Publications using TDT

Auditory neuropathy is a hearing disorder characterized by normal function of outer hair cells, evidenced by intact cochlear microphonic (CM) potentials and otoacoustic emissions (OAEs), with absent or severely dys-synchronized auditory brainstem responses (ABRs). To determine if selective lesions of inner hair cells (IHCs) and auditory nerve fibers (ANFs) can account for these primary clinical features of auditory neuropathy, we measured physiological responses from chinchillas with large lesions of ANFs (about 85%) and IHCs (45% loss in the apical half of the cochlea; 73% in the basal half). Distortion product OAEs and CM potentials were significantly enhanced, whereas summating potentials and compound action potentials (CAPs) were significantly reduced. CAP threshold was elevated by 7.5dB, but response synchrony was well preserved down to threshold levels of stimulation. Similarly, ABR threshold was elevated by 5.6dB, but all waves were present and well synchronized down to threshold levels in all animals. Thus, large lesions of IHCs and ANFs reduced response amplitudes but did not abolish or severely dys-synchronize CAPs or ABRs. Pathologies other than or in addition to ANF and IHC loss are likely to account for the evoked potential dys-synchrony that is a clinical hallmark of auditory neuropathy in humans.

There are many different needs for intraoperative mapping in both rodent as well as human brain. Whether the goal of the procedure is for epileptic mapping, removal of cancerous tissue, mapping the motor and sensory cortices, or understanding the underlying neural networks within the brain, dense three-dimensional electrode arrays are necessary. In this study, we outlined and validated thicker silicon probe designs for use in intracortical mapping applications. Multiple shank and electrode site configurations were implanted successfully through rat dura as a model for human pia, and all devices maintained the electrical functionality necessary for electrophysiological mapping applications.

Three-dimensional electrode arrays have a variety of potential applications in the fields of both intracortical mapping as well as basic research studies designed to characterize and understand the physiology of the brain. While higher channels counts are desired in brain-machine interface applications, the ability to analyze synchronous data from multiple cortical locations, including various depths is pivotal to fully mapping the underlying neurophysiology of sensory cortices. Within this study, we present a proof of concept validation of a 3D probe technology consisting of 16 silicon shanks in a 4x4 grid arrangement with four electrode sites per shank. This 3D array has been implanted in a rat primary auditory cortex and electrophysiological data are presented showing the utility of electrode sites spanning multilateral cortical space as well as cortical depth.

Traditional noise-suppression algorithms have been shown to improve speech quality, but not speech intelligibility. Motivated by prior intelligibility studies of speech synthesized using the ideal binary mask, an algorithm is proposed that decomposes the input signal into time-frequency (T-F) units and makes binary decisions, based on a Bayesian classifier, as to whether each T-F unit is dominated by the target or the masker. Speech corrupted at low signal-to-noise ratio (SNR) levels (−5 and 0dB) using different types of maskers is synthesized by this algorithm and presented to normal-hearing listeners for identification. Results indicated substantial improvements in intelligibility (over 60% points in −5dB babble) over that attained by human listeners with unprocessed stimuli. The findings from this study suggest that algorithms that can estimate reliably the SNR in each T-F unit can improve speech intelligibility.

The specific acoustic impedance of the cochlear partition was measured from 4 to 20 kHz in the basal turn of the gerbil cochlea, where the best frequency is approximately 40 kHz. The acoustic impedance was found as the ratio of driving pressure to velocity response. It is the physical attribute that governs cochlear mechanics and has never before been directly measured, to our knowledge. The basilar membrane velocity was measured through the transparent round window membrane. Simultaneously, the intracochlear pressure was measured close to the stapes and quite close to the cochlear partition. The impedance phase was close to -90 degrees and the magnitude decreased with frequency, consistent with stiffness-dominated impedance. The resistive component of the impedance was relatively small. Usually the resistance was negative at frequencies below 8 kHz; this unexpected finding might be due to other vibration modes within the cochlear partition.

