Waxholm Space atlas of the rat brain auditory system: Three-dimensional delineations based on structural and diffusion tensor magnetic resonance imaging.

The mammalian auditory system comprises a complex network of brain regions. Interpretations and comparisons of experimental results from this system depend on appropriate anatomical identification of auditory structures. The Waxholm Space (WHS) atlas of the Sprague Dawley rat brain (Papp et al., Neuroimage 97:374-86, 2014) is an open access, three-dimensional reference atlas defined in an ex-vivo magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI) volume. Version 2.0 of the atlas (Kjonigsen et al., Neuroimage 108:441-9, 2015) includes detailed delineations of the hippocampus and several major subcortical regions, but only few auditory structures. To amend this, we have delineated the complete ascending auditory system from the cochlea to the cerebral cortex. 40 new brain structure delineations have been added, and the delineations of 10 regions have been revised based on the interpretation of image features in the WHS rat brain MRI/DTI volumes. We here describe and validate the new delineations in relation to corresponding cell- and myelin-stained histological sections and previous literature. We found it possible to delineate all main regions and the majority of subregions and fibre tracts of the ascending auditory pathway, apart from the auditory cortex, for which delineations were extrapolated from a conventional two-dimensional atlas. By contrast, only parts of the descending pathways were discernible in the template. Version 3.0 of the atlas, with altogether 118 anatomical delineations, is shared via the NeuroImaging Tools and Resources Collaboratory (www.nitrc.org).

Three-Dimensional Analysis of the Fundus of the Human Internal Acoustic Canal.

OBJECTIVES: Documentation of the nerve components in the internal acoustic canal is essential before cochlea implantation surgery. Interpretations may be challenged by wide anatomical variations of the VIIIth nerve and their ramifications. Malformations may further defy proper nerve identification. DESIGN: Using microcomputed tomography, we analyzed the fundus bone channels in an archival collection of 113 macerated human temporal bones and 325 plastic inner molds. Data were subsequently processed by volume-rendering software using a bony tissue algorithm. Three-dimensional reconstructions were made, and through orthogonal sections, the topographic anatomy was established. RESULTS: The technique provided additional information regarding the anatomy of the nerve foramina/channels of the human fundus region, including variations and destinations. Channel anastomosis were found beyond the level of the fundus. A foramen of the transverse crest was identified. CONCLUSIONS: Three-dimensional reconstructions and cropping outlined the bone canals and demonstrated the highly variable VIIIth nerve anatomy at the fundus of the human inner acoustic canal. Myriad channel interconnections suggested an intricate system of neural interactive pathways in humans. Particularly striking was the variable anatomy of the saccule nerve channels. The results may assist in the preoperative interpretation of the VIIIth nerve anatomy.

Identification of cranial nerves near large vestibular schwannomas using superselective diffusion tensor tractography: experience with 23 cases.

BACKGROUND: The preservation of the facial nerve (FN) and acoustic function in large vestibular schwannoma (VS) surgery is challenging because of nerve course uncertainties and morphological deviations. Preoperative diffusion tensor tractography (DTT) has been proposed to predict the FN location. This study was conducted to evaluate the effectiveness of this technique for identifying the FN, cochlear nerve (CN) and trigeminal nerve (TN) in large VSs. METHODS: The study included 23 consecutive patients with VS of Hannover classification T3b to T4b from November 2013 through May 2014. Diffusion tensor images and anatomical images were acquired. The DTT images of the cranial nerves were extracted before surgery for each patient to determine the relationships of these nerves with the tumor. The results were then validated during the tumorectomy. RESULTS: In 21 (91.30%) patients, the location of the FN on the DTT images agreed with the intraoperative findings, including in 2 patients in whom the FN passed through the interface between the parenchyma and the cystic changes and in 3 patients with a membranoid FN. The CN or fibers of unclear function were observed on DTT images in four patients with functional hearing. One penetrating fiber of unknown function was effectively constructed. The TN was accurately detected on the DTT images for all patients. CONCLUSIONS: DTT effectively revealed the location of the FN, including cases in which the FN was membranoid or passed through the interface between an area exhibiting cystic changes and the tumor nodule. Fibers aside from the FN and the TN were revealed by DTT in patients who retained functional hearing. Penetrating fibers were also found using DTT. This technique can be useful during VS resection.

