Impaired motor-to-sensory transformation mediates auditory hallucinations.

Distinguishing reality from hallucinations requires efficient monitoring of agency. It has been hypothesized that a copy of motor signals, termed efference copy (EC) or corollary discharge (CD), suppresses sensory responses to yield a sense of agency; impairment of the inhibitory function leads to hallucinations. However, how can the sole absence of inhibition yield positive symptoms of hallucinations? We hypothesize that selective impairments in functionally distinct signals of CD and EC during motor-to-sensory transformation cause the positive symptoms of hallucinations. In an electroencephalography (EEG) experiment with a delayed articulation paradigm in schizophrenic patients with (AVHs) and without auditory verbal hallucinations (non-AVHs), we found that preparing to speak without knowing the contents (general preparation) did not suppress auditory responses in both patient groups, suggesting the absent of inhibitory function of CD. Whereas, preparing to speak a syllable (specific preparation) enhanced the auditory responses to the prepared syllable in non-AVHs, whereas AVHs showed enhancement in responses to unprepared syllables, opposite to the observations in the normal population, suggesting that the enhancement function of EC is not precise in AVHs. A computational model with a virtual lesion of an inhibitory inter-neuron and disproportional sensitization of auditory cortices fitted the empirical data and further quantified the distinct impairments in motor-to-sensory transformation in AVHs. These results suggest that "broken" CD plus "noisy" EC causes erroneous monitoring of the imprecise generation of internal auditory representation and yields auditory hallucinations. Specific impairments in functional granularity of motor-to-sensory transformation mediate positivity symptoms of agency abnormality in mental disorders.

Auditory areas are recruited for naturalistic visual meaning in early deaf people.

Congenital deafness enhances responses of auditory cortices to non-auditory tasks, yet the nature of the reorganization is not well understood. Here, naturalistic stimuli are used to induce neural synchrony across early deaf and hearing individuals. Participants watch a silent animated film in an intact version and three versions with gradually distorted meaning. Differences between groups are observed in higher-order auditory cortices in all stimuli, with no statistically significant effects in the primary auditory cortex. Comparison between levels of scrambling revealed a heterogeneity of function in secondary auditory areas. Both hemispheres show greater synchrony in the deaf than in the hearing participants for the intact movie and high-level variants. However, only the right hemisphere shows an increased inter-subject synchrony in the deaf people for the low-level movie variants. An event segmentation validates these results: the dynamics of the right secondary auditory cortex in the deaf people consist of shorter-length events with more transitions than the left. Our results reveal how deaf individuals use their auditory cortex to process visual meaning.

Auditory entrainment coordinates cortical-BNST-NAc triple time locking to alleviate the depressive disorder.

Listening to music is a promising and accessible intervention for alleviating symptoms of major depressive disorder. However, the neural mechanisms underlying its antidepressant effects remain unclear. In this study on patients with depression, we used auditory entrainment to evaluate intracranial recordings in the bed nucleus of the stria terminalis (BNST) and nucleus accumbens (NAc), along with temporal scalp electroencephalogram (EEG). We highlight music-induced synchronization across this circuit. The synchronization initiates with temporal theta oscillations, subsequently inducing local gamma oscillations in the BNST-NAc circuit. Critically, the incorporated external entrainment induced a modulatory effect from the auditory cortex to the BNST-NAc circuit, activating the antidepressant response and highlighting the causal role of physiological entrainment in enhancing the antidepressant response. Our study explores the pivotal role of the auditory cortex and proposes a neural oscillation triple time-locking model, emphasizing the capacity of the auditory cortex to access the BNST-NAc circuit.

Effect of lidocaine on salicylate-induced tinnitus in guinea pigs: A focus on the auditory cortex.

