Auditory Oddball Responses Across the Schizophrenia-Bipolar Spectrum and Their Relationship to Cognitive and Clinical Features.

OBJECTIVE: Neural activations during auditory oddball tasks may be endophenotypes for psychosis and bipolar disorder. The authors investigated oddball neural deviations that discriminate multiple diagnostic groups across the schizophrenia-bipolar spectrum (schizophrenia, schizoaffective disorder, psychotic bipolar disorder, and nonpsychotic bipolar disorder) and clarified their relationship to clinical and cognitive features. METHODS: Auditory oddball responses to standard and target tones from 64 sensor EEG recordings were compared across patients with psychosis (total N=597; schizophrenia, N=225; schizoaffective disorder, N=201; bipolar disorder with psychosis, N=171), patients with bipolar disorder without psychosis (N=66), and healthy comparison subjects (N=415) from the second iteration of the Bipolar-Schizophrenia Network for Intermediate Phenotypes (B-SNIP2) study. EEG activity was analyzed in voltage and in the time-frequency domain (low, beta, and gamma bands). Event-related potentials (ERPs) were compared with those from an independent sample collected during the first iteration of B-SNIP (B-SNIP1; healthy subjects, N=211; psychosis group, N=526) to establish the repeatability of complex oddball ERPs across multiple psychosis syndromes (r values >0.94 between B-SNIP1 and B-SNIP2). RESULTS: Twenty-six EEG features differentiated the groups; they were used in discriminant and correlational analyses. EEG variables from the N100, P300, and low-frequency ranges separated the groups along a diagnostic continuum from healthy to bipolar disorder with psychosis/bipolar disorder without psychosis to schizoaffective disorder/schizophrenia and were strongly related to general cognitive function (r=0.91). P50 responses to standard trials and early beta/gamma frequency responses separated the bipolar disorder without psychosis group from the bipolar disorder with psychosis group. P200, N200, and late beta/gamma frequency responses separated the two bipolar disorder groups from the other groups. CONCLUSIONS: Neural deviations during auditory processing are related to psychosis history and bipolar disorder. There is a powerful transdiagnostic relationship between severity of these neural deviations and general cognitive performance. These results have implications for understanding the neurobiology of clinical syndromes across the schizophrenia-bipolar spectrum that may have an impact on future biomarker research.

Functional magnetic resonance imaging of enhanced central auditory gain and electrophysiological correlates in a behavioral model of hyperacusis.

Hyperacusis is a debilitating hearing condition in which normal everyday sounds are perceived as exceedingly loud, annoying, aversive or even painful. The prevalence of hyperacusis approaches 10%, making it an important, but understudied medical condition. To noninvasively identify the neural correlates of hyperacusis in an animal model, we used sound-evoked functional magnetic resonance imaging (fMRI) to locate regions of abnormal activity in the central nervous system of rats with behavioral evidence of hyperacusis induced with an ototoxic drug (sodium salicylate, 250 mg/kg, i.p.). Reaction time-intensity measures of loudness-growth revealed behavioral evidence of salicylate-induced hyperacusis at high intensities. fMRI revealed significantly enhanced sound-evoked responses in the auditory cortex (AC) to 80 dB SPL tone bursts presented at 8 and 16 kHz. Sound-evoked responses in the inferior colliculus (IC) were also enhanced, but to a lesser extent. To confirm the main results, electrophysiological recordings of spike discharges from multi-unit clusters were obtained from the central auditory pathway. Salicylate significantly enhanced tone-evoked spike-discharges from multi-unit clusters in the AC from 4 to 30 kHz at intensities ≥60 dB SPL; less enhancement occurred in the medial geniculate body (MGB), and even less in the IC. Our results demonstrate for the first time that non-invasive sound-evoked fMRI can be used to identify regions of neural hyperactivity throughout the brain in an animal model of hyperacusis.

A 7 Tesla fMRI investigation of human tinnitus percept in cortical and subcortical auditory areas.

