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Auditory perception is established through experience-dependent stimuli exposure during sensitive developmental periods; however, little is known regarding the structural development of the central auditory pathway in humans. The present study characterized the regional developmental trajectories of the ascending auditory pathway from the brainstem to the auditory cortex from infancy through adolescence using a novel diffusion MRI-based tractography approach and along-tract analyses. We used diffusion tensor imaging (DTI) and neurite orientation dispersion and density imaging (NODDI) to quantify the magnitude and timing of auditory pathway microstructural maturation. We found spatially varying patterns of white matter maturation along the length of the tract, with inferior brainstem regions developing earlier than thalamocortical projections and left hemisphere tracts developing earlier than the right. These results help to characterize the processes that give rise to functional auditory processing and may provide a baseline for detecting abnormal development., (© 2024 The Author(s). Human Brain Mapping published by Wiley Periodicals LLC.)

Background: In school-age children, the myelination of the auditory radiation thalamocortical pathway is associated with the latency of auditory evoked responses, with the myelination of thalamocortical axons facilitating the rapid propagation of acoustic information. Little is known regarding this auditory system function-structure association in infants and toddlers., Methods and Participants: The present study tested the hypothesis that maturation of auditory radiation white-matter microstructure (e.g., fractional anisotropy (FA); measured using diffusion-weighted MRI) is associated with the latency of the infant auditory response (the P2m response, measured using magnetoencephalography, MEG) in a cross-sectional (N = 47, 2 to 24 months, 19 females) as well as longitudinal cohort (N = 18, 2 to 29 months, 8 females) of typically developing infants and toddlers. Of 18 longitudinal infants, 2 infants had data from 3 timepoints and 16 infants had data from 2 timepoints., Results: In the cross-sectional sample, non-linear maturation of P2m latency and auditory radiation diffusion measures were observed. Auditory radiation diffusion accounted for significant variance in P2m latency, even after removing the variance associated with age in both P2m latency and auditory radiation diffusion measures. In the longitudinal sample, latency and FA associations could be observed at the level of a single child., Conclusions: Findings provide strong support for the hypothesis that an increase in thalamocortical neural conduction velocity, due to increased axon diameter and/or myelin maturation, contributes to a decrease in the infant P2m auditory evoked response latency., Significance: Infant multimodal brain imaging identifies brain mechanisms contributing to the rapid changes in neural circuit activity during the first two years of life., (Copyright © 2024 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.)

Presbycusis, or age-related hearing loss, affects both elderly humans and dogs, significantly impairing their social interactions and cognition. In humans, presbycusis involves changes in peripheral and central auditory systems, with central changes potentially occurring independently. While peripheral presbycusis in dogs is well-documented, research on central changes remains limited. Diffusion tensor imaging (DTI) is a useful tool for detecting and quantifying cerebral white matter abnormalities. This study used DTI to explore the central auditory pathway of senior dogs, aiming to enhance our understanding of canine presbycusis. Dogs beyond 75% of their expected lifespan were recruited and screened with brainstem auditory evoked response testing to select dogs without severe peripheral hearing loss. Sixteen dogs meeting the criteria were scanned using a 3 T magnetic resonance scanner. Tract-based spatial statistics was used to analyze the central auditory pathways. A significant negative correlation between fractional lifespan and fractional anisotropy was found in the acoustic radiation, suggesting age-related white matter changes in the central auditory system. These changes, observed in dogs without severe peripheral hearing loss, may contribute to central presbycusis development., (© 2024. The Author(s).)

Introduction: This prospective cohort study aims to investigate the hearing dynamics and the changes in the central auditory pathways in infants with congenital cytomegalovirus (cCMV) infection., Materials and Methods: cCMV-infected neonates aged ≤3 weeks old were recruited and underwent clinical and laboratory tests to detect viremia and symptomatic infection, hearing examinations at three and six months of age, and radiological imaging of brain auditory pathways using diffusion tensor imaging., Results: From 26 eligible infants (52 ears), we detected symptomatic infection in nine (34.6%), viremia in 14 (14/25; 56.0%) and sensorineural hearing loss (SNHL) in 14 infants (53.8%). We observed 40 ears (76.9%) with unstable hearing thresholds, 17 (42.5%) of which fluctuated. Hearing fluctuation and progressivity were more common in symptomatic infection (66.7% vs. 14.7%, p<0.001; and 38.9% vs. 2.9%, p=0.002; respectively). A substantial proportion of ears had reduced fractional anisotropy (FA) in the medial geniculate body (59.1%), superior olivary nucleus (45.5%), trapezoid body (40.9%), auditory radiation (36.4%) and inferior colliculus (31.8%). Symptomatic infection was associated with an increased FA in the medial geniculate body (mean difference, MD: 0.12; 95% Confidence Intervals, 95%CI: 0.03, 0.22) and viremia in the inferior colliculus (MD: 0.09; 95%CI: 0.02, 0.16). An FA in the inferior colliculus of ≥0.404 had a sensitivity and specificity of 68.8% and 83.3% in predicting viremia (area under the curve 0.823; 95%CI: 0.633, 1.000, p=0.022)., Conclusion: SNHL along with its fluctuation and progression are common in cCMV-infected infants. cCMV infection may induce structural changes in the central auditory pathway.

Background: To investigate whether there is a difference in mean diffusivity (MD) and fractional anisotropy (FA) values in the auditory pathways of neurofibromatosis type 1 patients with and without focal areas of abnormal signal intensity (FASI) compared to healthy controls by using diffusion tensor imaging (DTI). Methods: Patients were classified as group 1 with focal areas of abnormal signal intensity in the brainstem, group 2 without focal areas of abnormal signal intensity, and healthy control group 3 according to the MRI findings. Mean diffusivity and fractional anisotropy values of lateral lemniscus, inferior colliculus, corpus geniculatum mediale, Heschl gyrus, and brainstem were compared between groups. The correlation between mean diffusivity and fractional anisotropy values of auditory pathways and age was investigated. Results: There was a significant difference between group 1 and group 2 in terms of mean diffusivity and fractional anisotropy values at lateral lemniscus, inferior colliculus, corpus geniculatum mediale, and Heschl gyrus. Increased mean diffusivity and decreased fractional anisotropy values at brainstem were found in group 1. There was a significant difference between group 1 and group 3 in terms of mean diffusivity values at all auditory pathways. Fractional anisotropy values obtained from lateral lemniscus, inferior colliculus, and Heschl gyrus decreased in group 1 compared with group 3. There was a negative correlation between mean diffusivity values and positive correlation between fractional anisotropy values at lateral lemniscus, inferior colliculus, Heschl gyrus, and age. Conclusions: Our diffusion tensor imaging findings show that the neuronal integrity of the auditory pathways is affected in neurofibromatosis type 1 patients with brainstem focal areas of abnormal signal intensity. We think that the disappearance of brainstem focal areas of abnormal signal intensity associated with myelin repair and the regression of diffusion tensor imaging changes in the auditory pathways occur simultaneously with advancing age in patients with neurofibromatosis type 1., Competing Interests: Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Objective: To assess the utility of diffusion tensor imaging of the auditory pathway in children with sensorineural hearing loss (SNHL)., Study Design: Retrospective cohort study., Setting: A single academic tertiary children's hospital., Patients: Sixteen pediatric patients with bilateral SNHL of at least moderate severity in the poorer ear (eight male; mean age, 5.3 ± 4.9 yrs). Controls consisted of age- and sex-matched children with normal hearing who were imaged for nonotologic, non-neurologic medical concerns and found to have normal magnetic resonance imaging (MRI)., Interventions: Three Tesla MRI scanners were used for diffusion tensor imaging., Main Outcome Measures: Quantitative diffusion tensor metrics were extracted from the superior olivary nucleus (SON), inferior colliculus (IC), and ipsilateral fiber tracts between the SON and IC delineated by tractography., Results: We identified differences in fractional anisotropy of the SON between the SNHL cohort and controls (0.377 ± 0.056 vs. 0.422 ± 0.052; p = 0.009), but not in the IC. There were no differences in the mean diffusivity (MD) values in the IC and SON. Among younger children (≤5 yrs), MD was decreased in the SNHL cohort compared with controls in the IC (0.918 ± 0.051 vs. 1.120 ± 0.142; p < 0.001). However, among older children (>5 yrs), there were no differences in MD (1.124 ± 0.198 vs. 0.997 ± 0.103; p = 0.119). There were no differences in MD or fractional anisotropy in the white matter fibers of the IC-SON tract., Conclusions: Our results suggest abnormal neural tracts along the central auditory pathway among children with SNHL. Longitudinal studies should assess the prognostic value of these MRI-based findings for assessing long-term outcomes and determining intervention efficacy., Competing Interests: Conflict of interest/financial disclosures: No competing financial interests exist., (Copyright © 2024, Otology & Neurotology, Inc.)