This study aimed to investigate the effects of the intravenous administration of lidocaine in the auditory cortex after the systemic administration of salicylate. Healthy male albino Hartley guinea pigs were divided into two groups. The control group received only lidocaine, whereas the experimental group received lidocaine after checking for the effects of salicylate. Extracellular recordings of spikes in the primary auditory cortex and dorsocaudal areas in healthy albino Hartley guinea pigs were continuously documented (pre- and post-lidocaine, pre- and post-salicylate, and post-salicylate after adding lidocaine to post-salicylate). We recorded 160 single units in the primary auditory cortex from five guinea pigs and 155 single units in the dorsocaudal area from another five guinea pigs to confirm the effects of lidocaine on untreated animals. No significant change was detected in either the threshold or Q10dB value after lidocaine administration in the primary auditory cortex and dorsocaudal areas. Spontaneous firing activity significantly decreased after lidocaine administration in the primary auditory cortex and dorsocaudal areas. Next, we recorded 160 single units in the primary auditory cortex from five guinea pigs and 137 single units in the dorsocaudal area from another five guinea pigs to determine the effects of lidocaine on salicylate-treated animals. The threshold was significantly elevated after salicylate administration; however, no additional change was detected after adding lidocaine to the primary auditory cortex and dorsocaudal areas. Regarding the Q10dB value, lidocaine negated the significant changes induced by salicylate in the primary auditory cortex and dorsocaudal areas. Moreover, lidocaine negated the significant changes in spontaneous firing activities induced by salicylate in the primary auditory cortex and dorsocaudal areas. In conclusion, changes in the Q10dB value and spontaneous firing activities induced by salicylate administration are abolished by lidocaine administration, suggesting that these changes are related to the presence of tinnitus.

Corollary discharge and anomalous self-experiences in schizophrenia and bipolar disorder: A specificity analysis.

OBJECTIVE: The Corollary Discharge (CD) mechanism inhibits self-generated speech sound perception, appearing disrupted in schizophrenia and potentially contributing to Anomalous Self-Experiences (ASEs). However, it remains unclear if this alteration and its correlation with ASEs extend to other psychotic disorders. METHODS: Electroencephalography was used to study the N1 Event-Related Potential (ERP) as an index of CD-mediated suppression in the auditory cortex across thirty-five participants with schizophrenia, twenty-six with bipolar disorder, and thirty healthy controls. Auditory N1 was elicited by two conditions: real-time listening to self-pronounced vowels while speaking through connected microphone and earphones (listen/talk -or talk condition in previous literature-) and passive listening to the same previously recorded self-uttered vowels (listen/no talk -or listen condition-). RESULTS: N1 ERP amplitude was lower in the listen/talk condition compared to listen/no talk across all groups. However, N1 suppression was significantly reduced in schizophrenia, with bipolar patients showing intermediate attenuation between both groups (i.e., non-significantly different from controls). Furthermore, N1 suppression inversely correlated with ASEs severity only in schizophrenia. CONCLUSIONS: Dysfunction of the CD mechanism may be a defining feature of schizophrenia, where it is connected to ASEs. SIGNIFICANCE: These results corroborate previous findings linking auditory N1 ERP suppression with disrupted CD mechanism in schizophrenia, but not in bipolar disorder.

Cochlear implant induced changes in cortical networks associated with tinnitus severity.

Objective.We investigated tinnitus-related cortical networks in cochlear implant users who experience tinnitus and whose perception of tinnitus changes with use of their implant. Tinnitus, the perception of unwanted sounds which are not present externally, can be a debilitating condition. In individuals with cochlear implants, use of the implant is known to modulate tinnitus, often improving symptoms but worsening them in some cases. Little is known about underlying cortical changes with use of the implant, which lead to changes in tinnitus perception. In this study we investigated whether changes in brain networks with the cochlear implant turned on and off, were associated with changes in tinnitus perception, as rated subjectively.Approach.Using functional near-infrared spectroscopy, we recorded cortical activity at rest, from 14 cochlear implant users who experienced tinnitus. Recordings were performed with the cochlear implant turned off and on. For each condition, participants rated the loudness and annoyance of their tinnitus using a visual rating scale. Changes in neural synchrony have been reported in humans and animal models of tinnitus. To assess neural synchrony, functional connectivity networks with the implant turned on and off, were compared using two network features: node strength and diversity coefficient.Main results.Changes in subjective ratings of loudness were significantly correlated with changes in node strength, averaged across occipital channels (r=-0.65, p=0.01). Changes in both loudness and annoyance were significantly correlated with changes in diversity coefficient averaged across all channels (r=-0.79,p<0.001 and r=-0.86,p<0.001). More distributed connectivity with the implant on, compared to implant off, was associated with a reduction in tinnitus loudness and annoyance.Significance.A better understanding of neural mechanisms underlying tinnitus suppression with cochlear implant use, could lead to their application as a tinnitus treatment and pave the way for effective use of other less invasive stimulation-based treatments.

