MRI compatible MS2 nanoparticles designed to cross the blood-brain-barrier: providing a path towards tinnitus treatment.

Fundamental challenges of targeting specific brain regions for treatment using pharmacotherapeutic nanoparticle (NP) carriers include circumventing the blood-brain-barrier (BBB) and tracking delivery. Angiopep-2 (AP2) has been shown to facilitate the transport of large macromolecules and synthetic nanoparticles across the BBB. Thus, conjugation of AP2 to an MS2 bacteriophage based NP should also permit transport across the BBB. We have fabricated and tested a novel MS2 capsid-based NP conjugated to the ligand AP2. The reaction efficiency was determined to be over 70%, with up to two angiopep-2 conjugated per MS2 capsid protein. When linked with a porphyrin ring, manganese (Mn2+) remained stable within MS2 and was MRI detectable. Nanoparticles were introduced intracerebroventricularly or systemically. Systemic delivery yielded dose dependent, non-toxic accumulation of NPs in the midbrain. Design of a multifunctional MRI compatible NP platform provides a significant step forward for the diagnosis and treatment of intractable brain conditions, such as tinnitus.

Vestibular, balance, microvascular and white matter neuroimaging characteristics of blast injuries and mild traumatic brain injury: Four case reports.

BACKGROUND: Case reports are presented on four Veterans, aged 29-46 years, who complained of chronic dizziness and/or postural instability following blast exposures. Two of the four individuals were diagnosed with mild traumatic brain injury and three of the four were exposed to multiple blasts. Comprehensive vestibular, balance, gait, audiometry and neuroimaging procedures were used to characterize their injuries. CASE REPORT: Vestibular assessment included videonystagmography, rotary chair and cervical and ocular vestibular evoked myogenic potentials. Balance and gait testing included the sensory organization test, preferred gait speed and the dynamic gait index. Audiometric studies included pure tone audiometry and middle-ear measurements. Neuroimaging procedures included high resolution structural magnetic resonance imaging, susceptibility-weighted imaging and diffusion-tensor imaging. FINDINGS: Based on the neuroimaging and vestibular and balance test results, it was found that all individuals had diffuse axonal injuries and all had one or more micro-hemorrhages or vascular anomalies. Three of the four individuals had abnormal vestibular function, all had abnormally slow walking speeds and two had abnormal gait and balance dysfunction. CONCLUSION: The use of contemporary neuroimaging studies in conjunction with comprehensive vestibular and balance assessment provided a better understanding of the pathophysiology and pathoanatomy of dizziness following blast exposures than standard vestibular and balance testing alone.

Altered gait parameters in distracted walking: a bio-evolutionary and prognostic health perspective on passive listening and active responding during cell phone use.

The underpinnings of bipedal gait are reviewed from an evolutionary biology and prognostic health perspective to better understand issues and concerns related to cell phone use during ambulation and under conditions of distraction and interference. We also consider gait-related health issues associated with the fear of or risk of falling and include prognostic dimensions associated with cognitive decline, dementia, and mortality. Data were acquired on 21 healthy young adults without hearing loss, vestibular, balance, otological or neurological dysfunction using a computerized walkway (GAITRite® Walkway System) combined with specialized software algorithms to extract gait parameters. Four experimental conditions and seven temporo-spatial gait parameters were studied: gait velocity, cadence, stride length, ambulatory time, single-support time, double-support time, and step count. Significant main effects were observed for ambulation time, velocity, stride velocity, and double-support time. The greatest impact of distraction and interference occurred during the texting condition, although other significant effects occurred when participants were verbally responding to queries and passively listening to a story. These experimental observations show that relatively simple distraction and interference tasks implemented through the auditory sensory modality can induce significant perturbations in gait while individuals were ambulating and using a cell phone. Herein, emphasis is placed on the use of quantifiable gait parameters in medical, psychological, and audiological examinations to serve as a foundation for identifying and potentially averting gait-related disturbances.

Blast Overpressures as a Military and Occupational Health Concern.