Tinnitus is a clinical condition defined by hearing a sound in the absence of an objective source. Early experiments in animal models have suggested that tinnitus stems from an alteration of processing in the auditory system. However, translating these results to humans has proven challenging. One limiting factor has been the insufficient spatial resolution of non-invasive measurement techniques to investigate responses in subcortical auditory nuclei, like the inferior colliculus and the medial geniculate body (MGB). Here we employed ultra-high field functional magnetic resonance imaging (UHF-fMRI) at 7 Tesla to investigate the frequency-specific processing in sub-cortical and cortical regions in a cohort of six tinnitus patients and six hearing loss matched controls. We used task-based fMRI to perform tonotopic mapping and compared the magnitude and tuning of frequency-specific responses between the two groups. Additionally, we used resting-state fMRI to investigate the functional connectivity. Our results indicate frequency-unspecific reductions in the selectivity of frequency tuning that start at the level of the MGB and continue in the auditory cortex, as well as reduced thalamocortical and cortico-cortical connectivity with tinnitus. These findings suggest that tinnitus may be associated with reduced inhibition in the auditory pathway, potentially leading to increased neural noise and reduced functional connectivity. Moreover, these results indicate the relevance of high spatial resolution UHF-fMRI for the investigation of the role of sub-cortical auditory regions in tinnitus.

Bilateral bone conduction stimulation provides reliable binaural cues for localization.

This study aimed to characterize binaural hearing abilities with bone conduction stimulation in simulated conductive hearing loss. Bone conduction hearing devices (BCDs) are a common method of rehabilitating conductive hearing loss. However, little is known about the access these devices provide to binaural cues. To study the ability of BCDs to restore access to binaural cues in conductive loss, normal hearing listeners were plugged unilaterally and bilaterally and localization ability was assessed using a non-surgical BCD attached to the mastoid/s via an adhesive (MED-EL, Corp). The results demonstrate that 1) application of the BCD in simulated unilateral conductive hearing loss does not restore access to binaural cues, evidenced by poor localization abilities. 2) bilateral application of BCDs in simulated bilateral conductive hearing loss provides access to binaural cues, 2) unilateral application of BCDs in simulated bilateral conductive hearing loss disrupts these cues and impairs localization performance, The transcutaneous stimulation of the adhesive BCD resulted in decreased access to sound compared to the normal open ear, resulting in asymmetries in aided versus non-aided hearing thresholds. Symmetrical hearing results in improved localization abilities, while asymmetric hearing disrupts sound localization abilities.

Impaired Subcortical Detection of Auditory Changes in Schizophrenia but Not in Major Depression.

The mismatch negativity is a cortical response to auditory changes and its reduction is a consistent finding in schizophrenia. Recent evidence revealed that the human brain detects auditory changes already at subcortical stages of the auditory pathway. This finding, however, raises the question where in the auditory hierarchy the schizophrenic deficit first evolves and whether the well-known cortical deficit may be a consequence of dysfunction at lower hierarchical levels. Finally, it should be resolved whether mismatch profiles differ between schizophrenia and affective disorders which exhibit auditory processing deficits as well. We used functional magnetic resonance imaging to assess auditory mismatch processing in 29 patients with schizophrenia, 27 patients with major depression, and 31 healthy control subjects. Analysis included whole-brain activation, region of interest, path and connectivity analysis. In schizophrenia, mismatch deficits emerged at all stages of the auditory pathway including the inferior colliculus, thalamus, auditory, and prefrontal cortex. In depression, deficits were observed in the prefrontal cortex only. Path analysis revealed that activation deficits propagated from subcortical to cortical nodes in a feed-forward mechanism. Finally, both patient groups exhibited reduced connectivity along this processing stream. Auditory mismatch impairments in schizophrenia already manifest at the subcortical level. Moreover, subcortical deficits contribute to the well-known cortical deficits and show specificity for schizophrenia. In contrast, depression is associated with cortical dysfunction only. Hence, schizophrenia and major depression exhibit different neural profiles of sensory processing deficits. Our findings add to a converging body of evidence for brainstem and thalamic dysfunction as a hallmark of schizophrenia.

