and white-dominant neurons were nearly equal in the thalamocortical input layer 4c. These results strongly suggest that the black-over-white preference is generated or greatly amplified in V1. The predominance of OFF neurons in layers 2/3 of V1, which provide visual input to higher cortical areas, may explain why human subjects detect black more easily than white. Furthermore, our results agree with human EEG and fMRI findings that V1 responses to decrements are stronger than to increments, though the OFF/ON imbalance we found in layers 2/3 of macaque V1 is much larger than in the whole V1 population in the human V1 experiments (Zemon et al., 1988, 1995; Olman et al., 2008).

The present study aimed to identify morphological correlates of environment‐induced changes at excitatory synapses of the primary auditory cortex (A1). We used the Golgi‐Cox stain technique to compare pyramidal cells dendritic properties of Sprague‐Dawley rats exposed to different environmental manipulations. Sholl analysis, dendritic length measures, and spine density counts were used to monitor the effects of sensory deafness and an auditory version of environmental enrichment (EE). We found that deafness decreased apical dendritic length leaving basal dendritic length unchanged, whereas EE selectively increased basal dendritic length without changing apical dendritic length. On the contrary, deafness decreased while EE increased spine density in both basal and apical dendrites of A1 Layer 2/3 (LII/III) neurons. To determine whether stress contributed to the observed morphological changes in A1, we studied neural morphology in a restraint‐induced model that lacked behaviorally relevant acoustic cues. We found that stress selectively decreased apical dendritic length in the auditory but not in the visual primary cortex. Similar to the acoustic manipulation, stress‐induced changes in dendritic length possessed a layer‐specific pattern displaying LII/III neurons from stressed animals with normal apical dendrites but shorter basal dendrites, while infragranular neurons (Layers V and VI) displayed shorter apical dendrites but normal basal dendrites. The same treatment did not induce similar changes in the visual cortex, demonstrating that the auditory cortex is an exquisitely sensitive target of neocortical plasticity, and that prolonged exposure to different acoustic as well as emotional environmental manipulation may produce specific changes in dendritic shape and spine density. Synapse 64:97–110, 2010. © 2009 Wiley‐Liss, Inc.

Binaural signal detection in an NoSpi task relies on interaural disparities introduced by adding an antiphasic signal to diotic noise. What metric of interaural disparity best predicts performance? Some models use interaural correlation; others differentiate between dynamic interaural time differences (ITDs) and interaural level differences (ILDs) of the effective stimulus. To examine the relative contributions of ITDs and ILDs in binaural detection, we developed a novel signal processing technique that selectively degrades different aspects (potential cues) of binaural stimuli (e.g., only ITDs are scrambled). Degrading a particular cue will affect performance only if that cue is relevant to the binaural processing underlying detection. This selective scrambling technique was applied to the stimuli of a classic N0Spi task in which the listener had to detect an antiphasic 500-Hz signal in the presence of a diotic wideband noise masker. Data obtained from five listeners showed that (1) selective scrambling of ILDs had little effect on binaural detection, (2) selective scrambling of ITDs significantly degraded detection, and (3) combined scrambling of ILDs and ITDs had the same effect as exclusive scrambling of ITDs. Regarding the question which stimulus properties determine detection, we conclude that for this binaural task (1) dynamic ITDs dominate detection performance, (2) ILDs are largely irrelevant, and (3) interaural correlation of the stimulus is a poor predictor of detection. Two simple stimulus-based models that each reproduce all binaural aspects of the data quite well are described: (1) a single-parameter detection model using ITD variance as detection criterion and (2) a compressive transformation followed by a crosscorrelation analysis. The success of both of these contrasting models shows that our data alone cannot reveal the mechanisms underlying the dominance of ITD cues. The physiological implications of our findings are discussed.

Tone detection and temporal gap detection thresholds were determined in CBA/CaJ mice using a Go/No-go procedure and the psychophysical method of constant stimuli. In the first experiment, audiograms were constructed for five CBA/CaJ mice. Thresholds were obtained for eight pure tones ranging in frequency from 1 to 42 kHz. Audiograms showed peak sensitivity between 8 and 24 kHz, with higher thresholds at lower and higher frequencies. In the second experiment, thresholds for gap detection in broadband and narrowband noise bursts were measured at several sensation levels. For broadband noise, gap thresholds were between 1 and 2 ms, except at very low sensation levels, where thresholds increased significantly. Gap thresholds also increased significantly for low pass-filtered noise bursts with a cutoff frequency below 18 kHz. Our experiments revised absolute auditory thresholds in the CBA/CaJ mouse strain and demonstrated excellent gap detection ability in the mouse. These results add to the baseline behavioral data from normal-hearing mice which have become increasingly important for assessing auditory abilities in genetically altered mice.