PURPOSE: This tutorial reviews effects of environmental stressors like blast overpressures and other well-known acoustic contaminants (continuous, intermittent, and impulsive noise) on hearing, tinnitus, vestibular, and balance-related functions. Based on the overall outcome of these effects, detailed consideration is given to the health and well-being of individuals. METHOD: Because hearing loss and tinnitus are consequential in affecting quality of life, novel neuromodulation paradigms are reviewed for their positive abatement and treatment-related effects. Examples of clinical data, research strategies, and methodological approaches focus on repetitive transcranial magnetic stimulation (rTMS) and electrical stimulation of the vagus nerve paired with tones (VNSt) for their unique contributions to this area. RESULTS: Acoustic toxicants transmitted through the atmosphere are noteworthy for their propensity to induce hearing loss and tinnitus. Mounting evidence also indicates that high-level rapid onset changes in atmospheric sound pressure can significantly impact vestibular and balance function. Indeed, the risk of falling secondary to loss of, or damage to, sensory receptor cells in otolith organs (utricle and saccule) is a primary reason for this concern. As part of the complexities involved in VNSt treatment strategies, vocal dysfunction may also manifest. In addition, evaluation of temporospatial gait parameters is worthy of consideration based on their ability to detect and monitor incipient neurological disease, cognitive decline, and mortality. CONCLUSION: Highlighting these respective areas underscores the need to enhance information exchange among scientists, clinicians, and caregivers on the benefits and complications of these outcomes.

Missing links in some curious auditory phenomena: a tale from the middle ear.

BACKGROUND: Broadband middle ear power reflectance (BMEPR) is an emerging noninvasive electroacoustic measure that evaluates transmission/reflection properties of the middle ear in high resolution. It is applicable over the entire age continuum and is rapid to perform. However, it remains to be determined if BMEPR is just an incremental step in the evolution of middle ear assessment or a major advance in the way middle ear function can be evaluated. PURPOSE: To evaluate effects of age, gender, ear, and frequency on BMEPR measurements in adults without a history of middle ear disease and to assess whether these factors require consideration in test development; to review how these data may influence active physiologic process within the inner ear; to consider how they reconcile with previously published results; and to suggest applications for future research. RESEARCH DESIGN: Prospective, cross-sectional, multivariate analysis to evaluate the effects of age, gender, ear, and frequency on BMEPR in humans without a history of middle ear disease and no air-bone gaps exceeding 10 dB for any frequency. STUDY SAMPLE: Fifty-six adults in two age groups (Group 1: 18-25 yr, n = 28; Group 2: ≥50 and <66 yr, n = 28). Each age group was stratified by ear and gender in a balanced design. DATA COLLECTION AND ANALYSIS: Pure tone air conduction and bone-conduction audiometry was conducted in a commercial sound booth, using a clinical audiometer with standard earphones enclosed in supra-aural ear cushions, and a standard bone-conduction oscillator and headband to evaluate for air-bone gaps. Broadband middle ear power reflectance was measured using a calibrated, commercially available computer-controlled system that incorporated a high quality probe assembly to transduce stimuli and record acoustic responses from the ear canal. Data were analyzed with a four-way (2 × 2 × 2 × 16) repeated measures analysis-of-variance (ANOVA) to evaluate the effects of age group (young vs. old), gender (male vs. female), ear (left vs. right), and frequency (258 to 5040 Hz) on BMEPR. RESULTS: The ANOVA revealed a significant main effect of frequency. There were also gender × ear, gender × frequency, and age × gender × ear interactions. The three-way, age × gender × ear interaction captured the essence of results and revealed lowest power reflectance values in younger females and for right ears. This trend partially reversed in the older age group where higher power reflectance values were observed only in right ears of older females. CONCLUSIONS: The significant effects of age, gender, ear, and frequency on BMEPR parallel ear- and gender-related differences in hearing sensitivity, ear, and gender differences in the prevalence of spontaneous otoacoustic emissions (OAEs), gender differences in the magnitude of transient evoked OAEs, and ear differences in transient evoked contralateral OAE suppression effects reported in the literature. While original discussions of these aforementioned effects focused primarily on endocochlear and olivocochlear mechanisms, the BMEPR measurements reported herein suggest that middle ear transmission characteristics may also play a role.

Central presbycusis: a review and evaluation of the evidence.