Background: We aimed to investigate the changes that may occur in the auditory neural network in pediatric congenital hearing loss cases., Methods: Fifty-four cochlear implant candidates and 47 normal-hearing controls were included in this retrospective study. Fractional anisotropy, radial diffusivity, and apparent diffusion coefficient maps were generated. We placed region of interest on the cochlear nucleus, superior olivary nucleus, lateral lemniscus, medial geniculate body, auditory radiation, Heschl's gyrus, inferior fronto-occipital fasciculus, superior longitudinal fascicle, and corpus callosum splenium. The area of the cochlear nerve was measured. Diffusion tensor imaging metrics, children's ages, and cochlear nerve area were compared., Results: Apparent diffusion coefficient and radial diffusivity values of patients were higher than the control group in all places except the radial diffusivity values of medial geniculate body. The fractional anisotropy values of the patients in lateral lemniscus, auditory radiation, Heschl's gyrus, inferior fronto-occipital fasciculus, superior longitudinal fascicle, and corpus callosum splenium were lower than the control group. There is a positive correlation between fractional anisotropy and age in both patient and control groups for all locations. The cochlear nerve area is lower in patients (0.88 ± 0.29) than in the control group (1.18 ± 0.14) (P = .000). The cochlear nerve area has a positive correlation with age in the patient group (P = .000) but has not in the control group. The cochlear nerve area positively correlates with fractional anisotropy values of all locations except fractional anisotropy values of medial geniculate body., Conclusion: The alterations of diffusion tensor imaging metrics on the auditory pathway reflect the microstructural changes of white matter tracts.

Autism spectrum disorder (ASD) is characterised by social communication difficulties. These difficulties have been mainly explained by cognitive, motivational, and emotional alterations in ASD. The communication difficulties could, however, also be associated with altered sensory processing of communication signals. Here, we assessed the functional integrity of auditory sensory pathway nuclei in ASD in three independent functional magnetic resonance imaging experiments. We focused on two aspects of auditory communication that are impaired in ASD: voice identity perception, and recognising speech-in-noise. We found reduced processing in adults with ASD as compared to typically developed control groups (pairwise matched on sex, age, and full-scale IQ) in the central midbrain structure of the auditory pathway (inferior colliculus [IC]). The right IC responded less in the ASD as compared to the control group for voice identity, in contrast to speech recognition. The right IC also responded less in the ASD as compared to the control group when passively listening to vocal in contrast to non-vocal sounds. Within the control group, the left and right IC responded more when recognising speech-in-noise as compared to when recognising speech without additional noise. In the ASD group, this was only the case in the left, but not the right IC. The results show that communication signal processing in ASD is associated with reduced subcortical sensory functioning in the midbrain. The results highlight the importance of considering sensory processing alterations in explaining communication difficulties, which are at the core of ASD., (© 2022 The Authors. Human Brain Mapping published by Wiley Periodicals LLC.)

Objective: To explore the differences of functional brain networks in processing auditory phonological tasks between Cantonese-Mandarin bilinguals and Mandarin monolinguals., Methods: 31 Cantonese-Mandarin bilinguals and 31 Mandarin monolinguals performed auditory rhyming tasks under a functional magnetic resonance imaging (fMRI) scanning. Bilinguals performed two language tasks (Cantonese, CC; Mandarin, CM), while monolinguals performed only one task (Mandarin, MM). Graph theory and network-based statistic (NBS) analyses were used to reveal the differences of functional brain networks among CC, CM and MM., Results: The functional brain networks of CC, CM and MM were all small-world, and there were no differences in network properties, but widespread differences in functional connectivity among distributed brain regions., Conclusions: The Cantonese-Mandarin bilingualism and Mandarin monolingualism shared similar efficient topological structure of brain network for auditory phonological processing, but varied in widespread functional connectivity. And the two languages within bilingualism employed different functional brain networks for auditory phonological processing., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Objective: To assess diffusion and perfusion changes of the auditory pathway in pediatric medulloblastoma patients exposed to ototoxic therapies., Study Design: Retrospective cohort study., Setting: A single academic tertiary children's hospital., Patients: Twenty pediatric medulloblastoma patients (13 men; mean age 12.0 ± 4.8 yr) treated with platinum-based chemotherapy with or without radiation and 18 age-and-sex matched controls were included. Ototoxicity scores were determined using Chang Ototoxicity Grading Scale., Interventions: Three Tesla magnetic resonance was used for diffusion tensor and arterial spin labeling perfusion imaging., Main Outcome Measures: Quantitative diffusion tensor metrics were extracted from the Heschl's gyrus, auditory radiation, and inferior colliculus. Arterial spin labeling perfusion of the Heschl's gyrus was also examined., Results: Nine patients had clinically significant hearing loss, or Chang grades more than or equal to 2a; 11 patients had mild/no hearing loss, or Chang grades less than 2a. The clinically significant hearing loss group showed reduced mean diffusivity in the Heschl's gyrus (p = 0.018) and auditory radiation (p = 0.037), and decreased perfusion in the Heschl's gyrus (p = 0.001). Mild/no hearing loss group showed reduced mean diffusivity (p = 0.036) in Heschl's gyrus only, with a decrease in perfusion (p = 0.008). There were no differences between groups in the inferior colliculus. There was no difference in fractional anisotropy between patients exposed to ototoxic therapies and controls., Conclusions: Patients exposed to ototoxic therapies demonstrated microstructural and physiological alteration of the auditory pathway. The present study shows proof-of-concept use of diffusion tensor imaging to gauge ototoxicity along the auditory pathway. Future larger cohort studies are needed to assess significance of changes in diffusion tensor imaging longitudinally, and the relationship between these changes and hearing loss severity and longitudinal changes of the developing auditory white matter., Competing Interests: The authors disclose no conflicts of interest., (Copyright © 2021, Otology & Neurotology, Inc.)