Natural sounds possess characteristic statistical regularities. Recent research suggests that mammalian auditory processing maximizes information about these regularities in its internal representation while minimizing encoding cost [Smith, E. C. and Lewicki, M. S. (2006). Nature (London) 439, 978–982]. Evidence for this “efficient coding hypothesis” comes largely from neurophysiology and theoretical modeling [Olshausen, B. A., and Field, D. (2004). Curr. Opin. Neurobiol. 14, 481–487; DeWeese, M., et al. (2003). J. Neurosci. 23, 7940–7949; Klein, D. J., et al. (2003). EURASIP J. Appl. Signal Process. 7, 659–667]. The present research provides behavioral evidence for efficient coding in human auditory perception using six-channel noise-vocoded speech, which drastically limits spectral information and degrades recognition accuracy. Two experiments compared recognition accuracy of vocoder speech created using theoretically-motivated, efficient coding filterbanks derived from the statistical regularities of speech against recognition using standard cochleotopic (logarithmic) or linear filterbanks. Recognition of the speech created using efficient encoding filterbanks was significantly more accurate than either of the other classes. These findings suggest potential applications to cochlear implant design.

Humans rely on interaural level differences (ILDs) to determine the location of sound sources, particularly for high-frequency sounds. Previously, ILD-discrimination performance with a 4-kHz pure tone was reported to improve with multi-hour training. Here the effect of the same training regimen on ILD discrimination with a 4-kHz tone sinusoidally amplitude modulated (SAM) at 0.3 kHz was examined. Ten of the 16 trained listeners improved more than untrained controls, demonstrating training-induced learning. However, compared to the learning previously obtained with the 4-kHz pure tone, learning with the SAM tone was less predictable based on starting performance, took longer to complete, and was characterized by specificity to stimulus type (SAM vs pure tones) rather than stimulus frequency. These differences demonstrate an influence of amplitude modulation on learning of ILD discrimination. This influence suggests that the auditory system makes use of amplitude envelope information in determining ILD-discrimination performance, a form of interaction between time and level processing in the binaural system.

Current research in motor neural prosthetics has focused primarily on issues related to the extraction of motor command signals from the brain (e.g. brain-machine interfaces) to direct the motion of prosthetic limbs. Patients using these types of systems could benefit from a somatosensory neural interface that conveys natural tactile and kinesthetic sensations for the prosthesis. Electrical microstimulation within the dorsal root ganglia (DRG) has been proposed as one method to accomplish this, yet little is known about the recruitment properties of electrical microstimulation in activating nerve fibers in this structure. Current-controlled microstimulation pulses in the range of 1-15 microA (200 micros, leading cathodic pulse) were delivered to the L7 DRG in four anesthetized cats using penetrating microelectrode arrays. Evoked responses and their corresponding conduction velocities (CVs) were measured in the sciatic nerve with a 5-pole nerve cuff electrode arranged as two adjacent tripoles. It was found that in 76% of the 69 electrodes tested, the stimulus threshold was less than or equal to 3 microA, with the lowest recorded threshold being 1.1 microA. The CVs of afferents recruited at threshold had a bimodal distribution with peaks at 70 m s(-1) and 85 m s(-1). In 53% of cases, the CV of the response at threshold was slower (i.e. smaller diameter fiber) than the CVs of responses observed at increasing stimulation amplitudes. In summary, we found that microstimulation applied through penetrating microelectrodes in the DRG provides selective recruitment of afferent fibers from a range of sensory modalities (as identified by CVs) at very low stimulation intensities. We conclude that the DRG may serve as an attractive location from which to introduce surrogate somatosensory feedback into the nervous system.

The need to sleep grows with the duration of wakefulness and dissipates with time spent asleep, a process called sleep homeostasis. What are the consequences of staying awake on brain cells, and why is sleep needed? Surprisingly, we do not know whether the firing of cortical neurons is affected by how long an animal has been awake or asleep. Here, we found that after sustained wakefulness cortical neurons fire at higher frequencies in all behavioral states. During early NREM sleep after sustained wakefulness, periods of population activity (ON) are short, frequent, and associated with synchronous firing, while periods of neuronal silence are long and frequent. After sustained sleep, firing rates and synchrony decrease, while the duration of ON periods increases. Changes in firing patterns in NREM sleep correlate with changes in slow-wave activity, a marker of sleep homeostasis. Thus, the systematic increase of firing during wakefulness is counterbalanced by staying asleep.