BACKGROUND: The authors reviewed the evidence regarding the existence of age-related declines in central auditory processes and the consequences of any such declines for everyday communication. PURPOSE: This report summarizes the review process and presents its findings. DATA COLLECTION AND ANALYSIS: The authors reviewed 165 articles germane to central presbycusis. Of the 165 articles, 132 articles with a focus on human behavioral measures for either speech or nonspeech stimuli were selected for further analysis. RESULTS: For 76 smaller-scale studies of speech understanding in older adults reviewed, the following findings emerged: (1) the three most commonly studied behavioral measures were speech in competition, temporally distorted speech, and binaural speech perception (especially dichotic listening); (2) for speech in competition and temporally degraded speech, hearing loss proved to have a significant negative effect on performance in most of the laboratory studies; (3) significant negative effects of age, unconfounded by hearing loss, were observed in most of the studies of speech in competing speech, time-compressed speech, and binaural speech perception; and (4) the influence of cognitive processing on speech understanding has been examined much less frequently, but when included, significant positive associations with speech understanding were observed. For 36 smaller-scale studies of the perception of nonspeech stimuli by older adults reviewed, the following findings emerged: (1) the three most frequently studied behavioral measures were gap detection, temporal discrimination, and temporal-order discrimination or identification; (2) hearing loss was seldom a significant factor; and (3) negative effects of age were almost always observed. For 18 studies reviewed that made use of test batteries and medium-to-large sample sizes, the following findings emerged: (1) all studies included speech-based measures of auditory processing; (2) 4 of the 18 studies included nonspeech stimuli; (3) for the speech-based measures, monaural speech in a competing-speech background, dichotic speech, and monaural time-compressed speech were investigated most frequently; (4) the most frequently used tests were the Synthetic Sentence Identification (SSI) test with Ipsilateral Competing Message (ICM), the Dichotic Sentence Identification (DSI) test, and time-compressed speech; (5) many of these studies using speech-based measures reported significant effects of age, but most of these studies were confounded by declines in hearing, cognition, or both; (6) for nonspeech auditory-processing measures, the focus was on measures of temporal processing in all four studies; (7) effects of cognition on nonspeech measures of auditory processing have been studied less frequently, with mixed results, whereas the effects of hearing loss on performance were minimal due to judicious selection of stimuli; and (8) there is a paucity of observational studies using test batteries and longitudinal designs. CONCLUSIONS: Based on this review of the scientific literature, there is insufficient evidence to confirm the existence of central presbycusis as an isolated entity. On the other hand, recent evidence has been accumulating in support of the existence of central presbycusis as a multifactorial condition that involves age- and/or disease-related changes in the auditory system and in the brain. Moreover, there is a clear need for additional research in this area.

Lack of a coherent theory limits the diagnostic and prognostic value of the (central) auditory processing disorder: a theoretical and clinical perspective.

PURPOSE OF REVIEW: To consider pertinent issues towards developing a coherent theory of the auditory processing disorder (APD). By identifying the conceptual and methodological shortcomings that have thwarted development in this area for decades, we propose solutions to achieve a veridical endpoint to advance the field. RECENT FINDINGS: Concerted efforts in the theoretical, experimental, and clinical domains have focused on validating the APD by demonstrating the " modality specificity " of the deficit. The importance of this conceptual framework is the delineation of auditory-perceptual dysfunctions from more generalized " supra modal" deficits, like those related to attention, memory, and language. Because contemporary schemata have limited the assessment of APD to auditory tasks alone ( unimodal testing), functional dissociations cannot be established, indeterminate diagnoses are problematic, and progress remains unduly constrained. The use of matched tasks in multiple sensory modalities is advocated as a diagnostic imperative to remedy this deficiency. SUMMARY: Themes covered by this review include the need to develop a coherent theory of APD, to identify and limit factors which confound a valid diagnosis, and to validate the diagnosis by demonstrating the " modality specificity " of the deficit. Without an obligatory theoretical designation, the APD will remain as an obscure and controversial entity, limited to indeterminate test results and misdiagnoses.

The mitochondrial connection in auditory neuropathy.

'Auditory neuropathy' (AN), the term used to codify a primary degeneration of the auditory nerve, can be linked directly or indirectly to mitochondrial dysfunction. These observations are based on the expression of AN in known mitochondrial-based neurological diseases (Friedreich's ataxia, Mohr-Tranebjærg syndrome), in conditions where defects in axonal transport, protein trafficking, and fusion processes perturb and/or disrupt mitochondrial dynamics (Charcot-Marie-Tooth disease, autosomal dominant optic atrophy), in a common neonatal condition known to be toxic to mitochondria (hyperbilirubinemia), and where respiratory chain deficiencies produce reductions in oxidative phosphorylation that adversely affect peripheral auditory mechanisms. This body of evidence is solidified by data derived from temporal bone and genetic studies, biochemical, molecular biologic, behavioral, electroacoustic, and electrophysiological investigations.

