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Auditory steady-state response (ASSR) has been studied as a potential biomarker for abnormal auditory sensory processing in autism spectrum disorder (ASD), with mixed results. Motivated by prior somatosensory findings of group differences in inter-trial coherence (ITC) between ASD and typically developing (TD) individuals at twice the steady-state stimulation frequency, we examined ASSR at 25 and 50 as well as 43 and 86 Hz in response to 25-Hz and 43-Hz auditory stimuli, respectively, using magnetoencephalography. Data were recorded from 22 ASD and 31 TD children, ages 6-17 years. ITC measures showed prominent ASSRs at the stimulation and double frequencies, without significant group differences. These results do not support ASSR as a robust ASD biomarker of abnormal auditory processing in ASD. Furthermore, the previously observed atypical double-frequency somatosensory response in ASD did not generalize to the auditory modality. Thus, the hypothesis about modality-independent abnormal local connectivity in ASD was not supported., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Cerebellar differences have long been documented in autism spectrum disorder (ASD), yet the extent to which such differences might impact language processing in ASD remains unknown. To investigate this, we recorded brain activity with magnetoencephalography (MEG) while ASD and age-matched typically developing (TD) children passively processed spoken meaningful English and meaningless Jabberwocky sentences. Using a novel source localization approach that allows higher resolution MEG source localization of cerebellar activity, we found that, unlike TD children, ASD children showed no difference between evoked responses to meaningful versus meaningless sentences in right cerebellar lobule VI. ASD children also had atypically weak functional connectivity in the meaningful versus meaningless speech condition between right cerebellar lobule VI and several left-hemisphere sensorimotor and language regions in later time windows. In contrast, ASD children had atypically strong functional connectivity for in the meaningful versus meaningless speech condition between right cerebellar lobule VI and primary auditory cortical areas in an earlier time window. The atypical functional connectivity patterns in ASD correlated with ASD severity and the ability to inhibit involuntary attention. These findings align with a model where cerebro-cerebellar speech processing mechanisms in ASD are impacted by aberrant stimulus-driven attention, which could result from atypical temporal information and predictions of auditory sensory events by right cerebellar lobule VI., (© 2023 The Authors. Human Brain Mapping published by Wiley Periodicals LLC.)

Individuals with autism spectrum disorder (ASD) commonly display speech processing abnormalities. Binding of acoustic features of speech distributed across different frequencies into coherent speech objects is fundamental in speech perception. Here, we tested the hypothesis that the cortical processing of bottom-up acoustic cues for speech binding may be anomalous in ASD. We recorded magnetoencephalography while ASD children (ages 7-17) and typically developing peers heard sentences of sine-wave speech (SWS) and modulated SWS (MSS) where binding cues were restored through increased temporal coherence of the acoustic components and the introduction of harmonicity. The ASD group showed increased long-range feedforward functional connectivity from left auditory to parietal cortex with concurrent decreased local functional connectivity within the parietal region during MSS relative to SWS. As the parietal region has been implicated in auditory object binding, our findings support our hypothesis of atypical bottom-up speech binding in ASD. Furthermore, the long-range functional connectivity correlated with behaviorally measured auditory processing abnormalities, confirming the relevance of these atypical cortical signatures to the ASD phenotype. Lastly, the group difference in the local functional connectivity was driven by the youngest participants, suggesting that impaired speech binding in ASD might be ameliorated upon entering adolescence., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Inc.)

