Auditory Sensory Processing Research Articles

Triple model of auditory sensory processing: a novel gating stream directly links primary auditory areas to executive prefrontal cortex.

SUMMARYThe generally accepted model of sensory processing of visual and auditory stimuli assumes two major parallel processing streams, ventral and dorsal, which comprise functionally and anatomically distinct but interacting processes in which the ventral stream supports stimulus identification, and the dorsal stream is involved in recognizing the stimulus spatial location and sensori-motor integration functions. However, recent studies suggest the existence of a third, very fast sensory processing pathway, a gating stream that directly links the primary auditory cortices to the executive prefrontal cortex within the first 50 milliseconds after presentation of a stimulus, bypassing hierarchical structure of the ventral and dorsal pathways. Gating stream propagates the sensory gating phenomenon, which serves as a basic protective mechanism preventing irrelevant, repeated information from recurrent sensory processing. The goal of the present paper is to introduce the novel ‘three-stream’ model of auditory processing, including the new fast sensory processing stream, i.e. gating stream, alongside the well-affirmed dorsal and ventral sensory processing pathways. The impairments in sensory processing along the gating stream have been found to be strongly involved in the pathophysiological sensory processing in Alzheimer’s disease and could be the underlying issue in numerous neuropsychiatric disorders and diseases that are linked to the pathological sensory gating inhibition, such as schizophrenia, post-traumatic stress disorder, bipolar disorder or attention deficit hyperactivity disorder.

Effect of mild and chronic neonatal hypothyroidism on sensory information processing in a rodent model: A behavioral and electrophysiological study

Thyroid hormones are essential for neonatal brain development. It is well established that absence of thyroid hormones during critical periods of development can alter sensory functions such as visual and auditory processing, but there are few studies on rat somatosensory system development at mild, long-term, and irreversible neonatal hypothyroidism. Thus, the current study was conducted to investigate whether chronic thyroid hormone insufficiency would alter different cognitive aspects of tactile information processing and sensory motor filtering at behavioral or neuronal levels. Neonatal Wistar male rats were exposed to 0 and 6 ppm of propylthiouracil for 150 days. Behavioral tests including tactile discrimination tests and acoustic startle reflex test were performed. Using extracellular single unit recording technique, barrel cortex neurons’ excitatory and inhibitory responses to controlled displacement of whiskers were evaluated. Results indicated that percentage of correct choice in tactile learning and discrimination of a new texture decreased in hypothyroid group compared to the control group (P < 0.05). In addition, acoustic startle reflex of hypothyroid group significantly decreased compared to the control rats when the prepulse intensity was 71 dB (P < 0.05). Data obtained from electrophysiological tests showed that spontaneous activity and response magnitude of barrel cortex neurons decreased in hypothyroid group compared to the control group (P < 0.05). It is concluded that, thyroid hormones can regulate tactile and auditory sensory processing in male rats, and mild and long-term absence of these hormones can result in deficiency in natural functions of these sensory systems.

No intermodal interference effects of threatening information during concurrent audiovisual stimulation

Changes in attention can result in sensory processing trade-off effects, in which sensory cortical responses to attended stimuli are heightened and responses to competing distractors are attenuated. However, it is unclear if competition or facilitation effects will be observed at the level of sensory cortex when attending to competing stimuli in two modalities. The present study used electroencephalogram (EEG) and frequency-tagging to quantitatively assess auditory-visual interactions during sustained multimodal sensory stimulation. The emotional content of a 6.66 Hz rapid serial visual presentation (RSVP) was manipulated to elicit well-established emotional attention effects, while a constant 63 dB tone with a 40.8 Hz modulation served as a concurrent auditory stimulus in two experiments. As a directed attention manipulation, participants were instructed to detect transient sound level events in the auditory stream in Experiment 1. To manipulate attention through threat anticipation, participants were instructed to expect an aversive noise burst after a higher 40.8 Hz modulated tone in Experiment 2. Each stimulus evoked reliable steady-state sensory cortical responses in all participants (n = 30) in both experiments. The visual cortical responses were modulated by the auditory detection task, but not by threat anticipation: Visual responses were smaller during auditory streams with a transient target as compared to uninterrupted auditory streams. Conversely, visual stimulus condition had no significant effects on auditory sensory cortical responses in either experiment. These results indicate that there is neither a competition nor facilitation effect of visual content on concurrent auditory sensory cortical processing. They further indicate that competition effects of auditory stream content on sustained visuocortical responses are limited to auditory target processing.

