Changes in primary visual and auditory cortex of blind and sighted adults following 10 weeks of click-based echolocation training.

Recent work suggests that the adult human brain is very adaptable when it comes to sensory processing. In this context, it has also been suggested that structural "blueprints" may fundamentally constrain neuroplastic change, e.g. in response to sensory deprivation. Here, we trained 12 blind participants and 14 sighted participants in echolocation over a 10-week period, and used MRI in a pre-post design to measure functional and structural brain changes. We found that blind participants and sighted participants together showed a training-induced increase in activation in left and right V1 in response to echoes, a finding difficult to reconcile with the view that sensory cortex is strictly organized by modality. Further, blind participants and sighted participants showed a training induced increase in activation in right A1 in response to sounds per se (i.e. not echo-specific), and this was accompanied by an increase in gray matter density in right A1 in blind participants and in adjacent acoustic areas in sighted participants. The similarity in functional results between sighted participants and blind participants is consistent with the idea that reorganization may be governed by similar principles in the two groups, yet our structural analyses also showed differences between the groups suggesting that a more nuanced view may be required.

Developmental hearing loss-induced perceptual deficits are rescued by genetic restoration of cortical inhibition.

Even a transient period of hearing loss during the developmental critical period can induce long-lasting deficits in temporal and spectral perception. These perceptual deficits correlate with speech perception in humans. In gerbils, these hearing loss-induced perceptual deficits are correlated with a reduction of both ionotropic GABAA and metabotropic GABAB receptor-mediated synaptic inhibition in auditory cortex, but most research on critical period plasticity has focused on GABAA receptors. Therefore, we developed viral vectors to express proteins that would upregulate gerbil postsynaptic inhibitory receptor subunits (GABAA, Gabra1; GABAB, Gabbr1b) in pyramidal neurons, and an enzyme that mediates GABA synthesis (GAD65) presynaptically in parvalbumin-expressing interneurons. A transient period of developmental hearing loss during the auditory critical period significantly impaired perceptual performance on two auditory tasks: amplitude modulation depth detection and spectral modulation depth detection. We then tested the capacity of each vector to restore perceptual performance on these auditory tasks. While both GABA receptor vectors increased the amplitude of cortical inhibitory postsynaptic potentials, only viral expression of postsynaptic GABAB receptors improved perceptual thresholds to control levels. Similarly, presynaptic GAD65 expression improved perceptual performance on spectral modulation detection. These findings suggest that recovering performance on auditory perceptual tasks depends on GABAB receptor-dependent transmission at the auditory cortex parvalbumin to pyramidal synapse and point to potential therapeutic targets for developmental sensory disorders.

Congenital deafness reduces alpha-gamma cross-frequency coupling in the auditory cortex.

Neurons within a neuronal network can be grouped by bottom-up and top-down influences using synchrony in neuronal oscillations. This creates the representation of perceptual objects from sensory features. Oscillatory activity can be differentiated into stimulus-phase-locked (evoked) and non-phase-locked (induced). The former is mainly determined by sensory input, the latter by higher-level (cortical) processing. Effects of auditory deprivation on cortical oscillations have been studied in congenitally deaf cats (CDCs) using cochlear implant (CI) stimulation. CI-induced alpha, beta, and gamma activity were compromised in the auditory cortex of CDCs. Furthermore, top-down information flow between secondary and primary auditory areas in hearing cats, conveyed by induced alpha oscillations, was lost in CDCs. Here we used the matching pursuit algorithm to assess components of such oscillatory activity in local field potentials recorded in primary field A1. Additionally to the loss of induced alpha oscillations, we also found a loss of evoked theta activity in CDCs. The loss of theta and alpha activity in CDCs can be directly related to reduced high-frequency (gamma-band) activity due to cross-frequency coupling. Here we quantified such cross-frequency coupling in adult 1) hearing-experienced, acoustically stimulated cats (aHCs), 2) hearing-experienced cats following acute pharmacological deafening and subsequent CIs, thus in electrically stimulated cats (eHCs), and 3) electrically stimulated CDCs. We found significant cross-frequency coupling in all animal groups in > 70% of auditory-responsive sites. The predominant coupling in aHCs and eHCs was between theta/alpha phase and gamma power. In CDCs such coupling was lost and replaced by alpha oscillations coupling to delta/theta phase. Thus, alpha/theta oscillations synchronize high-frequency gamma activity only in hearing-experienced cats. The absence of induced alpha and theta oscillations contributes to the loss of induced gamma power in CDCs, thereby signifying impaired local network activity.

