Macrostructural Changes of the Acoustic Radiation in Humans with Hearing Loss and Tinnitus Revealed with Fixel-Based Analysis.

Age-related hearing loss is the most prevalent sensory impairment in the older adult population and is related to noise-induced damage or age-related deterioration of the peripheral auditory system. Hearing loss may affect the central auditory pathway in the brain, which is a continuation of the peripheral auditory system located in the ear. A debilitating symptom that frequently co-occurs with hearing loss is tinnitus. Strikingly, investigations into the impact of acquired hearing loss, with and without tinnitus, on the human central auditory pathway are sparse. This study used diffusion-weighted imaging (DWI) to investigate changes in the largest central auditory tract, the acoustic radiation, related to hearing loss and tinnitus. Participants with hearing loss, with and without tinnitus, and a control group were included. Both conventional diffusion tensor analysis and higher-order fixel-based analysis were applied. The fixel-based analysis was used as a novel framework providing insight into the axonal density and macrostructural morphologic changes of the acoustic radiation in hearing loss and tinnitus. The results show tinnitus-related atrophy of the left acoustic radiation near the medial geniculate body. This finding may reflect a decrease in myelination of the auditory pathway, instigated by more profound peripheral deafferentation or reflecting a preexisting marker of tinnitus vulnerability. Furthermore, age was negatively correlated with the axonal density in the bilateral acoustic radiation. This loss of fiber density with age may contribute to poorer speech understanding observed in older adults.SIGNIFICANCE STATEMENT Age-related hearing loss is the most prevalent sensory impairment in the older adult population. Older individuals are subject to the cumulative effects of aging and noise exposure on the auditory system. A debilitating symptom that frequently co-occurs with hearing loss is tinnitus: the perception of a phantom sound. In this large DWI-study, we provide evidence that in hearing loss, the additional presence of tinnitus is related to degradation of the acoustic radiation. Additionally, older age was related to axonal loss in the acoustic radiation. It appears that older adults have the aggravating circumstances of age, hearing loss, and tinnitus on central auditory processing, which may partly be because of the observed deterioration of the acoustic radiation with age.

Altered white matter structure in auditory tracts following early monocular enucleation.

PURPOSE: Similar to early blindness, monocular enucleation (the removal of one eye) early in life results in crossmodal behavioral and morphological adaptations. Previously it has been shown that partial visual deprivation from early monocular enucleation results in structural white matter changes throughout the visual system (Wong et al., 2018). The current study investigated structural white matter of the auditory system in adults who have undergone early monocular enucleation compared to binocular control participants. METHODS: We reconstructed four auditory and audiovisual tracts of interest using probabilistic tractography and compared microstructural properties of these tracts to binocularly intact controls using standard diffusion indices. RESULTS: Although both groups demonstrated asymmetries in indices in intrahemispheric tracts, monocular enucleation participants showed asymmetries opposite to control participants in the auditory and A1-V1 tracts. Monocular enucleation participants also demonstrated significantly lower fractional anisotropy in the audiovisual projections contralateral to the enucleated eye relative to control participants. CONCLUSIONS: Partial vision loss from early monocular enucleation results in altered structural connectivity that extends into the auditory system, beyond tracts primarily dedicated to vision.

Auditory brainstem responses after electrolytic lesions in bilateral subdivisions of the medial geniculate body of tree shrews.

This study aimed to establish a tree shrew model of bilateral electrolytic lesions in the medial geniculate body (MGB) to determine the advantages of using a tree shrew model and to assess the pattern of sound processing in tree shrews after bilateral electrolytic damage in different parts of the MGB. The auditory brainstem responses (ABRs) of a normal control group (n = 30) and an electrical damage group (n = 30) were tested at 0 h, 24 h, 48 h, 72 h, 7 days, 15 days, and 30 days after surgery. (1) The bilateral ablations group exhibited a significant increase in the ABR threshold of the electrolytic damage group between pre- and post-operation. (2) There were significant increases in the I-VI latencies at 0 h after MGBd and MGBm lesions and at 24 h after MGBv lesion. (3) The amplitudes of wave VI were significantly decreased at 24 h and 48 h after MGBd lesion, at 72 h and 7 days after MGBm lesion, and at 24 h, 48 h, 72 h, and 7 days after MGBv lesion. (1) The electrolytic damage group suffered hearing loss that did not recover and appeared to be difficult to fully repair after bilateral ablation. (2) The latencies and amplitudes of responses in the MGB following bilateral electrolytic lesion were restored to pre-operation levels after 15-30 days, suggesting that a portion of the central nuclei lesion was reversible. (3) The tree shrew auditory animal model has many advantages compared to other animal models, such as greater complexity of brain structure and auditory nuclei fiber connections, which make the results of this experiment more useful for clinical diagnoses compared with studies using rats and guinea pigs.