Dichotic and dichoptic digit perception in normal adults.

BACKGROUND: Verbally based dichotic-listening experiments and reproduction-mediated response-selection strategies have been used for over four decades to study perceptual/cognitive aspects of auditory information processing and make inferences about hemispheric asymmetries and language lateralization in the brain. Test procedures using dichotic digits have also been used to assess for disorders of auditory processing. However, with this application, limitations exist and paradigms need to be developed to improve specificity of the diagnosis. Use of matched tasks in multiple sensory modalities is a logical approach to address this issue. Herein, we use dichotic listening and dichoptic viewing of visually presented digits for making this comparison. PURPOSE: To evaluate methodological issues involved in using matched tasks of dichotic listening and dichoptic viewing in normal adults. RESEARCH DESIGN: A multivariate assessment of the effects of modality (auditory vs. visual), digit-span length (1-3 pairs), response selection (recognition vs. reproduction), and ear/visual hemifield of presentation (left vs. right) on dichotic and dichoptic digit perception. STUDY SAMPLE: Thirty adults (12 males, 18 females) ranging in age from 18 to 30 yr with normal hearing sensitivity and normal or corrected-to-normal visual acuity. DATA COLLECTION AND ANALYSIS: A computerized, custom-designed program was used for all data collection and analysis. A four-way repeated measures analysis of variance (ANOVA) evaluated the effects of modality, digit-span length, response selection, and ear/visual field of presentation. RESULTS: The ANOVA revealed that performances on dichotic listening and dichoptic viewing tasks were dependent on complex interactions between modality, digit-span length, response selection, and ear/visual hemifield of presentation. Correlation analysis suggested a common effect on overall accuracy of performance but isolated only an auditory factor for a laterality index. CONCLUSIONS: The variables used in this experiment affected performances in the auditory modality to a greater extent than in the visual modality. The right-ear advantage observed in the dichotic-digits task was most evident when reproduction mediated response selection was used in conjunction with three-digit pairs. This effect implies that factors such as "speech related output mechanisms" and digit-span length (working memory) contribute to laterality effects in dichotic listening performance with traditional paradigms. Thus, the use of multiple-digit pairs to avoid ceiling effects and the application of verbal reproduction as a means of response selection may accentuate the role of nonperceptual factors in performance. Ideally, tests of perceptual abilities should be relatively free of such effects.

Vagus nerve stimulation paired with tones for tinnitus suppression: Effects on voice and hearing.

OBJECTIVE: In individuals with chronic tinnitus, our interest was to determine whether daily low-level electrical stimulation of the vagus nerve paired with tones (paired-VNSt) for tinnitus suppression had any adverse effects on motor-speech production and physiological acoustics of sustained vowels. Similarly, we were also interested in evaluating for changes in pure-tone thresholds, word-recognition performance, and minimum-masking levels. Both voice and hearing functions were measured repeatedly over a period of 1 year. STUDY DESIGN: Longitudinal with repeated-measures. METHODS: Digitized samples of sustained frontal, midline, and back vowels (/e/, /o/, /ah/) were analyzed with computer software to quantify the degree of jitter, shimmer, and harmonic-to-noise ratio contained in these waveforms. Pure-tone thresholds, monosyllabic word-recognition performance, and MMLs were also evaluated for VNS alterations. Linear-regression analysis was the benchmark statistic used to document change over time in voice and hearing status from a baseline condition. RESULTS: Most of the regression functions for the vocal samples and audiometric variables had slope values that were not significantly different from zero. Four of the nine vocal functions showed a significant improvement over time, whereas three of the pure tone regression functions at 2-4 kHz showed some degree of decline; all changes observed were for the left ear, all were at adjacent frequencies, and all were ipsilateral to the side of VNS. However, mean pure-tone threshold changes did not exceed 4.29 dB from baseline and therefore, would not be considered clinically significant. In some individuals, larger threshold shifts were observed. No significant regression/slope effects were observed for word-recognition or MMLs. CONCLUSION: Quantitative voice analysis and assessment of audiometric variables showed minimal if any evidence of adverse effects using paired-VNSt over a treatment period of 1 year. Therefore, we conclude that paired-VNSt is a safe tool for tinnitus abatement in humans without significant side effects. LEVEL OF EVIDENCE: Level IV.