Despite the multidimensional and temporally fleeting nature of auditory signals we quickly learn to assign novel sounds to behaviorally relevant categories. The neural systems underlying the learning and representation of novel auditory categories are far from understood. Current models argue for a rigid specialization of hierarchically organized core regions that are fine-tuned to extracting and mapping relevant auditory dimensions to meaningful categories. Scaffolded within a dual-learning systems approach, we test a competing hypothesis: the spatial and temporal dynamics of emerging auditory-category representations are not driven by the underlying dimensions but are constrained by category structure and learning strategies. To test these competing models, we used functional Magnetic Resonance Imaging (fMRI) to assess representational dynamics during the feedback-based acquisition of novel non-speech auditory categories with identical dimensions but differing category structures: rule-based (RB) categories, hypothesized to involve an explicit sound-to-rule mapping network, and information integration (II) based categories, involving pre-decisional integration of dimensions via a procedural-based sound-to-reward mapping network. Adults were assigned to either the RB (n = 30, 19 females) or II (n = 30, 22 females) learning tasks. Despite similar behavioral learning accuracies, learning strategies derived from computational modeling and involvements of corticostriatal systems during feedback processing differed across tasks. Spatiotemporal multivariate representational similarity analysis revealed an emerging representation within an auditory sensory-motor pathway exclusively for the II learning task, prominently involving the superior temporal gyrus (STG), inferior frontal gyrus (IFG), and posterior precentral gyrus. In contrast, the RB learning task yielded distributed neural representations within regions involved in cognitive-control and attentional processes that emerged at different time points of learning. Our results unequivocally demonstrate that auditory learners' neural systems are highly flexible and show distinct spatial and temporal patterns that are not dimension-specific but reflect underlying category structures and learning strategies., Competing Interests: Declaration of Competing Interest Patrick C. M. Wong is a founder of a company in Hong Kong supported by a Hong Kong SAR government startup scheme for universities., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Behaviorally relevant sounds are often composed of distinct acoustic units organized into specific temporal sequences. The meaning of such sound sequences can therefore be fully recognized only when they have terminated. However, the neural mechanisms underlying the perception of sound sequences remain unclear. Here, we use two-photon calcium imaging in the auditory cortex of behaving mice to test the hypothesis that neural responses to termination of sound sequences ("Off-responses") encode their acoustic history and behavioral salience. We find that auditory cortical Off-responses encode preceding sound sequences and that learning to associate a sound sequence with a reward induces enhancement of Off-responses relative to responses during the sound sequence ("On-responses"). Furthermore, learning enhances network-level discriminability of sound sequences by Off-responses. Last, learning-induced plasticity of Off-responses but not On-responses lasts to the next day. These findings identify auditory cortical Off-responses as a key neural signature of acquired sound-sequence salience., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)

Purpose: The aim of the present study is to show a MR procedure for the evaluation of simultaneous left and right auditory functions with functional MRI, and high-resolution acquisition of anatomical auditory pathway using parallel-transmit (pTx) methods at 7T., Methods: The time-efficient MR acquisition included two steps: RF weights were optimized for the regions-of-interest and high-resolution MR images of the inner-ear were acquired for the first 30 min (400 μm-iso resolution) followed by functional MRI acquisitions along the whole auditory pathway during the next 20 minutes. Data was processed with a linear cross-correlation analysis to define frequency preferences for each voxel in the auditory relays., Results: Tonotopic maps revealed ordered bilateral frequency gradients in the auditory relays whereas at the level of the cochlear nuclei and superior olivary complexes the frequency gradients were less evident. A 21% increase in transmit-field efficiency was achieved over the left/right inner-ear regions and thus its main structures were clearly discernible using the pTx methods, compared to a single transmit RF coil., Conclusion: Using 7T pTx allows a fast (less than 60 min in total) and qualitative evaluation of the simultaneous left and right auditory response along the entire auditory pathway, together with high-resolution anatomical images of the inner-ear. This could be further used for patient examination at 7T., Competing Interests: The authors have declared that no competing interests exist.

The cultural transmission of spoken language and music relies on human capacities for encoding and recalling auditory patterns. In this experiment, we show that interindividual differences in this ability are associated with variation in the organization of cross-callosal white matter pathways. First, high-angular resolution diffusion MRI (dMRI) data were analyzed in a large participant sample (N = 51). Subsequently, these participants underwent a behavioral test that models in the laboratory the cultural transmission of auditory symbolic systems: the signaling game. Cross-callosal and intrahemispheric (arcuate fasciculus) pathways were reconstructed and analyzed using conventional diffusion tensor imaging (DTI) as well as a more advanced dMRI technique: fixel-based analysis (FBA). The DTI metric of fractional anisotropy (FA) in auditory callosal pathways predicted-weeks after scanning-the fidelity of transmission of an artificial tone system. The ability to coherently transmit auditory signals in one signaling game, irrespective of the signals learned during the previous game, was predicted by morphological properties of the fiber bundles in the most anterior portions of the corpus callosum. The current study is the first application of dMRI in the field of cultural transmission, and the first to connect individual characteristics of callosal pathways to core behaviors in the transmission of auditory symbolic systems.

The cerebellum, a structure historically associated with motor control, has more recently been implicated in several higher-order auditory-cognitive functions. However, the exact functional pathways that mediate cerebellar influences on auditory cortex (AC) remain unclear. Here, we sought to identify auditory cortico-cerebellar pathways based on intrinsic functional connectivity magnetic resonance imaging. In contrast to previous connectivity studies that principally consider the AC as a single functionally homogenous unit, we mapped the cerebellar connectivity across different parts of the AC. Our results reveal that auditory subareas demonstrating different levels of interindividual functional variability are functionally coupled with distinct cerebellar regions. Moreover, auditory and sensorimotor areas show divergent cortico-cerebellar connectivity patterns, although sensorimotor areas proximal to the AC are often functionally grouped with the AC in previous connectivity-based network analyses. Lastly, we found that the AC can be functionally segmented into highly similar subareas based on either cortico-cerebellar or cortico-cortical functional connectivity, suggesting the existence of multiple parallel auditory cortico-cerebellar circuits that involve different subareas of the AC. Overall, the present study revealed multiple auditory cortico-cerebellar pathways and provided a fine-grained map of AC subareas, indicative of the critical role of the cerebellum in auditory processing and multisensory integration., (© The Author(s) 2021. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permission@oup.com.)

Across many species, scream calls signal the affective significance of events to other agents. Scream calls were often thought to be of generic alarming and fearful nature, to signal potential threats, with instantaneous, involuntary, and accurate recognition by perceivers. However, scream calls are more diverse in their affective signaling nature than being limited to fearfully alarming a threat, and thus the broader sociobiological relevance of various scream types is unclear. Here we used 4 different psychoacoustic, perceptual decision-making, and neuroimaging experiments in humans to demonstrate the existence of at least 6 psychoacoustically distinctive types of scream calls of both alarming and non-alarming nature, rather than there being only screams caused by fear or aggression. Second, based on perceptual and processing sensitivity measures for decision-making during scream recognition, we found that alarm screams (with some exceptions) were overall discriminated the worst, were responded to the slowest, and were associated with a lower perceptual sensitivity for their recognition compared with non-alarm screams. Third, the neural processing of alarm compared with non-alarm screams during an implicit processing task elicited only minimal neural signal and connectivity in perceivers, contrary to the frequent assumption of a threat processing bias of the primate neural system. These findings show that scream calls are more diverse in their signaling and communicative nature in humans than previously assumed, and, in contrast to a commonly observed threat processing bias in perceptual discriminations and neural processes, we found that especially non-alarm screams, and positive screams in particular, seem to have higher efficiency in speeded discriminations and the implicit neural processing of various scream types in humans., Competing Interests: The authors have declared that no competing interests exist.

