Auditory Processing Deficits Research Articles

Effects of the Glycine Transporter-1 Inhibitor Iclepertin (BI 425809) on Sensory Processing, Neural Network Function, and Cognition in Animal Models Related to Schizophrenia.

N-methyl-D-aspartate (NMDA) receptor hypofunction leading to neural network dysfunction is thought to play an important role in the pathophysiology of cognitive impairment associated with schizophrenia (CIAS). Increasing extracellular concentrations of the NMDA receptor co-agonist glycine through inhibition of glycine transporter-1 (GlyT1) has the potential to treat CIAS by improving cortical network function through enhanced glutamatergic signaling. Indeed, the novel GlyT1 inhibitor iclepertin (BI 425809) improved cognition in a recent clinical study in patients with schizophrenia. The present study tested the ability of iclepertin to reverse deficits in auditory sensory processing and cortical network function induced by the uncompetetive NMDA receptor antagonist, MK-801, using electroencephalography (EEG) to measure auditory event-related potentials (AERPs) and 40 Hz auditory steady-state response (ASSR). In addition, improvements in memory performance with iclepertin were evaluated using the T-maze spontaneous alternation test in MK-801-treated mice and the social recognition test in naïve rats. Iclepertin reversed MK-801-induced deficits in the AERP readouts N1 amplitude and N1 gating, as well as reversing deficits in 40 Hz ASSR power and intertrial coherence. Additionally, iclepertin significantly attenuated an MK-801-induced increase in basal gamma power. Furthermore, iclepertin reversed MK-801-induced working memory deficits in mice and improved social recognition memory performance in rats. Overall, this study demonstrates that inhibition of GlyT1 is sufficient to attenuate MK-801-induced deficits in translatable EEG parameters relevant to schizophrenia. Moreover, iclepertin showed memory-enhancing effects in rodent cognition tasks, further demonstrating the potential for GlyT1 inhibition to treat CIAS. SIGNIFICANCE STATEMENT: Despite the significant patient burden caused by cognitive impairment associated with schizophrenia, there are currently no approved pharmacotherapies. In this preclinical study, the novel glycine transporter inhibitor iclepertin (BI 425809) reversed sensory processing deficits and neural network dysfunction evoked by inhibition of N-methyl-D-aspartate receptors and enhanced working memory performance and social recognition in rodents. These findings support previous clinical evidence for the procognitive effects of iclepertin.

The development, validity, reliability, and norm of a preschool auditory processing assessment scale in China

BackgroundChildren with auditory processing deficits may face problems with language, learning, and social communication. AimsTo develop a Chinese auditory processing assessment scale for preschool children and establish the norms of the scale. Methods and proceduresThe predictive version of the scale was formed by a literature review, qualitative interviews, expert consultation, and a pre-test with a small sample. Nine kindergartens in Nanjing were selected by a stratified cluster sampling plan. First, 734 children from two kindergartens were selected for the large sample pre-test of the scale. Then, 1526 children from four kindergartens and 1151 children from three kindergartens were selected for the reliability and validity analysis and confirmatory factor analysis, respectively. The standardized norm data of the scale were established based on the 3411 points of scale data of the nine kindergartens. Finally, the clinical usefulness of the scale was analyzed by comparing the results of objective auditory processing tests in children with normal and abnormal auditory processing prompted by the score on the scale. Outcomes and resultsThe preschool auditory processing assessment scale includes 5 dimensions and 30 items. The Cronbach's alpha value of the scale is greater than 0.9. The confirmatory factor analysis results verify that the scale structure is reasonable. The percentile norm of the scale was established. The results of electrophysiological tests of the normal and abnormal auditory processing groups were statistically different (P < 0.05). Conclusions and implicationsThe developed preschool auditory processing assessment scale has good reliability and validity. The scale is suitable for clinical application.