Changes in visually and auditory attended audiovisual speech processing in cochlear implant users: A longitudinal ERP study.

Limited auditory input, whether caused by hearing loss or by electrical stimulation through a cochlear implant (CI), can be compensated by the remaining senses. Specifically for CI users, previous studies reported not only improved visual skills, but also altered cortical processing of unisensory visual and auditory stimuli. However, in multisensory scenarios, it is still unclear how auditory deprivation (before implantation) and electrical hearing experience (after implantation) affect cortical audiovisual speech processing. Here, we present a prospective longitudinal electroencephalography (EEG) study which systematically examined the deprivation- and CI-induced alterations of cortical processing of audiovisual words by comparing event-related potentials (ERPs) in postlingually deafened CI users before and after implantation (five weeks and six months of CI use). A group of matched normal-hearing (NH) listeners served as controls. The participants performed a word-identification task with congruent and incongruent audiovisual words, focusing their attention on either the visual (lip movement) or the auditory speech signal. This allowed us to study the (top-down) attention effect on the (bottom-up) sensory cortical processing of audiovisual speech. When compared to the NH listeners, the CI candidates (before implantation) and the CI users (after implantation) exhibited enhanced lipreading abilities and an altered cortical response at the N1 latency range (90-150 ms) that was characterized by a decreased theta oscillation power (4-8 Hz) and a smaller amplitude in the auditory cortex. After implantation, however, the auditory-cortex response gradually increased and developed a stronger intra-modal connectivity. Nevertheless, task efficiency and activation in the visual cortex was significantly modulated in both groups by focusing attention on the visual as compared to the auditory speech signal, with the NH listeners additionally showing an attention-dependent decrease in beta oscillation power (13-30 Hz). In sum, these results suggest remarkable deprivation effects on audiovisual speech processing in the auditory cortex, which partially reverse after implantation. Although even experienced CI users still show distinct audiovisual speech processing compared to NH listeners, pronounced effects of (top-down) direction of attention on (bottom-up) audiovisual processing can be observed in both groups. However, NH listeners but not CI users appear to show enhanced allocation of cognitive resources in visually as compared to auditory attended audiovisual speech conditions, which supports our behavioural observations of poorer lipreading abilities and reduced visual influence on audition in NH listeners as compared to CI users.

Neural processing in the primary auditory cortex following cholinergic lesions of the basal forebrain in ferrets.

Cortical acetylcholine (ACh) release has been linked to various cognitive functions, including perceptual learning. We have previously shown that cortical cholinergic innervation is necessary for accurate sound localization in ferrets, as well as for their ability to adapt with training to altered spatial cues. To explore whether these behavioral deficits are associated with changes in the response properties of cortical neurons, we recorded neural activity in the primary auditory cortex (A1) of anesthetized ferrets in which cholinergic inputs had been reduced by making bilateral injections of the immunotoxin ME20.4-SAP in the nucleus basalis (NB) prior to training the animals. The pattern of spontaneous activity of A1 units recorded in the ferrets with cholinergic lesions (NB ACh-) was similar to that in controls, although the proportion of burst-type units was significantly lower. Depletion of ACh also resulted in more synchronous activity in A1. No changes in thresholds, frequency tuning or in the distribution of characteristic frequencies were found in these animals. When tested with normal acoustic inputs, the spatial sensitivity of A1 neurons in the NB ACh- ferrets and the distribution of their preferred interaural level differences also closely resembled those found in control animals, indicating that these properties had not been altered by sound localization training with one ear occluded. Simulating the animals' previous experience with a virtual earplug in one ear reduced the contralateral preference of A1 units in both groups, but caused azimuth sensitivity to change in slightly different ways, which may reflect the modest adaptation observed in the NB ACh- group. These results show that while ACh is required for behavioral adaptation to altered spatial cues, it is not required for maintenance of the spectral and spatial response properties of A1 neurons.