Electrophysiological markers of skill-related neuroplasticity.

Neuroplasticity involved in acquiring a new cognitive skill was investigated with standard time domain event-related potentials (ERPs) of scalp-recorded electroencephalographic (EEG) activity and frequency domain analysis of EEG oscillations looking at the event-related synchronization (ERS) and desynchronization (ERD) of neural activity. Electroencephalographic activity was recorded before and after practice, while participants performed alphabet addition (i.e., E+3=G, true or false?). Participant's performance became automated with practice through a switch in cognitive strategy from mentally counting-up in the alphabet to retrieving the answer from memory. Time domain analysis of the ERPs revealed a prominent positive peak at approximately 300 ms that was not reactive to problem attributes but was reduced with practice. A second prominent positive peak observed at approximately 500 ms was found to be larger after practice, mainly for problems presented with correct answers. Frequency domain spectral analyses yielded two distinct findings: (1) a frontal midline ERS of theta activity that was greater after practice, and (2) a beta band ERD that increased with problem difficulty before, but not after practice. Because the EEG oscillations were not phase locked to the stimulus, they were viewed as being independent of the time domain results. Consequently, use of time and frequency domain analyses provides a more comprehensive account of the underlying electrophysiological data than either method alone. When used in combination with a well-defined cognitive/behavioral paradigm, this approach serves to constrain the interpretations of EEG data and sets a new standard for studying the neuroplasticity involved in skill acquisition.

Repetitive transcranial magnetic stimulation in veterans with debilitating tinnitus: a pilot study.

OBJECTIVE: Available evidence suggests tinnitus arises from excessive spontaneous activity in the left superior temporal gyrus, and repetitive transcranial magnetic stimulation (rTMS) may suppress this activity. Our hypothesis is that rTMS applied to this region would decrease tinnitus complaints in veterans. STUDY DESIGN: Prospective, nonrandomized trial. SUBJECTS AND METHODS: Eight patients with tinnitus received 5 consecutive days of rTMS (0.5 Hz, 20 minutes) to the left temporoparietal area. Tinnitus Handicap Inventory (THI) measures before sessions 1 and 3 and after session 5 were used to evaluate efficacy. RESULTS: Patient 1's THI decreased 40 to 34 to 26, patient 4 reported a subjective improvement, patient 8 withdrew, and the remaining patients reported no improvement. Adverse effects included temporary soreness, restlessness, and photophobia. CONCLUSION: The parameters for this rTMS study are different from those that reported success with its use. With these current parameters, rTMS did not improve tinnitus in veterans. There were no permanent adverse outcomes.

Glutamate is down-regulated and tinnitus loudness-levels decreased following rTMS over auditory cortex of the left hemisphere: A prospective randomized single-blinded sham-controlled cross-over study.

Using a prospective randomized single-blinded sham-controlled cross-over design, we studied the efficacy of low frequency (1-Hz) repetitive transcranial magnetic stimulation (rTMS) over auditory cortex of the left temporal lobe as an experimental treatment modality for noise-induced tinnitus. Pre/post outcome measures for sham vs. active rTMS conditions included differential changes in tinnitus loudness, self-perceived changes in the Tinnitus Handicap Questionnaire (THQ), and neurochemical changes of brain metabolite concentrations using single voxel proton magnetic resonance spectroscopy (1H-MRS) obtained from left and right auditory cortical areas. While no subject in our sample had complete abatement of their tinnitus percept, active but not sham rTMS significantly reduced the loudness level of the tinnitus perception on the order of 4.5 dB; improved subscales in several content areas on the THQ, and down regulated (reduced) glutamate concentrations specific to the auditory cortex of the left temporal lobe that was stimulated. In addition, significant pair-wise correlations were observed among questionnaire variables, metabolite variables, questionnaire-metabolite variables, and metabolite-loudness variables. As part of this correlation analysis, we demonstrate for the first time that active rTMS produced a down regulation in the excitatory neurotransmitter glutamate that was highly correlated (r = 0.77, p < 0.05) with a reduction in tinnitus loudness levels measured psychoacoustically with a magnitude estimation procedure. Overall, this study provides unique information on neurochemical, psychoacoustic, and questionnaire-related profiles which emphasizes the emerging fields of perceptual and cognitive MRS and provides a perspective on a new frontier in auditory and tinnitus-related research.