Auditory prediction errors and auditory white matter microstructure associated with psychotic-like experiences in healthy individuals.

Our sensory systems actively predict sensory information based on previously learnt patterns, which are continuously updated with information from the actual sensory input via prediction errors. Individuals with schizophrenia consistently show reduced auditory prediction errors as well as altered fractional anisotropy (indicative of white matter changes) in the arcuate fasciculus and the auditory interhemispheric pathway, both of which are auditory white matter pathways associated with prediction errors. However, it is not clear if healthy individuals with psychotic-like experiences exhibit similar deficits. Participants underwent electroencephalography (EEG) recordings while listening to a classical two-tone duration deviant oddball paradigm (n = 103) and a stochastic oddball paradigm (n = 89). A subset of participants (n = 89) also underwent diffusion-weighted magnetic resonance imaging (MRI). Fractional anisotropy (FA), was extracted from the arcuate fasciculi and the auditory interhemispheric pathway. While prediction errors evoked by the classical oddball paradigm failed to reveal significant effects, the stochastic oddball paradigm elicited significant clusters at the typical mismatch negativity time window. Furthermore, we observed that FA of the arcuate fasciculi and auditory interhemispheric pathway significantly improved predictive models of psychotic-like experiences in healthy individuals over and above predictions made by auditory prediction error responses alone. Specifically, we observed that decreasing FA in the auditory interhemispheric pathway and reducing ability to learn stochastic irregularities are associated with increasing CAPE + scores. To the extent that these associations have previously been reported in patients with schizophrenia, the findings from this study suggest that both, auditory prediction errors and white matter changes in the auditory interhemispheric pathway, may have the potential to be translated into early screening markers for psychosis.

Analyzing the FFR: A tutorial for decoding the richness of auditory function.

The frequency-following response, or FFR, is a neurophysiological response to sound that precisely reflects the ongoing dynamics of sound. It can be used to study the integrity and malleability of neural encoding of sound across the lifespan. Sound processing in the brain can be impaired with pathology and enhanced through expertise. The FFR can index linguistic deprivation, autism, concussion, and reading impairment, and can reflect the impact of enrichment with short-term training, bilingualism, and musicianship. Because of this vast potential, interest in the FFR has grown considerably in the decade since our first tutorial. Despite its widespread adoption, there remains a gap in the current knowledge of its analytical potential. This tutorial aims to bridge this gap. Using recording methods we have employed for the last 20 + years, we have explored many analysis strategies. In this tutorial, we review what we have learned and what we think constitutes the most effective ways of capturing what the FFR can tell us. The tutorial covers FFR components (timing, fundamental frequency, harmonics) and factors that influence FFR (stimulus polarity, response averaging, and stimulus presentation/recording jitter). The spotlight is on FFR analyses, including ways to analyze FFR timing (peaks, autocorrelation, phase consistency, cross-phaseogram), magnitude (RMS, SNR, FFT), and fidelity (stimulus-response correlations, response-to-response correlations and response consistency). The wealth of information contained within an FFR recording brings us closer to understanding how the brain reconstructs our sonic world.

Choice of test stimulus matters for pitch matching performance: Comparison between pure tone and narrow band noise.