Sex differences during development in cortical temporal processing and event related potentials in wild-type and fragile X syndrome model mice.

BACKGROUND: Autism spectrum disorder (ASD) is currently diagnosed in approximately 1 in 44 children in the United States, based on a wide array of symptoms, including sensory dysfunction and abnormal language development. Boys are diagnosed ~ 3.8 times more frequently than girls. Auditory temporal processing is crucial for speech recognition and language development. Abnormal development of temporal processing may account for ASD language impairments. Sex differences in the development of temporal processing may underlie the differences in language outcomes in male and female children with ASD. To understand mechanisms of potential sex differences in temporal processing requires a preclinical model. However, there are no studies that have addressed sex differences in temporal processing across development in any animal model of ASD. METHODS: To fill this major gap, we compared the development of auditory temporal processing in male and female wildtype (WT) and Fmr1 knock-out (KO) mice, a model of Fragile X Syndrome (FXS), a leading genetic cause of ASD-associated behaviors. Using epidural screw electrodes, we recorded auditory event related potentials (ERP) and auditory temporal processing with a gap-in-noise auditory steady state response (ASSR) paradigm at young (postnatal (p)21 and p30) and adult (p60) ages from both auditory and frontal cortices of awake, freely moving mice. RESULTS: The results show that ERP amplitudes were enhanced in both sexes of Fmr1 KO mice across development compared to WT counterparts, with greater enhancement in adult female than adult male KO mice. Gap-ASSR deficits were seen in the frontal, but not auditory, cortex in early development (p21) in female KO mice. Unlike male KO mice, female KO mice show WT-like temporal processing at p30. There were no temporal processing deficits in the adult mice of both sexes. CONCLUSIONS: These results show a sex difference in the developmental trajectories of temporal processing and hypersensitive responses in Fmr1 KO mice. Male KO mice show slower maturation of temporal processing than females. Female KO mice show stronger hypersensitive responses than males later in development. The differences in maturation rates of temporal processing and hypersensitive responses during various critical periods of development may lead to sex differences in language function, arousal and anxiety in FXS.

Intensity-dependent modulation of the early auditory gamma-band response in first-episode schizophrenia and its association with disease symptoms.

BACKGROUND: Gamma-band activity has been the focus of considerable research in schizophrenia. Discrepancies exist regarding the integrity of the early auditory gamma-band response (EAGBR), a stimulus-evoked oscillation, and its relationship to symptoms in early disease. Variability in task design may play a role. This study examined sensitivity of the EAGBR to stimulus intensity and its relation to symptoms and functional impairments in the first-episode schizophrenia spectrum (FESz). METHOD: Magnetoencephalography was recorded from 35 FESz and 40 matched healthy controls (HC) during presentation of 3 tone intensities (75 dB, 80 dB, 85 dB). MRIs were collected to localize auditory cortex activity. Wavelet-transformed single trial epochs and trial averages were used to assess EAGBR intertrial phase coherence (ITPC) and evoked power, respectively. Symptoms were assessed using the Positive and Negative Syndrome Scale. RESULTS: Groups did not differ in overall EAGBR power or ITPC. While HC exhibited EAGBR enhancement to increasing intensity, FESz exhibited reduced power to the 80 dB tone and, relative to HC, increased power to the 75 dB tone. Larger power and ITPC were correlated with more severe negative, thought disorganization, and resistance symptoms. Stronger ITPC was associated with impaired social functioning. DISCUSSION: EAGBR showed no overall deficit at disease onset. Rather, FESz exhibited a differential response across tone intensity relative to HC, emphasizing the importance of stimulus characteristics in EAGBR studies. Associations between larger EAGBR and more severe symptoms suggest aberrant synchronization driving overinclusive perceptual binding that may relate to deficits in executive inhibition of initial sensory activity.

