Otolaryngology and Head and Neck Surgery

Chronic subjective tinnitus is a prevalent condition that causes significant distress to millions of Americans. Effective tinnitus treatments are urgently needed, but evaluating them is hampered by the lack of standardized measures that are validated for both intake assessment and evaluation of treatment outcomes. This work was designed to develop a new self-report questionnaire, the Tinnitus Functional Index (TFI), that would have documented validity both for scaling the severity and negative impact of tinnitus for use in intake assessment and for measuring treatment-related changes in tinnitus (responsiveness) and that would provide comprehensive coverage of multiple tinnitus severity domains.

Abstract—In this paper, the details of processing algorithms used in a training program with language learning-impaired children (LLI's) are described. The training program utilized computer games, speech/language training exercises, books-on-tape and educational CD-ROM's. ...

Two fundamental aspects of frequency analysis shape the functional organization of primary auditory cortex. For one, the decomposition of complex sounds into different frequency components is reflected in the tonotopic organization of auditory cortical fields. Second, recent findings suggest that this decomposition is carried out in parallel for a wide range of frequency resolutions by neurons with frequency receptive fields of different sizes (bandwidths). A systematic representation of the range of frequency resolution and, equivalently, spectral integration shapes the functional organization of the iso-frequency domain. Distinct subregions, or "modules," along the iso-frequency domain can be demonstrated with various measures of spectral integration, including pure-tone tuning curves, noise masking, and electrical cochlear stimulation. This modularity in the representation of spectral integration is expressed by intrinsic cortical connections. This organization has implications for our understanding of psychophysical spectral integration measures such as the critical band and general cortical coding strategies.

WORK COMPLETED DURING THIS QUARTER 1) Two neonatally deafened subjects continued chronic electrical stimulation with CII TM processors (TM Advanced Bionics Corp) throughout the past quarter and during the next quarter will be studied in terminal acute electrophysiological studies recording from the inferior colliculus. Data collection will focus on spatial tuning curves (multichannel probe recording), forward masking (single-and 2channel paradigms), modulation depth studies with sinusoidally amplitude modulated (SAM) pulse trains, and 2-channel interaction experiments. 2) Data analyses of spiral ganglion survival, and cochlear nuclear morphology along with electrophysiological data will continue in the new experimental group of subjects that have been deafened at 30 days rather than neonatally (including the new subject studied acutely last quarter). The goal of this series to examine possible critical periods in the anatomical effects of deafness and chronic electrical stimulation on the cochlea and cochlear nucleus.

The basis for multiple representations of equivalent frequency ranges in auditory cortex was studied with physiological and anatomical methods. Our goal was to trace the convergence of thalamic, commissural, and corticocortical information upon two tonotopic fields in the cat, the primary auditory cortex (AI) and the anterior auditory field (AAF). Both fields are among the first cortical levels of processing. After neurophysiological mapping of characteristic frequency, we injected different retrograde tracers at separate, frequency-matched loci in AI and AAF. We found differences in their projections that support the notion of largely segregated parallel processing streams in the auditory thalamus and cerebral cortex. In each field, ipsilateral cortical input amounts to ∼70% of the number of cells projecting to an isofrequency domain, while commissural and thalamic sources are each ∼15%. Labeled thalamic and cortical neurons were concentrated in tonotopically predicted regions and in smaller loci far from their spectrally predicted positions. The few double-labeled thalamic neurons (<2%) are consistent with the hypothesis that information to AI and AAF travels along independent processing streams despite widespread regional overlap of thalamic input sources. Double labeling is also sparse in both the corticocortical and commissural systems (∼1%), confirming their independence. The segregation of frequency-specific channels within thalamic and cortical systems is consistent with a model of parallel processing in auditory cortex. The global convergence of cells outside the targeted frequency domain in AI and AAF could contribute to context-dependent processing and to intracortical plasticity and reorganization.

Properties of sequence-sensitive neurons in primary auditory cortex of cats were explored in detail. Stimuli were sequences of two tones, in which the frequency and intensity of the first tone and the temporal separation between the first and second, or probe, tone were parametrically varied. After presentation of the first tone, the responses of 32 single units and 48 multiunits to the probe tone were found to be enhanced up to 140-5270% (median 340%) above the response obtained in the single-tone condition. Probe tone enhancement was induced from a considerable number of sequence conditions and depended on the frequency and intensity of the first tone and on the temporal separation between the onsets of the first and the probe tone. On average, the maximally enhanced response occurred when the first tone was 1 octave below or above the probe tone and its intensity was 14 dB louder than the probe tone. The most effective temporal separation of the tones for an enhancement effect was ∼100 ms. The range of enhancing tones was largely outside the excitatory tuning curve of a neuron. Results extend previous findings of properties of sequence-sensitive neurons in the auditory cortex of echolocating bats and non-echolocating mammals, and suggest that sequence-sensitive neurons are quite common and involved in the cortical representation of spectrotemporal patterns of acoustic signals.