Loss of \u03b24-spectrin impairs Nav channel clustering at the heminode and temporal fidelity of presynaptic spikes in developing auditory brain

Beta-4 (β4)-spectrin, encoded by the gene Sptbn4, is a cytoskeleton protein found at nodes and the axon initial segments (AIS). Sptbn4 mutations are associated with myopathy, neuropathy, and auditory deficits in humans. Related to auditory dysfunction, however, the expression and roles of β4-spectrin at axon segments along the myelinated axon in the developing auditory brain are not well explored. We found during postnatal development, β4-spectrin is critical for voltage-gated sodium channel (Nav) clustering at the heminode along the nerve terminal, but not for the formation of nodal and AIS structures in the auditory brainstem. Presynaptic terminal recordings in Sptbn4geo mice, β4-spectrin null mice, showed an elevated threshold of action potential and increased failures during action potential train at high-frequency. Sptbn4geo mice exhibited a slower central conduction and showed no startle responses, but had normal cochlear function. Taken together, the lack of β4-spectrin impairs Nav clustering at the heminode along the nerve terminal and the temporal fidelity and reliability of presynaptic spikes, leading to central auditory processing deficits during postnatal development.

Deficits in Acoustic Startle Reactivity and Auditory Temporal Processing after Traumatic Brain Injury.

Traumatic brain injury (TBI) exacts significant neurological and financial costs on patients and their families. In adult patients with moderate-to-severe TBI, central auditory impairments have been reported. These auditory impairments may interfere with language receptivity, as observed in children with developmental brain injury. Although rodent models of TBI have been widely used to examine behavioral outcomes, few studies have evaluated how TBI affects higher-order central auditory processing across a range of cue complexities. Here, auditory processing was assessed using a modified acoustic startle paradigm. We used a battery of progressively complex stimuli (single-tone, silent gaps in white noise, and frequency-modulated [FM] sweeps) in adult rats that received unilateral controlled cortical impact injury. TBI subjects showed significant reductions in acoustic startle absolute responses across nearly all stimuli, regardless of cue, duration of stimuli, or cue complexity. Despite this overall reduction of startle magnitudes in injured animals, the detection of single-tone stimuli was comparable between TBI and sham-injured subjects, indicating intact hearing after TBI. TBI subjects showed deficits in rapid gap (5 ms) and FM sweep (175 ms) detection, and, in contrast to shams, they did not improve on detecting silent gaps and FM sweeps across days of testing. Our findings provide evidence for both low-level (brainstem-mediated) and higher-order central auditory processing deficits in a rodent model of TBI, which parallel sensory impairments observed in TBI patients. The present findings support the use of modified pre-pule auditory detection paradigms to investigate clinically relevant processes in TBI.

Benefits of app-based speech in noise screener for children

Current hearing screening methods focus on assessing a child’s ability to hear tones in quiet. However, this isn’t reflective of real-world classroom situations. Our proposed screening test uses speech in quiet and noise to evaluate a child’s auditory comprehension and possible auditory processing abilities. In this study, we investigate whether a speech in noise screener, Hearing Assessment in Response to Noise Screener (HeARS), is sensitive to detecting possible listening difficulties. We measured responses to a four-choice task with adapting signal to noise ratios based on individual performance. Following an auditory stimulus, the child is presented with four choices that are visual images of the spoken words. The child selects the correct image they hear, and based on their performance the signal to noise ratios increase or decrease in difficulty. Scores are reported as percent correct. We hypothesized that results from the screener would capture differences between speech understanding in noise and quiet conditions. In addition, a speech in noise screener may be more sensitive to deficits in auditory comprehension than traditional screening methods. Preliminary data suggest that the accuracy of understanding words in background noise increases with age. Results have implications for identifying children with auditory comprehension and processing deficits sooner, especially in underserved populations.

N-methyl-D-aspartate receptor antagonism impairs sensory gating in the auditory cortex in response to speech stimuli.