Abnormalities in both stimulus-induced and baseline MEG alpha oscillations in the auditory cortex of children with Autism Spectrum Disorder.

The neurobiology of Autism Spectrum Disorder (ASD) is hypothetically related to the imbalance between neural excitation (E) and inhibition (I). Different studies have revealed that alpha-band (8-12 Hz) activity in magneto- and electroencephalography (MEG and EEG) may reflect E and I processes and, thus, can be of particular interest in ASD research. Previous findings indicated alterations in event-related and baseline alpha activity in different cortical systems in individuals with ASD, and these abnormalities were associated with core and co-occurring conditions of ASD. However, the knowledge on auditory alpha oscillations in this population is limited. This MEG study investigated stimulus-induced (Event-Related Desynchronization, ERD) and baseline alpha-band activity (both periodic and aperiodic) in the auditory cortex and also the relationships between these neural activities and behavioral measures of children with ASD. Ninety amplitude-modulated tones were presented to two groups of children: 20 children with ASD (5 girls, Mage = 10.03, SD = 1.7) and 20 typically developing controls (9 girls, Mage = 9.11, SD = 1.3). Children with ASD had a bilateral reduction of alpha-band ERD, reduced baseline aperiodic-adjusted alpha power, and flattened aperiodic exponent in comparison to TD children. Moreover, lower raw baseline alpha power and aperiodic offset in the language-dominant left auditory cortex were associated with better language skills of children with ASD measured in formal assessment. The findings highlighted the alterations of E / I balance metrics in response to basic auditory stimuli in children with ASD and also provided evidence for the contribution of low-level processing to language difficulties in ASD.

Central Auditory Changes Associated with Age-related Hearing Loss.

Objective. This study aimed to investigate age-related changes in cortical auditory evoked potentials (CAEPs) while considering three crucial factors: aging, high-frequency hearing loss and sensation level of the CAEP stimulus. Method. The electrophysiological and audiometric data of 71 elderly participants were analyzed using multiple regression analysis to investigate the association of CAEPs with the factors of aging, high-frequency hearing loss and sensation level of the CAEP test stimulus. Results. Aging was significantly associated with prolonged N1 and P2 latencies and reduced P2 amplitude. Elevated thresholds related to the sensation level of the CAEP stimulus were significantly associated with increased N1 and P2 amplitudes and decreased N1 latency. A significant relationship was detected between high-frequency hearing thresholds and the shortening of P2 latencies and the reduction of P2 amplitudes. Conclusion. The results of this study highlight the complex interplay of aging, high-frequency hearing loss and the sensation level of the CAEP stimulus on CAEP components in elderly people. These factors should be considered in future research using CAEPs to enhance overall understanding of auditory processing in the aging population.

Surface electrical stimulation of the auditory cortex preserves efferent medial olivocochlear neurons and reduces cochlear traits of age-related hearing loss.

The auditory cortex is the source of descending connections providing contextual feedback for auditory signal processing at almost all levels of the lemniscal auditory pathway. Such feedback is essential for cognitive processing. It is likely that corticofugal pathways are degraded with aging, becoming important players in age-related hearing loss and, by extension, in cognitive decline. We are testing the hypothesis that surface, epidural stimulation of the auditory cortex during aging may regulate the activity of corticofugal pathways, resulting in modulation of central and peripheral traits of auditory aging. Increased auditory thresholds during ongoing age-related hearing loss in the rat are attenuated after two weeks of epidural stimulation with direct current applied to the surface of the auditory cortex for two weeks in alternate days (Fernández del Campo et al., 2024). Here we report that the same cortical electrical stimulation protocol induces structural and cytochemical changes in the aging cochlea and auditory brainstem, which may underlie recovery of age-degraded auditory sensitivity. Specifically, we found that in 18 month-old rats after two weeks of cortical electrical stimulation there is, relative to age-matched non-stimulated rats: a) a larger number of choline acetyltransferase immunoreactive neuronal cell body profiles in the ventral nucleus of the trapezoid body, originating the medial olivocochlear system.; b) a reduction of age-related dystrophic changes in the stria vascularis; c) diminished immunoreactivity for the pro-inflammatory cytokine TNFα in the stria vascularis and spiral ligament. d) diminished immunoreactivity for Iba1 and changes in the morphology of Iba1 immunoreactive cells in the lateral wall, suggesting reduced activation of macrophage/microglia; d) Increased immunoreactivity levels for calretinin in spiral ganglion neurons, suggesting excitability modulation by corticofugal stimulation. Altogether, these findings support that non-invasive neuromodulation of the auditory cortex during aging preserves the cochlear efferent system and ameliorates cochlear aging traits, including stria vascularis dystrophy, dysregulated inflammation and altered excitability in primary auditory neurons.