Probabilistic Fiber-Tracking Reveals Degeneration of the Contralateral Auditory Pathway in Patients with Vestibular Schwannoma.

BACKGROUND AND PURPOSE: Vestibular schwannomas cause progressive hearing loss by direct damage to the vestibulocochlear nerve. The cerebral mechanisms of degeneration or plasticity are not well-understood. Therefore, the goal of our study was to show the feasibility of probabilistic fiber-tracking of the auditory pathway in patients with vestibular schwannomas and to compare the ipsi- and contralateral volume and integrity, to test differences between the hemispheres. MATERIALS AND METHODS: Fifteen patients with vestibular schwannomas were investigated before surgery. Diffusion-weighted imaging (25 directions) was performed on a 3T MR imaging system. Probabilistic tractography was performed for 3 partial sections of the auditory pathway. Volume and fractional anisotropy were determined and compared ipsilaterally and contralaterally. The laterality ratio was correlated with the level of hearing loss. RESULTS: Anatomically reasonable tracts were depicted in all patients for the acoustic radiation. Volume was significantly decreased on the hemisphere contralateral to the tumor side for the acoustic radiation and diencephalic section, while fractional anisotropy did not differ significantly. Tracking did not yield meaningful tracts in 3 patients for the thalamocortical section and in 5 patients for the diencephalic section. No statistically significant correlations between the laterality quotient and classification of hearing loss were found. CONCLUSIONS: For the first time, this study showed that different sections of the auditory pathway between the inferior colliculus and the auditory cortex can be visualized by using probabilistic tractography. A significant volume decrease of the auditory pathway on the contralateral hemisphere was observed and may be explained by transsynaptic degeneration of the crossing auditory pathway.

Relationship between M100 Auditory Evoked Response and Auditory Radiation Microstructure in 16p11.2 Deletion and Duplication Carriers.

BACKGROUND AND PURPOSE: Deletion and duplication of chromosome 16p11.2 (BP4-BP5) have been associated with developmental disorders such as autism spectrum disorders, and deletion subjects exhibit a large (20-ms) delay of the auditory evoked cortical response as measured by magnetoencephalography (M100 latency). The purpose of this study was to use a multimodal approach to test whether changes in white matter microstructure are associated with delayed M100 latency. MATERIALS AND METHODS: Thirty pediatric deletion carriers, 9 duplication carriers, and 39 control children were studied with both magnetoencephalography and diffusion MR imaging. The M100 latency and auditory system DTI measures were compared between groups and tested for correlation. RESULTS: In controls, white matter diffusivity significantly correlated with the speed of the M100 response. However, the relationship between structure and function appeared uncoupled in 16p11.2 copy number variation carriers. The alterations to auditory system white matter microstructure in the 16p11.2 deletion only partially accounted for the 20-ms M100 delay. Although both duplication and deletion groups exhibit abnormal white matter microstructure, only the deletion group has delayed M100 latency. CONCLUSIONS: These results indicate that gene dosage impacts factors other than white matter microstructure, which modulate conduction velocity.

Auditory Pathway Features Determined by DTI in Subjects with Unilateral Acoustic Neuroma.

PURPOSE: In the studies concerning the pathology of the auditory pathway in the vestibulocochlear system, few use advanced neuroimaging applications of magnetic resonance imaging (MRI) such as diffusion tensor imaging (DTI). Those who did use reported DTI changes only at the lateral lemniscus and inferior colliculus level. The aim of our study was to determine diffusion changes in the bilateral auditory pathways of subjects with unilateral acoustic neuroma (AN) and compare them with healthy controls. MATERIAL AND METHODS: A total of 15 subjects with unilateral AN along with 11 controls underwent routine MRI and DTI. Apparent diffusion coefficient (ADC) and fractional anisotropy (FA) values obtained from the lateral lemniscus, inferior colliculus, corpus geniculatum mediale, and Heschl's gyrus of the auditory pathway were then compared. RESULTS: The subjects' ADC values measured from the contralateral side were significantly higher at the lateral lemniscus, inferior colliculus, and corpus geniculatum mediale compared with those of the controls. Also, decreased FA values were noted at the inferior colliculus for both the contralateral and ipsilateral sides. The highest ADC values were detected in the inferior colliculus of the auditory pathway. CONCLUSIONS: In the auditory pathway of subjects with AN, the contralateral side is more affected than the ipsilateral side, the most affected region being the inferior colliculus. DTI is an advanced neuroimaging technique that can be used to determine the presence of microstructural damage to the auditory pathway in subjects with AN, whereas conventional MRI is not sensitive enough to detect damage.