Applications of magnetic resonance spectroscopy to tinnitus research: initial data, current issues, and future perspectives.

Conducting tinnitus research on humans poses challenges for investigators because of its subjective nature, the complexities involved in establishing underlying generator sites, the diversity of potential causes, and the inherent difficulties in dissociating reactive changes in the central nervous system (CNS), secondary to peripheral hearing loss, from those effects that may be due to tinnitus. One area of considerable interest concerns biomarker development, particularly in the areas of metabolism and biochemistry. Establishing a biomarker or a profile of metabolic and neurobiochemical constituents of tinnitus-related activity within the CNS could be of considerable importance for understanding the fundamental properties of this disorder. Therefore, in an effort to gain greater insight into mechanisms of tinnitus, magnetic resonance spectroscopy (MRS) is being proposed as one of the several tools that can address pertinent issues. Apart from its long-standing use in analytical chemistry and physics, MRS is also being applied with greater frequency in the neurosciences to gain insight into human brain function under normal and pathological states. By considering the history of this method and advances made to date, MRS has the potential to: (1) identify unique in vivo metabolic and neurobiochemical biomarkers associated with tinnitus in specific regions of the CNS, (2) clarify and track disease pathogenesis, (3) monitor short and long-term treatment effects, and (4) serve as a tool in testing of drugs that may be used in treatment of tinnitus.

The importance of modality specificity in diagnosing central auditory processing disorder.

PURPOSE: This article argues for the use of modality specificity as a unifying framework by which to conceptualize and diagnose central auditory processing disorder (CAPD). The intent is to generate dialogue and critical discussion in this area of study. METHOD: Research in the cognitive, behavioral, and neural sciences that relates to the concept of modality specificity was reviewed and synthesized. RESULTS: Modality specificity has a long history as an organizing construct within a diverse collection of mainstream scientific disciplines. The principle of modality specificity was contrasted with the unimodal inclusive framework, which holds that auditory tests alone are sufficient to make the CAPD diagnosis. Evidence from a large body of data demonstrated that the unimodal framework was unable to delineate modality-specific processes from more generalized dysfunction; it lacked discriminant validity and resulted in an incomplete assessment. Consequently, any hypothetical model resulting from incomplete assessments or potential therapies that are based on indeterminate diagnoses are themselves questionable, and caution should be used in their application. CONCLUSIONS: Improving specificity of diagnosis is an imperative core issue to the area of CAPD. Without specificity, the concept has little explanatory power. Because of serious flaws in concept and design, the unimodal inclusive framework should be abandoned in favor of a more valid approach that uses modality specificity.

Quantifying signal-to-noise ratio of mismatch negativity in humans.

Mismatch negativity (MMN) is thought to represent a neurophysiological index of auditory information processing that is independent of attention. Because this measure does not require an overt behavioral response, MMN has potential to evaluate higher order perceptual abilities in infants, young children and difficult-to-test populations, thereby extending results obtained from more basic physiologic and electroacoustic measures (auditory brainstem responses, ABRs; otoacoustic emissions, OAEs). Whereas the basic tenet of MMN is appealing, several issues-of-contention remain to be solved before this event related potential (ERP) can be applicable for routine clinical use. These issues include the consistent identification of MMN within individuals (vs. groups), its stability over time, and its reportedly poor signal-to-noise ratio (SNR). Herein, we focus on the issue of SNR, by comparing and contrasting SNR of MMN with other long latency auditory ERPs.

Expanding the biological basis of tinnitus: crossmodal origins and the role of neuroplasticity.

Tinnitus is most often initiated by modality specific otopathologic disturbances affecting peripheral and central auditory pathways. However, there is growing evidence indicating that the anatomical location generating tinnitus occurs at sites different from the initial pathology. Support for this notion is found in individuals where tinnitus can be triggered or modulated by inputs from other sensory modalities or sensorimotor systems (somatosensory, somatomotor, visual-motor). The use of functional imaging methods combined with psychophysics, detailed physical examinations and questionnaire-based assessments has reinforced and validated these observations. Available data suggest that tinnitus-related crossmodal interactions are more common than previously anticipated. This communication reviews these advancements and suggests that a relatively broad multimodal network of neurons is involved in generating and sustaining the tinnitus perception in some forms of the disorder. Also implicated as part of the tinnitus experience are interactions within large-scale neural networks subserving attention, cognition, and emotion. Incorporating this knowledge into contemporary psychophysiological models will help facilitate the conceptualization of this phantom perception in a more comprehensive manner.