Chronic tinnitus, a symptom of high prevalence, is a persistent hearing sensation in the absence of an external sound source. Recent electrophysiological studies indicate that tinnitus generation is to a high degree the result of maladaptive plasticity in the central auditory pathway. The pitch of the tinnitus sensation can be assessed by performing a pitch matching procedure. In the most frequent "tonal tinnitus" type pure tones are used as test stimuli. However, in the case of tonal tinnitus not a single malfunctioning neuron, but rather a population of neighbouring neurons is involved in the generation process of tinnitus and patients typically perceive their tinnitus as a sound having a prominent centre frequency with some spectral extent. Thus, the question arises, why not to use narrow band noise (NBN) instead of pure tones as test stimuli in pitch matching procedures? To investigate this, we first evaluated the pitch matching performance of healthy subjects. In a recursive two alternative choice testing, driven by a computer based automated procedure, the subjects were asked to match the pitch of two sounds. In a crosswise design, NBNs and pure tones were used both as target and as test stimuli. We were able to show that across all four possible combinations the pitch matching performance was least favourable when a sinusoidal sound had to be matched to an NBN target. Even though matching two sinusoidal sounds results in the lowest error, considering that the tinnitus percept typically includes some spectral extent, an NBN should be preferably used as a test stimulus against a pure tone.

Why and how music can be used to rehabilitate and develop speech and language skills in hearing-impaired children.

This paper presents evidence for a strong connection between the development of speech and language skills and musical activities of children and adolescents with hearing impairment and/or cochlear implants. This conclusion is partially based on findings for typically hearing children and adolescents, showing better speech and language skills in children and adolescents with musical training, and importantly, showing increases of speech and language skills in children and adolescents taking part in musical training. Further, studies of hearing-impaired children show connections between musical skills, involvement in musical hobbies, and speech and language skills. Even though the field is still lacking large-scale randomised controlled trials on the effects of musical interventions on the speech and language skills of children and adolescents with hearing impairments and cochlear implants, the current evidence seems enough to urge speech therapists, music therapists, music teachers, parents, and children and adolescents with hearing impairments and/or cochlear implants to start using music for enhancing speech and language skills. For this reason, we give our recommendations on how to use music for language skill enhancement in this group.

Dynamic Changes of Functional Neuronal Activities Between the Auditory Pathway and Limbic Systems Contribute to Noise-Induced Tinnitus with a Normal Audiogram.

Tinnitus is thought to be triggered by aberrant neural activity in the central auditory pathway and is often accompanied by comorbidities of emotional distress and anxiety, which imply maladaptive functional connectivity to limbic structures, such as the amygdala and hippocampus. Tinnitus patients with normal audiograms can also have accompanying anxiety and depression, clinically. To test the role of functional connectivity between the central auditory pathway and limbic structures in patients with tinnitus with normal audiograms, we developed a murine noise-induced tinnitus model with a temporary threshold shift (TTS). Tinnitus mice exhibited reduced auditory brainstem response wave I amplitude, and an enhanced wave IV amplitude and wave IV/I amplitude ratio, as compared with control and non-tinnitus mice. Resting-state functional magnetic resonance imaging (fMRI) was used to identify abnormal connectivity of the amygdala and hippocampus and to determine the relationship with tinnitus characteristics. We found increased fMRI responses with amplitude of low-frequency fluctuation (ALFF) in the auditory cortex and decreased ALFF in the amygdala and hippocampus at day 1, but decreased ALFF in the auditory cortex and increased ALFF in the amygdala at day 28 post-noise exposure in tinnitus mice. Decreased functional connectivity between auditory brain regions and limbic structures was demonstrated at day 28 in tinnitus mice. Therefore, aberrant neural activities in tinnitus mice with TTS involved not only the central auditory pathway, but also limbic structures, and there was maladaptive functional connectivity between the central auditory pathway and limbic structures, such as the amygdala and hippocampus.

Auditory localization accuracy and auditory spatial discrimination in children with auditory processing disorders.

The present study investigated spatial hearing in children aged 6-12 years diagnosed with Auditory Processing Disorders (APD) and compared their results to those of a group of control children matched in age. Sound source localization accuracy was quantified using an absolute localization task and sound source discrimination by measuring the minimum audible angle. Low- and high-frequency noise bursts were presented from eight loudspeaker positions in the left and right hemifields (0°, 30, 60°, and 90° azimuth). Median absolute localization accuracy did not differ between children with APD and control children. However, the intra-individual variability of pointing behavior was higher for children with APD. In contrast, children with APD had significantly higher minimum audible angle thresholds than control children. These findings show that APD impairs sound source discrimination, but does not affect the median relationship between actual and judged sound source locations.