Hearing disorders in brainstem lesions.

Auditory processing can be disrupted by brainstem lesions. It is estimated that approximately 57% of brainstem lesions are associated with auditory disorders. However diseases of the brainstem usually involve many structures, producing a plethora of other neurologic deficits, often relegating "auditory symptoms in the background." Lesions below or within the cochlear nuclei result in ipsilateral auditory-processing abnormalities detected in routine testing; disorders rostral to the cochlear nuclei may result in bilateral abnormalities or may be silent. Lesions in the superior olivary complex and trapezoid body show a mixture of ipsilateral, contralateral, and bilateral abnormalities, whereas lesions of the lateral lemniscus, inferior colliculus, and medial geniculate body do not affect peripheral auditory processing and result in predominantly subtle contralateral abnormalities that may be missed by routine auditory testing. In these cases psychophysical methods developed for the evaluation of central auditory function should be employed (e.g., dichotic listening, interaural time perception, sound localization). The extensive connections of the auditory brainstem nuclei not only are responsible for binaural interaction but also assure redundancy in the system. This redundancy may explain why small brainstem lesions are sometimes clinically silent. Any disorder of the brainstem (e.g., neoplasms, vascular disorders, infections, trauma, demyelinating disorders, neurodegenerative diseases, malformations) that involves the auditory pathways and/or centers may produce hearing abnormalities.

Morphometric changes in subcortical structures of the central auditory pathway in mice with bilateral nodular heterotopia.

Malformations of cortical development (MCD) have been observed in human reading and language impaired populations. Injury-induced MCD in rodent models of reading disability show morphological changes in the auditory thalamic nucleus (medial geniculate nucleus; MGN) and auditory processing impairments, thus suggesting a link between MCD, MGN, and auditory processing behavior. Previous neuroanatomical examination of a BXD29 recombinant inbred strain (BXD29-Tlr4(lps-2J)/J) revealed MCD consisting of bilateral subcortical nodular heterotopia with partial callosal agenesis. Subsequent behavioral characterization showed a severe impairment in auditory processing-a deficient behavioral phenotype seen across both male and female BXD29-Tlr4(lps-2J)/J mice. In the present study we expanded upon the neuroanatomical findings in the BXD29-Tlr4(lps-2J)/J mutant mouse by investigating whether subcortical changes in cellular morphology are present in neural structures critical to central auditory processing (MGN, and the ventral and dorsal subdivisions of the cochlear nucleus; VCN and DCN, respectively). Stereological assessment of brain tissue of male and female BXD29-Tlr4(lps-2J)/J mice previously tested on an auditory processing battery revealed overall smaller neurons in the MGN of BXD29-Tlr4(lps-2J)/J mutant mice in comparison to BXD29/Ty coisogenic controls, regardless of sex. Interestingly, examination of the VCN and DCN revealed sexually dimorphic changes in neuronal size, with a distribution shift toward larger neurons in female BXD29-Tlr4(lps-2J)/J brains. These effects were not seen in males. Together, the combined data set supports and further expands the observed co-occurrence of MCD, auditory processing impairments, and changes in subcortical anatomy of the central auditory pathway. The current stereological findings also highlight sex differences in neuroanatomical presentation in the presence of a common auditory behavioral phenotype.

Alteration of glycine receptor immunoreactivity in the auditory brainstem of mice following three months of exposure to radiofrequency radiation at SAR 4.0 W/kg.