Spectral dynamics of electroencephalographic activity during auditory information processing.

Dynamics of electroencephalographic (EEG) activity during auditory information processing were evaluated in response to changes in stimulus complexity, stimulus discriminability and attention using the oddball paradigm. In comparison to pre-stimulus baseline conditions, auditory stimulation synchronized EEG activity in delta, theta and alpha frequency bands. Event-related synchronization (ERS) effects were greatest at approximately 3 Hz (theta frequency band), and their magnitude depended on stimulus and task demands. Event-related desynchronization (ERD) of EEG activity was observed in the beta frequency band. This effect was greatest at approximately 21 Hz but occurred only for easily discriminable stimuli in attention-related target conditions. Because active discrimination tasks also required a button-press response with the right hand, ERDs involved more complex responses that may be related to a combination of perceptual, motor and cognitive processes. These results demonstrate that oddball and attention-related EEG responses to auditory stimulation could be characterized in the frequency domain. The specific design and analysis features described herein may prove useful since they provide a simple index of the brain's response to stimulation while at the same time provide powerful information not contained in typical time domain analysis.

Separating stimulus-locked and unlocked components of the auditory event-related potential.

A new method is evaluated for separating stimulus-locked and unlocked components of auditory event-related EEG activity. The new method uses a regression based subtraction procedure as a way to account for latency and amplitude variability within individual trials. It was applied using the oddball paradigm under conditions of active and passive listening and analyzed as spectral correlations (normalized differences) between post-stimulus epochs of standard, target or deviant stimulus conditions and silent pre-stimulus baseline activity. The regression-subtraction procedure accounted for a greater amount of variance than a method that uses linear subtraction alone. The major component of the response to auditory stimulation was an event-related synchronization in the delta and theta (2-4 Hz) frequency range. Event-related desynchronizations were also observed in the 10 Hz (alpha/mu) and in the 20-30 Hz (beta) frequency range. The regression based subtraction procedure provides better separation of stimulus-locked and unlocked components of event-related EEG activity then linear subtraction alone. Stimulus-locked and unlocked components show different patterns and topographies of effects related to attention and active discrimination. Studying both stimulus-locked and unlocked components of event-related EEG reactivity in the frequency domain provides a more comprehensive account of dynamic brain activity subserving auditory information processing.

Relationships between otoacoustic emissions and auditory brainstem responses in neonates and young children: a correlation and factor analytical study.

OBJECTIVES: To establish relationships among transient evoked otoacoustic emission (TEOAE) and auditory brainstem response (ABR) variables in a sample of normal hearing neonates and young children, ranging in age from approximately 3 weeks to 4 years. STUDY DESIGN: Retrospective, non-randomized, cross-sectional analysis of clinical data obtained at a tertiary care medical center. METHODS: Pearson product moment and Spearman rank order correlation analyses to evaluate pairwise relationships between TEOAE variables, ABR variables and age; factor analysis, to identify the structural composition and dimensionality of these relationships. RESULTS: Significant pairwise correlations were obtained between variables within each test paradigm (TEOAEs, ABRs) and between ABR absolute and interpeak latencies with age. However, the most striking effect was the absence of strong correlations between ABR and TEOAE variables, indicating that these test measures provide independent information about auditory system integrity and sensitivity. Two factors, accounting for over 55% of the variance, characterized this data set: 1) a frequency-dependent OAE factor, which showed an inverse relation between biologic noise and whole wave percent reproducibility and half-octave band TEOAE amplitudes; and 2) a central nervous system (CNS) maturational factor, which showed an inverse relationship between age and certain absolute and interpeak ABR latency components. CONCLUSIONS: TEOAE and ABR test results provide unique and functionally independent information about normal auditory system integrity and sensitivity. Therefore, a combination of both tests is well suited for use within a pediatric test battery. These results confirm that biologic noise and age at test differentially affect OAE and ABR test measures, and both effects require consideration during data acquisition and interpretation.