Deficits in early auditory sensory processing in schizophrenia have been linked to N-methyl-D-aspartate receptor (NMDAR) hypofunction, but the role of NMDARs in aberrant auditory sensory gating (SG) in this disorder is unclear. This study, conducted in 22 healthy humans, examined the acute effects of a subanesthetic dose of the NMDAR antagonist ketamine on SG as measured electrophysiologically by suppression of the P50 event-related potential (ERP) to the second (S2) relative to the first (S1) of two closely paired (500ms) identical speech stimuli. Ketamine induced impairment in SG indices at sensor (scalp)-level and at source-level in the auditory cortex (as assessed with eLORETA). Together with preliminary evidence of modest positive associations between impaired gating and dissociative symptoms elicited by ketamine, tentatively support a model of NMDAR hypofunction underlying disturbances in auditory SG in schizophrenia.

Age-related central gain with degraded neural synchrony in the auditory brainstem of mice and humans

Aging is associated with auditory nerve (AN) functional deficits and decreased inhibition in the central auditory system, amplifying central responses in a process referred to here as central gain. Although central gain increases response amplitudes, central gain may not restore disrupted response timing. In this translational study, we measured responses putatively generated by the AN and auditory midbrain in younger and older mice and humans. We hypothesized that older mice and humans exhibit increased central gain without an improvement in inter-trial synchrony in the midbrain. Our data demonstrated greater age-related deficits in AN response amplitudes than auditory midbrain response amplitudes, as shown by significant interactions between inferred neural generator and age group, indicating increased central gain in auditory midbrain. However, synchrony decreases with age in both the AN and midbrain responses. These results reveal age-related increases in central gain without concomitant improvements in synchrony, consistent with those predictions based on decreases in inhibition. Persistent decreases in synchrony may contribute to auditory processing deficits in older mice and humans.

Classification of EEG signals from young adults with dyslexia combining a Brain Computer Interface device and an Interactive Linguistic Software Tool

The magnocellular pathway deficit theory has long been considered to be a possible cause for dyslexia, providing an alternative method to explain auditory and visual processing deficits. Several studies have attempted to classify these deficits with the application of machine learning in anatomical brain imaging, rendering the classification techniques using EEG graph measures both robust and reliable. In this paper, a classification of university students with and without dyslexia is attempted with the use of a Brain Computer Interface (BCI) Device and an Interactive Linguistic Software Tool in order to validate the application of such a device in classifying dyslexia in a higher education population. EEG signals acquired from a wearable, sensory EEG recording device from 12 university students with dyslexia along with 14 typically developed, age matched individuals are recorded, while participants were examined in three different experimental conditions: a) auditory discrimination, b) visual recognition c) visual recognition with background music. Spectral features extracted from each EEG rhythm (δ, θ, α, β, γ) are used to train a Random Forests classifier, aiming to identify quantitative EEG features that characterize dyslexia in different brain regions. Results show high levels of accuracy, sensitivity and specificity (above 95%) in the entire brain, followed by the left and right hemisphere, with the highest discrimination performance reported during the third experimental condition with the presence of background music. Different experimental conditions provide high classification accuracy that results in correct discrimination between higher education students with and without dyslexia.

Open-Set Phoneme Recognition Performance With Varied Temporal Cues in Younger and Older Cochlear Implant Users.

The goal of this study was to investigate the effect of age on phoneme recognition performance in which the stimuli varied in the amount of temporal information available in the signal. Chronological age is increasingly recognized as a factor that can limit the amount of benefit an individual can receive from a cochlear implant (CI). Central auditory temporal processing deficits in older listeners may contribute to the performance gap between younger and older CI users on recognition of phonemes varying in temporal cues. Phoneme recognition was measured at three stimulation rates (500, 900, and 1800 pulses per second) and two envelope modulation frequencies (50 Hz and unfiltered) in 20 CI participants ranging in age from 27 to 85 years. Speech stimuli were multiple word pairs differing in temporal contrasts and were presented via direct stimulation of the electrode array using an eight-channel continuous interleaved sampling strategy. Phoneme recognition performance was evaluated at each stimulation rate condition using both envelope modulation frequencies. Duration of deafness was the strongest subject-level predictor of phoneme recognition, with participants with longer durations of deafness having poorer performance overall. Chronological age did not predict performance for any stimulus condition. Additionally, duration of deafness interacted with envelope filtering. Participants with shorter durations of deafness were able to take advantage of higher frequency envelope modulations, while participants with longer durations of deafness were not. Age did not significantly predict phoneme recognition performance. In contrast, longer durations of deafness were associated with a reduced ability to utilize available temporal information within the signal to improve phoneme recognition performance.