P1-N1-P2 Cortical Auditory Evoked Potentials in Chronic Unilateral Acquired Conductive Hearing Loss in Adults.

BACKGROUND:  Chronic unilateral hearing loss causes imbalanced auditory input to the brain that triggers cortical reorganization. The effect of sensorineural hearing loss on the central auditory system (CAS) has been thoroughly studied, while there is a paucity of research on the effect of conductive hearing loss (CHL). The aim of this study was to assess the P1-N1-P2 cortical auditory evoked response potential (CAEP) in adult individuals with chronic acquired unilateral CHL. METHODS:  This study included 108 participants of both genders: 54 patients with unilateral chronic CHL who were compared to well-matched 54 controls. All were subjected to history-taking, otologic examination, basic audiological evaluation, and bone conduction N1-P2 CAEP. RESULTS:  The affected ears of the cases showed highly statistically significant shorter CAEPs N1, P2, N1-P2 latencies but not P1, and showed highly statistically significant larger N1, P2, N1P2, amplitude than the control group. Latencies decreased and amplitudes increased as the degree of CHL increased, but were not affected by patients' age, side, or duration of the CHL. Cases with tinnitus had statistically significant and worse results than those without tinnitus. CONCLUSION:  Unilateral chronic CHL might enhance neurocortical plasticity, with greater changes occurring at greater degrees of the CHL.

Biomarkers of auditory cortical plasticity and development of binaural pathways in children with unilateral hearing loss using a hearing aid.

Congenital or early-onset unilateral hearing loss (UHL) can disrupt the normal development of the auditory system. In extreme cases of UHL (i.e., single sided deafness), consistent cochlear implant use during sensitive periods resulted in cortical reorganization that partially reversed the detrimental effects of unilateral sensory deprivation. There is a gap in knowledge, however, regarding cortical plasticity i.e. the brain's capacity to adapt, reorganize, and develop binaural pathways in milder degrees of UHL rehabilitated by a hearing aid (HA). The current study was set to investigate early-stage cortical processing and electrophysiological manifestations of binaural processing by means of cortical auditory evoked potentials (CAEPs) to speech sounds, in children with moderate to severe-to-profound UHL using a HA. Fourteen children with UHL (CHwUHL), 6-14 years old consistently using a HA for 3.5 (±2.3) years participated in the study. CAEPs were elicited to the speech sounds /m/, /g/, and /t/ in three listening conditions: monaural [Normal hearing (NH), HA], and bilateral [BI (NH + HA)]. Results indicated age-appropriate CAEP morphology in the NH and BI listening conditions in all children. In the HA listening condition: (1) CAEPs showed similar morphology to that found in the NH listening condition, however, the mature morphology observed in older children in the NH listening condition was not evident; (2) P1 was elicited in all but two children with severe-to-profound hearing loss, to at least one speech stimuli, indicating effective audibility; (3) A significant mismatch in timing and synchrony between the NH and HA ear was found; (4) P1 was sensitive to the acoustic features of the eliciting stimulus and to the amplification characteristics of the HA. Finally, a cortical binaural interaction component (BIC) was derived in most children. In conclusion, the current study provides first-time evidence for cortical plasticity and partial reversal of the detrimental effects of moderate to severe-to-profound UHL rehabilitated by a HA. The derivation of a cortical biomarker of binaural processing implies that functional binaural pathways can develop when sufficient auditory input is provided to the affected ear. CAEPs may thus serve as a clinical tool for assessing, monitoring, and managing CHwUHL using a HA.

Developmental trajectory and sex differences in auditory processing in a PTEN-deletion model of autism spectrum disorders.