The increasing use of mobile communication has triggered an interest in its possible effects on the regulation of neurotransmitter signals. Due to the close proximity of mobile phones to hearing-related brain regions during usage, its use may lead to a decrease in the ability to segregate sounds, leading to serious auditory dysfunction caused by the prolonged exposure to radiofrequency (RF) radiation. The interplay among auditory processing, excitation and inhibitory molecule interactions plays a major role in auditory function. In particular, inhibitory molecules, such a glycine, are predominantly localized in the auditory brainstem. However, the effects of exposure to RF radiation on auditory function have not been reported to date. Thus, the aim of the present study was to investigate the effects of exposure to RF radiation on glycine receptor (GlyR) immunoreactivity (IR) in the auditory brainstem region at 835 MHz with a specific absorption rate of 4.0 W/kg for three months using free-floating immunohistochemistry. Compared with the sham control (SC) group, a significant loss of staining intensity of neuropils and cells in the different subdivisions of the auditory brainstem regions was observed in the mice exposed to RF radiation (E4 group). A decrease in the number of GlyR immunoreactive cells was also noted in the cochlear nuclear complex [anteroventral cochlear nucleus (AVCN), 31.09%; dorsal cochlear nucleus (DCN), 14.08%; posteroventral cochlear nucleus (PVCN), 32.79%] and the superior olivary complex (SOC) [lateral superior olivary nucleus (LSO), 36.85%; superior paraolivary nucleus (SPN), 24.33%, medial superior olivary nucleus (MSO), 23.23%; medial nucleus of the trapezoid body (MNTB), 10.15%] of the mice in the E4 group. Auditory brainstem response (ABR) analysis also revealed a significant threshold elevation of in the exposed (E4) group, which may be associated with auditory dysfunction. The present study suggests that the auditory brainstem region is susceptible to chronic exposure to RF radiation, which may affect the function of the central auditory system.

The vestibulocochlear nerve (VIII).

The vestibulocochlear nerve (8th cranial nerve) is a sensory nerve. It is made up of two nerves, the cochlear, which transmits sound and the vestibular which controls balance. It is an intracranial nerve which runs from the sensory receptors in the internal ear to the brain stem nuclei and finally to the auditory areas: the post-central gyrus and superior temporal auditory cortex. The most common lesions responsible for damage to VIII are vestibular Schwannomas. This report reviews the anatomy and various investigations of the nerve.

Temporal processing in the auditory system: insights from cochlear and auditory midbrain implantees.

Central auditory processing in humans was investigated by comparing the perceptual effects of temporal parameters of electrical stimulation in auditory midbrain implant (AMI) and cochlear implant (CI) users. Four experiments were conducted to measure the following: effect of interpulse intervals on detection thresholds and loudness; temporal modulation transfer functions (TMTFs); effect of duration on detection thresholds; and forward masking decay. The CI data were consistent with a phenomenological model that based detection or loudness decisions on the output of a sliding temporal integration window, the input to which was the hypothetical auditory nerve response to each stimulus pulse. To predict the AMI data, the model required changes to both the neural response input (i.e., midbrain activity to AMI stimuli, compared to auditory nerve activity to CI stimuli) and the shape of the integration window. AMI data were consistent with a neural response that decreased more steeply compared to CI stimulation as the pulse rate increased or interpulse interval decreased. For one AMI subject, the data were consistent with a significant adaptation of the neural response for rates above 200 Hz. The AMI model required an integration window that was significantly wider (i.e., decreased temporal resolution) than that for CI data, the latter being well fit using the same integration window shape as derived from normal-hearing data. These models provide a useful way to conceptualize how stimulation of central auditory structures differs from stimulation of the auditory nerve and to better understand why AMI users have difficulty processing temporal cues important for speech understanding.

New developments in aminoglycoside therapy and ototoxicity.

After almost seven decades in clinical use, aminoglycoside antibiotics still remain indispensible drugs for acute infections and specific indications such as tuberculosis or the containment of pseudomonas bacteria in patients with cystic fibrosis. The review will describe the pathology and pathophysiology of aminoglycoside-induced auditory and vestibular toxicity in humans and experimental animals and explore contemporary views of the mechanisms of cell death. It will also outline the current state of protective therapy and recent advances in the development of aminoglycoside derivatives with low toxicity profiles for antimicrobial treatment and for stop-codon suppression in the attenuation of genetic disorders.