Dorsal location of the cochlear nerve on vestibular schwannoma: preoperative evaluation, frequency, and functional outcome.

The cochlear nerve is most commonly located on the caudoventral portion of the capsule of vestibular schwannomas and rarely on the dorsal portion. In such a condition, total removal of the tumor without cochlear nerve dysfunction is extremely difficult. The purpose of our study was to identify the frequency of this anatomical condition and the status of postoperative cochlear nerve function; we also discuss the preoperative radiological findings. The study involved 114 patients with unilateral vestibular schwannomas operated on via a retrosigmoid (lateral suboccipital) approach. Locations of the cochlear nerve on the tumor capsule were ventral, dorsal, caudal, and rostral. Ventral and dorsal locations were further subdivided into rostral, middle, and caudal third of the tumor capsule. The postoperative cochlear nerve function and preoperative magnetic resonance (MR) findings were reviewed retrospectively. In 56 patients that had useful preoperative hearing, useful hearing was retained in 50.0% (28 of 56) of patients after surgery. The cochlear nerve was located on the dorsal portion of the tumor capsule in four patients (3.5%), and useful hearing was preserved in only one of these patients (25%) in whom the tumor had been partially resected. This tumor-nerve anatomical relationship was identified in all tumors of <2 cm at preoperative MR cisternography. MR cisternography has the potential to identify the tumor-nerve anatomical relationship, especially in small-sized tumors that usually require therapeutic intervention that ensures hearing preservation. Hence, careful evaluation of the preoperative MR cisternography is important in deciding the therapeutic indications.

Clustering is a feature of the spiral ganglion in the basal turn.

OBJECTIVE: To demonstrate the organization of the spiral ganglion in the mammalian species. METHODS: Temporal bone (TB) specimens from man (n = 2), monkey (n = 2), lion (n = 2) and cat (n = 20) were stained, decalcified and dissected according to the Sudan black B method of Rasmussen. These TB specimens were examined under a Zeiss operating microscope and photographed with a Canon 100 camera interfaced with the microscope. RESULTS: Spiral ganglion cells occurred in clusters within Rosenthal's canal in all four species. The location of the clusters was marked by the interface between axon and dendritic bundles as well as groups of ganglion cells. In monkey and man the clusters were more separated than in lion and cat. CONCLUSIONS: These observations indicate that the spiral ganglion forms clusters of neurons within Rosenthal's canal at the basal cochlear turn in the mammals investigated here. The formation of clusters may be related to the principles of neurogenesis.

Anastomoses of the vestibular, cochlear, and facial nerves.

The internal auditory canal (IAC) is 10 to 17 mm in length, and the facial nerve and vestibulocochlear nerve, which consist of the cochlear nerve, the superior vestibular nerve, and the inferior vestibular nerve, run together in the IAC packaged in dura mater. Oort first described the vestibulocochlear anastomoses in 1918, which is important for the understanding of the pathogenesis and pathophysiology of otologic disorders. The current study documents the existence of vestibulofacial and vestibulocochlear neural connections and topographical relationship of the nerves as part of a radiologic evaluation of 73 human temporal bones from brainstem to the lateral portion of IAC.

Projection from the cochlear nucleus to the peripheral vestibule in Wistar rats.

OBJECTIVE: To find morphological evidence of a direct projection from the cochlear nucleus (CN; at the brainstem level) in the auditory system to the peripheral end organs in the vestibular system. METHODS: Experiments were conducted on male Wistar rats (n = 24). Two neuronal tracers were used: (1) 5% molecular probe F-8793 was injected into the unilateral peripheral vestibule and used as a retrograde tracer; (2) PHA-L (Invitrogen L-11270) was injected into the unilateral CN and used as an anterograde tracer. All animals were allowed to recover for 7 days after surgery to facilitate sufficient transportation of the tracers. Subsequently, brainstems in the retrograde group and inner ears in the anterograde group were sliced coronally on a freezing microtome and observed under a fluorescence microscope. RESULTS: After PHA-L injection into the CN, terminal labeling was observed in the peripheral vestibule, especially in the inferior vestibular nerve. The retrograde tracing study showed that the positive cells could be found in the ventral part of the CN. CONCLUSIONS: These results suggest that there is a novel pathway with a consanguineous functional connection between the CN and peripheral vestibule.