Cortical ensemble activity discriminates auditory attentional states

Selective attention modulates sensory cortical activity. It remains unclear how auditory cortical activity represents stimuli that differ behaviorally. We designed a cross-modality task in which mice made decisions to obtain rewards based on attended visual or auditory stimuli. We recorded auditory cortical activity in behaving mice attending to, ignoring, or passively hearing auditory stimuli. Engaging in the task bidirectionally modulates neuronal responses to the auditory stimuli in both the attended and ignored conditions compared to passive hearing. Neuronal ensemble activity in response to stimuli under attended, ignored and passive conditions are readily distinguishable. Furthermore, ensemble activity under attended and ignored conditions are in closer states compared to passive condition, and they share a component of attentional modulation which drives them to the same direction in the population activity space. Our findings suggest that the ignored condition is very different from the passive condition, and the auditory cortical sensory processing under ignored, attended and passive conditions are modulated differently.

Abnormal development of early auditory processing in 22q11.2 Deletion Syndrome

The 22q11.2 Deletion Syndrome (22q11.2 DS) is one of the highest genetic risk factors for the development of schizophrenia spectrum disorders. In schizophrenia, reduced amplitude of the frequency mismatch negativity (fMMN) has been proposed as a promising neurophysiological marker for progressive brain pathology. In this longitudinal study in 22q11.2 DS, we investigate the progression of fMMN between childhood and adolescence, a vulnerable period for brain maturation. We measured evoked potentials to auditory oddball stimuli in the same sample of 16 patients with 22q11.2 DS and 14 age-matched controls in childhood and adolescence. In addition, we cross-sectionally compared an increased sample of 51 participants with 22q11.2 DS and 50 controls divided into two groups (8–14 and 14–20 years). The reported results are obtained using the fMMN difference waveforms. In the longitudinal design, the 22q11.2 deletion carriers exhibit a significant reduction in amplitude and a change in topographic patterns of the mismatch negativity response from childhood to adolescence. The same effect, reduced mismatch amplitude in adolescence, while preserved during childhood, is observed in the cross-sectional study. These results point towards functional changes within the brain network responsible for the fMMN. In addition, the adolescents with 22q11.2 DS displayed a significant increase in amplitude over central electrodes during the auditory N1 component. No such differences, reduced mismatch response nor increased N1, were observed in the typically developing group. These findings suggest different developmental trajectories of early auditory sensory processing in 22q11.2 DS and functional changes that emerge during the critical period of increased risk for schizophrenia spectrum disorders.

EEG and ANS markers of attention response in vegetative state: Different responses to own vs. other names

ABSTRACT Covert measures of information-processing are valuable tools to support assessment of patients’ disorders of consciousness because of their potential in revealing what seem to be hidden. Those measures allow to overcome some limitations of traditional behavioural methods, which are often biased by difficulties in detecting reliable patients’ responses. Therefore, we aimed at exploring patterns of psychophysiological responses (electroencephalography – EEG, skin conductance level – SCL, skin conductance response – SCR, heart rate – HR) marking potentially-preserved processing of personally-relevant stimuli in a sample of VS patients. In particular, we compared the processing of own vs. other names due to the intrinsic salience, relevance, and familiarity of such stimuli. Analysis of electroencephalography, skin conductance and heart rate modulations highlighted a consistent pattern of increased skin conductance and heart rate measures in response to patients’ own name with respect to other names. Further, we observed increased delta and decreased alpha activity over frontal areas in response to their own name with respect to other names. Own-name stimuli might preserve their peculiar qualification even after severe brain damage and might call on residual attention orientation and preferred coding resources, suggesting the existence of partly preserved information-processing pathways that extends beyond basic auditory sensory processing.