Auditory cortical columns have been studied for decades, but intracolumnar processing in auditory cortex is still poorly understood, relative to what is known about such processsing in visual cortex and somatosensory cortex. While there are certainly striking similarities in cortical structure across the modalities, investigations of auditory cortex anatomy and synaptic physiology have also found important differences from the columnar organization of other sensory cortices. In vitro and in vivo studies of thalamocortical transformations in the auditory system have begun to reveal the functional significance of these differences, and have defined the earliest stages of auditory cortical processing. However, the question of what transformations are performed within auditory cortical columns remains unresolved. Attempts to find laminar differences in auditory cortex, which could provide the key to understanding columnar transformations, have so far produced contradictory and inconclusive results. Direct analogies to primary visual and somatic sensory cortices would suggest that response properties such as bandwidth, inhibitory sideband structure, preferred modulation rate and modulation phase sensitivity might vary across layers in auditory cortex. While such analogies could prove useful as guidelines for future research, the best hope for understanding auditory columnar transformations may lie instead with a more modality-specific, functional approach.

Understanding the neural mechanisms of invariant object recognition remains one of the major unsolved problems in neuroscience. A common solution that is thought to be employed by diverse sensory systems is to create hierarchical representations of increasing complexity and tolerance. However, in the mammalian auditory system many aspects of this hierarchical organization remain undiscovered, including the prominent classes of high-level representations (that would be analogous to face selectivity in the visual system or selectivity to bird's own song in the bird) and the dominant types of invariant transformations. Here we review the recent progress that begins to probe the hierarchy of auditory representations, and the computational approaches that can be helpful in achieving this feat.

AI primary auditory cortex BB broadband CF characteristic frequency fMRI functional magnetic resonance imaging IC inferior colliculus MGB medial geniculate body MGBm medial division of the MGB MGBv ventral division of the MGB NB narrowband PFC prefrontal cortex Q 40 inverse bandwidth SPLs sound pressure levels VI primary visual cortex VII second visual cortical area

Auditory cortical maps have been a long-standing focus of studies that assess the expression, mechanisms, and consequences of sensory plasticity. Here we discuss recent progress in understanding how auditory experience transforms spatially organized sound representations at higher levels of the central auditory pathways. New insights into the mechanisms underlying map changes have been achieved and more refined interpretations of various map plasticity effects and their consequences in terms of behavioral corollaries and learning as well as other cognitive aspects have been offered. The systematic organizational principles of cortical sound processing remain a key aspect in studying and interpreting the role of plasticity in hearing.

The theoretical concepts underlying the neural origin of tinnitus are outlined. Several neurophysiological models are reviewed critically and the impact of the pathological ensemble spontaneous activity of the auditory system for the diagnosis and therapy of tinnitus is described in more detail.

There is a growing interest in the use of mice as a model system for species-specific communication. In particular, ultrasonic calls emitted by mouse pups communicate distress, and elicit a search and retrieval response from mothers. Behaviorally, mothers prefer and recognize these calls in two-alternative choice tests, in contrast to pup-naïve females that do not have experience with pups. Here, we explored whether one particular acoustic feature that defines these calls) the repetition rate of calls within a bout) is represented differently in the auditory cortex of these two animal groups. Multiunit recordings in anesthetized CBA ⁄ CaJ mice revealed that: (i) neural entrainment to repeated stimuli extended up to the natural pup call repetition rate (5 Hz) in mothers; but (ii) neurons in naïve females followed repeated stimuli well only at slower repetition rates; and (iii) entrained responses to repeated pup calls were less sensitive to natural pup call variability in mothers than in pup-naïve females. In the broader context, our data suggest that auditory cortical responses to communication sounds are plastic, and that communicative significance is correlated with an improved cortical representation.

Electrophysiological studies in mammal primary auditory cortex have demonstrated neuronal tuning and cortical spatial organization based upon spectral and temporal qualities of the stimulus including: its frequency, intensity, amplitude modulation and frequency modulation. Although communication and other behaviourally relevant sounds are usually complex, most response characterizations have used tonal stimuli. To better understand the mechanisms necessary to process complex sounds, we investigated neuronal responses to a specific class of broadband stimuli, auditory gratings or ripple stimuli, and compared the responses with single tone responses. Ripple stimuli consisted of 150-200 frequency components with the intensity of each component adjusted such that the envelope of the frequency spectrum is sinusoidal. It has been demonstrated that neurons are tuned to specific characteristics of those ripple stimulus including the intensity, the spacing of the peaks, and the location of the peaks and valleys (C. E. Schreiner and B. M. Calhoun, Auditory Neurosci., 1994; 1: 39-61). Although previous results showed that neuronal response strength varied with the intensity and the fundamental frequency of the stimulus, it is shown here that the relative response to different ripple spacings remains essentially constant with changes in the intensity and the fundamental frequency. These findings support a close relationship between pure-tone receptive fields and ripple transfer functions. However, variations of other stimulus characteristics, such as spectral modulation depth, result in non-linear alterations in the ripple transformation. The processing between the basilar membrane and the primary auditory cortex of broadband stimuli appears generally to be non-linear, although specific stimulus qualities, including the phase of the spectral envelope, are processed in a nearly linear manner.