Autism Spectrum Disorders (ASD) encompass a wide array of debilitating symptoms, including severe sensory deficits and abnormal language development. Sensory deficits early in development may lead to broader symptomatology in adolescents and adults. The mechanistic links between ASD risk genes, sensory processing and language impairment are unclear. There is also a sex bias in ASD diagnosis and symptomatology. The current study aims to identify the developmental trajectory and genotype- and sex-dependent differences in auditory sensitivity and temporal processing in a Pten-deletion (phosphatase and tensin homolog missing on chromosome 10) mouse model of ASD. Auditory temporal processing is crucial for speech recognition and language development and deficits will cause language impairments. However, very little is known about the development of temporal processing in ASD animal models, and if there are sex differences. To address this major gap, we recorded epidural electroencephalography (EEG) signals from the frontal (FC) and auditory (AC) cortex in developing and adult Nse-cre PTEN mice, in which Pten is deleted in specific cortical layers (layers III-V) (PTEN conditional knock-out (cKO). We quantified resting EEG spectral power distribution, auditory event related potentials (ERP) and temporal processing from awake and freely moving male and female mice. Temporal processing is measured using a gap-in-noise-ASSR (auditory steady state response) stimulus paradigm. The experimental manipulation of gap duration and modulation depth allows us to measure cortical entrainment to rapid gaps in sounds. Temporal processing was quantified using inter-trial phase clustering (ITPC) values that account for phase consistency across trials. The results show genotype differences in resting power distribution in PTEN cKO mice throughout development. Male and female cKO mice have significantly increased beta power but decreased high frequency oscillations in the AC and FC. Both male and female PTEN cKO mice show diminished ITPC in their gap-ASSR responses in the AC and FC compared to control mice. Overall, deficits become more prominent in adult (p60) mice, with cKO mice having significantly increased sound evoked power and decreased ITPC compared to controls. While both male and female cKO mice demonstrated severe temporal processing deficits across development, female cKO mice showed increased hypersensitivity compared to males, reflected as increased N1 and P2 amplitudes. These data identify a number of novel sensory processing deficits in a PTEN-ASD mouse model that are present from an early age. Abnormal temporal processing and hypersensitive responses may contribute to abnormal development of language function in ASD.

Neurophysiological, structural, and molecular alterations in the prefrontal and auditory cortices following noise-induced hearing loss.

It is well established that hearing loss can lead to widespread plasticity within the central auditory pathway, which is thought to contribute to the pathophysiology of audiological conditions such as tinnitus and hyperacusis. Emerging evidence suggests that hearing loss can also result in plasticity within brain regions involved in higher-level cognitive functioning like the prefrontal cortex; findings which may underlie the association between hearing loss and cognitive impairment documented in epidemiological studies. Using the 40-Hz auditory steady state response to assess sound-evoked gamma oscillations, we previously showed that noise-induced hearing loss results in impaired gamma phase coherence within the prefrontal but not the auditory cortex. To determine whether region-specific structural or molecular changes accompany this differential plasticity following hearing loss, in the present study we utilized Golgi-Cox staining to assess dendritic organization and synaptic density, as well as Western blotting to measure changes in synaptic signaling proteins in these cortical regions. We show that following noise exposure, impaired gamma phase coherence within the prefrontal cortex is accompanied by alterations in pyramidal cell dendritic morphology and decreased expression of proteins involved in GABAergic (GAD65) and glutamatergic (NR2B) neurotransmission; findings that were not observed in the auditory cortex, where gamma phase coherence remained unchanged post-noise exposure. In contrast to the noise-induced effects we observed in the prefrontal cortex, plasticity in the auditory cortex was characterized by an increase in NR2B suggesting increased excitability, as well as increases in the synaptic proteins PSD95 and synaptophysin within the auditory cortex. Overall, our results highlight the disparate effect of noise-induced hearing loss on auditory and higher-level brain regions as well as potential structural and molecular mechanisms by which hearing loss may contribute to impaired cognitive and sensory functions mediated by the prefrontal and auditory cortices.

Altered neural synchronization in response to 2 Hz amplitude-modulated tones in the auditory cortex of children with Autism Spectrum Disorder: An MEG study.

OBJECTIVE: Some studies have hypothesized that atypical neural synchronization at the delta frequency band in the auditory cortex is associated with phonological and language skills in children with Autism Spectrum Disorder (ASD), but it is still poorly understood. This study investigated this neural activity and addressed the relationships between auditory response and behavioral measures of children with ASD. METHODS: We used magnetoencephalography and individual brain models to investigate 2 Hz Auditory Steady-State Response (ASSR) in 20 primary-school-aged children with ASD and 20 age-matched typically developing (TD) controls. RESULTS: First, we found a between-group difference in the localization of the auditory response, so as the topology of 2 Hz ASSR was more superior and posterior in TD children when comparing to children with ASD. Second, the power of 2 Hz ASSR was reduced in the ASD group. Finally, we observed a significant association between the amplitude of neural response and language skills in children with ASD. CONCLUSIONS: The study provided the evidence of reduced neural response in children with ASD and its relation to language skills. SIGNIFICANCE: These findings may inform future interventions targeting auditory and language impairments in ASD population.