Efectos de la glicina sobre los trastornos de conducción del nervio auditivo en pacientes diabéticos tipo 2 con otoneuropatía / Effects of glycine on auditory evoked potentials among diabetic patients with auditory pathway neuropathy

Background: Glycine inhibits the formation of advanced glycation end products that may cause central and peripheral neuronal damage, affecting also the auditory nerve. Aim: To evaluate the effect of glycine on auditory nerve conduction and hearing level among patients with type 2 diabetes mellitus and auditory neuropathy. Material and Methods: Twenty grams of oral glycine per day were administered during 6 months to 28 type 2 diabetic patients aged 58 ± 6 years, with auditory pathway neuropathy. Hearing tests and evoked otoacustic potentials were performed regularly. Fifteen diabetic patients aged 49 ± 8 years, without auditory nerve neuropathy did not receive glycine and were followed as a control group. Results: Among patients receiving glycine, a significant improvement in left ear audiometry at 125, 250 and 500 Hz and right ear audiometry at 500 Hz, was observed. Waves I, III and V (p= 0.02) of evoked otoacustic potentials improved significantly in the left ear and wave I in the right ear. Among controls, waves V and III of evoked otoacoustic potentials had a significant impairment in the left ear. Conclusions: There was an improvement in auditory evoked potentials in patients receiving glycine and an impairment in untreated control patients.

Histochemical and fluorescent analyses of mitochondrial integrity in chick auditory neurons following deafferentation.

BACKGROUND: Neurons rely exclusively on mitochondrial oxidative phosphorylation to meet cellular energy demands, and disruption of mitochondrial function often precipitates neuronal cell death. Auditory neurons in the chick brain stem (n. magnocellularis [NM]) receive glutamatergic innervation exclusively from ipsilateral eighth nerve afferents. Cochlea removal permanently disrupts afferent support and ultimately triggers apoptotic cell death in 30-50% of ipsilateral, deafferented neurons. Here, we evaluated whether disruption of mitochondrial function occurs during deafferentation-induced neuronal cell death. PURPOSE: To determine whether mitochondrial dysfunction occurs preferentially within dying NM neurons. RESEARCH DESIGN: An experimental study. All birds underwent unilateral cochlea removal. Normally innervated neurons contralateral to surgery served as within-animal controls. STUDY SAMPLE: Hatchling broiler chickens between 8 and 12 days of age served as subjects. A total of 62 birds were included in the study. INTERVENTION: Cochlea removal was performed to deafferent ipsilateral NM neurons and trigger neuronal cell death. DATA COLLECTION AND ANALYSIS: Following unilateral cochlea removal, birds were sacrificed 12, 24, 48, or 168 hours later, and brain tissue was harvested. Brainstems were sectioned through NM and evaluated histochemically for oxidative enzyme reaction product accumulation or reacted for Mitotracker Red, an indicator of mitochondrial membrane potential (m) and cytoplasmic TdT-mediated dUTP Nick-End Labeling (TUNEL), an indicator of cell death. Histochemical staining intensities for three mitochondrial enzymes, succinate dehydrogenase (SDH), cytochrome c oxidase (CO), and ATP synthase (ATPase) were measured in individual neurons and compared in ipsilateral and contralateral NM. Comparisons were made using unpaired t-tests (CO) or Kruskal Wallis one way ANOVA followed by Dunn's post hoc pairwise comparisons (ATPase, SDH). Mitotracker Red tissue was examined qualitatively for the presence of and extent of colocalization between Mitotracker Red and TUNEL label in NM. RESULTS: RESULTS showed global upregulation of all three oxidative enzymes within deafferented NM neurons compared to contralateral, unperturbed NM neurons. In addition, differential SDH and ATPase staining intensities were detected across neurons within the ipsilateral nucleus, suggesting functional differences in mitochondrial metabolism across deafferented NM. Quantitative analyses revealed that deafferented neurons with preferentially elevated SDH and ATPase activities represent the subpopulation destined to die following cochlea removal. In addition, Mitotracker Red accumulated intensely within the subset of deafferented NM neurons that also exhibited cytoplasmic TdT-mediated dUTP Nick-End Labeling (TUNEL) and subsequently died. CONCLUSIONS: Taken together, our results demonstrate that a subset of deafferented NM neurons, presumably those that die, preferentially upregulates SDH, perhaps via the tricarboxylic acid (TCA) cycle. These same neurons undergo ATPase uncoupling and an eventual loss of Deltapsi(m).

[Neuronal degeneration of the auditory nervous center in the mouse model of cochlear ablation].