Residual inhibition: From the putative mechanisms to potential tinnitus treatment.

Neurons in various sensory systems show some level of spontaneous firing in the absence of sensory stimuli. In the auditory system spontaneous firing has been shown at all levels of the auditory pathway from spiral ganglion neurons in the cochlea to neurons of the auditory cortex. This internal "noise" is normal for the system and it does not interfere with our ability to perceive silence or analyze sound. However, this internal noise can be elevated under pathological conditions, leading to the perception of a phantom sound known as tinnitus. The efforts of many research groups, including our own, led to the development of a mechanistic understanding of this process: After cochlear insult the input to the central auditory system becomes markedly reduced. As a result, the neural activity in the central auditory system is enhanced to compensate for this reduced input. Such hyperactivity is hypothesized to be interpreted by the brain as a presence of sound. This implies that suppression of hyperactivity should reduce/eliminate tinnitus. This review explores research from our laboratory devoted to identifying the mechanism underlying residual inhibition of tinnitus, a brief suppression of tinnitus following a sound stimulus. The key mechanisms that govern neural suppression of spontaneous activity in animals closely resemble clinical psychoacoustic findings of residual inhibition (RI) observed in tinnitus patients. This suppression is mediated by metabotropic glutamate receptors (mGluRs). Lastly, drugs targeting mGluRs suppress spontaneous activity in auditory neurons and reduce/eliminate behavioral signs of tinnitus in mice. Thus, these drugs are therapeutically relevant for tinnitus suppression in humans.

Assessment of the efferent auditory system in children with suspected auditory processing disorder: the Middle ear muscle reflex and contralateral inhibition of OAEs.

OBJECTIVE: To determine whether children aged 7 to 12 years with listening difficulties show objective evidence for efferent auditory function based on measurements of medial olivo-cochlear and middle ear muscle reflexes. DESIGN: Click-evoked otoacoustic emissions recorded with and without contralateral broadband noise and ipsilateral and contralateral tonal (1000, 2000 Hz) middle ear muscle reflex thresholds were examined. STUDY SAMPLE: 29 children diagnosed with suspected auditory processing disorder (APD) and a control group of 34 typically developing children participated in this study. RESULTS: Children with suspected APD had poorer performance on auditory processing tests than the control group. Middle ear muscle reflex thresholds were significantly higher at 2000 Hz in the suspected APD group for contralateral stimulation. MOC inhibition effects did not differ between APD and control groups. CONCLUSIONS: This research supports earlier studies showing altered acoustic reflexes in children with APD. No group differences were found for the MOC reflex measures, consistent with some earlier studies in children with APD.

An improved method of obtaining electrocochleography recordings from Nucleus Hybrid cochlear implant users.

Interest in electrocochleography (ECoG) has recently resurged as a potential tool to assess peripheral auditory function in cochlear implant (CI) users. ECoG recordings can be evoked using acoustic stimulation and recorded from an extra- or intra-cochlear electrode in CI users. Recordings reflect contributions from cochlear hair cells and the auditory nerve. We recently demonstrated the feasibility of using Custom Sound EP (clinically available software) to record ECoG responses in Nucleus Hybrid CI users with preserved acoustic hearing in the implanted ear (Abbas et al, 2017). While successful, the recording procedures were time intensive, limiting clinical applications. The current report describes how we improved data collection efficiency by writing custom software using Python programming language. The software interfaced with Nucleus Implant Communicator (NIC) routines to record responses from an intracochlear electrode. ECoG responses were recorded in eight CI users with preserved acoustic hearing using Custom Sound EP and the Python-based software. Responses were similar across both recording systems, but the recording time decreased significantly using the Python-based software. Seven additional CI users underwent repeated testing using the Python-based software and showed high test-retest reliability. The improved efficiency and high reliability increases the likelihood of translating intracochlear ECoG to clinical practice.