Early Auditory Processing Predicts Efficient Working Memory Functioning in Schizophrenia.

Early auditory processing (EAP) deficits have been consistently documented in individuals diagnosed with schizophrenia (SZ). However, a relationship between EAP and executive attention has not been confirmed in SZ versus healthy controls (HC). The current study aimed to demonstrate that unlike HC, in SZ patients, auditory change-detection event-related potentials (ERPs) are significantly associated with executive working memory (WM) functioning. Additionally, correlational analyses investigated the relationships between patients’ auditory ERPs, WM performance, and schizophrenia symptom severity scores. We examined verbal WM accuracy associated with “executive-control” prefrontal cortex mechanisms and EAP ERPs under midline prefrontal electrodes in 12 SZ patients versus 12 demographically matched HC. Mismatch negativity (MMN) amplitudes and latencies in SZ patients were not significantly different from HC, however, their verbal WM performance was significantly impaired versus HC. Importantly, prolonged MMN latencies in the SZ group were correlated with better WM accuracy. In the HC group, WM accuracy was unrelated to MMN latencies. Patients’ MMN parameters were unrelated to schizophrenia symptom-domain severity. However, patients’ WM RTs and accuracy were significantly related to illness severity and negative symptom severity, respectively. Therefore, inefficient sensory excitation related to EAP timing may underlie poor executive verbal WM functioning and might indirectly exacerbate the severity of negative symptoms in SZ. Treatments targeting prefrontal cortex dysfunction in schizophrenia are discussed.

The Resting State Central Auditory Network: a Potential Marker of HIV-Related Central Nervous System Alterations.

HIV positive (HIV+) individuals with otherwise normal hearing ability show central auditory processing deficits as evidenced by worse performance in speech-in-noise perception compared with HIV negative (HIV-) controls. HIV infection and treatment are also associated with lower neurocognitive screening test scores, suggesting underlying central nervous system damage. To determine how central auditory processing deficits in HIV+ individuals relate to brain alterations in the cortex involved with auditory processing, we compared auditory network (AN) functional connectivity between HIV+ adults with or without speech-in-noise perception difficulties and age-matched HIV- controls using resting-state fMRI. Based on the speech recognition threshold of the hearing-in-noise test, twenty-seven HIV+ individuals were divided into a group with speech-in-noise perception abnormalities (HIV+SPabnl, 38.2 ± 6.8 years; 11 males and 2 females) and one without (HIV+SPnl 34.4 ± 8.8 years; 14 males). An HIV- group with normal speech-in-noise perception (HIV-, 31.3 ± 5.2 years; 9 males and 3 females) was also enrolled. All of these younger and middle-aged adults had normal peripheral hearing determined by audiometry. Participants were studied using resting-state fMRI. Independent component analysis was applied to identify the AN. Group differences in the AN were identified using statistical parametric mapping. Both HIV+ groups had increased functional connectivity (FC) in parts of the AN including the superior temporal gyrus, middle temporal gyrus, supramarginal gyrus, and Rolandic operculum compared to the HIV- group. Compared with the HIV+SPnl group, the HIV+SPabnl group showed greater FC in parts of the AN including the middle frontal and inferior frontal gyri. The classical auditory areas in the temporal lobe are affected by HIV regardless of speech perception ability. Increased temporal FC in HIV+ individuals might reflect functional compensation to achieve normal primary auditory perception. Furthermore, increased frontal FC in the HIV+SPabnl group compared with the HIV+SPnl group suggest that speech-in-noise perception difficulties in HIV-infected adults also affect areas involved in higher-level cognition, providing imaging evidence consistent with the hypothesis that HIV-related neurocognitive deficits can include central auditory processing deficits.

Differences Between Young and Older Adults in Working Memory and Performance on the Test of Basic Auditory Capabilities†.