OBJECTIVE: To study the long-term effect of cochlear ablation on cochlear nucleus (CN). METHODS: A total of 40 BALB/c adult mice were used in the present study. Mice were divided into experimental group and control group at random. In experimental group, the cochlea was destroyed with stainless steel needle under the anatomy microscopy. Mice were tested for ABR thresholds at second day and 4 months after operation to assess hearing sensitivity. Animals were allowed to survive for four months. Histological sections of the cochlear nucleus were evaluated with serial sections stained with Nissl staining and silver staining alternatively. Morphological change in anteroventral cochlear nucleus (AVCN), posteroventral cochlear nucleus (PVCN), dorsal cochlear nucleus (DCN) and octopus cell area (OCA) was observed evaluated four month later after the cochlear ablation. RESULTS: In the experimental group, after operation, early components of ABR couldn't be recognized. The volume of CN was decreased dramatically and the cells were less comparing to the control group. The volume of AVCN after cochlear ablation showed a decline to 22% less than the control group, and the number of neurons also dropped by 25%. In PVCN, the decreased volume by 40% with significant neuronal loss of 47% was observed four month later after the cochlear ablation. And in DCN, the volume shrinking to 24% and the loss of neurons reached to 39%. The most significant change was observed in OCA (octopus cell area), with the neuron numbers, the area and the volume of OCA decreased by 60%, 19%, and 47% respectively. There was a statistically significant difference (P<0.05, Mann-Whitney U test) in the morphological changes between the two groups. CONCLUSION: Neuronal degeneration was observed in cochlear nucleus after four months cochlear ablation.

Pitch discrimination in cerebellar patients: evidence for a sensory deficit.

In the last two decades, a growing body of research showing cerebellar involvement in an increasing number of nonmotor tasks and systems has prompted an expansion of speculations concerning the function of the cerebellum. Here, we tested the predictions of a hypothesis positing cerebellar involvement in sensory data acquisition. Specifically, we examined the effect of global cerebellar degeneration on primary auditory sensory function by means of a pitch discrimination task. The just noticeable difference in pitch between two tones was measured in 15 healthy controls and in 15 high functioning patients afflicted with varying degrees of global cerebellar degeneration caused by hereditary, idiopathic, paraneoplastic, or postinfectious pancerebellitis. Participants also performed an auditory detection task assessing sustained attention, a test of verbal auditory working memory, and an audiometric test. Patient pitch discrimination thresholds were on average five and a half times those of controls and were proportional to the degree of cerebellar ataxia assessed independently. Patients and controls showed normal hearing thresholds and similar performance in control tasks in sustained attention and verbal auditory working memory. These results suggest there is an effect of cerebellar degeneration on primary auditory function. The findings are consistent with other recent demonstrations of cerebellar-related sensory impairments, and with robust cerebellar auditorily evoked activity, confirmed by quantitative meta-analysis, across a range of functional neuroimaging studies dissociated from attention, motor, affective, and cognitive variables. The data are interpreted in the context of a sensory hypothesis of cerebellar function.

A model for auditory brain stem implants: bilateral surgical deafferentation of the cochlear nuclei in the macaque monkey.

BACKGROUND: Patients with extensive bilateral lesions of the auditory nerve have a profound and irreversible sensorineural hearing loss (SNHL), which can only be overcome with individually-fitted auditory brain stem implants that directly stimulate the cochlear nuclei. Despite the enormous potential of this increasingly applied treatment, the auditory performance of many implanted patients is limited, and the variability between cases hinders a complete understanding of the role played by the multiple parameters related to the efficacy of the implant. OBJECTIVES: To mimic the condition of patients who have bilateral lesions of the auditory nerve, we developed an experimental model of bilateral deafferentation of the cochlear nuclei by surgical transection of the cochlear nerves of adult primates. MATERIALS AND METHODS: We performed bilateral transection of the cochlear nerves of six adult, healthy, male captive-bred macaques (Macaca fascicularis). Before surgery, brain stem auditory evoked potentials were recorded. The histological material obtained from these animals was compared with similarly processed sections from seven macaques with intact cochlear nerves. The surgical technique, similar to that used in human neuro-otology, combined a labyrinthectomy and a neurectomy of the cochlear nerves, and caused deafness. We analyzed immunocytochemically the expression in cochlear nerve fibers of neurofilaments (SMI-32), and cytosolic calcium binding proteins calretinin, parvalbumin and calbindin, and also applied a histochemical reaction for acetylcholinesterase. RESULTS: None of the primates had any major complications due to the surgical procedure. The lesions produced massive anterograde degeneration of the cochlear nerves, evidenced by marked gliosis and by loss of both type I fibers (which in this species are immunoreactive for calretinin, parvalbumin and neurofilaments) and type II fibers (which are acetylcholinesterase positive). The model of surgical transection described herein causes extensive damage to the cochlear nerves while leaving the cochlea intact, thus mimicking the condition of patients with profound SNHL due to bilateral cochlear nerve degeneration. CONCLUSIONS: The phylogenetic proximity of primates to humans, and the paramount advantage of close anatomical and physiological similarities, allowed us to use the same surgical technique applied to human patients, and to perform a thorough evaluation of the consequences of neurectomy. Thus, bilateral surgical deafferentation of the macaque cochlear nuclei may constitute an advantageous model for study of auditory brain stem implants.