Topography and Ensemble Activity in the Auditory Cortex of a Mouse Model of Fragile X Syndrome.

Autism spectrum disorder (ASD) is often associated with social communication impairments and specific sound processing deficits, for example, problems in following speech in noisy environments. To investigate underlying neuronal processing defects located in the auditory cortex (AC), we performed two-photon Ca2+ imaging in FMR1 (fragile X messenger ribonucleoprotein 1) knock-out (KO) mice, a model for fragile X syndrome (FXS), the most common cause of hereditary ASD in humans. For primary AC (A1) and the anterior auditory field (AAF), topographic frequency representation was less ordered compared with control animals. We additionally analyzed ensemble AC activity in response to various sounds and found subfield-specific differences. In A1, ensemble correlations were lower in general, while in secondary AC (A2), correlations were higher in response to complex sounds, but not to pure tones. Furthermore, sound specificity of ensemble activity was decreased in AAF. Repeating these experiments 1 week later revealed no major differences regarding representational drift. Nevertheless, we found subfield- and genotype-specific changes in ensemble correlation values between the two times points, hinting at alterations in network stability in FMR1 KO mice. These detailed insights into AC network activity and topography in FMR1 KO mice add to the understanding of auditory processing defects in FXS.

A systematic review of altered resting-state networks in early deafness and implications for cochlear implantation outcomes.

Auditory deprivation following congenital/pre-lingual deafness (C/PD) can drastically affect brain development and its functional organisation. This systematic review intends to extend current knowledge of the impact of C/PD and deafness duration on brain resting-state networks (RSNs), review changes in RSNs and spoken language outcomes post-cochlear implant (CI) and draw conclusions for future research. The systematic literature search followed the PRISMA guideline. Two independent reviewers searched four electronic databases using combined keywords: 'auditory deprivation', 'congenital/prelingual deafness', 'resting-state functional connectivity' (RSFC), 'resting-state fMRI' and 'cochlear implant'. Seventeen studies (16 cross-sectional and one longitudinal) met the inclusion criteria. Using the Crowe Critical Appraisal Tool, the publications' quality was rated between 65.0% and 92.5% (mean: 84.10%), ≥80% in 13 out of 17 studies. A few studies were deficient in sampling and/or ethical considerations. According to the findings, early auditory deprivation results in enhanced RSFC between the auditory network and brain networks involved in non-verbal communication, and high levels of spontaneous neural activity in the auditory cortex before CI are evidence of occupied auditory cortical areas with other sensory modalities (cross-modal plasticity) and sub-optimal CI outcomes. Overall, current evidence supports the idea that moreover intramodal and cross-modal plasticity, the entire brain adaptation following auditory deprivation contributes to spoken language development and compensatory behaviours.

Locus coeruleus activity improves cochlear implant performance.