The Test of Basic Auditory Capabilities (TBAC) is a battery of auditory-discrimination tasks and speech-identification tasks that has been normed on several hundred young normal-hearing adults. Previous research with the TBAC suggested that cognitive function may impact the performance of older adults. Here, we examined differences in performance on several TBAC tasks between a group of 34 young adults with a mean age of 22.5 years (SD = 3.1 years) and a group of 115 older adults with a mean age of 69.2 years (SD = 6.2 years) recruited from the local community. Performance of the young adults was consistent with prior norms for this age group. Not surprisingly, the two groups differed significantly in hearing loss and working memory with the older adults having more hearing loss and poorer working memory than the young adults. The two age groups also differed significantly in performance on six of the nine measures extracted from the TBAC (eight test scores and one average test score) with the older adults consistently performing worse than the young adults. However, when these age-group comparisons were repeated with working memory and hearing loss as covariates, the groups differed in performance on only one of the nine auditory measures from the TBAC. For eight of the nine TBAC measures, working memory was a significant covariate and hearing loss never emerged as a significant factor. Thus, the age-group deficits observed initially on the TBAC most often appeared to be mediated by age-related differences in working memory rather than deficits in auditory processing. The results of these analyses of age-group differences were supported further by linear-regression analyses with each of the 9 TBAC scores serving as the dependent measure and age, hearing loss, and working memory as the predictors. Regression analyses were conducted for the full set of 149 adults and for just the 115 older adults. Working memory again emerged as the predominant factor impacting TBAC performance. It is concluded that working memory should be considered when comparing the performance of young and older adults on auditory tasks, including the TBAC.

Disturbed Balance of Inhibitory Signaling Links Hearing Loss and Cognition.

Neuronal hyperexcitability in the central auditory pathway linked to reduced inhibitory activity is associated with numerous forms of hearing loss, including noise damage, age-dependent hearing loss, and deafness, as well as tinnitus or auditory processing deficits in autism spectrum disorder (ASD). In most cases, the reduced central inhibitory activity and the accompanying hyperexcitability are interpreted as an active compensatory response to the absence of synaptic activity, linked to increased central neural gain control (increased output activity relative to reduced input). We here suggest that hyperexcitability also could be related to an immaturity or impairment of tonic inhibitory strength that typically develops in an activity-dependent process in the ascending auditory pathway with auditory experience. In these cases, high-SR auditory nerve fibers, which are critical for the shortest latencies and lowest sound thresholds, may have either not matured (possibly in congenital deafness or autism) or are dysfunctional (possibly after sudden, stressful auditory trauma or age-dependent hearing loss linked with cognitive decline). Fast auditory processing deficits can occur despite maintained basal hearing. In that case, tonic inhibitory strength is reduced in ascending auditory nuclei, and fast inhibitory parvalbumin positive interneuron (PV-IN) dendrites are diminished in auditory and frontal brain regions. This leads to deficits in central neural gain control linked to hippocampal LTP/LTD deficiencies, cognitive deficits, and unbalanced extra-hypothalamic stress control. Under these conditions, a diminished inhibitory strength may weaken local neuronal coupling to homeostatic vascular responses required for the metabolic support of auditory adjustment processes. We emphasize the need to distinguish these two states of excitatory/inhibitory imbalance in hearing disorders: (i) Under conditions of preserved fast auditory processing and sustained tonic inhibitory strength, an excitatory/inhibitory imbalance following auditory deprivation can maintain precise hearing through a memory linked, transient disinhibition that leads to enhanced spiking fidelity (central neural gain⇑) (ii) Under conditions of critically diminished fast auditory processing and reduced tonic inhibitory strength, hyperexcitability can be part of an increased synchronization over a broader frequency range, linked to reduced spiking reliability (central neural gain⇓). This latter stage mutually reinforces diminished metabolic support for auditory adjustment processes, increasing the risks for canonical dementia syndromes.

Tracing Links Between Early Auditory Information Processing and Negative Symptoms in Schizophrenia: An ERP Study.