Acoustic trauma damages inner ear neural structures including cochlear hair cells which result in hearing loss and neurotransmitter imbalances within the synapses of the central auditory pathway. Disruption of GABA/glutamate levels underlies, tinnitus, a phantom perception of sound that persists post-exposure to blast noise which may manifest in tandem with acute/chronic loss of hearing. Many putative theories explain tinnitus physiology based on indirect and direct assays in animal models and humans, although there is no comprehensive evidence to explain the phenomenon. Here, GABA/glutamate levels were imaged and quantified in a blast overpressure model of chinchillas using Fourier transform ion cyclotron resonance mass spectrometry imaging. The direct measurement from whole-brain sections identified the relative levels of GABA/glutamate in the central auditory neuraxis centers including the cochlear nucleus, inferior colliculus, and auditory cortex. These preliminary results provide insight on the homeostasis of GABA/glutamate within whole-brain sections of chinchilla for investigation of the pathomechanism of blast-induced tinnitus., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Accumulating evidence shows that auditory cortex (AC) of humans, and other primates, is involved in more complex cognitive processes than feature segregation only, which are shaped by experience-dependent plasticity and thus likely show substantial individual variability. However, thus far, individual variability of ACs has been considered a methodological impediment rather than a phenomenon of theoretical importance. Here, we examined the variability of ACs using intrinsic functional connectivity patterns in humans and macaques. Our results demonstrate that in humans, interindividual variability is greater near the nonprimary than primary ACs, indicating that variability dramatically increases across the processing hierarchy. ACs are also more variable than comparable visual areas and show higher variability in the left than in the right hemisphere, which may be related to the left lateralization of auditory-related functions such as language. Intriguingly, remarkably similar modality differences and lateralization of variability were also observed in macaques. These connectivity-based findings are consistent with a confirmatory task-based functional magnetic resonance imaging analysis. The quantification of variability in auditory function, and the similar findings in both humans and macaques, will have strong implications for understanding the evolution of advanced auditory functions in humans., (© The Author(s) 2020. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permission@oup.com.)

Congenital blindness has been shown to result in behavioral adaptation and neuronal reorganization, but the underlying neuronal mechanisms are largely unknown. Brain rhythms are characteristic for anatomically defined brain regions and provide a putative mechanistic link to cognitive processes. In a novel approach, using magnetoencephalography resting state data of congenitally blind and sighted humans, deprivation-related changes in spectral profiles were mapped to the cortex using clustering and classification procedures. Altered spectral profiles in visual areas suggest changes in visual alpha-gamma band inhibitory-excitatory circuits. Remarkably, spectral profiles were also altered in auditory and right frontal areas showing increased power in theta-to-beta frequency bands in blind compared with sighted individuals, possibly related to adaptive auditory and higher cognitive processing. Moreover, occipital alpha correlated with microstructural white matter properties extending bilaterally across posterior parts of the brain. We provide evidence that visual deprivation selectively modulates spectral profiles, possibly reflecting structural and functional adaptation., (© The Author(s) 2020. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permission@oup.com.)

Absolute pitch (AP) is known as the ability to recognize and label the pitch chroma of a given tone without external reference. The neural mechanism and its asymmetry of AP musicians remain unclear. We herein report a 41-year-old AP musician who developed a right putaminal hemorrhage. On a postoperative day 5, a fluid-attenuated inversion recovery image revealed the rest of the hematoma and edematous lesion at the right white matter between the Heschl's gyrus and other cortices. Diffusion tensor tractography with the region of interest at the Heschl's gyrus was performed. In the left hemisphere, the anterior part of the arcuate fiber and middle longitudinal fasciculus were observed. However, these connections were absent in the right hemisphere, but her AP ability was maintained. Our case suggested that the fibers from the right Heschl's gyrus to the right frontal lobe via the right ventral stream is not associated with AP., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background and Purpose: Idiopathic sudden sensorineural hearing loss is an acute unexplained onset of hearing loss. We examined the central auditory pathway abnormalities in patients with unilateral idiopathic sudden sensorineural hearing loss using diffusion spectrum imaging and the relationships between hearing recovery and diffusion spectrum imaging parameters., Materials and Methods: Forty-eight patients with unilateral idiopathic sudden sensorineural hearing loss with a duration of ≤2 weeks (range, 8.9 ± 4.3 days) and 20 healthy subjects underwent diffusion spectrum imaging tractography. Hearing levels were evaluated using a pure-tone average at initial presentation and 3-month follow-up. Clinical characteristics and MR imaging findings were assessed., Results: Compared with healthy control subjects, the generalized fractional anisotropy values of patients decreased significantly in the bilateral posterior limbs of the internal capsule, with no differences between the ipsilateral and contralateral sides. The quantitative anisotropy values decreased in the Brodmann area 41, contralateral medial geniculate body, bilateral lateral lemniscus, anterior limb of internal capsule, middle temporal gyrus, and anterior corona radiata. Furthermore, at 3-month follow-up, 14 patients had <15 dB of hearing gain. Receiver operating characteristic curve analysis demonstrated that generalized fractional anisotropy in the ipsilateral medial geniculate body was related to prognosis (sensitivity = 64.7%; specificity = 85.7%; area under the curve = 0.796, 95% CI, 0.661-0.931; P  < .01)., Conclusions: Diffusion spectrum imaging can detect abnormalities of white matter microstructure along the central auditory pathway in patients with unilateral idiopathic sudden sensorineural hearing loss. The generalized fractional anisotropy value of the ipsilateral medial geniculate body may help to predict recovery outcomes., (© 2021 by American Journal of Neuroradiology.)

Purpose: Hearing loss (HL) is one of the most common age-related diseases. Here, we investigate the central auditory correlates of HL in people with normal cognition and mild cognitive impairment (MCI) and test their association with genetic markers with the aim of revealing pathogenic mechanisms., Methods: Brain glucose metabolism based on FDG-PET, self-reported HL status, and genetic data were obtained from the Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort. FDG-PET data was analysed from 742 control subjects (non-HL with normal cognition or MCI) and 162 cases (HL with normal cognition or MCI) with age ranges of 72.2 ± 7.1 and 77.4 ± 6.4, respectively. Voxel-wise statistics of FDG uptake differences between cases and controls were computed using the generalised linear model in SPM12. An additional 1515 FDG-PET scans of 618 participants were analysed using linear mixed effect models to assess longitudinal HL effects. Furthermore, a quantitative trait genome-wide association study (GWAS) was conducted on the glucose uptake within regions of interest (ROIs), which were defined by the voxel-wise comparison, using genotyping data with 5,082,878 variants available for HL cases and HL controls (N = 817)., Results: The HL group exhibited hypometabolism in the bilateral Heschl's gyrus (k left  = 323; k right  = 151; T left  = 4.55; T right  = 4.14; peak P uncorr  < 0.001), the inferior colliculus (k = 219;T = 3.53; peak P uncorr  < 0.001) and cochlear nucleus (k = 18;T = 3.55; peak P uncorr  < 0.001) after age correction and using a cluster forming height threshold P < 0.005 (FWE-uncorrected). Moreover, in an age-matched subset, the cluster comprising the left Heschl's gyrus survived the FWE-correction (k left  = 1903; T left  = 4.39; cluster P FWE-corr  = 0.001). The quantitative trait GWAS identified no genome-wide significant locus in the three HL ROIs. However, various loci were associated at the suggestive threshold (p < 1e-05)., Conclusion: Compared to the non-HL group, glucose metabolism in the HL group was lower in the auditory cortex, the inferior colliculus, and the cochlear nucleus although the effect sizes were small. The GWAS identified candidate genes that might influence FDG uptake in these regions. However, the specific biological pathway(s) underlying the role of these genes in FDG-hypometabolism in the auditory pathway requires further investigation., (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)