Differential of Frequency and Duration Mismatch Negativity and Theta Power Deficits in First-Episode and Chronic Schizophrenia.

Background: Due to its impairment in patients with schizophrenia, mismatch negativity (MMN) generation has been identified as a potential biomarker for identifying primary impairments in auditory sensory processing. This study aimed to investigate the dysfunctional differences in different MMN deviants and evoked theta power in patients with first-episode schizophrenia (FES) and chronic schizophrenia (CS).Methods: We measured frequency and duration MMN from 40 FES, 40 CS, and 40 healthy controls (HC). Evoked theta power was analyzed by event-related spectral perturbation (ERSP) approaches.Results: Deficits in duration MMN were observed in both FES (p = 0.048, Bonferroni-adjusted) and CS (p < 0.001, Bonferroni-adjusted). However, deficits in frequency MMN were restricted to the CS (p < 0.001, Bonferroni-adjusted). Evoked theta power deficits were observed in both patient groups when compared with the HC (p FES = 0.001, p CS < 0.001, Bonferroni-adjusted), yet no significant differences were found between FES and CS. Frequency MMN was correlated with the MATRICS consensus cognitive battery (MCCB) combined score (r = -0.327, p < 0.05) and MCCB verbal learning (r = -0.328, p < 0.05) in FES. Evoked theta power was correlated with MCCB working memory in both FES (r = 0.347, p < 0.05) and CS (r = 0.408, p < 0.01).Conclusion: These findings suggest that duration MMN and evoked theta power deficits may be more sensitive for detection of schizophrenia during its early stages. Moreover, frequency MMN and theta power could potentially linked to poor cognitive functioning in schizophrenic patients. The findings mentioned above indicated that the neural mechanisms of the three indexes may vary between people.

Auditory perception is associated with implicit language learning and receptive language ability in autism spectrum disorder

BackgroundAutism spectrum disorder (ASD) is associated with language impairment as well as atypical auditory sensory processing. The current study investigated associations among auditory perception, implicit language learning and receptive language ability in youth with ASD. MethodsWe measured auditory event related potentials (ERP) during an artificial language statistical learning task in 76 youth with ASD and 27 neurotypical (NT) controls. Participants with ASD had a broad range of cognitive and language abilities. ResultsNT youth showed evidence of implicit learning via attenuated P1 amplitude in the left hemisphere. In contrast, among youth with ASD, implicit learning elicited bilateral attenuation that was increasingly evident with greater receptive language skill. ConclusionsEfficient early auditory perception reflects language learning and is a marker of language ability among youth with ASD. Atypical lateralization of word learning is evident in ASD across a broad range of receptive language abilities.

Neph2/Kirrel3 regulates sensory input, motor coordination, and home-cage activity in rodents.

Adhesion molecules of the immunoglobulin superfamily (IgSF) are essential for neuronal synapse development across evolution and control various aspects of synapse formation and maturation. Neph2, also known as Kirrel3, is an IgSF adhesion molecule implicated in synapse formation, synaptic transmission and ultrastructure. In humans, defects in the NEPH2 gene have been associated with neurodevelopmental disorders such as Jacobsen syndrome, intellectual disability, and autism-spectrum disorders. However, the precise role in development and function of the nervous system is still unclear. Here, we present the histomorphological and phenotypical analysis of a constitutive Neph2-knockout mouse line. Knockout mice display defects in auditory sensory processing, motor skills, and hyperactivity in the home-cage analysis. Olfactory, memory and metabolic testing did not differ from controls. Despite the wide-spread expression of Neph2 in various brain areas, no gross anatomic defects could be observed. Neph2 protein could be located at the cerebellar pinceaux. It interacted with the pinceau core component neurofascin and other synaptic proteins thus suggesting a possible role in cerebellar synapse formation and circuit assembly. Our results suggest that Neph2/Kirrel3 acts on the synaptic ultrastructural level and neuronal wiring rather than on ontogenetic events affecting macroscopic structure. Neph2-knockout mice may provide a valuable rodent model for research on autism spectrum diseases and neurodevelopmental disorders.