Histological considerations of the cleavage plane for preservation of facial and cochlear nerve functions in vestibular schwannoma surgery.

OBJECT: The authors analyzed the tumor capsule and the tumor-nerve interface in vestibular schwannomas (VSs) to define the ideal cleavage plane for maximal tumor removal with preservation of facial and cochlear nerve functions. METHODS: Surgical specimens from 21 unilateral VSs were studied using classical H & E, Masson trichrome, and immunohistochemical staining against myelin basic protein. RESULTS: The authors observed a continuous thin connective tissue layer enveloping the surfaces of the tumors. Some nerve fibers, which were immunopositive to myelin basic protein and considered to be remnants of vestibular nerve fibers, were also identified widely beneath the connective tissue layer. These findings indicated that the socalled "tumor capsule" in VSs is the residual vestibular nerve tissue itself, consisting of the perineurium and underlying nerve fibers. There was no structure bordering the tumor parenchyma and the vestibular nerve fibers. In specimens of tumors removed en bloc with the cochlear nerves, the authors found that the connective tissue layer, corresponding to the perineurium of the cochlear nerve, clearly bordered the nerve fibers and tumor tissue. CONCLUSIONS: Based on these histological observations, complete tumor resection can be achieved by removal of both tumor parenchyma and tumor capsule when a clear border between the tumor capsule and facial or cochlear nerve fibers can be identified intraoperatively. Conversely, when a severe adhesion between the tumor and facial or cochlear nerve fibers is observed, dissection of the vestibular nerve-tumor interface (the subcapsular or subperineurial dissection) is recommended for preservation of the functions of these cranial nerves.

A simulation of chopper neurons in the cochlear nucleus with wideband input from onset neurons.

The unique temporal and spectral properties of chopper neurons in the cochlear nucleus cannot be fully explained by current popular models. A new model of sustained chopper neurons was therefore suggested based on the assumption that chopper neurons receive input both from onset neurons and the auditory nerve (Bahmer and Langner in Biol Cybern 95:4, 2006). As a result of the interaction of broadband input from onset neurons and narrowband input from the auditory nerve, the chopper neurons in our model are characterized by a remarkable combination of sharp frequency tuning to pure tones and faithful periodicity coding. Our simulations show that the width of the spectral integration of the onset neuron is crucial for both the precision of periodicity coding and their resolution of single components of sinusoidally amplitude-modulated sine waves. One may hypothesize, therefore, that it would be an advantage if the hearing system were able to adapt the spectral integration of onset neurons to varying stimulus conditions.

[Functional anatomy of the cochlear nerve and the central auditory system]. / Anatomie fonctionnelle du nerf cochléaire et du système auditif central.

The auditory pathways are a system of afferent fibers (through the cochlear nerve) and efferent fibers (through the vestibular nerve), which are not limited to a simple information transmitting system but create a veritable integration of the sound stimulus at the different levels, by analyzing its three fundamental elements: frequency (pitch), intensity, and spatial localization of the sound source. From the cochlea to the primary auditory cortex, the auditory fibers are organized anatomically in relation to the characteristic frequency of the sound signal that they transmit (tonotopy). Coding the intensity of the sound signal is based on temporal recruitment (the number of action potentials) and spatial recruitment (the number of inner hair cells recruited near the cell of the frequency that is characteristic of the stimulus). Because of binaural hearing, commissural pathways at each level of the auditory system and integration of the phase shift and the difference in intensity between signals coming from both ears, spatial localization of the sound source is possible. Finally, through the efferent fibers in the vestibular nerve, higher centers exercise control over the activity of the cochlea and adjust the peripheral hearing organ to external sound conditions, thus protecting the auditory system or increasing sensitivity by the attention given to the signal.

The Cochlear Spiral Ganglion Neurons: The Auditory Portion of the VIII Nerve.