Knowledge of brain circuitry is critical for understanding the organization, function, and evolution of central nervous systems. Most commonly, brain connections have been elucidated using histological and experimental methods that require animal sacrifice. On the other hand, magnetic resonance diffusion tensor imaging and associated tractography have emerged as a preferred method to noninvasively visualize brain white matter tracts. However, existing studies have primarily examined large, heavily myelinated fiber tracts. Whether tractography can visualize fiber bundles that contain thin and poorly myelinated axons is uncertain. To address this question, the midbrain auditory pathway to the thalamus was investigated in Alligator. This species was chosen because of its evolutionary importance as it is the reptilian group most closely related to birds and because its brain contains many thin and poorly myelinated tracts. Furthermore, this auditory pathway is well documented in other reptiles, including a related crocodilian. Histological observations and experimental determination of anterograde connections confirmed this path in Alligator. Tractography identified these tracts in Alligator and provided a 3-dimensional picture that accurately identified the neural elements of this circuit. In addition, tractography identified one possible unrecognized pathway. These results demonstrate that tractography can visualize circuits containing thin, poorly myelinated fibers. These findings open the door for future studies to examine these types of pathways in other vertebrates., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Purpose: It has long been thought that the acoustic radiation (AR) white matter fibre tract from the medial geniculate body of the thalamus to the Heschl's gyrus cannot be reconstructed via single-fibre analysis of clinical diffusion tensor imaging (DTI) scans. A recently developed single-fibre probabilistic method suggests otherwise. The method uses dynamic programming (DP) to compute the most probable paths between two regions of interest. This study aims to observe the ability of single-fibre probabilistic analysis via DP to visualise the AR in clinical DTI scans from legacy pilot cohorts of subjects with normal hearing (NH) and profound hearing loss (HL)., Methods: Single-fibre probabilistic analysis via DP was applied to reconstruct 3D models of the AR in the two cohorts. DTI and T1 data at 1.5 T for subjects with NH (n = 11) and HL (n = 5), as well as 3 T for NH (n = 1) and HL (n = 1), were used., Results: The topographical features of AR previously observed in post-mortem and multi-fibre analyses can be visualised in DTI scans of 16 subjects and 2 atlases with a success rate of 100%. Relative to MNI coordinates, there was no significant difference in the varifold distances between the topography of the tracts in the 1.5 T cohort., Conclusion: The AR can be visualised in clinical 1.5 T and 3 T DTI scans using single-fibre probabilistic analysis via DP, hence, the potential for DP to visualise the AR in medical and pre-surgical applications in pathologies such as vestibular schwannoma, multiple sclerosis, thalamic tumours and stroke as well as hearing loss.

Objective: Major depressive disorder (MDD) is a ubiquitous mental illness with heterogeneous symptoms, however, the pathophysiology mechanisms are still not fully understood. Clinical and preclinical studies suggested that depression could cause disturbances in sensory perception systems, disruptions in auditory and visual functions may serve as an essential clinical features underlying MDD., Methods: The current study investigated the abnormal intrinsic connectivity within and between visual and auditory networks in 95 MDD patients and 97 age-, gender-, education level-matched healthy controls (HCs) by using resting-state functional magnetic resonance imaging (fMRI). One auditory network (AN) and three visual components including visual component 1 (VC1), VC2, and VC3 were identified by using independent component analysis method based on the fMRI networks during the resting state with the largest spatial correlations, combining with brain regions and specific network templates., Results: We found that MDD could be characterized by the following disrupted network model relative to HCs: (i) reduced within-network connectivity in the AN, VC2, and VC3; (ii) reduced between-network connectivity between the AN and the VC3. Furthermore, aberrant functional connectivity (FC) within the visual network was linked to the clinical symptoms., Conclusions: Overall, our results demonstrated that abnormalities of FC in perception systems including intrinsic visual and auditory networks may explain neurobiological mechanisms underlying MDD and could serve as a potential effective biomarker., Competing Interests: Declaration of Competing Interest The authors declare that there is no conflict of interest., (Copyright © 2020 Elsevier Inc. All rights reserved.)

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., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Purpose: The purpose of this study was to evaluate the structural integrity of the auditory neural pathway in patients with unilateral sensorineural hearing loss using quantitative diffusion-tensor tractography., Methods: Diffusion-tensor tractography imaging was performed using a 3T magnetic resonance imaging system to evaluate structural alterations in the auditory neural pathway of patients with unilateral sensorineural hearing loss. The two diffusion-tensor tractography parameters, fractional anisotropy and the apparent diffusion coefficient were compared between the ipsilateral side and the contralateral side in patients and controls. Additionally, correlations between the parameter values and the hearing loss level in patients were evaluated., Results: A total of 24 sensorineural hearing loss patients (14 males; age range, 17-65 years; average age, 45.3 years) and 24 age and sex-matched control subjects were enrolled. Fractional anisotropy values on the ipsilateral and contralateral sides were significantly lower in patients than in the control group (p = 0.004 and 0.001, respectively). The differences in the apparent diffusion coefficient values for the ipsilateral and contralateral sides between the two groups were not significant (p = 0.279 and 0.248, respectively). There was an inverse relationship between fractional anisotropy and the severity of hearing impairment on the ipsilateral and contralateral sides (r = -0.519, p = 0.005 and r = -0.454, p = 0.015, respectively). No significant correlation was found between the apparent diffusion coefficient and hearing loss level on the ipsilateral and contralateral sides (r = 0.172, p = 0.380 and r = 0.131, p = 0.508, respectively)., Conclusion: Quantitative diffusion-tensor tractography can be used to detect microstructural alterations in the auditory neural pathway in sensorineural hearing loss patients with normal results in standard imaging studies.

Objective: The functional importance of the superior temporal lobe at the level of Heschl's gyrus is well known. However, the organization and function of these cortical areas and the underlying fiber tracts connecting them remain unclear. The goal of this study was to analyze the area formed by the organization of the intersection of Heschl's gyrus-related fiber tracts, which the authors have termed the "Heschl's gyrus fiber intersection area" (HGFIA)., Methods: The subcortical connectivity of Heschl's gyrus tracts was analyzed by white matter fiber dissection and by diffusion tensor imaging tractography. The white matter tracts organized in relation to Heschl's gyrus were isolated in 8 human hemispheres from cadaveric specimens and in 8 MRI studies in 4 healthy volunteers. In addition, these tracts and their functions were described in the surgical cases of left temporal gliomas next to the HGFIA in 6 patients who were awake during surgery and underwent intraoperative electrical stimulation mapping., Results: Five tracts were observed to pass through the HGFIA: the anterior segment of the arcuate fasciculus, the middle longitudinal fasciculus, the acoustic radiation, the inferior fronto-occipital fasciculus, and the optic radiation. In addition, U fibers originating at the level of Heschl's gyrus and heading toward the middle temporal gyrus were identified., Conclusions: This investigation of the HGFIA, a region where 5 fiber tracts intersect in a relationship with the primary auditory area, provides new insights into the subcortical organization of Wernicke's area. This information is valuable when a temporal surgical approach is planned, in order to assess the surgical risk related to language disturbances.