The temporal mismatch across listening sides affects cortical auditory evoked responses in normal hearing listeners and cochlear implant users with contralateral acoustic hearing.

Combining a cochlear implant with contralateral acoustic hearing typically enhances speech understanding, although this improvement varies among CI users and can lead to an interference effect. This variability may be associated with the effectiveness of the integration between electric and acoustic stimulation, which might be affected by the temporal mismatch between the two listening sides. Finding methods to compensate for the temporal mismatch might contribute to the optimal adjustment of bimodal devices and to improve hearing in CI users with contralateral acoustic hearing. The current study investigates cortical auditory evoked potentials (CAEPs) in normal hearing listeners (NH) and CI users with contralateral acoustic hearing. In NH, the amplitude of the N1 peak and the maximum phase locking value (PLV) were analyzed under monaural, binaural, and binaural temporally mismatched conditions. In CI users, CAEPs were measured when listening with CI only (CIS_only), acoustically only (AS_only) and with both sides together (CIS+AS). When listening with CIS+AS, various interaural delays were introduced between the electric and acoustic stimuli. In NH listeners, interaural temporal mismatch resulted in decreased N1 amplitude and PLV. Moreover, PLV is suggested as a more sensitive measure to investigate the integration of information between the two listening sides. CI users showed varied N1 latencies between the AS_only and CIS_only listening conditions, with increased N1 amplitude when the temporal mismatch was compensated. A tendency towards increased PLV was also observed, however, to a lesser extent than in NH listeners, suggesting a limited integration between electric and acoustic stimulation. This work highlights the potential of CAEPs measurement to investigate cortical processing of the information between two listening sides in NH and bimodal CI users.

A systematic review of acoustic change complex (ACC) measurements and applicability in children for the assessment of the neural capacity for sound and speech discrimination.

OBJECTIVE: The acoustic change complex (ACC) is a cortical auditory evoked potential (CAEP) and can be elicited by a change in an otherwise continuous sound. The ACC has been highlighted as a promising tool in the assessment of sound and speech discrimination capacity, and particularly for difficult-to-test populations such as infants with hearing loss, due to the objective nature of ACC measurements. Indeed, there is a pressing need to develop further means to accurately and thoroughly establish the hearing status of children with hearing loss, to help guide hearing interventions in a timely manner. Despite the potential of the ACC method, ACC measurements remain relatively rare in a standard clinical settings. The objective of this study was to perform an up-to-date systematic review on ACC measurements in children, to provide greater clarity and consensus on the possible methodologies, applications, and performance of this technique, and to facilitate its uptake in relevant clinical settings. DESIGN: Original peer-reviewed articles conducting ACC measurements in children (< 18 years). Data were extracted and summarised for: (1) participant characteristics; (2) ACC methods and auditory stimuli; (3) information related to the performance of the ACC technique; (4) ACC measurement outcomes, advantages, and challenges. The systematic review was conducted using PRISMA guidelines for reporting and the methodological quality of included articles was assessed. RESULTS: A total of 28 studies were identified (9 infant studies). Review results show that ACC responses can be measured in infants (from < 3 months), and there is evidence of age-dependency, including increased robustness of the ACC response with increasing childhood age. Clinical applications include the measurement of the neural capacity for speech and non-speech sound discrimination in children with hearing loss, auditory neuropathy spectrum disorder (ANSD) and central auditory processing disorder (CAPD). Additionally, ACCs can be recorded in children with hearing aids, auditory brainstem implants, and cochlear implants, and ACC results may guide hearing intervention/rehabilitation strategies. The review identified that the time taken to perform ACC measurements was often lengthy; the development of more efficient ACC test procedures for children would be beneficial. Comparisons between objective ACC measurements and behavioural measures of sound discrimination showed significant correlations for some, but not all, included studies. CONCLUSIONS: ACC measurements of the neural capacity to discriminate between speech and non-speech sounds are feasible in infants and children, and a wide range of possible clinical applications exist, although more time-efficient procedures would be advantageous for clinical uptake. A consideration of age and maturational effects is recommended, and further research is required to investigate the relationship between objective ACC measures and behavioural measures of sound and speech perception for effective clinical implementation.