Surgical Neuromodulation of Tinnitus: A Review of Current Therapies and Future Applications.

INTRODUCTION: Tinnitus is the conscious perception of an auditory sensation in the absence of external stimulus. Proposed theories are based on neuroplastic changes that occur due to sensory deprivation. The authors review the relevant literature on functional imaging and neuromodulation of tinnitus and describe potential targets for deep brain stimulation (DBS). MATERIALS AND METHODS: A MEDLINE keyword and Medical Subject Heading term literature search was performed using PubMed for tinnitus, neuromodulation, DBS, transcranial magnetic stimulation, epidural electrode stimulation, intradural electrode stimulation, functional imaging, and connectivity. Data from these reports were extracted and reviewed. RESULTS: Multiple imaging studies are employed to understand the pathophysiology of tinnitus. Abnormal regions and altered connectivity implicated in tinnitus include auditory pathway and limbic structures. Neuromodulation attempts to correct this hyperexcitable state by disrupting these aberrant oscillations and returning activity to baseline. Applied treatment modalities include transcranial magnetic stimulation, epidural/intradural electrode stimulation, and DBS. More recently, modulation of autonomic pathways through vagus nerve stimulation and paired auditory sounds has demonstrated tinnitus improvement via plasticity changes. CONCLUSIONS: DBS shows much promise as a therapeutic option for tinnitus. Stimulation of the auditory pathway, particularly the medial geniculate body, could counteract thalamocortical dysrhythmias and reduce gamma activity implicated in the tinnitus percept. Stimulation of the limbic pathway could decrease attention to and perception of tinnitus. Additional studies, focusing on the involvement of thalamic and limbic structures in the pathophysiology of tinnitus, are needed to support the use of DBS.

Contralateral suppression of human hearing sensitivity in single-sided deaf cochlear implant users.

Cochlear implants (CIs) are being implanted in people with unilateral hearing loss because they can improve speech intelligibility and sound source localization. Though designed to restore the afferent auditory stimulation, the CI possibly restores some efferent effects. The present study aimed at investigating this possibility. Five single-sided deaf CI users with less than 30 dB hearing loss up to 4 kHz in their acoustic ear participated in the study. Absolute thresholds for their acoustic ears were measured for pure tones of 500 and 4000 Hz with durations of 10 and 200 ms in the presence and in the absence of contralateral broadband electrical stimulation (CBES) delivered with the CI. The electrical stimulus consisted of pulse trains (symmetric biphasic pulses with phase duration 36 µs) on all 16 electrodes sequentially stimulated at a rate of 843 Hz. Its intensity was set to sound as loud as broadband noise at 50 or 60 dB SPL in the acoustic ear. Thresholds were measured using a three-interval, three-alternative, forced-choice procedure with a two-down, one-up adaptive rule to estimate the level for 71% correct in the psychometric function. Thresholds measured without the CBES were lower for the longer than for the shorter tones, and the difference was larger at 500 than at 4000 Hz. CBES equivalent to 50 or 60 dB SPL caused significant threshold elevation only for short (10 ms) and low frequency (500 Hz) acoustic tones of 1.2 and 2.2 dB. These increases appear smaller than previously reported for normal hearing listeners in related experiments. These results support the notion that for single-sided deaf CI users, the CI modulates hearing in the acoustic ear. The possible mechanisms that may be contributing this effect are discussed.

A Computational Model of Thalamocortical Dysrhythmia in People With Tinnitus.