Amplitude by Peak Interaction but No Evidence of Auditory Mismatch Response Deficits to Frequency Change in Preschool-Aged Children with Fetal Alcohol Spectrum Disorders.

Prior studies indicate that the auditory mismatch response is sensitive to early alterations in brain development in multiple developmental disorders. Prenatal alcohol exposure is known to impact early auditory processing. The current study hypothesized alterations in the mismatch response in young children with fetal alcohol spectrum disorders (FASD). Participants in this study were 9 children with a FASD and 17 control children (Control) aged 3 to 6years. Participants underwent magnetoencephalography and structural magnetic resonance imaging scans separately. We compared groups on neurophysiological mismatch negativity (MMN) responses to auditory stimuli measured using the auditory oddball paradigm. Frequent (1,000Hz) and rare (1,200Hz) tones were presented at 72dB. There was no significant group difference in MMN response latency or amplitude represented by the peak located ~200ms after stimulus presentation in the difference time course between frequent and infrequent tones. Examining the time courses to the frequent and infrequent tones separately, repeated measures analysis of variance with condition (frequent vs. rare), peak (N100m and N200m), and hemisphere as within-subject factors and diagnosis and sex as the between-subject factors showed a significant interaction of peak by diagnosis (p=0.001), with a pattern of decreased amplitude from N100m to N200m in Control children and the opposite pattern in children with FASD. However, no significant difference was found with the simple effects comparisons. No group differences were found in the response latencies of the rare auditory evoked fields. The results indicate that there was no detectable effect of alcohol exposure on the amplitude or latency of the MMNm response to simple tones modulated by frequency change in preschool-aged children with FASD. However, while discrimination abilities to simple tones may be intact, early auditory sensory processing revealed by the interaction between N100m and N200m amplitude indicates that auditory sensory processing may be altered in children with FASD.

Audio-motor but not visuo-motor temporal recalibration speeds up sensory processing.

Perception of synchrony between one's own action (a finger tap) and the sensory feedback thereof (a visual flash or an auditory pip) can be recalibrated after exposure to an artificially inserted delay between them (temporal recalibration effect: TRE). TRE might be mediated by a compensatory shift of motor timing (when did I tap?) and/or the sensory timing of the feedback (when did I hear/see the feedback?). To examine this, we asked participants to voluntarily tap their index finger at a constant pace while receiving visual or auditory feedback (a flash or pip) that was either synced or somewhat delayed relative to the tap. Following this exposure phase, they then performed a simple reaction time (RT) task to measure the sensory timing of the exposure stimulus, and a sensorimotor synchronization (SMS) task (tapping in synchrony with a flash or pip as pacing stimulus) to measure the point of subjective synchrony between the tap and pacing stimulus. The results showed that after exposure to delayed auditory feedback, participants tapped earlier (~21.5 ms) relative to auditory pacing stimuli (= temporal recalibration) and reacted faster (~5.6 ms) to auditory stimuli. For visual exposure and test stimuli, there were no such compensatory effects. These results indicate that adjustments of audio-motor synchrony can to some extent be explained by a change in the speed of auditory sensory processing. We discuss this in terms of an attentional modulation of sensory processing.

Clinical and Cognitive Significance of Auditory Sensory Processing Deficits in Schizophrenia.

Although patients with schizophrenia exhibit impaired suppression of the P50 event-related brain potential in response to the second of two identical auditory stimuli during a paired-stimulus paradigm, uncertainty remains over whether this deficit in inhibitory gating of auditory sensory processes has relevance for patients' clinical symptoms or cognitive performance. The authors examined associations between P50 suppression deficits and several core features of schizophrenia to address this gap. P50 was recorded from 52 patients with schizophrenia and 41 healthy comparison subjects during a standard auditory paired-stimulus task. Clinical symptoms were assessed with the Scale for the Assessment of Positive Symptoms and the Scale for the Assessment of Negative Symptoms. The MATRICS Consensus Cognitive Battery was utilized to measure cognitive performance in a subsample of 39 patients. Correlation and regression analyses were conducted to examine P50 suppression in relation to clinical symptom and cognitive performance measures. Schizophrenia patients demonstrated a deficit in P50 suppression when compared with healthy subjects, replicating prior research. Within the patient sample, impaired P50 suppression covaried reliably with greater difficulties in attention, poorer working memory, and reduced processing speed. Impaired suppression of auditory stimuli was associated with core pathological features of schizophrenia, increasing confidence that P50 inhibitory processing can inform the development of interventions that target cognitive impairments in this chronic and debilitating mental illness.