Cochlear implants (CIs) are neuroprosthetic devices that can provide hearing to deaf people1. Despite the benefits offered by CIs, the time taken for hearing to be restored and perceptual accuracy after long-term CI use remain highly variable2,3. CI use is believed to require neuroplasticity in the central auditory system, and differential engagement of neuroplastic mechanisms might contribute to the variability in outcomes4-7. Despite extensive studies on how CIs activate the auditory system4,8-12, the understanding of CI-related neuroplasticity remains limited. One potent factor enabling plasticity is the neuromodulator noradrenaline from the brainstem locus coeruleus (LC). Here we examine behavioural responses and neural activity in LC and auditory cortex of deafened rats fitted with multi-channel CIs. The rats were trained on a reward-based auditory task, and showed considerable individual differences of learning rates and maximum performance. LC photometry predicted when CI subjects began responding to sounds and longer-term perceptual accuracy. Optogenetic LC stimulation produced faster learning and higher long-term accuracy. Auditory cortical responses to CI stimulation reflected behavioural performance, with enhanced responses to rewarded stimuli and decreased distinction between unrewarded stimuli. Adequate engagement of central neuromodulatory systems is thus a potential clinically relevant target for optimizing neuroprosthetic device use.

Hyperexcitable and immature-like neuronal activity in the auditory cortex of adult rats lacking the language-linked CNTNAP2 gene.

The contactin-associated protein-like 2 gene, CNTNAP2, is a highly penetrant risk gene thought to play a role in the genetic etiology of language-related disorders, such as autism spectrum disorder and developmental language disorder. Despite its candidacy for influencing language development, few preclinical studies have examined the role of CNTNAP2 in auditory processing. Using in vivo and in vitro electrophysiological recordings in a rat model with translational validity, we report that a loss of the Cntnap2 gene function caused immature-like cortical evoked potentials, delayed multiunit response latencies to acoustic stimuli, impaired temporal processing, and led to a pattern of hyperexcitability in both multiunit and single cell recordings in adulthood. These collective results provide direct evidence that a constitutive loss of Cntnap2 gene function in rats can cause auditory processing impairments similar to those seen in language-related human disorders, indicating that its contribution in maintaining cortical neuron excitability may underlie the cortical activity alterations observed in Cntnap2-/- rats.

Reduced Learning of Sound Categories in Dyslexia Is Associated with Reduced Regularity-Induced Auditory Cortex Adaptation.

A main characteristic of dyslexia is poor use of sound categories. We now studied within-session learning of new sound categories in dyslexia, behaviorally and neurally, using fMRI. Human participants (males and females) with and without dyslexia were asked to discriminate which of two serially-presented tones had a higher pitch. The task was administered in two protocols, with and without a repeated reference frequency. The reference condition introduces regularity, and enhances frequency sensitivity in typically developing (TD) individuals. Enhanced sensitivity facilitates the formation of "high" and "low" pitch categories above and below this reference, respectively. We found that in TDs, learning was paralleled by a gradual decrease in activation of the primary auditory cortex (PAC), and reduced activation of the superior temporal gyrus (STG) and left posterior parietal cortex (PPC), which are important for using sensory history. No such sensitivity was found among individuals with dyslexia (IDDs). Rather, IDDs showed reduced behavioral learning of stimulus regularities and no regularity-associated adaptation in the auditory cortex or in higher-level regions. We propose that IDDs' reduced cortical adaptation, associated with reduced behavioral learning of sound regularities, underlies their impoverished use of stimulus history, and consequently impedes their formation of rich sound categories.SIGNIFICANCE STATEMENT Reading difficulties in dyslexia are often attributed to poor use of phonological categories. To test whether poor category use could result from poor learning of new sound categories in general, we administered an auditory discrimination task that examined the learning of new pitch categories above and below a repeated reference sound. Individuals with dyslexia (IDDs) learned categories slower than typically developing (TD) individuals. TD individuals showed adaptation to the repeated sounds that paralleled the category learning in their primary auditory cortex (PAC) and other higher-level regions. In dyslexia, no brain region showed such adaptation. We suggest that poor learning of sound statistics in sensory regions may underlie the poor representations of both speech and nonspeech categories in dyslexia.

Striatal networks for tinnitus treatment targeting.