Background: Negative symptoms represent a heterogeneous dimension with a strong impact on functioning of subjects with schizophrenia (SCZ). Five constructs are included in this dimension: anhedonia, asociality, avolition, blunted affect, and alogia. Factor analyses revealed that these symptoms cluster in two domains: experiential domain (avolition, asociality, and anhedonia) and the expressive deficit (alogia and blunted affect), that might be linked to different neurobiological alterations. Few studies investigated associations between N100, an electrophysiological index of early sensory processing, and negative symptoms, reporting controversial results. However, none of these studies investigated electrophysiological correlates of the two negative symptom domains.Objectives: The aim of our study was to evaluate, within the multicenter study of the Italian Network for Research on Psychoses, the relationships between N100 and negative symptom domains in SCZ.Methods: Auditory N100 was analyzed in 114 chronic stabilized SCZ and 63 healthy controls (HCs). Negative symptoms were assessed with the Brief Negative Symptom Scale (BNSS). Repeated measures ANOVA and correlation analyses were performed to evaluate differences between SCZ and HCs and association of N100 features with negative symptoms.Results: Our findings demonstrated a significant N100 amplitude reduction in SCZ compared with HCs. In SCZ, N100 amplitude for standard stimuli was associated with negative symptoms, in particular with the expressive deficit domain. Within the expressive deficit, blunted affect and alogia had the same pattern of correlation with N100.Conclusion: Our findings revealed an association between expressive deficit and N100, suggesting that these negative symptoms might be related to deficits in early auditory processing in SCZ.

Early evoked brain activity underlies auditory and audiovisual speech recognition deficits in schizophrenia

ObjectivesPeople with Schizophrenia (SZ) show deficits in auditory and audiovisual speech recognition. It is possible that these deficits are related to aberrant early sensory processing, combined with an impaired ability to utilize visual cues to improve speech recognition. In this electroencephalography study we tested this by having SZ and healthy controls (HC) identify different unisensory auditory and bisensory audiovisual syllables at different auditory noise levels. MethodsSZ (N = 24) and HC (N = 21) identified one of three different syllables (/da/, /ga/, /ta/) at three different noise levels (no, low, high). Half the trials were unisensory auditory and the other half provided additional visual input of moving lips. Task-evoked mediofrontal N1 and P2 brain potentials triggered to the onset of the auditory syllables were derived and related to behavioral performance. ResultsIn comparison to HC, SZ showed speech recognition deficits for unisensory and bisensory stimuli. These deficits were primarily found in the no noise condition. Paralleling these observations, reduced N1 amplitudes to unisensory and bisensory stimuli in SZ were found in the no noise condition. In HC the N1 amplitudes were positively related to the speech recognition performance, whereas no such relationships were found in SZ. Moreover, no group differences in multisensory speech recognition benefits and N1 suppression effects for bisensory stimuli were observed. ConclusionOur study suggests that reduced N1 amplitudes reflect early auditory and audiovisual speech processing deficits in SZ. The findings that the amplitude effects were confined to salient speech stimuli and the attenuated relationship with behavioral performance in patients compared to HC, indicates a diminished decoding of the auditory speech signals in SZs. Our study also revealed relatively intact multisensory benefits in SZs, which implies that the observed auditory and audiovisual speech recognition deficits were primarily related to aberrant processing of the auditory syllables.