Mismatch negativity impairment is associated with deficits in identifying real-world environmental sounds in schizophrenia

BackgroundPatients with schizophrenia (SZ) have impairments in processing auditory information that have been linked to deficits in cognitive and psychosocial functioning. Dysfunction in auditory sensory processing in SZ has been indexed by mismatch negativity (MMN), an event-related potential evoked by a rare, deviant stimulus embedded within a sequence of identical standard stimuli. Although MMN deficits in SZ have been studied extensively, relatively little is known about how these deficits relate to accurately identifying real-world, ecologically-salient sounds. MethodsMMN was assessed in SZ patients (n=21) and non-psychiatric comparison subjects (NCS; n=16). Participants were also assessed in their ability to identify common environmental sounds using a subset of 80 sound clips from the International Affective Digitized Sounds 2nd Ed collection. ResultsSZ patients made significantly more errors in environmental sound identification (p<0.001, d=0.86) and showed significantly reduced MMN amplitude deficits in MMN compared to NCS (p<0.01, d=0.97). In SZ patients, MMN deficits were associated with significantly greater environmental sound identification errors (r=0.61, p<0.01). ConclusionsImpairments in early auditory information processing in schizophrenia account for significant proportions of variance in the ability to identify real-world, functionally relevant environmental sounds. This study supports the view that interventions targeting deficits in low-level auditory sensory processing may also impact more complex cognitive brain processes relevant to psychosocial disability.

Auditory Pitch Perception in Autism Spectrum Disorder Is Associated With Nonverbal Abilities.

Atypical sensory perception and heterogeneous cognitive profiles are common features of autism spectrum disorder (ASD). However, previous findings on auditory sensory processing in ASD are mixed. Accordingly, auditory perception and its relation to cognitive abilities in ASD remain poorly understood. Here, children with ASD, and age- and intelligence quotient (IQ)-matched typically developing children, were tested on a low- and a higher level pitch processing task. Verbal and nonverbal cognitive abilities were measured using the Wechsler's Abbreviated Scale of Intelligence. There were no group differences in performance on either auditory task or IQ measure. However, there was significant variability in performance on the auditory tasks in both groups that was predicted by nonverbal, not verbal skills. These results suggest that auditory perception is related to nonverbal reasoning rather than verbal abilities in ASD and typically developing children. In addition, these findings provide evidence for preserved pitch processing in school-age children with ASD with average IQ, supporting the idea that there may be a subgroup of individuals with ASD that do not present perceptual or cognitive difficulties. Future directions involve examining whether similar perceptual-cognitive relationships might be observed in a broader sample of individuals with ASD, such as those with language impairment or lower IQ.

Response characteristics of the rat anterior cingulate cortex to ultrasonic communicative vocalizations.

Emotional communication involves transmitting information on affective states. Rat 50- and 22-kHz ultrasonic vocalizations (USVs) are emotional communication signals that reflect positive or negative states, respectively. In general, emotional communication signals that elicit changes in event-related potentials (ERPs), suggesting a specific mechanism for processing these signals. As this is observed in several communication systems including humans, we hypothesized that rat USVs can also trigger such changes. In this study, we measured rat local field potentials and used them to calculate ERPs from the anterior cingulate cortex (ACC), an area related to motor production of USVs. In Experiment 1, we measured ERPs to pure tones with peak frequencies around 50 or 22 kHz to examine whether the ACC is involved in auditory sensory processing related to pitch. The results showed that pure tones around 50 kHz elicited large amplitude ERPs, whereas those around 22 kHz resulted in smaller ERPs. In Experiment 2, we compared ERPs in response to rat USVs (emotional stimuli) with ERPs to pure tones modeled after USVs (neutral stimuli). The peak frequencies were the same between USVs and neutral sounds, but USVs showed more frequency modulation than neutral sounds. USVs elicited larger changes in the amplitude of ERP components than neutral stimuli did. These experiments suggest that the rat ACC is sensitive to frequencies around 50 and 22 kHz, and is especially tuned to frequency modulation around these frequencies. Taken together, the rat ACC may process the emotional content of communication signals on the basis of pitch and frequency modulation.