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., (© The Author(s) 2019. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

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., Competing Interests: Declaration of Competing Interest The content of this article does not reflect the opinion of Cochlear Ltd. and Cochlear Ltd. did not affect the content of this article. The creation of this article is not financed by Cochlear Ltd., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Auditory verbal hallucinations (AVH) are hallmark symptoms of schizophrenia and have been linked to abnormal activation, connectivity and integration within the auditory, language, and memory brain networks. The interhemispheric miscommunication theory of AVH is based on a steadily growing number of studies using a variety of modalities (EEG, fMRI, DTI) reporting that both altered integrity of the interhemispheric auditory pathways and disturbed functional gamma-band synchrony between right and left auditory cortices significantly contribute to abnormal auditory processing and the emergence of AVH. Moreover, initial studies using pharmacological EEG and 1 H MR spectroscopy provided first insights into the underlying neurochemistry of AVH. It has been suggested that the observed interhemispheric gamma-band alterations might be mediated by an excitatory-to-inhibitory (E/I) imbalance due to dysfunction of N-methyl-d-aspartate receptor (NMDAR). In support, a potential NMDAR hypofunction is proposed to be compensated by increased levels of glutamate in prefrontal and auditory brain areas. In this mini-review paper, we used the levels of explanation approach and present how interhemispheric brain connectivity (brain-imaging level) corresponds to auditory perception (cognitive level), and eventually how these parameters are related to changes in neurotransmission (cellular level) and to the occurrence of AVH (clinical level). To the best of our knowledge, this is the first overview that overcomes traditional boundaries and presents converging evidence from different levels of knowledge that validate and support each other, and particularly point toward the role of an interhemispheric miscommunication in AVH., (Copyright © 2019 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Diffusion tensor imaging is currently the only noninvasive way to map subcortical white matter tractography. Radiologists and neurologists often fail to reconstruct the complex auditory pathways when applying the most commonly used approach, deterministic fiber tracking, as this method is limited in spatial and angular resolution. A different fiber-tracking method involving a probabilistic approach could partly compensate for these limitations. We investigated efficiency and potential usefulness of probabilistic fiber tracking in depicting human auditory pathways in healthy individuals and patients with unilateral vestibular schwannoma (VS)., Methods: Eight healthy volunteers and 14 patients with unilateral VS underwent diffusion tensor imaging. Probabilistic fiber tracking of the auditory pathways for each subject was carried out using FSL software. Tracking rate, reliability of results, fiber volume, fiber length, and fractional anisotropy values were considered in assessing reliability and sensitivity of this method. Fiber length and fiber volume were analyzed separately for the healthy group and VS group., Results: Good tracking sensitivity and consistency were shown in healthy subjects and patients with VS. For fiber length, the 8 healthy subjects exhibited significant between-sides differences, whereas the 14 patients with VS showed no such difference. For fiber volume, there was a statistically significant difference between groups, as the patients with VS displayed a smaller fiber volume on the nontumor side. Fractional anisotropy values revealed no significant autologous or between-group differences. These results match results of previous anatomic and neurologic studies., Conclusions: The auditory pathway can be depicted well by probabilistic fiber tracking. This method can compensate in part for weaknesses of the widely used deterministic tractography approach in depicting fine and complicated subcortical fibers., (Copyright © 2019. Published by Elsevier Inc.)

Humans and other animals use spatial hearing to rapidly localize events in the environment. However, neural encoding of sound location is a complex process involving the computation and integration of multiple spatial cues that are not represented directly in the sensory organ (the cochlea). Our understanding of these mechanisms has increased enormously in the past few years. Current research is focused on the contribution of animal models for understanding human spatial audition, the effects of behavioural demands on neural sound location encoding, the emergence of a cue-independent location representation in the auditory cortex, and the relationship between single-source and concurrent location encoding in complex auditory scenes. Furthermore, computational modelling seeks to unravel how neural representations of sound source locations are derived from the complex binaural waveforms of real-life sounds. In this article, we review and integrate the latest insights from neurophysiological, neuroimaging and computational modelling studies of mammalian spatial hearing. We propose that the cortical representation of sound location emerges from recurrent processing taking place in a dynamic, adaptive network of early (primary) and higher-order (posterior-dorsal and dorsolateral prefrontal) auditory regions. This cortical network accommodates changing behavioural requirements and is especially relevant for processing the location of real-life, complex sounds and complex auditory scenes.

Growing evidence shows that partial auditory deprivation leads to extensive neural functional plasticity, which occurs not only in the auditory cortex but also in other sensory regions and cognitive areas. However, studies in structural topological properties are still limited, especially those investigating the relationship between structural connectome alterations and auditory abilities. To clarify this, we investigated white matter structural connectivity changes and the relationship between connection strength and hearing abilities in individuals with long-term single-sided deafness (SSD), a common form of partial hearing deprivation, using diffusion tensor imaging and network-based analysis. The results showed globally improved connection efficiency, locally weakened visual networks, and strengthened fronto-parietal sub-networks in SSD compared to normal hearing controls. Furthermore, a strong positive correlation between hearing abilities (including speech recognition in noise and sound localization) and connection strength, mainly in the fronto-parietal areas, was found in SSD. Our study reveals alteration of the structural network connections in SSD, especially in cognitive related networks, which showed close correlation with hearing abilities. Our findings provide new insights into topological white matter reorganization of the brain after partial sensory deprivation., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Auditory target detection has been explored by a number of studies, but none have demonstrated activity in the auditory subcortical centers evoked by the top-down attentional mechanism related to target detection in humans. We applied functional magnetic resonance imaging (fMRI) with sparse sampling to explore activity in the auditory centers, particularly in the subcortex, during an active auditory target detection task. Fourteen healthy subjects with normal hearing tapped the left index finger in response to target tonal stimuli presented among other (non-target) stimuli during continuous white noise stimulation. General linear model, region-of-interest, and connectivity analyses were performed. In the cortex, bilateral auditory cortices as well as the cingulate gyrus, thalamus, and supramarginal gyrus were activated to target stimuli and functionally connected to each other. In the subcortex, the superior olivary complex (SOC) and locus coeruleus were activated to the target but not to the non-target or background noise stimuli. The SOC was the only auditory subcortical center that displayed connectivity to the auditory cortical areas as well as the cingulate and supramarginal gyri during target presentation but not during other conditions. SOC activation appears to be the first fMRI evidence of direct cortico-olivary projections in the human brain as well as SOC participation in auditory target detection. Our results may be an initial step towards developing a noninvasive methodology to evaluate the functional integrity of the auditory efferent system in humans., (Copyright © 2019 Elsevier B.V. All rights reserved.)

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., (Copyright © 2019 IBRO. Published by Elsevier Ltd. All rights reserved.)

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., (© 2018 International Neuromodulation Society.)