Evidence of functional connectivity between auditory cortical areas revealed by amplitude modulation sound processing.

The human auditory cortex includes several interconnected areas. A better understanding of the mechanisms involved in auditory cortical functions requires a detailed knowledge of neuronal connectivity between functional cortical regions. In human, it is difficult to track in vivo neuronal connectivity. We investigated the interarea connection in vivo in the auditory cortex using a method of directed coherence (DCOH) applied to depth auditory evoked potentials (AEPs). This paper presents simultaneous AEPs recordings from insular gyrus (IG), primary and secondary cortices (Heschl's gyrus and planum temporale), and associative areas (Brodmann area [BA] 22) with multilead intracerebral electrodes in response to sinusoidal modulated white noises in 4 epileptic patients who underwent invasive monitoring with depth electrodes for epilepsy surgery. DCOH allowed estimation of the causality between 2 signals recorded from different cortical sites. The results showed 1) a predominant auditory stream within the primary auditory cortex from the most medial region to the most lateral one whatever the modulation frequency, 2) unidirectional functional connection from the primary to secondary auditory cortex, 3) a major auditory propagation from the posterior areas to the anterior ones, particularly at 8, 16, and 32 Hz, and 4) a particular role of Heschl's sulcus dispatching information to the different auditory areas. These findings suggest that cortical processing of auditory information is performed in serial and parallel streams. Our data showed that the auditory propagation could not be associated to a unidirectional traveling wave but to a constant interaction between these areas that could reflect the large adaptive and plastic capacities of auditory cortex. The role of the IG is discussed.

Superior longitudinal fasciculus subserves vestibular network in humans.

Vestibular function is known to be represented in a large-scale network within the brain. Although much is known about the topography of this cortical network, the subcortical anatomo-functional connectivity has received less attention. We present three patients operated on while conscious for cerebral low-grade gliomas, in which we elicited vestibular symptoms during subcortical stimulation. Anatomo-functional correlations between postoperative imaging and intraoperative findings suggest the involvement of the superior longitudinal fasciculus in the spreading of the vestibular symptoms. We argue that this fasciculus plays a major role in the functional connectivity of the areas involved in the complex multimodal network that controls vestibular function.

Magnetic resonance imaging findings in the auditory pathway of patients with sudden deafness.

OBJECTIVES: The objectives of this study were to evaluate magnetic resonance imaging (MRI) findings of patients with sudden sensorineural hearing loss (SSNHL) and to grade the findings based on their clinical importance. STUDY DESIGN: A prospective clinical study. SETTING: A tertiary referral center (university hospital). PATIENTS: MRI findings of 82 consecutive patients with SSNHL fulfilling the inclusion criteria. MAIN OUTCOME MEASURES: We studied 1.0-T MR images that were analyzed by one experienced neuroradiologist. RESULTS: Of the six cases (7%) in which clearly hearing loss was obviously associated with the observed pathology, four patients had an acoustic neuroma in the internal auditory canal or cerebellopontine angle, one patient had changes at the level of pons, and one patient had an obliterated internal carotid artery. Of the six other patients (7%) in which MRI revealed changes that suggest a possible etiology to hearing loss, two patients showed a demyelinating process and four patients showed blood vessel abnormalities such as caroticocavernous fistula, abnormally locating vertebral or basilar artery, and a venous angioma. CONCLUSIONS: Enhanced MR imaging seems to be a useful examination in patients with SSNHL. The aim should not be only to exclude specific retrocochlear etiologies, but by appropriate techniques, MRI could reveal both peripheral and central abnormalities.