Beyond Auditory Sensory Processing Deficits: Lexical Tone Perception Deficits in Chinese Children With Developmental Dyslexia

Increasing evidence suggests that children with developmental dyslexia exhibit a deficit not only at the segmental level of phonological processing but also, by extension, at the suprasegmental level. However, it remains unclear whether such a suprasegmental phonological processing deficit is due to a difficulty in processing acoustic cues of speech rhythm, such as rise time and intensity. This study set out to investigate to what extent suprasegmental phonological processing (i.e., Cantonese lexical tone perception) and rise time sensitivity could distinguish Chinese children with dyslexia from typically developing children. Sixteen children with dyslexia and 44 age-matched controls were administered a Cantonese lexical tone perception task, psychoacoustic tasks, a nonverbal reasoning ability task, and word reading and dictation tasks. Children with dyslexia performed worse than controls on Cantonese lexical tone perception, rise time, and intensity. Furthermore, Cantonese lexical tone perception appeared to be a stable indicator that distinguishes children with dyslexia from controls, even after controlling for basic auditory processing skills. These findings suggest that suprasegmental phonological processing (i.e., lexical tone perception) is a potential factor that accounts for reading difficulty in Chinese.

Bioelectrical brain effects of one's own voice identification in pitch of voice auditory feedback.

Control of voice fundamental frequency (F0) relies in part on comparison of the intended F0 level and auditory feedback. This comparison impacts "sense of agency", or SoA, commonly defined as being the agent of one's own actions and plays a key role for self-awareness and social interactions. SoA is aberrant in several psychiatric disorders. Knowledge about brain activity reflecting SoA can be used in clinical practice for these disorders. It was shown that perception of voice feedback as one's own voice, reflecting the recognition of SoA, alters auditory sensory processing. Using a voice perturbation paradigm we contrasted vocal and bioelectrical brain responses to auditory stimuli that differed in magnitude: 100 and 400 cents. Results suggest the different magnitudes were perceived as a pitch error in self-vocalization (100 cents) or as a pitch shift generated externally (400 cents). Vocalizations and neural responses to changes in pitch of self-vocalization were defined as those made to small magnitude pitch-shifts (100 cents) and which did not show differential neural responses to upward versus downward changes in voice pitch auditory feedback. Vocal responses to large magnitude pitch shifts (400 cents) were smaller than those made to small pitch shifts, and neural responses differed according to upwards versus downward changes in pitch. Our results suggest that the presence of SoA for self-produced sounds may modify bioelectrical brain responses reflecting differences in auditory processing of the direction of a pitch shift. We suggest that this modification of bioelectrical response can be used as a biological index of SoA. Possible neuronal mechanisms of this modification of bioelectrical brain response are discussed.

Mild Cognitive Impairment Is Characterized by Deficient Brainstem and Cortical Representations of Speech.