The functional role of correlated neural activity in auditory cortex for the processing of sounds was explored by investigating whether and how cross-correlation parameters are related to receptive ®eld similarities of neurons. Multi-unit activity was recorded simultaneously from several sites of isofrequency domains in primary auditory cortex. At each site various receptive ®eld properties were determined. From the discharges of pairs of clusters, normalized cross-correlation histograms (CCH) were calculated for extended periods of spontaneous activity and for periods with noise-burst stimulation. In both conditions, most CCHs exhibited a symmetrical positivity near the origin of the CCH, a few to several tens of milliseconds wide. Cross-correlation histograms were characterized with two parameters: the correlation strength, which was estimated from the peak correlation, and the correlation width, i.e. the time period of correlated ®ring, which was measured as the width of the positivity at half height. It was found that correlation strength increased and correlation width narrowed with increasing similarity of the receptive ®elds of two clusters. These relationships were observed both in the acoustically-driven and spontaneous conditions. Speci®cally, correlation strength was most strongly associated with similarity in binaural interaction and in temporal response properties such as response onset, response offset and the temporal pattern of the response. Correlation width was predominantly associated with similarity in characteristic frequency, bandwidth and intensity threshold. Results suggest that correlated activity, re¯ecting potential mechanisms involved in the neural computation in auditory cortex, provides a means to evaluate the properties of the functional organization of auditory cortex. Systematic relationships were found between correlation properties and the receptive ®eld-based organization of cortical processing, suggesting that similar general mechanisms are utilized in many parts of the sensory cortex. In particular, the magnitude and/or the time period of synchronized ®ring of neurons is increased if the receptive ®eld properties of the involved neurons are similar.

Individual nuclei of the auditory pathway contribute in a speciWc way to the processing of complex acoustical signals. We investigated the responses of single neurons to typical guinea pig vocalizations (purr, chutter, chirp and whistle) in the ventral part of the medial geniculate body (MGB) of anesthetized guinea pigs. The neuronal and population peristimulus time histograms (PSTHs) reXected the repetition frequency of individual phrases in the calls. The patterns of PSTHs correlated well with the sound temporal envelope in calls with short phrases (purr, chirp). The dominant onset character of the neuronal responses resulted in a lower correlation between the sound envelope and the PSTH pattern in the case of longer calls (chutter and whistle). A time-reversed version of whistle elicited on average a 13% weaker response than did the natural whistle. The rate-characteristic frequency (CF) proWle provided only a coarse representation of the sound frequency spectrum without detailed information about the individual spectral peaks and their relative magnitudes. In comparison with the inferior colliculus (Kuta et al. in J Neurophysiol 90:3794-3808, 2003), the processing of species-speciWc vocalizations in the MGB diVers in: (1) a less precise representation of the temporal envelope in the case of longer calls, but not in the case of calls consisting of one or more short phrases; (2) a less precise rate-CF representation of the spectral envelope in the case of low-frequency calls, but not in the case of broad-band calls; (3) a smaller diVerence between the responses to natural and time-reversed whistle.

We investigated the ability of cats to discriminate differences between vowel-like spectra, assessed their discrimination ability over time, and compared spectral receptive fields in primary auditory cortex (AI) of trained and untrained cats. Animals were trained to discriminate changes in the spectral envelope of a broad-band harmonic complex in a 2-alternative forced choice procedure. The standard stimulus was an acoustic grating consisting of a harmonic complex with a sinusoidally modulated spectral envelope (''ripple spectrum''). The spacing of spectral peaks was conserved at 1, 2, or 2.66 peaks/octave. Animals were trained to detect differences in the frequency location of energy peaks, corresponding to changes in the spectral envelope phase. Average discrimination thresholds improved continuously during the course of the testing from phase-shifts of 96°at the beginning to 44°after 4-6 months of training with a 1 ripple/octave spectral envelope. Responses of AI single units and small groups of neurons to pure tones and ripple spectra were modified during perceptual discrimination training with vowel-like ripple stimuli. The transfer function for spectral envelope frequencies narrowed and the tuning for pure tones sharpened significantly in discriminant versus naïve animals. By contrast, control animals that used the ripple spectra only in a lateralization task showed broader ripple transfer functions and narrower pure-tone tuning than naïve animals.