Since its inception 30 years ago, diffusion-weighted magnetic resonance imaging (dMRI) has advanced to become a common component of routine clinical MRI examinations. Diffusion-weighted magnetic resonance offers a way to measure anisotropic diffusion in-vivo, which has led to the development of techniques capable of characterising the orientation of diffusion within living tissue. These modelling techniques can be used to investigate the microstructure and connectivity of white matter tracts within the human brain. Such techniques have been used to study many neural networks within the human body. There is, however, a notable paucity of research utilising dMRI techniques to investigate the white matter tracts of the auditory brainstem. In this review we provide a brief introduction to the basic principles of dMRI analysis and consider some of the difficulties associated with applying dMRI techniques to study the auditory pathways of the brainstem. We also consider aspects of current dMRI methodologies relevant to the auditory brainstem to inform future research in this area., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Locked-in syndrome (LIS) is a state of quadriplegia and anarthria with preserved consciousness, which is generally triggered by a disruption of specific white matter fiber tracts, following a lesion in the ventral part of the pons. However, the impact of focal lesions on the whole brain white matter microstructure and structural connectivity pathways remains unknown. We used diffusion tensor magnetic resonance imaging (DT-MRI) and tract-based statistics to characterise the whole white matter tracts in seven consecutive LIS patients, with ventral pontine injuries but no significant supratentorial lesions detected with morphological MRI. The imaging was performed in the acute phase of the disease (26 ± 13 days after the accident). DT-MRI-derived metrics were used to quantitatively assess global white matter alterations. All diffusion coefficient Z-scores were decreased for almost all fiber tracts in all LIS patients, with diffuse white matter alterations in both infratentorial and supratentorial areas. A mixture model of two multidimensional Gaussian distributions was fitted to cluster the white matter fiber tracts studied in two groups: the least (group 1) and most injured white matter fiber tracts (group 2). The greatest injuries were revealed along pathways crossing the lesion responsible for the LIS: left and right medial lemniscus (98.4% and 97.9% probability of belonging to group 2, respectively), left and right superior cerebellar peduncles (69.3% and 45.7% probability) and left and right corticospinal tract (20.6% and 46.5% probability). This approach demonstrated globally compromised white matter tracts in the acute phase of LIS, potentially underlying cognitive deficits., Competing Interests: The authors have declared that no competing interests exist.

Objective: Recent reports demonstrated that acoustic nerve disorders affect the auditory pathway on diffusion tensor imaging (DTI). The aim was to investigate whether auditory pathway fractional anisotropy (FA) values are associated with audibility in patients with cerebellopontine angle tumors., Patients and Methods: Patients with cerebellopontine angle tumors were included in this retrospective study. Preoperatively, all patients underwent magnetic resonance imaging (MRI) including DTI. Two regions of interest on the lateral lemniscus (LL) and inferior colliculus (IC) were set bilaterally on DTI. FA values were calculated using software. Correlations between FA values and audibility were evaluated using Spearman's rank correlation coefficient. Statistical significance was defined as p < 0.05., Results: Seventeen patients with cerebellopontine angle tumors were included in this study. FA values in the bilateral LL showed a significant negative correlation with hearing impairment severity (r = -0.758, -0.600, p < 0.05). FA values on the ipsilateral side of the IC showed a significant negative correlation with hearing impairment severity (r = -0.477, p < 0.05). FA values on the contralateral side of the IC did not correlate with hearing impairment severity (r = -0.201, p > 0.05). One patient with a low FA value on the contralateral side of the IC had postoperative hearing impairment despite good preoperative hearing ability., Conclusions: FA values in the bilateral LL and on the ipsilateral side of the IC reflected hearing impairment severity. Decreased FA values on the contralateral side of the IC might predict hearing impairment postoperatively., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Diffusion MRI tractography allows in-vivo characterization of white matter architecture, including the localization and description of brain fibre bundles. However, some primary bundles are still only partially reconstructed, or not reconstructed at all. The acoustic radiation (AR) represents a primary sensory pathway that has been largely omitted in many tractography studies because its location and anatomical features make it challenging to reconstruct. In this study, we investigated the effects of acquisition and tractography parameters on the AR reconstruction using publicly available Human Connectome Project data. The aims of this study are: (i) using a subgroup of subjects and a reference AR for each subject, define an optimum set of parameters for AR reconstruction, and (ii) use the optimum parameters set on the full group to build a tractography-based atlas of the AR. Starting from the same data, the use of different acquisition and tractography parameters lead to very different AR reconstructions. Optimal results in terms of topographical accuracy and correspondence to the reference were obtained for probabilistic tractography, high b-values and default tractography parameters: these parameters were used to build an AR probabilistic tractography atlas. A significant left-hemispheric lateralization was found in the AR reconstruction of the 34 subjects.

Objectives: We report on a patient with sensorineural hearing loss from injury of the auditory radiation following mild TBI, diagnosed by diffusion tensor tractography (DTT)., Method: A 35-year-old female patient suffered head trauma. While walking in a crosswalk, her left lumbar area was hit by a turning car and she fell to the ground. She was pulled behind the car for several meters while her occipital area repeatedly hit the ground. She complained that she began to feel hearing impairment approximately two weeks after the head trauma, that aggravated over time. Approximately 1.5 years after head trauma, when she visited a university hospital for evaluation of the brain, she complained of severe hearing impairment. To characterize the patient's hearing loss, pure tone audiometry was evaluated in a sound proof room to screen her hearing status for the frequencies 250-8000 Hz. A pure tone threshold in the range of 41-60 dB HL was considered moderate sensorineural hearing loss and 61-80 dB HL severe. However, no abnormality was observed in either ear on physical examination. The patient was diagnosed with bilateral moderate sensorineural hearing loss., Results: On 1.5 year DTT, the auditory radiation was narrowed in both hemispheres., Conclusion: Neural injury of the auditory radiation was demonstrated in a patient with sensorineural hearing loss following mild TBI, using DTT.

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., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

Chronic subjective tinnitus is a widespread disorder. This perceptual anomaly is assumed to result from a dysbalance of excitatory and inhibitory mechanisms on different levels of the auditory pathways. However, the brain areas involved are still under discussion. Using resting-state functional magnetic resonance imaging, we investigate differences in cerebral regional homogeneity (ReHo) between patients with unilateral chronic tinnitus and nontinnitus control subjects. To our knowledge, our study is the first to investigate the intraregional connectivity of patients with unilateral tinnitus in relation to hearing loss. Our analyses, based on strict recruitment and characterization of the participants, showed reduced ReHo in the primary auditory cortex contralateral to the side of the perceived tinnitus percept in patients. Reduced ReHo in this same region was also correlated with increased Tinnitus Handicap Inventory and Visual Analogue Scale for loudness scores, reflecting an alteration of synchronization in this region related to the perceived loudness of the tinnitus and the related distress. Furthermore, increased ReHo in the supramarginal and angular gyri ipsilateral to the tinnitus side was correlated with increased tinnitus duration and hearing threshold at the tinnitus pitch. The correlations observed in these brain areas, which are normally related to the nontinnitus ear, could highlight compensatory mechanisms in these secondary auditory regions.

Functional neuroimaging has identified that the temporal, frontal and parietal cortex support core aspects of speech processing. An objective measure of speech intelligibility based on cortical activation in these brain regions would be extremely useful to speech communication and hearing device applications. In the current study, we used noise-vocoded speech to examine cortical correlates of speech intelligibility in normally-hearing listeners using functional near-infrared spectroscopy (fNIRS), a non-invasive, neuroimaging technique that is fully-compatible with hearing devices, including cochlear implants. In twenty-three normally-hearing adults we measured (1) activation in superior temporal, inferior frontal and inferior parietal cortex bilaterally and (2) behavioural speech intelligibility. Listeners heard noise-vocoded sentences targeting five equally spaced levels of intelligibility between 0 and 100% correct. Activation in superior temporal regions increased linearly with intelligibility. This relationship appears to have been driven in part by changing acoustic properties across stimulation conditions, rather than solely by intelligibility per se. Superior temporal activation was also predictive of individual differences in intelligibility in a challenging listening condition. Beyond superior temporal cortex, we identified regions in which activation varied non-linearly with intelligibility. For example, in left inferior frontal cortex, activation peaked in response to heavily degraded, yet still somewhat intelligible, speech. Activation in this region was linearly related to response time on a simultaneous behavioural task, suggesting it may contribute to decision making. Our results indicate that fNIRS has the potential to provide an objective measure of speech intelligibility in normally-hearing listeners. Should these results be found to apply similarly in the case of individuals listening through a cochlear implant, fNIRS would demonstrate potential for a clinically useful measure not only of speech intelligibility, but also of listening effort., (Crown Copyright © 2018. Published by Elsevier B.V. All rights reserved.)