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.

Dissociated Representation of Binaural Cues in Single-Sided Deafness: Implications for Cochlear Implantation.

Congenital single-sided deafness (SSD) leads to an aural preference syndrome that is characterized by overrepresentation of the hearing ear in the auditory system. Cochlear implantation (CI) of the deaf ear is an effective treatment for SSD. However, the newly introduced auditory input in congenital SSD often does not reach expectations in late-implanted CI recipients with respect to binaural hearing and speech perception. In a previous study, a reduction of the interaural time difference (ITD) sensitivity has been shown in unilaterally congenitally deaf cats (uCDCs). In the present study, we focused on the interaural level difference (ILD) processing in the primary auditory cortex. The uCDC group was compared with hearing cats (HCs) and bilaterally congenitally deaf cats (CDCs). The ILD representation was reorganized, replacing the preference for the contralateral ear with a preference for the hearing ear, regardless of the cortical hemisphere. In accordance with the previous study, uCDCs were less sensitive to interaural time differences than HCs, resulting in unmodulated ITD responses, thus lacking directional information. Such incongruent ITDs and ILDs cannot be integrated for binaural sound source localization. In normal hearing, the predominant effect of each ear is excitation of the auditory cortex in the contralateral cortical hemisphere and inhibition in the ipsilateral hemisphere. In SSD, however, auditory pathways reorganized such that the hearing ear produced greater excitation in both cortical hemispheres and the deaf ear produced weaker excitation and preserved inhibition in both cortical hemispheres.

Switching tinnitus on or off: An initial investigation into the role of the pregenual and rostral to dorsal anterior cingulate cortices.

Research indicates that hearing loss significantly contributes to tinnitus, but it alone does not fully explain its occurrence, as many people with hearing loss do not experience tinnitus. To identify a secondary factor for tinnitus generation, we examined a unique dataset of individuals with intermittent chronic tinnitus, who experience fluctuating periods of tinnitus. EEGs of healthy controls were compared to EEGs of participants who reported perceiving tinnitus on certain days, but no tinnitus on other days.. The EEG data revealed that tinnitus onset is associated with increased theta activity in the pregenual anterior cingulate cortex and decreased theta functional connectivity between the pregenual anterior cingulate cortex and the auditory cortex. Additionally, there is increased alpha effective connectivity from the dorsal anterior cingulate cortex to the pregenual anterior cingulate cortex. When tinnitus is not perceived, differences from healthy controls include increased alpha activity in the pregenual anterior cingulate cortex and heightened alpha connectivity between the pregenual anterior cingulate cortex and auditory cortex. This suggests that tinnitus is triggered by a switch involving increased theta activity in the pregenual anterior cingulate cortex and decreased theta connectivity between the pregenual anterior cingulate cortex and auditory cortex, leading to increased theta-gamma cross-frequency coupling, which correlates with tinnitus loudness. Increased alpha activity in the dorsal anterior cingulate cortex correlates with distress. Conversely, increased alpha activity in the pregenual anterior cingulate cortex can transiently suppress the phantom sound by enhancing theta connectivity to the auditory cortex. This mechanism parallels chronic neuropathic pain and suggests potential treatments for tinnitus by promoting alpha activity in the pregenual anterior cingulate cortex and reducing alpha activity in the dorsal anterior cingulate cortex through pharmacological or neuromodulatory approaches.

Electrophysiological auditory measures to identify potential cortical markers of tinnitus.