Background Auditory brainstem responses (ABRs) are used to study auditory acuity in animal-based medical research. ABRs are evoked by acoustic stimuli, and consist of an electrical signal resulting from summated activity in the auditory nerve and brainstem nuclei. ABR analysis determines the sound intensity at which a neural response first appears (hearing threshold). Traditionally, threshold has been assessed by visual estimation of a series of ABRs evoked by different sound intensities. Here we develop an automated threshold detection method that eliminates the variability and subjectivity associated with visual estimation. Results The automated method is a robust computational procedure that detects the sound level at which the peak amplitude of the evoked ABR signal first exceeds four times the standard deviation of the baseline noise. Implementation of the procedure was achieved by evoking ABRs in response to click and tone stimuli, under normal and experimental conditions (adult stem cell transplantation into cochlea). Automated detection revealed that the threshold shift from pre- to post-surgery hearing levels was similar in mice receiving stem cell transplantation or sham injection for click and tone stimuli. Visual estimation by independent observers corroborated these results but revealed variability in ABR threshold shifts and significance levels for stem cell-transplanted and sham-injected animals. Conclusion In summary, the automated detection method avoids the subjectivity of visual analysis and offers a rapid, easily accessible http://axograph.com/source/abr.html approach to measure hearing threshold levels in auditory brainstem response.

Hearing relies on Ca 2+ influx-triggered exocytosis in cochlear inner hair cells (IHCs). Here we studied the role of the Ca 2+ channel subunit Ca V β 2 in hearing. Of the Ca V β 1–4 mRNAs, IHCs predominantly contained Ca V β 2 . Hearing was severely impaired in mice lacking Ca V β 2 in extracardiac tissues ( Ca V β 2 −/− ). This involved deficits in cochlear amplification and sound encoding. Otoacoustic emissions were reduced or absent in Ca V β 2 −/− mice, which showed strongly elevated auditory thresholds in single neuron recordings and auditory brainstem response measurements. Ca V β 2 −/− IHCs showed greatly reduced exocytosis (by 68%). This was mostly attributable to a decreased number of membrane-standing Ca V 1.3 channels. Confocal Ca 2+ imaging revealed presynaptic Ca 2+ microdomains albeit with much lower amplitudes, indicating synaptic clustering of fewer Ca V 1.3 channels. The coupling of the remaining Ca 2+ influx to IHC exocytosis appeared unaffected. Extracellular recordings of sound-evoked spiking in the cochlear nucleus and auditory nerve revealed reduced spike rates in the Ca V β 2 −/− mice. Still, sizable onset and adapted spike rates were found during suprathreshold stimulation in Ca V β 2 −/− mice. This indicated that residual synaptic sound encoding occurred, although the number of presynaptic Ca V 1.3 channels and exocytosis were reduced to one-third. The normal developmental upregulation, clustering, and gating of large-conductance Ca 2+ activated potassium channels in IHCs were impaired in the absence of Ca V β 2 . Moreover, we found the developmental efferent innervation to persist in Ca V β 2 -deficient IHCs. In summary, Ca V β 2 has an essential role in regulating the abundance and properties of Ca V 1.3 channels in IHCs and, thereby, is critical for IHC development and synaptic encoding of sound.

The responses of neocortical cells to sensory stimuli are variable and state dependent. It has been hypothesized that intrinsic cortical dynamics play an important role in trial-to-trial variability; the precise nature of this dependence, however, is poorly understood. We show here that in auditory cortex of urethane-anesthetized rats, population responses to click stimuli can be quantitatively predicted on a trial-by-trial basis by a simple dynamical system model estimated from spontaneous activity immediately preceding stimulus presentation. Changes in cortical state correspond consistently to changes in model dynamics, reflecting a nonlinear, self-exciting system in synchronized states and an approximately linear system in desynchronized states. We propose that the complex and state-dependent pattern of trial-to-trial variability can be explained by a simple principle: sensory responses are shaped by the same intrinsic dynamics that govern ongoing spontaneous activity.

Normal-hearing (NH) listeners and hearing-impaired (HI) listeners detected and discriminated time-reversed harmonic complexes constructed of equal-amplitude harmonic components with fundamental frequencies (F0s) ranging from 50 to 800 Hz. Component starting phases were selected according to the positive and negative Schroeder-phase algorithms to produce within-period frequency sweeps with relatively flat temporal envelopes. Detection thresholds were not affected by component starting phases for either group of listeners. At presentation levels of 80 dB SPL, NH listeners could discriminate the two waveforms nearly perfectly when the F0s were less than 300-400 Hz but fell to chance performance for higher F0s. HI listeners performed significantly poorer, with reduced discrimination at several of the F0s. In contrast, at a lower presentation level meant to nearly equate sensation levels for the two groups, NH listeners' discrimination was poorer than HI listeners at most F0s. Roving presentation levels had little effect on performance by NH listeners but reduced performance by HI listeners. The differential impact of roving level suggests a weaker perception of timbre differences and a greater susceptibility to the detrimental effects of experimental uncertainty in HI listeners.