We developed a new method to estimate the spatial extent of summation, the cortical spread, of the local field potential (LFP) throughout all layers of macaque primary visual cortex V1 by taking advantage of the V1 retinotopic map. We mapped multi-unit activity and LFP visual responses with sparse-noise at several cortical sites simultaneously. The cortical magnification factor near the recording sites was precisely estimated by track reconstruction. The new method combined experimental measurements together with a model of signal summation to obtain the cortical spread of the LFP. This new method could be extended to cortical areas that have topographic maps such as S1 or A1, and to cortical areas without functional columnar maps, such as rodent visual cortex. In macaque V1, the LFP was the sum of signals from a very local region, the radius of which was on average 250 μm. The LFP's cortical spread varied across cortical layers, reaching a minimum value of 120 μm in layer 4B. An important functional consequence of the small cortical spread of the LFP is that the visual field maps of LFP and MUA recorded at a single electrode site were very similar. The similar spatial scale of the visual responses, the restricted cortical spread, and their laminar variation led to new insights about the sources and possible applications of the LFP.

Comodulation masking release (CMR) has been attributed to auditory processing within one auditory channel (within-channel cues) and/or across several auditory channels (across-channel cues). The present flanking-band (FB) experiment-using a 25-Hz-wide on-frequency noise masker (OFM) centered at the signal frequency of 10 kHz and a single 25-Hz-wide noise FB-was designed to separate the amount of CMR due to within- and across-channel cues and to investigate the role of temporal cues on the size of within-channel CMR. The results demonstrated within-channel CMR in the Naval Medical Research Institute mouse, while no unambiguous evidence could be found for CMR occurring due to across-channel processing (i.e., "true CMR"). The amount of within-channel CMR was dependent on the frequency separation between the FB and the OFM. CMR increased from 4 to 6 dB for a frequency separation of 1 kHz to 18 dB for a frequency separation of 100 Hz. The large increase for a frequency separation of 100 Hz is likely to be due to the exploitation of changes in the temporal pattern of the stimulus upon the addition of the signal. Temporal interaction between both masker bands results in modulations with a large depth at a modulation frequency equal to the beating rate. Adding a signal to the maskers reduces the depth of the modulation. The auditory system of mice might be able to use the change in modulation depth at a beating frequency of 100 Hz as a cue for signal detection, while being unable to detect changes in modulation depth at high modulation frequencies. These results are consistent with other experiments and model predictions for CMR in humans which suggested that the main contribution to the CMR effect stems from processing of within-channel cues.

Atoh1 is a basic helix–loop–helix transcription factor necessary for the specification of inner ear hair cells and central auditory system neurons derived from the rhombic lip. We used the Cre–loxP system and two Cre -driver lines ( Egr2 Cre and Hoxb1 Cre ) to delete Atoh1 from different regions of the cochlear nucleus (CN) and accessory auditory nuclei (AAN). Adult Atoh1 -conditional knock-out mice ( Atoh1 CKO ) are behaviorally deaf, have diminished auditory brainstem evoked responses, and have disrupted CN and AAN morphology and connectivity. In addition, Egr2; Atoh1 CKO mice lose spiral ganglion neurons in the cochlea and AAN neurons during the first 3 d of life, revealing a novel critical period in the development of these neurons. These new mouse models of predominantly central deafness illuminate the importance of the CN for support of a subset of peripheral and central auditory neurons.

Although many studies have examined the performance of animals in detecting a frequency change in a sequence of tones, few have measured animals’ discrimination of the fundamental frequency (F0) of complex, naturalistic stimuli. Additionally, it is not yet clear if animals perceive the pitch of complex sounds along a continuous, low-to-high scale. Here, four ferrets (Mustela putorius) were trained on a two-alternative forced choice task to discriminate sounds that were higher or lower in F0 than a reference sound using pure tones and artificial vowels as stimuli. Average Weber fractions for ferrets on this task varied from ∼20% to 80% across references (200–1200 Hz), and these fractions were similar for pure tones and vowels. These thresholds are approximately ten times higher than those typically reported for other mammals on frequency change detection tasks that use go/no-go designs. Naive human listeners outperformed ferrets on the present task, but they showed similar effects of stimulus type and reference F0. These results suggest that while non-human animals can be trained to label complex sounds as high or low in pitch, this task may be much more difficult for animals than simply detecting a frequency change.