The VIII nerve is formed by sensory neurons that innervate the inner ear, i.e., the vestibular and the auditory receptors. Neurons of the auditory portion, the cochlear afferent fibers that innervate the sensory hair cells of the organ of Corti, have their somas in the cochlear spiral ganglion where two types of neurons can be distinguished. Afferent Type-I neurons are the 95% of the total population. Bipolar and myelinated fibers, each one innervates only one cochlear inner hair cell (IHC). In contrast, afferent Type-II neurons are only the 5% of the spiral ganglion population. They are pseudounipolar and unmyelinated fibers and innervate the cochlear outer hair cells (OHC) so that one afferent Type-II fiber contacts with multiple OHCs, but each OHC only receives one contact from one Type-II neuron. Both types of VIII nerve fibers are glutamatergic, but these asymmetric innervations of the cochlear sensory cells could suggest that the IHC codifies the truly auditory message but the OHC only informs about mechanical aspects of the state of the organ of Corti. In fact, the central nervous system (CNS) has control over the information transmitted by the Type-I neuron by means of axons from the superior olivary complex that innervate them to modulate, filter and/or inhibit the entry of auditory message to CNS. The aim of this paper is to review the current knowledge about the anatomy and physiology of the auditory portion of the VIII nerve. Anat Rec, 302:463-471, 2019. © 2018 Wiley Periodicals, Inc.

Gerbil middle-ear sound transmission from 100 Hz to 60 kHz.

Middle-ear sound transmission was evaluated as the middle-ear transfer admittance H(MY) (the ratio of stapes velocity to ear-canal sound pressure near the umbo) in gerbils during closed-field sound stimulation at frequencies from 0.1 to 60 kHz, a range that spans the gerbil's audiometric range. Similar measurements were performed in two laboratories. The H(MY) magnitude (a) increased with frequency below 1 kHz, (b) remained approximately constant with frequency from 5 to 35 kHz, and (c) decreased substantially from 35 to 50 kHz. The H(MY) phase increased linearly with frequency from 5 to 35 kHz, consistent with a 20-29 micros delay, and flattened at higher frequencies. Measurements from different directions showed that stapes motion is predominantly pistonlike except in a narrow frequency band around 10 kHz. Cochlear input impedance was estimated from H(MY) and previously-measured cochlear sound pressure. Results do not support the idea that the middle ear is a lossless matched transmission line. Results support the ideas that (1) middle-ear transmission is consistent with a mechanical transmission line or multiresonant network between 5 and 35 kHz and decreases at higher frequencies, (2) stapes motion is pistonlike over most of the gerbil auditory range, and (3) middle-ear transmission properties are a determinant of the audiogram.

Electrophysiology of Cranial Nerve Testing: Auditory Nerve.

The electrocochleogram and brainstem auditory evoked potentials (BAEPs) are electrophysiologic signals used to assess the auditory nerve. The electrocohleogram includes the cochlear microphonic, the cochlear summating potential, and the eighth nerve compound action potential. It is used predominantly for hearing assessment and for diagnosis of Ménière disease and auditory neuropathy. Brainstem auditory evoked potentials are used for hearing assessment, diagnosis of dysfunction within the cochlea, the auditory nerve, and the brainstem auditory pathways up to the level of the mesencephalon, and intraoperative monitoring of these structures. The earliest BAEP component, wave I, and the eighth nerve compound action potential reflect the same process-the initial depolarization in the distal auditory nerve. Brainstem auditory evoked potential wave II receives contributions from the region of the cochlear nucleus and from the second depolarization in the distal auditory nerve. Wave III and later components are entirely generated rostral to the auditory nerve. Interpretation of BAEP studies is based on waves I, III, and V; auditory nerve dysfunction is manifested as prolongation of the I-III interpeak interval or absence of waves III and V. Eighth nerve tumors can cause a variety of BAEP abnormalities depending on which structures they affect. Adverse intraoperative BAEP changes can have many etiologies, including direct mechanical or thermal injury of tissue, ischemia (including cochlear ischemia or infarction due to compromise of the internal auditory artery), eighth nerve stretch, systemic or localized hypothermia, and artifactual BAEP changes due to technical factors.

Olivocochlear efferents: Their action, effects, measurement and uses, and the impact of the new conception of cochlear mechanical responses.