Mild cognitive impairment (MCI) is recognized as a transitional phase in the progression toward more severe forms of dementia and is an early precursor to Alzheimer's disease. Previous neuroimaging studies reveal that MCI is associated with aberrant sensory-perceptual processing in cortical brain regions subserving auditory and language function. However, whether the pathophysiology of MCI extends to speech processing before conscious awareness (brainstem) is unknown. Using a novel electrophysiological approach, we recorded both brainstem and cortical speech-evoked brain event-related potentials (ERPs) in older, hearing-matched human listeners who did and did not present with subtle cognitive impairment revealed through behavioral neuropsychological testing. We found that MCI was associated with changes in neural speech processing characterized as hypersensitivity (larger) brainstem and cortical speech encoding in MCI compared with controls in the absence of any perceptual speech deficits. Group differences also interacted with age differentially across the auditory pathway; brainstem responses became larger and cortical ERPs smaller with advancing age. Multivariate classification revealed that dual brainstem-cortical speech activity correctly identified MCI listeners with 80% accuracy, suggesting its application as a biomarker of early cognitive decline. Brainstem responses were also a more robust predictor of individuals' MCI severity than cortical activity. Our findings suggest that MCI is associated with poorer encoding and transfer of speech signals between functional levels of the auditory system and advance the pathophysiological understanding of cognitive aging by identifying subcortical deficits in auditory sensory processing mere milliseconds (<10 ms) after sound onset and before the emergence of perceptual speech deficits.SIGNIFICANCE STATEMENT Mild cognitive impairment (MCI) is a precursor to dementia marked by declines in communication skills. Whether MCI pathophysiology extends below cerebral cortex to affect speech processing before conscious awareness (brainstem) is unknown. By recording neuroelectric brain activity to speech from brainstem and cortex, we show that MCI hypersensitizes the normal encoding of speech information across the hearing brain. Deficient neural responses to speech (particularly those generated from the brainstem) predicted the presence of MCI with high accuracy and before behavioral deficits. Our findings advance the neurological understanding of MCI by identifying a subcortical biomarker in auditory-sensory processing before conscious awareness, which may be a precursor to declines in speech understanding.

15q13.3 homozygous knockout mouse model display epilepsy-, autism- and schizophrenia-related phenotypes.

The 15q13.3 microdeletion syndrome is caused by a 1.5-MB hemizygous microdeletion located on 15q13.3 affecting seven genes: FAN1; MTMR10; TRPM1; miR-211; KLF13; OTUD7A; and CHRNA7. The 15q13.3 microdeletion increases the risk of intellectual disability, epilepsy, autism spectrum disorder and schizophrenia, though the clinical profile varies considerably. Two mouse models of this syndrome, with hemizygous deletion of the orthologous region in the murine genome, have recently been shown to recapitulate a number of the behavioral and physiological deficits that characterize the human condition. Still, little is known of the underlying biological mechanisms. Eleven human cases with homozygous deletion of the 15q13.3 region have been reported, all with severe functional and physiological impairments. We therefore hypothesized that a 15q13.3 homozygous knockout would confer more pronounced behavioral and physiological deficits in mice than the 15q13.3 hemizygous deletion. Here we report the characterization of a 15q13.3 knockout mouse. We observed marked deficits including altered seizure susceptibility, autistic behavior-related phenotypes, and auditory sensory processing. Several of these deficits, albeit less pronounced, were also found in the 15q13.3 hemizygous littermates indicating a gene-dosage dependency. Our findings strongly indicate that studies of the hemi- and homozygous 15q13.3 mouse strains will facilitate understanding of the biological mechanisms of severe mental disorders.

Mapping the spatiotemporal dynamics of processing task-relevant and task-irrelevant sound feature changes using concurrent EEG-fMRI.

The cortical processing of changes in auditory input involves auditory sensory regions as well as different frontoparietal brain networks. The spatiotemporal dynamics of the activation spread across these networks has, however, not been investigated in detail so far. We here approached this issue using concurrent functional magnetic resonance imaging (fMRI) and electroencephalography (EEG), providing us with simultaneous information on both the spatial and temporal patterns of change-related activity. We applied an auditory stimulus categorization task with switching categorization rules, allowing to analyze change-related responses as a function of the changing sound feature (pitch or duration) and the task relevance of the change. Our data show the successive progression of change-related activity from regions involved in early change detection to the ventral and dorsal attention networks, and finally the central executive network. While early change detection was found to recruit feature-specific networks involving auditory sensory but also frontal and parietal brain regions, the later spread of activity across the frontoparietal attention and executive networks was largely independent of the changing sound feature, suggesting the existence of a general feature-independent processing pathway of change-related information. Task relevance did not modulate early auditory sensory processing, but was mainly found to affect processing in frontal brain regions. Hum Brain Mapp 37:3400-3416, 2016. © 2016 Wiley Periodicals, Inc.