A brain-computer interface (BCI) is a communication system that takes recorded brain signals and translates them into real-time actions, in this case movement of a cursor on a computer screen. This work applied Fitts' law to the evaluation of performance on a target acquisition task during sensorimotor rhythm-based BCI training. Fitts' law, which has been used as a predictor of movement time in studies of human movement, was used here to determine the information transfer rate, which was based on target acquisition time and target difficulty. The information transfer rate was used to make comparisons between control modalities and subject groups on the same task. Data were analyzed from eight able-bodied and five motor disabled participants who wore an electrode cap that recorded and translated their electroencephalogram (EEG) signals into computer cursor movements. Direct comparisons were made between able-bodied and disabled subjects, and between EEG and joystick cursor control in able-bodied subjects. Fitts' law aptly described the relationship between movement time and index of difficulty for each task movement direction when evaluated separately and averaged together. This study showed that Fitts' law can be successfully applied to computer cursor movement controlled by neural signals.

Recent findings have revealed the importance of orthonasal and retronasal olfaction in food memory, especially in conditioned odor aversion (COA); however, little is known about the dynamics of the cerebral circuit involved in the recognition of an odor as a toxic food signal and whether the activated network depends on the way (orthonasal vs retronasal) the odor was first experienced. In this study, we mapped the modulations of odor-induced oscillatory activities through COA learning using multisite recordings of local field potentials in behaving rats. During conditioning, orthonasal odor alone or associated with ingested odor was paired with immediate illness. For all animals, COA retrieval was assessed by orthonasal smelling only. Both types of conditioning induced similarly strong COA. Results pointed out (1) a predictive correlation between the emergence of powerful beta (15–40 Hz) activity and the behavioral expression of COA and (2) a differential network distribution of this beta activity according to the way the animals were exposed to the odor during conditioning. Indeed, for both types of conditioning, the aversive behavior was predicted by the emergence of a strong beta oscillatory activity in response to the odor in the olfactory bulb, piriform cortex, orbitofrontal cortex, and basolateral amygdala. This network was selectively extended to the infralimbic and insular cortices when the odor was ingested during acquisition. These differential networks could participate in different food odor memory; these results are discussed in line with recent behavioral results that indicate that COA can be formed over long odor-illness delays only if the odor is ingested.

Mutations in the CLRN1 gene cause Usher syndrome type 3 (USH3), a human disease characterized by progressive blindness and deafness. Clarin 1, the protein product of CLRN1, is a four-transmembrane protein predicted to be associated with ribbon synapses of photoreceptors and cochlear hair cells, and recently demonstrated to be associated with the cytoskeleton. To study Clrn1, we created a Clrn1 knockout (KO) mouse and characterized the histological and functional consequences of Clrn1 deletion in the retina and cochlea. Clrn1 KO mice do not develop a retinal degeneration phenotype, but exhibit progressive loss of sensory hair cells in the cochlea and deterioration of the organ of Corti by 4 months. Hair cell stereocilia in KO animals were longer and disorganized by 4 months, and some Clrn1 KO mice exhibited circling behavior by 5-6 months of age. Clrn1 mRNA expression was localized in the retina using in situ hybridization (ISH), laser capture microdissection (LCM), and RT-PCR. Retinal Clrn1 transcripts were found throughout development and adulthood by RT-PCR, although expression peaked at P7 and declined to undetectable levels in adult retina by ISH. LCM localized Clrn1 transcripts to the retinas inner nuclear layer, and WT levels of retinal Clrn1 expression were observed in photoreceptor-less retinas. Examination of Clrn1 KO mice suggests that CLRN1 is unnecessary in the murine retina but essential for normal cochlear development and function. This may reflect a redundancy in the mouse retina not present in human retina. In contrast to mouse KO models of USH1 and USH2, our data indicate that Clrn1 expression in the retina is restricted to the Müller glia. This is a novel finding, as most retinal degeneration associated proteins are expressed in photoreceptors, not in glia. If CLRN1 expression in humans is comparable to the expression pattern observed in mice, this is the first report of an inner retinal protein that, when mutated, causes retinal degeneration.