Electrocorticogram (ECoG) recordings of the 6-hydroxydopamine (6-OHDA)–lesioned parkinsonian rat have shown an increase in the power of cortical β-band (15–30 Hz) oscillations ipsilateral to the lesion. The power of these oscillations is decreased with dopamine agonist administration. Here, we demonstrate that stimulation of an electrode implanted in the subthalamic nucleus alters the power of cortical β and γ oscillations in 6-OHDA–lesioned animals. These alterations are dependent on stimulation frequency, charge, and amplitude/pulse width. Oscillations were significantly reduced during 200- and 350-Hz stimulation. A minimum charge of 4 nC was required to elicit a reduction in oscillation power. A number of amplitude and pulse width combinations that reached 4 nC were tested; it was found that only the combinations of 33 μA/120 μs and 65 μA/60 μs significantly reduced cortical oscillations. The reduction in β/γ oscillation power due to deep brain stimulation (DBS) was consistent with a significant reduction in the animals' rotational behavior, a typical symptom of parkinsonism in the rat. A significant shift from high β to low γ was observed in the peak frequencies of ECoG recordings while animals were at rest versus walking on a treadmill. However, DBS exhibited no differential effect on oscillations between these two states. EEG recordings from rodent models of DBS may provide surrogate information about the neural signatures of Parkinson's disease relative to the efficacy of DBS.

The barn owl's midbrain and forebrain contain neurons tuned to sound direction. The spatial receptive fields of these neurons result from sensitivity to combinations of interaural time (ITD) and level (ILD) differences over a broad frequency range. While a map of auditory space has been described in the midbrain, no similar topographic representation has been found in the forebrain. The first nuclei that belong exclusively to the forebrain and midbrain pathways are the thalamic nucleus ovoidalis (Ov) and the external nucleus of the inferior colliculus (ICx), respectively. The midbrain projects to the auditory thalamus before sharp spatial receptive fields emerge; although Ov and ICx receive projections from the same midbrain nuclei, they are not directly connected. We compared the spatial tuning in Ov and ICx. Thalamic neurons respond to a broader frequency range and their ITD and ILD tuning varied more across frequency. However, neurons in Ov showed spatial receptive fields as selective as neurons in ICx. Thalamic spatial receptive fields were tuned to frontal and contralateral space and correlated with their tuning to ITD and ILD. Our results indicate that spatial tuning emerges in both pathways by similar combination selectivity to ITD and ILD. However, the midbrain and the thalamus do not appear to repeat exactly the same processing, as indicated by the difference in frequency range and the broader tuning to binaural cues. The differences observed at the initial stages of these sound-localization pathways may reflect diverse functions and coding schemes of midbrain and forebrain.

Responses of neural units in two areas of the medial auditory belt (middle medial area [MM] and rostral medial area [RM]) were tested with tones, noise bursts, monkey calls (MC), and environmental sounds (ES) in microelectrode recordings from two alert rhesus monkeys. For comparison, recordings were also performed from two core areas (primary auditory area [A1] and rostral area [R]) of the auditory cortex. All four fields showed cochleotopic organization, with best (center) frequency [BF(c)] gradients running in opposite directions in A1 and MM than in R and RM. The medial belt was characterized by a stronger preference for band-pass noise than for pure tones found medially to the core areas. Response latencies were shorter for the two more posterior (middle) areas MM and A1 than for the two rostral areas R and RM, reaching values as low as 6 ms for high BF(c) in MM and A1, and strongly depended on BF(c). The medial belt areas exhibited a higher selectivity to all stimuli, in particular to noise bursts, than the core areas. An increased selectivity to tones and noise bursts was also found in the anterior fields; the opposite was true for highly temporally modulated ES. Analysis of the structure of neural responses revealed that neurons were driven by low-level acoustic features in all fields. Thus medial belt areas RM and MM have to be considered early stages of auditory cortical processing. The anteroposterior difference in temporal processing indices suggests that R and RM may belong to a different hierarchical level or a different computational network than A1 and MM.

In the pallid bat auditory cortex and inferior colliculus (IC), the majority of neurons tuned in the echolocation range is selective for the direction and rate of frequency-modulated (FM) sweeps used in echolocation. Such selectivity is shaped mainly by spectrotemporal asymmetries in sideband inhibition. An early-arriving, low-frequency inhibition (LFI) shapes direction selectivity. A delayed, high-frequency inhibition (HFI) shapes rate selectivity for downward sweeps. Using iontophoretic blockade of GABAa receptors, we show that cortical FM sweep selectivity is at least partially shaped locally. GABAa receptor antagonists, bicuculline or gabazine, reduced or eliminated direction and rate selectivity in ∼50% of neurons. Intracortical GABA shapes FM sweep selectivity by either creating the underlying sideband inhibition or by advancing the arrival time of inhibition relative to excitation. Given that FM sweep selectivity and asymmetries in sideband inhibition are already present in the IC, these data suggest a refinement or recreation of similar response properties at the cortical level.