Evaluation of sensory gating efficiency in adults with Down syndrome

AbstractBackgroundIn Down syndrome (DS), the amyloid precursor protein (APP) gene‐dosing effect drives a lifelong over‐production of amyloid‐beta (Aβ). The accumulation of Aβ begins to manifest as amyloid plaques as early as the teens and virtually in all by 40 years. The progression of Alzheimer’s Disease(AD)‐related neuropathology may underlie inhibitory disruption leading to over‐ or under‐sensitivity to auditory processing and cognitive deficits in DS. In positron electromagnetic tomography (PET) studies in DS, amyloid deposition has a defined temporal‐spatial profile that begins in the striatum and predictably progresses to the dorsolateral pre‐frontal cortex (DLPFC) and ventral pre‐frontal cortex (VPFC). Typically developing (TD) individuals with AD exhibit deficits of sensory gating, which can lead to sensory overload and disruption of higher cognitive processes. The auditory paired‐click paradigm has been used to evaluate sensory gating deficits in AD. We extend this inquiry to a cohort with DS to assess sensory gating in adults with DS by measuring the P50 and the N100 event‐related potential (ERP) components. The P50 component is elicited 50 ms post‐stimulus, involves the DLPFC and is sensitive to striatum‐dependent sensory gating. The N100 is elicited 100 ms post‐stimulus by auditory stimuli in absence of task demands.MethodIn this cross‐sectional study, data were collected using high‐density QEEG in 39 DS adults and 39 age‐matched TD controls. In this paradigm, two identical auditory stimuli (S1 and S2) were presented. For each stimuli, the response latency and amplitudes of the P50, and more salient N100 component were measured at the Cz and Fz electrode sites. General linear models examined the modulation of the ERP responses to S1 and S2 between the two groups.ResultWith P50 and N100 response amplitudes, an effect of stimulus was found. In the DS group, longer response latencies for the P50 and N100 corresponding to both S1 and S2 were observed.ConclusionIn DS, the ability to gate‐out irrelevant sensory information is intact when compared to TD; however, there is an overall slower processing of auditory stimuli, which may be attributed to amyloidopathy. The EEG‐based paired‐click paradigm offers functional insight into potential biomarkers for pre‐clinical AD in DS.

Deficits in central auditory processing among migraine patients

BackgroundMigraine is a neurological disease associated with abnormal excitability in visual, somatosensory, and motor cortex. This study aimed to verify and compare auditory processing performance in migraine patients with and without dizziness and healthy controls.ResultsSixty subjects were divided into 3 groups: control group, twenty normal healthy subjects, and study group I (twenty subjects diagnosed with migraine) and study group II (twenty subjects diagnosed with vestibular migraine). They were evaluated using the Central Auditory Processing Questionnaire for adults, tympanometry, pure tone audiometry, Psychophysical Central Auditory Tests, including Arabic Speech Intelligibility in Noise Test for adults, Arabic Dichotic Digit Test [version II], Gap in Noise Test, Duration Pattern Test, and Arabic Memory Tests. No significant difference was found between the two study groups I and II, but the significant difference was found between the study groups and the control group in all central auditory test results. Statistically significant difference was found between the control group and study groups I and II regarding all memory tests. The highest percentage of abnormality was present in temporal resolution and selective auditory attention in both study groups. There was no significant statistical correlation between the number of attacks/month and central auditory test results. There was no significant statistical correlation between the frequency of attacks in VM patients and central auditory test results.ConclusionsPatients with migraine and vestibular migraine had an inferior performance in all psychophysical central auditory tests when compared with control. Also, there was no significant difference between the 2 study groups regarding central auditory test results which may support that both migraine with and without dizziness have the same pathophysiology.

Basic auditory processing and emotion recognition in individuals at clinical high risk for psychosis

The ability to understand others' emotions from subtle cues is a critical skill for navigating the complex social world, with increasing demands placed on this capability as children enter adolescence. Individuals at clinical high-risk (CHR) of developing psychosis exhibit social isolation with specific impairments in social cognition (Thompson et al., 2011) and emotion recognition (Addington et al., 2008; Amminger et al., 2011; Corcoran et al., 2015). The degree of social impairment and the severity of emotion recognition deficits are greater in individuals who later convert to psychosis than in those who do not (Cornblatt et al., 2011). Emotion recognition deficits thus represent promising targets for improving early identification and intervention strategies (Addington et al., 2008; Amminger et al., 2011; Cornblatt et al., 2011; Kee et al., 2003; Niemi et al., 2005). A significant challenge remains however, to identify a precursor of emotional recognition deficits for use as a salient diagnostic tool and therapeutic target. Impairments in basic auditory processes may underlie the auditory emotion identification deficits and social functioning deficits associated with psychotic disorders and at-risk states. The auditory properties of speech convey emotional content (Banse and Scherer, 1996; Hammerschmidt and Jurgens, 2007), and the ability to identify emotion from these vocal cues is impaired in schizophrenia (Addington et al., 2008; Amminger et al., 2011; Bach et al., 2009; Corcoran et al., 2015; Cornblatt et al., 2011; Dickey et al., 2010; Dickey et al., 2008; Kee et al., 2003; Leitman et al., 2007; Leitman et al., 2010; Niemi et al., 2005; Thompson et al., 2011), schizotypal personality disorder (Dickey et al., 2010; Dickey et al., 2008), and CHR subjects (Corcoran et al., 2015; Thompson et al., 2011). We recently reported that individuals with schizophrenia exhibit wide ranging basic auditory processing deficits, and that additional basic auditory processing abilities, including formant discrimination, sinusoidal amplitude modulation detection, and duration discrimination are associated with the ability to recognize emotion in voice (Kraus et al., 2019). In this study, we have aimed to determine whether CHR individuals exhibit similar widespread auditory processing deficits associated with impaired emotion recognition.