The anatomy and physiology of olivocochlear (OC) efferents are reviewed. To help interpret these, recent advances in cochlear mechanics are also reviewed. Lateral OC (LOC) efferents innervate primary auditory-nerve (AN) fiber dendrites. The most important LOC function may be to reduce auditory neuropathy. Medial OC (MOC) efferents innervate the outer hair cells (OHCs) and act to turn down the gain of cochlear amplification. Cochlear amplification had been thought to act only through basilar membrane (BM) motion, but recent reports show that motion near the reticular lamina (RL) is amplified more than BM motion, and that RL-motion amplification extends to several octaves below the local characteristic frequency. Data on efferent effects on AN-fiber responses, otoacoustic emissions (OAEs) and human psychophysics are reviewed and reinterpreted in the light of the new cochlear-mechanical data. The possible origin of OAEs in RL motion is considered. MOC-effect measuring methods and MOC-induced changes in human responses are also reviewed, including that ipsilateral and contralateral sound can produce MOC effects with different patterns across frequency. MOC efferents help to reduce damage due to acoustic trauma. Many, but not all, reports show that subjects with stronger contralaterally-evoked MOC effects have better ability to detect signals (e.g. speech) in noise, and that MOC effects can be modulated by attention.

Design and fabrication of multichannel cochlear implants for animal research.

The effectiveness of multichannel cochlear implants depends on the activation of perceptually distinct regions of the auditory nerve. Increased information transfer is possible as the number of channels and dynamic range are increased and electrical and neural interaction among channels is reduced. Human and animal studies have demonstrated that specific design features of the intracochlear electrode directly affect these performance factors. These features include the geometry, size, and orientation of the stimulating sites, proximity of the device to spiral ganglion neurons, shape and position of the insulating carrier, and the stimulation mode (monopolar, bipolar, etc.). Animal studies to directly measure the effects of changes in electrode design are currently constrained by the lack of available electrodes that model contemporary clinical devices. This report presents methods to design and fabricate species-specific customizable electrode arrays. We have successfully implanted these arrays in guinea pigs and cats for periods of up to 14 months and have conducted acute electrophysiological experiments in these animals. Modifications enabling long-term intracochlear drug infusion are also described. Studies using these scale model arrays will improve our understanding of how these devices function in human subjects and how we can best optimize future cochlear implants.

Significance of the tentorial alignment in approaching the trigeminal nerve and the ventral petrous region through the suboccipital retrosigmoid technique.

OBJECT: In this study, the authors aimed to identify the factors that would predict the operative distance between the trigeminal nerve (fifth cranial nerve) and the acousticofacial nerve complex (seventh-eighth cranial nerves) preoperatively when approaching the cerebellopontine angle (CPA) through the suboccipital retrosigmoid approach. METHODS: In 40 consecutive patients who underwent microvascular decompression of the trigeminal nerve via a suboccipital retrosigmoid approach for trigeminal neuralgia, the following three parameters were assessed on preoperative magnetic resonance images: 1) the angle between the tentorium and the line drawn from the hard palate (tentorial angle); 2) the angle between the lines drawn along the petrous bones ventral to the internal auditory canals (petrous angle); and 3) the angle between the tentorium and the line connecting the opisthion to the inion (occipital angle). The distance between the trigeminal nerve and the acousticofacial nerve complex (referred to as "distance") was measured intraoperatively. Statistical analysis was performed using the Pearson correlation test. RESULTS: The mean values were 50.9 +/- 11.5 degrees for the tentorial angle, 102.5 +/- 13.1 degrees for the petrous angle, 83.4 +/- 9.7 degrees for the occipital angle, and 3.1 +/- 1.5 mm for distance. There was a strong inverse correlation between the tentorial angle and distance (r = -0.228, p = 0.08). The mean distance was 3.5 +/- 1.9 mm for a tentorial angle less than 51 degrees and 2.7 +/- 1.1 mm for a tentorial angle of at least 51 degrees. No correlation existed between either the petrous or occipital angles and distance. CONCLUSIONS: The distance between the trigeminal nerve and acousticofacial nerve complex decreases in the presence of a steep tentorial angle. This limits the operating field between these cranial nerves when reaching the petroclival or the superior CPA regions through the retrosigmoid approach. Awareness of such anatomical features at the time of preoperative planning is of paramount importance in selecting the optimum surgical approach and minimizing operative complications.