Neuromodulation treatment effect size for bothersome tinnitus may be larger and more predictable by adopting a target selection approach guided by personalized striatal networks or functional connectivity maps. Several corticostriatal mechanisms are likely to play a role in tinnitus, including the dorsal/ventral striatum and the putamen. We examined whether significant tinnitus treatment response by deep brain stimulation (DBS) of the caudate nucleus may be related to striatal network increased functional connectivity with tinnitus networks that involve the auditory cortex or ventral cerebellum. The first study was a cross-sectional 2-by-2 factorial design (tinnitus, no tinnitus; hearing loss, normal hearing, n = 68) to define cohort level abnormal functional connectivity maps using high-field 7.0 T resting-state fMRI. The second study was a pilot case-control series (n = 2) to examine whether tinnitus modulation response to caudate tail subdivision stimulation would be contingent on individual level striatal connectivity map relationships with tinnitus networks. Resting-state fMRI identified five caudate subdivisions with abnormal cohort level functional connectivity maps. Of those, two connectivity maps exhibited increased connectivity with tinnitus networks-dorsal caudate head with Heschl's gyrus and caudate tail with the ventral cerebellum. DBS of the caudate tail in the case-series responder resulted in dramatic reductions in tinnitus severity and loudness, in contrast to the nonresponder who showed no tinnitus modulation. The individual level connectivity map of the responder was in alignment with the cohort expectation connectivity map, where the caudate tail exhibited increased connectivity with tinnitus networks, whereas the nonresponder individual level connectivity map did not.

The effectiveness of the combined transcranial direct current stimulation (tDCS) and tailor-made notched music training (TMNMT) on psychoacoustic, psychometric, and cognitive indices of tinnitus patients.

PURPOSE: Tinnitus network(s) consists of pathways in the auditory cortex, frontal cortex, and the limbic system. The cortical hyperactivity caused by tinnitus may be suppressed by neuromodulation techniques. Due to the lack of definitive treatment for tinnitus and limited usefulness of the individual methods, in this study, a combination of transcranial direct current stimulation (tDCS) over the dorsolateral prefrontal cortex (DLPFC) and tailor-made notched music training (TMNMT) was used. MATERIAL AND METHODS: In this descriptive-analytic study, 26 patients with chronic unilateral tinnitus of the right ear were randomly divided into the clinical trial group (CTG) and the control group (CG). In both groups, six sessions of tDCS with 2 mA intensity for 20 min, with anode on F4 and cathode on F3, were conducted. Simultaneous with tDCS sessions, and based on TMNMT, the participant was asked to listen passively for 120 min/day, to a CD containing her/his favorite music with a proper notch applied in its spectrum according to the individual's tinnitus The treatment outcome was measured by, psychoacoustic (loudness-matching), psychometric (awareness, loudness and annoyance Visual Analogue Scale (VAS) scores, and Tinnitus Handicap Inventory (THI)) scores, and cognitive assessments (randomized dichotic digits test (RDDT) and dichotic auditory-verbal memory test (DAVMT)). Repeated measurement test was used for statistical analyses. RESULTS: In the CTG, the tinnitus loudness and annoyance VAS scores, and THI were reduced significantly (p = 0.001). In addition, the DAVMT and RDDT scores were enhanced (p = 0.001). Such changes were not observed in the CG (p > 0.05). CONCLUSION: The combination of tDCS and TMNMT led to a reduction in the loudness, awareness, annoyance, and also disability induced by tinnitus in CTG. Furthermore, this method showed an improvement of cognitive functions (auditory divided attention, selective attention and working memory) in the CTG.

Cross-modal connectivity effects in age-related hearing loss.

Age-related sensorineural hearing loss (HL) leads to localized brain changes in the primary auditory cortex, long-range functional alterations, and is considered a risk factor for dementia. Nonhuman studies have repeatedly highlighted cross-modal brain plasticity in sensorial brain networks other than those primarily involved in the peripheral damage, thus in this study, the possible cortical alterations associated with HL have been analyzed using a whole-brain multimodal connectomic approach. Fifty-two HL and 30 normal hearing participants were examined in a 3T MRI study along with audiological and neurological assessments. Between-regions functional connectivity and whole-brain probabilistic tractography were calculated in a connectome-based manner and graph theory was used to obtain low-dimensional features for the analysis of brain connectivity at global and local levels. The HL condition was associated with a different functional organization of the visual subnetwork as revealed by a significant increase in global efficiency, density, and clustering coefficient. These functional effects were mirrored by similar (but more subtle) structural effects suggesting that a functional repurposing of visual cortical centers occurs to compensate for age-related loss of hearing abilities.