Tinnitus is a problem that affects a diverse range of people. One common trait amongst people with tinnitus is the presence of hearing loss, which is apparent in over 90% of the cohort. It is postulated that the remainder of people with tinnitus have hidden hearing loss in the form of cochlear synaptopathy. The loss of hearing sensation is thought to cause a reduction in the bottom-up excitatory signals of the auditory pathway leading to a change in the frequency of thalamocortical oscillations known as thalamocortical dysrhythmia (TCD). The downward shift in oscillatory behavior, characteristic of TCD, has been recorded experimentally but the underlying mechanisms responsible for TCD in tinnitus subjects cannot be directly observed. This paper investigates these underlying mechanisms by creating a biologically faithful model of the auditory periphery and thalamocortical network, called the central auditory processing (CAP) model. The proposed model replicates tinnitus related activity in the presence of hearing loss and hidden hearing loss in the form of cochlear synaptopathy. The results of this paper show that, both the bottom-up and top-down changes are required in the auditory system for tinnitus related hyperactivity to coexist with TCD, contrary to the theoretical model for TCD. The CAP model provides a novel modeling approach to account for tinnitus related activity with and without hearing loss. Moreover, the results provide additional clarity to the understanding of TCD and tinnitus and provide direction for future approaches to treating tinnitus.

Development of electrophysiological and behavioural measures of electrode discrimination in adult cochlear implant users.

The plasticity of the auditory system enables it to adjust to electrical stimulation from cochlear implants (CI). Whilst speech perception may develop for many years after implant activation, very little is known about the changes in auditory processing that underpin these improvements. Such an understanding could help guide interventions that improve hearing performance. In this longitudinal study, we examine how electrode discrimination ability changes over time in newly implanted adult CI users. Electrode discrimination was measured with a behavioural task as well as the spatial auditory change complex (ACC), which is a cortical response to a change in place of stimulation. We show that there was significant improvement in electrode discrimination ability over time, though in certain individuals the process of accommodation was slower and more limited. We found a strong relationship between objective and behavioural measures of electrode discrimination using pass-fail rules. In several cases, the development of the spatial ACC preceded accurate behavioural discrimination. These data provide evidence for plasticity of auditory processing in adult CI users. Behavioural electrode discrimination score but not spatial ACC amplitude was found to be a significant predictor of speech perception. We suggest that it would be beneficial to measure electrode discrimination in CI users and that interventions that exploit the plastic capacity of the auditory system to improve basic auditory processing, could be used to optimize performance in CI users.

Manipulation of Auditory Inputs as Rehabilitation Therapy for Maladaptive Auditory Cortical Reorganization.

Neurophysiological and neuroimaging data suggest that the brains of not only children but also adults are reorganized based on sensory inputs and behaviors. Plastic changes in the brain are generally beneficial; however, maladaptive cortical reorganization in the auditory cortex may lead to hearing disorders such as tinnitus and hyperacusis. Recent studies attempted to noninvasively visualize pathological neural activity in the living human brain and reverse maladaptive cortical reorganization by the suitable manipulation of auditory inputs in order to alleviate detrimental auditory symptoms. The effects of the manipulation of auditory inputs on maladaptively reorganized brain were reviewed herein. The findings obtained indicate that rehabilitation therapy based on the manipulation of auditory inputs is an effective and safe approach for hearing disorders. The appropriate manipulation of sensory inputs guided by the visualization of pathological brain activities using recent neuroimaging techniques may contribute to the establishment of new clinical applications for affected individuals.

Auditory function in Pelizaeus-Merzbacher disease.

Pelizaeus-Merzbacher disease (PMD; MIM 312080), an inherited defect of central nervous system myelin formation, affects individuals in many ways, including their hearing and language abilities. The aim of this study was to assess the auditory abilities in 18 patients with PMD by examining the functional processes along the central auditory pathways using auditory brainstem responses (ABR) and cortical auditory evoked potentials (CAEP) in response to speech sounds. The significant ABR anomalies confirm the existence of dyssynchrony previously described at the level of the brainstem in patients with PMD. Despite the significant auditory dyssynchrony observed at the level of the brainstem, CAEPs were present in most patients, albeit somehow abnormal in terms of morphology and latency, resembling a type of auditory neuropathy spectrum disorder.