Music learning has received increasing attention in the last decades due to the variety of functions and brain plasticity effects involved during its practice. Most previous reports interpreted the differences between music experts and laymen as the result of training. However, recent investigations suggest that these differences are due to a combination of genetic predispositions with the effect of music training. Here, we tested the relationship of the dorsal auditory-motor pathway with individual behavioural differences in short-term music learning. We gathered structural neuroimaging data from 44 healthy non-musicians (28 females) before they performed a rhythm- and a melody-learning task during a single behavioural session, and manually dissected the arcuate fasciculus (AF) in both hemispheres. The macro- and microstructural organization of the AF (i.e., volume and FA) predicted the learning rate and learning speed in the musical tasks, but only in the right hemisphere. Specifically, the volume of the right anterior segment predicted the synchronization improvement during the rhythm task, the FA in the right long segment was correlated with the learning rate in the melody task, and the volume and FA of the right whole AF predicted the learning speed during the melody task. This is the first study finding a specific relation between different branches within the AF and rhythmic and melodic materials. Our results support the relevant function of the AF as the structural correlate of both auditory-motor transformations and the feedback-feedforward loop, and suggest a crucial involvement of the anterior segment in error-monitoring processes related to auditory-motor learning. These findings have implications for both the neuroscience of music field and second-language learning investigations., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Activation studies with positron emission tomography (PET) in auditory implant users explained some of the mechanisms underlying the variability of achieved speech comprehension. Since future developments of auditory implants will include studies in rodents, we aimed to inversely translate functional PET imaging to rats. In normal hearing rats, activity in auditory and non-auditory regions was studied using 18F-fluorodeoxyglucose (18F-FDG) PET with 3 different acoustic conditions: sound attenuated laboratory background, continuous white noise and rippled noise. Additionally, bilateral cochlea ablated animals were scanned. 3D image data were transferred into a stereotaxic standard space and evaluated using volume of interest (VOI) analyses and statistical parametric mapping (SPM). In normal hearing rats alongside the auditory pathway consistent activations of the nucleus cochlearis (NC), olivary complex (OC) and inferior colliculus (IC) were seen comparing stimuli with background. In this respect, no increased activation could be detected in the auditory cortex (AC), which even showed deactivation with white noise stimulation. Nevertheless, higher activity in the AC in normal hearing rats was observed for all 3 auditory conditions against the cochlea ablated status. Vice versa, in ablated status activity in the olfactory nucleus (ON) was higher compared to all auditory conditions in normal hearing rats. Our results indicate that activations can be demonstrated in normal hearing animals based on 18F-FDG PET in nuclei along the central auditory pathway with different types of noise stimuli. However, in the AC missing activation with respect to the background advises the need for more rigorous background noise attenuation for non-invasive reference conditions. Finally, our data suggest cross-modal activation of the olfactory system following cochlea ablation-underlining, that 18F-FDG PET appears to be well suited to study plasticity in rat models for cochlear implantation., Competing Interests: The authors have declared that no competing interests exist.

Bayesian models of brain function such as active inference and predictive coding offer a general theoretical framework with which to explain several aspects of normal and disordered brain function. Of particular interest to the present study is the potential for such models to explain the pathology of auditory phantom perception, i.e. tinnitus. To test this framework empirically, we perform an fMRI experiment on a large clinical sample (n = 75) of the human chronic tinnitus population. The experiment features a within-subject design based on two experimental conditions: subjects were presented with sound stimuli matched to their tinnitus frequency (TF) as well as similar stimuli presented at a control frequency (CF). The responses elicited by these stimuli, as measured using both activity and functional connectivity, were then analyzed both within and between conditions. Given the Bayesian-brain framework, we hypothesize that TF stimuli will elicit greater activity and/or functional connectivity in areas related to the cognitive and emotional aspects of tinnitus, i.e. tinnitus-related distress. We conversely hypothesize that CF stimuli will elicit greater activity/connectivity in areas related to auditory perception and attention. We discuss our results in the context of this framework and suggest future directions for empirical testing., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Purpose: We aimed to evaluate the change in bilateral auditory pathways using diffusion tensor imaging (DTI) after gamma knife radiosurgery (GKR) and to determine the relationship between the radiosurgical treatment variables and DTI findings., Methods: In this study 13 patients with unilateral acoustic neuroma and 11 controls underwent routine magnetic resonance imaging (MRI) and DTI. The apparent diffusion coefficient (ADC) and fractional anisotropy (FA) were measured from the bilateral auditory pathways in all individuals before and after GKR., Results: Before GKR, subjects' ADC values obtained from the contralateral side were higher at the lateral lemniscus, medial geniculate body and Heschl's gyrus compared to those of the controls. No statistical differences were found in ADC and FA obtained at bilateral auditory pathways before and after GKR. The ADCs measured at the lateral lemniscus were positively correlated with the maximum radiation dose delivered to the brainstem (BS) and the brainstem volume receiving a radiation dose of 10 Gy (BS V10). A negative correlation was found between the FA measured from the inferior colliculus and the maximum radiation dose to the cochlea. The ADCs at the inferior colliculus were positively correlated with the mean radiation dose to the cochlea., Conclusion: There were no significant differences in the degree of involvement before and after GKR, revealing that GKR did not significantly affect the auditory pathways at 4 months. The major factors that may lead to microstructural injury to auditory pathways at the brainstem level are associated with maximum brainstem radiation dose, BS V10, and cochlear dose. These findings may suggest that more attention should be paid to anatomical structures including the cochlea and brainstem during treatment planning of GKR.

The influential dual-stream model of auditory processing stipulates that information pertaining to the meaning and to the position of a given sound object is processed in parallel along two distinct pathways, the ventral and dorsal auditory streams. Functional independence of the two processing pathways is well documented by conscious experience of patients with focal hemispheric lesions. On the other hand there is growing evidence that the meaning and the position of a sound are combined early in the processing pathway, possibly already at the level of early-stage auditory areas. Here, we investigated how early auditory areas integrate sound object meaning and space (simulated by interaural time differences) using a repetition suppression fMRI paradigm at 7 T. Subjects listen passively to environmental sounds presented in blocks of repetitions of the same sound object (same category) or different sounds objects (different categories), perceived either in the left or right space (no change within block) or shifted left-to-right or right-to-left halfway in the block (change within block). Environmental sounds activated bilaterally the superior temporal gyrus, middle temporal gyrus, inferior frontal gyrus, and right precentral cortex. Repetitions suppression effects were measured within bilateral early-stage auditory areas in the lateral portion of the Heschl's gyrus and posterior superior temporal plane. Left lateral early-stages areas showed significant effects for position and change, interactions Category x Initial Position and Category x Change in Position, while right lateral areas showed main effect of category and interaction Category x Change in Position. The combined evidence from our study and from previous studies speaks in favour of a position-linked representation of sound objects, which is independent from semantic encoding within the ventral stream and from spatial encoding within the dorsal stream. We argue for a third auditory stream, which has its origin in lateral belt areas and tracks sound objects across space., (Copyright © 2018. Published by Elsevier B.V.)