Neural auditory processing of parameterized speech envelopes

Speech perception depends highly on the neural processing of the speech envelope. Several auditory processing deficits are hypothesized to result in a reduction in fidelity of the neural representation of the speech envelope across the auditory pathway. Furthermore, this reduction in fidelity is associated with supra-threshold speech processing deficits. Investigating the mechanisms that affect the neural encoding of the speech envelope can be of great value to gain insight in the different mechanisms that account for this reduced neural representation, and to develop stimulation strategies for hearing prosthesis that aim to restore it. In this perspective, we discuss the importance of neural assessment of phase-locking to the speech envelope from an audiological view and introduce the Temporal Envelope Speech Tracking (TEMPEST) stimulus framework which enables the electrophysiological assessment of envelope processing across the auditory pathway in a systematic and standardized way. We postulate that this framework can be used to gain insight in the salience of speech-like temporal envelopes in the neural code and to evaluate the effectiveness of stimulation strategies that aim to restore temporal processing across the auditory pathway with auditory prostheses.

Auditory hypersensitivity and processing deficits in a rat model of fragile X syndrome

Fragile X (FX) syndrome is one of the leading inherited causes of autism spectrum disorder (ASD). A majority of FX and ASD patients exhibit sensory hypersensitivity, including auditory hypersensitivity or hyperacusis, a condition in which everyday sounds are perceived as much louder than normal. Auditory processing deficits in FX and ASD also afford the opportunity to develop objective and quantifiable outcome measures that are likely to translate between humans and animal models due to the well-conserved nature of the auditory system and well-developed behavioral read-outs of sound perception. Therefore, in this study we characterized auditory hypersensitivity in a Fmr1 knockout (KO) transgenic rat model of FX using an operant conditioning task to assess sound detection thresholds and suprathreshold auditory reaction time-intensity (RT-I) functions, a reliable psychoacoustic measure of loudness growth, at a variety of stimulus frequencies, bandwidths, and durations. Male Fmr1 KO and littermate WT rats both learned the task at the same rate and exhibited normal hearing thresholds. However, Fmr1 KO rats had faster auditory RTs over a broad range of intensities and steeper RT-I slopes than WT controls, perceptual evidence of excessive loudness growth in Fmr1 KO rats. Furthermore, we found that Fmr1 KO animals exhibited abnormal perceptual integration of sound duration and bandwidth, with diminished temporal but enhanced spectral integration of sound intensity. Because temporal and spectral integration of sound stimuli were altered in opposite directions in Fmr1 KO rats, this suggests that abnormal RTs in these animals are evidence of aberrant auditory processing rather than generalized hyperactivity or altered motor responses. Together, these results are indicative of fundamental changes to low-level auditory processing in Fmr1 KO animals. Finally, we demonstrated that antagonism of metabotropic glutamate receptor 5 (mGlu5) selectively and dose-dependently restored normal loudness growth in Fmr1 KO rats, suggesting a pharmacologic approach for alleviating sensory hypersensitivity associated with FX. This study leverages the tractable nature of the auditory system and the unique behavioral advantages of rats to provide important insights into the nature of a centrally important yet understudied aspect of FX and ASD.