Tinnitus, or the perception of a sound in the absence of an external acoustic stimulus, is a common condition that cannot yet be objectively diagnosed. Current diagnostic tests of tinnitus consist of case history and behavioral measures that rely on subjective responses. This study examined electrophysiological measures, specifically the auditory late response (ALR), mismatch negativity (MMN), and P300 as potential neural biomarkers of tinnitus in both a tinnitus and non-tinnitus control group while utilizing the pitch-matched tinnitus frequencies as the test stimuli. Results of this study found differences in MMN amplitudes and area under the curve, and in P300 topographic maps between tinnitus and control subjects. The differences in MMN responses across groups suggest that dysfunctional processing of acoustic stimuli located near the tinnitus frequency in individuals with tinnitus manifests as soon as 200 ms after initial onset of the stimulus. In addition, results from a global field power analysis and differences in spatial distributions on topographical maps indicate that deficits persist through higher levels of cortical processing. A secondary goal of this study was to determine if electrophysiological measures correlated with reported tinnitus severity on questionnaires. This analysis indicated that P2 latency was a significant predictor of Tinnitus Reaction Questionnaire, Tinnitus Handicap Inventory, and percent of the time participant's tinnitus was considered bothersome, suggesting that this measure could potentially be used to assess the efficacy of treatment programs for tinnitus.

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.

Layer-specific enhancement of visual-evoked activity in the audiovisual cortex following a mild degree of hearing loss in adult rats.

Following adult-onset hearing impairment, crossmodal plasticity can occur within various sensory cortices, often characterized by increased neural responses to visual stimulation in not only the auditory cortex, but also in the visual and audiovisual cortices. In the present study, we used an established model of loud noise exposure in rats to examine, for the first time, whether the crossmodal plasticity in the audiovisual cortex that occurs following a relatively mild degree of hearing loss emerges solely from altered intracortical processing or if thalamocortical changes also contribute to the crossmodal effects. Using a combination of an established pharmacological 'cortical silencing' protocol and current source density analysis of the laminar activity recorded across the layers of the audiovisual cortex (i.e., the lateral extrastriate visual cortex, V2L), we observed layer-specific changes post-silencing in the strength of the residual visual, but not auditory, input in the noise exposed rats with mild hearing loss compared to rats with normal hearing. Furthermore, based on a comparison of the laminar profiles pre- versus post-silencing in both groups, we can conclude that noise exposure caused a re-allocation of the strength of visual inputs across the layers of the V2L cortex, including enhanced visual-evoked activity in the granular layer; findings consistent with thalamocortical plasticity. Finally, we confirmed that audiovisual integration within the V2L cortex depends on intact processing within intracortical circuits, and that this form of multisensory processing is vulnerable to disruption by noise-induced hearing loss. Ultimately, the present study furthers our understanding of the contribution of intracortical and thalamocortical processing to crossmodal plasticity as well as to audiovisual integration under both normal and mildly-impaired hearing conditions.

Functional Connectivity of the Auditory Cortex in Women With Trauma-Related Disorders Who Hear Voices.

BACKGROUND: Voice hearing (VH) is a transdiagnostic experience that is common in trauma-related disorders. However, the neural substrates that underlie trauma-related VH remain largely unexplored. While auditory perceptual dysfunction is among the abnormalities implicated in VH in schizophrenia, whether VH in trauma-related disorders also involves auditory perceptual alterations is unknown. METHODS: We investigated auditory cortex (AC)-related functional connectivity (FC) in 65 women with trauma-related disorders stemming from childhood abuse with varying severities of VH. Using a novel, computationally driven and individual-specific method of functionally parcellating the brain, we calculated the FC of 2 distinct AC subregions-Heschl's gyrus (corresponding to the primary AC) and lateral superior temporal gyrus (in the nonprimary AC)-with both the cerebrum and cerebellum. Then, we measured the association between VH severity and FC using leave-one-out cross-validation in the cerebrum and voxelwise multiple regression analyses in the cerebellum. RESULTS: We found that VH severity was positively correlated with left lateral superior temporal gyrus-frontoparietal network FC, while it was negatively correlated with FC between the left lateral superior temporal gyrus and both cerebral and cerebellar representations of the default mode network. VH severity was not predicted by FC of the left Heschl's gyrus or right AC subregions. CONCLUSIONS: Our findings point to altered interactions between auditory perceptual processing and higher-level processes related to self-reference and executive functioning. This is the first study to show alterations in auditory cortical connectivity in trauma-related VH. While VH in trauma-related disorders appears to be mediated by brain networks that are also implicated in VH in schizophrenia, the results suggest a unique mechanism that could distinguish VH in trauma-related disorders.