Background: Infant crying is an important cue for mothers to respond adequately. Inappropriate response to infant crying can hinder social development in infants. In rodents, the pup-mother interaction largely depends on pup's calls. Mouse pups emit high frequency to ultrasonic vocalization (2-90 kHz) to communicate with their dam for maternal care. However, little is known about how the maternal response to infant crying or pup calls affects social development over the long term. Methodology/principal findings: Here we used mice lacking acid-sensing ion channel 3 (Asic3(-/-)) to create a hearing deficit to probe the effect of caregiver hearing on maternal care and adolescent social development. Female Asic3(-/-) mice showed elevated hearing thresholds for low to ultrasonic frequency (4-32 kHz) on auditory brain stem response, which thus hindered their response to their pups' wriggling calls and ultrasonic vocalization, as well as their retrieval of pups. In adolescence, pups reared by Asic3(-/-) mice showed a social deficit in juvenile social behaviors as compared with those reared by wild-type or heterozygous dams. The social-deficit phenotype in juvenile mice reared by Asic3(-/-) mice was associated with the reduced serotonin transmission of the brain. However, Asic3(-/-) pups cross-fostered to wild-type dams showed rescued social deficit. Conclusions/significance: Inadequate response to pups' calls as a result of ASIC3-dependent hearing loss confers maternal deficits in caregivers and social development deficits in their young.

Various physical aspects of room-acoustic simulation techniques have been extensively studied and refined, yet the perceptual attributes of the simulations have received relatively little attention. Here a method of evaluating the perceptual similarity between rooms is described and tested using 15 small-room simulations based on binaural room impulse responses (BRIRs) either measured from a real room or estimated using simple geometrical acoustic modeling techniques. Room size and surface absorption properties were varied, along with aspects of the virtual simulation including the use of individualized head-related transfer function (HRTF) measurements for spatial rendering. Although differences between BRIRs were evident in a variety of physical parameters, a multidimensional scaling analysis revealed that when at-the-ear signal levels were held constant, the rooms differed along just two perceptual dimensions: one related to reverberation time (T60) and one related to interaural coherence (IACC). Modeled rooms were found to differ from measured rooms in this perceptual space, but the differences were relatively small and should be easily correctable through adjustment of T60 and IACC in the model outputs. Results further suggest that spatial rendering using individualized HRTFs offers little benefit over nonindividualized HRTF rendering for room simulation applications where source direction is fixed.

Although research has focused on the perceptual contribution of consonants to spoken syllable or word intelligibility, in sentences vowels have a distinct perceptual advantage over consonants in determining intelligibility [Kewley-Port et al., J. Acoust. Soc. Am. 122, 2365–2375 (2007)]. The current study used a noise replacement paradigm to investigate how perceptual contributions of consonants and vowels are mediated by transitional information at segmental boundaries. The speech signal preserved between replacements is defined as a glimpse window. In the first experiment, glimpse windows contained proportional amounts of transitional boundary information that was either added to consonants or deleted from vowels. Results replicated a two-to-one vowel advantage for intelligibility at the traditional consonant-vowel boundary and suggest that vowel contributions remain robust against proportional deletions of the signal. The second experiment examined the combined effect of random glimpse windows not locked to segments and the distributions of durations measured from the consonant versus vowel glimpses observed in Experiment 1. Results demonstrated that, for random glimpses, the cumulative sentence duration glimpsed was an excellent predictor of performance. Comparisons across experiments confirmed that higher proportions of vowel information within glimpses yielded the highest sentence intelligibility.

Budgerigars learn their vocalizations by reference to auditory information and they retain the ability to learn new vocalizations throughout life. Auditory feedback of these vocalizations was manipulated in three experiments by training birds to produce vocalizations while wearing small earphones. Experiments 1 and 2 examined the effect of background noise level (Lombard effect) and the effect of manipulating feedback level from self-produced vocalizations (Fletcher effect), respectively. Results show that birds exhibit both a Lombard effect and a Fletcher effect. Further analysis showed that changes in vocal intensity were accompanied by changes in call fundamental frequency and duration. Experiment 3 tested the effect of delaying or altering auditory feedback during vocal production. Results showed subsequent production of incomplete and distorted calls in both feedback conditions. These distortions included changes in the peak fundamental frequency, amplitude, duration, and spectrotemporal structure of calls. Delayed auditory feedback was most disruptive to subsequent calls when the delay was 25 ms. Longer delays resulted in fewer errors.