Assessment of the anatomical relationship between the arcuate eminence and superior semicircular canal by computed tomography.

The anatomical relationship between the arcuate eminence (AE) and the superior semicircular canal (SSC) was examined by computed tomography (CT) in 52 petrous bones of 26 patients. After acquiring volume data by multidetector CT, 1-mm thick oblique bone window images perpendicular to the SSC were obtained from the axial images. The distances between the AE and the SSC, and the SSC and the superior surface of the petrous bone were measured. The AE corresponded exactly with the SSC in only 2/52 petrous bones, and corresponded well in 7/52. The AE was lateral to the SSC in 25/52 cases, medial to the SSC in 6/52 cases, intersected in 3/52 cases, and was indiscernible in 9/52 cases. The distance between the SSC and the petrous surface was 0 mm in 45/52 petrous bones, 1 mm in 5/52, 2 mm in 1/52, and 3 mm in 1/52. The SSC typically does not correspond exactly with the AE, and is generally located just under the surface of the petrous bone. Planning of the middle cranial fossa approach requires location of the SSC by CT.

A Comparison of Cochlear Nerve Size in Normal-Hearing Adults Using Magnetic Resonance Imaging.

OBJECTIVE: Cochlear implantation is a clinical and cost-effective treatment for severe hearing loss. Cochlear nerve size assessment by magnetic resonance imaging (MRI) has been investigated for use as a prognostic indicator following cochlear implantation. This study aimed to further that research by assessing nerve size in normal-hearing adults for symmetry. MATERIALS AND METHODS: Patients with tinnitus presenting to our center retrospectively had their nerve size assessed by MRI. RESULTS: The study found no significant differences between right and left cochlear nerves in normal-hearing adults, supporting our hypothesis of symmetry in these individuals. This was a previously unproven and uninvestigated hypothesis. CONCLUSION: Nerve size assessment should remain an active area of research in otological disease.

Classification and Current Management of Inner Ear Malformations.

Morphologically congenital sensorineural hearing loss can be investigated under two categories. The majority of congenital hearing loss causes (80%) are membranous malformations. Here, the pathology involves inner ear hair cells. There is no gross bony abnormality and, therefore, in these cases high-resolution computerized tomography and magnetic resonance imaging of the temporal bone reveal normal findings. The remaining 20% have various malformations involving the bony labyrinth and, therefore, can be radiologically demonstrated by computerized tomography and magnetic resonance imaging. The latter group involves surgical challenges as well as problems in decision-making. Some cases may be managed by a hearing aid, others need cochlear implantation, and some cases are candidates for an auditory brainstem implantation (ABI). During cochlear implantation, there may be facial nerve abnormalities, cerebrospinal fluid leakage, electrode misplacement or difficulty in finding the cochlea itself. During surgery for inner ear malformations, the surgeon must be ready to modify the surgical approach or choose special electrodes for surgery. In the present review article, inner ear malformations are classified according to the differences observed in the cochlea. Hearing and language outcomes after various implantation methods are closely related to the status of the cochlear nerve, and a practical classification of the cochlear nerve deficiency is also provided.

Spiral ganglion cell site of excitation II: numerical model analysis.

An anatomically based model of cochlear neuron electrophysiology has been developed and used to interpret the physiological responses of the auditory neuron to electrical summation and refractory pulse-pair stimuli. For summation pulses, the summation time constant, tau(sum), indicates the ability of the membrane to hold charge after cessation of a pulse. When a spiral ganglion cell with a cell body was simulated, the value of tau(sum) was elevated at the peripheral node adjacent to the cell body. For refraction pulses, the refraction time constant, tau(ref), indicates the duration of the relative refractory period of the membrane. In spiral ganglion cell simulations, tau(ref) was decreased at the peripheral node adjacent to the cell body and slightly elevated at other peripheral nodes. The extent of the cell body influence on tau(sum) and tau(ref) was high localized. Excitation times for the nodes adjacent to the cell body were either simultaneous or near simultaneous resulting in similar response latencies. Results indicate that values of tau(sum) and tau(ref) may be useful for distinguishing central and peripheral excitation sites while latency measures alone are not a good indication of site of excitation.