Changes in the spatiotemporal pattern of spontaneous activity across a cortical column after noise trauma.

In the auditory modality, noise trauma has often been used to investigate cortical plasticity as it causes cochlear hearing loss. One limitation of these past studies, however, is that the effects of noise trauma have been mostly documented at the granular layer, which is the main cortical recipient of thalamic inputs. Importantly, the cortex is composed of six different layers each having its own pattern of connectivity and specific role in sensory processing. The present study aims at investigating the effects of acute and chronic noise trauma on the laminar pattern of spontaneous activity (SA) in primary auditory cortex (A1) of the anesthetized guinea pig. We show that spontaneous activity is dramatically altered across cortical layers after acute and chronic noise-induced hearing loss. First, spontaneous activity was globally enhanced across cortical layers, both in terms of firing rate and amplitude of spike-triggered average of local field potentials. Second, current source density on (spontaneous) spike-triggered average of local field potentials indicates that current sinks develop in the supra- and infragranular layers. These latter results suggest that supragranular layers become a major input recipient and the propagation of spontaneous activity over a cortical column is greatly enhanced after acute and chronic noise-induced hearing loss. We discuss the possible mechanisms and functional implications of these changes.NEW & NOTEWORTHY The present study investigates the effects of acute and chronic noise trauma on the laminar pattern of spontaneous activity in the primary auditory cortex. Our study is first to report that noise trauma alters the sequence of cortical column activation during ongoing activity. In particular, we show that the supragranular layer becomes a major input recipient and the synaptic activity in the infragranular layers is enhanced.

Altered Response Dynamics and Increased Population Correlation to Tonal Stimuli Embedded in Noise in Aging Auditory Cortex.

Age-related hearing loss (presbycusis) is a chronic health condition that affects one-third of the world population. One hallmark of presbycusis is a difficulty hearing in noisy environments. Presbycusis can be separated into two components: alterations of peripheral mechanotransduction of sound in the cochlea and central alterations of auditory processing areas of the brain. Although the effects of the aging cochlea in hearing loss have been well studied, the role of the aging brain in hearing loss is less well understood. Therefore, to examine how age-related central processing changes affect hearing in noisy environments, we used a mouse model (Thy1-GCaMP6s X CBA) that has excellent peripheral hearing in old age. We used in vivo two-photon Ca2+ imaging to measure the responses of neuronal populations in auditory cortex (ACtx) of adult (2-6 months, nine male, six female, 4180 neurons) and aging mice (15-17 months, six male, three female, 1055 neurons) while listening to tones in noisy backgrounds. We found that ACtx neurons in aging mice showed larger responses to tones and have less suppressed responses consistent with reduced inhibition. Aging neurons also showed less sensitivity to temporal changes. Population analysis showed that neurons in aging mice showed higher pairwise activity correlations and showed a reduced diversity in responses to sound stimuli. Using neural decoding techniques, we show a loss of information in neuronal populations in the aging brain. Thus, aging not only affects the responses of single neurons but also affects how these neurons jointly represent stimuli.SIGNIFICANCE STATEMENT Aging results in hearing deficits particularly under challenging listening conditions. We show that auditory cortex contains distinct subpopulations of excitatory neurons that preferentially encode different stimulus features and that aging selectively reduces certain subpopulations. We also show that aging increases correlated activity between neurons and thereby reduces the response diversity in auditory cortex. The loss of population response diversity leads to a decrease of stimulus information and deficits in sound encoding, especially in noisy backgrounds. Future work determining the identities of circuits affected by aging could provide new targets for therapeutic strategies.