Autism Spectrum (AS) is defined primarily by differences in social interactions, with impairments in sensory processing also characterizing the condition. In the search for neurophysiological biomarkers associated with traits relevant to the condition, focusing on sensory processing offers a path that is likely to be translatable across populations with different degrees of ability, as well as into animal models and across imaging modalities. In a prior study, a somatosensory neurophysiological signature of AS was identified using magnetoencephalography (MEG). Specifically, source estimation results showed differences between AS and neurotypically developing (NTD) subjects in the brain response to 25-Hz vibrotactile stimulation of the right fingertips, with lower inter-trial coherence (ITC) observed in the AS group. Here, we examined whether these group differences can be detected without source estimation using scalp electroencephalography (EEG), which is more commonly available in clinical settings than MEG, and therefore offers a greater potential for clinical translation. To that end, we recorded simultaneous whole-head MEG and EEG in 14 AS and 10 NTD subjects (age 15-28 years) using the same vibrotactile paradigm. Based on the scalp topographies, small sets of left hemisphere MEG and EEG sensors showing the maximum overall ITC were selected for group comparisons. Significant differences between the AS and NTD groups in ITC at 25 Hz as well as at 50 Hz were recorded in both MEG and EEG sensor data. For each measure, the mean ITC was lower in the AS than in the NTD group. EEG ITC values correlated with behaviorally assessed somatosensory sensation avoiding scores. The results show that information about ITC from MEG and EEG signals have substantial overlap, and thus EEG sensor-based ITC measures of the AS somatosensory processing biomarker previously identified using source localized MEG data have a potential to be developed into clinical use in AS, thanks to the higher accessibility to EEG in clinical settings., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Ahlfors, Graham, Alho, Joseph, McGuiggan, Nayal, Hämäläinen, Khan and Kenet.)

Organizing sensory information into coherent perceptual objects is fundamental to everyday perception and communication. In the visual domain, indirect evidence from cortical responses suggests that children with autism spectrum disorder (ASD) have anomalous figure-ground segregation. While auditory processing abnormalities are common in ASD, especially in environments with multiple sound sources, to date, the question of scene segregation in ASD has not been directly investigated in audition. Using magnetoencephalography, we measured cortical responses to unattended (passively experienced) auditory stimuli while parametrically manipulating the degree of temporal coherence that facilitates auditory figure-ground segregation. Results from 21 children with ASD (aged 7-17 years) and 26 age- and IQ-matched typically developing children provide evidence that children with ASD show anomalous growth of cortical neural responses with increasing temporal coherence of the auditory figure. The documented neurophysiological abnormalities did not depend on age, and were reflected both in the response evoked by changes in temporal coherence of the auditory scene and in the associated induced gamma rhythms. Furthermore, the individual neural measures were predictive of diagnosis (83% accuracy) and also correlated with behavioral measures of ASD severity and auditory processing abnormalities. These findings offer new insight into the neural mechanisms underlying auditory perceptual deficits and sensory overload in ASD, and suggest that temporal-coherence-based auditory scene analysis and suprathreshold processing of coherent auditory objects may be atypical in ASD., Competing Interests: The authors have declared that no competing interests exist.

Autism spectrum disorder (ASD) is associated with widespread receptive language impairments, yet the neural mechanisms underlying these deficits are poorly understood. Neuroimaging has shown that processing of socially-relevant sounds, including speech and non-speech, is atypical in ASD. However, it is unclear how the presence of lexical-semantic meaning affects speech processing in ASD. Here, we recorded magnetoencephalography data from individuals with ASD (N = 22, ages 7-17, 4 females) and typically developing (TD) peers (N = 30, ages 7-17, 5 females) during unattended listening to meaningful auditory speech sentences and meaningless jabberwocky sentences. After adjusting for age, ASD individuals showed stronger responses to meaningless jabberwocky sentences than to meaningful speech sentences in the same left temporal and parietal language regions where TD individuals exhibited stronger responses to meaningful speech. Maturational trajectories of meaningful speech responses were atypical in temporal, but not parietal, regions in ASD. Temporal responses were associated with ASD severity, while parietal responses were associated with aberrant involuntary attentional shifting in ASD. Our findings suggest a receptive speech processing dysfunction in ASD, wherein unattended meaningful speech elicits abnormal engagement of the language system, while unattended meaningless speech, filtered out in TD individuals, engages the language system through involuntary attention capture., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

The processing of information conveyed by faces is a critical component of social communication. While the neurophysiology of processing upright faces has been studied extensively in autism spectrum disorder (ASD), less is known about the neurophysiological abnormalities associated with processing inverted faces in ASD. We used magnetoencephalography (MEG) to study both long-range and local functional connectivity, with the latter assessed using local cross-frequency coupling, in response to inverted faces stimuli, in 7-18 years old individuals with ASD and age and IQ matched typically developing (TD) individuals. We found abnormally reduced coupling between the phase of the alpha rhythm and the amplitude of the gamma rhythm in the fusiform face area (FFA) in response to inverted faces, as well as reduced long-range functional connectivity between the FFA and the inferior frontal gyrus (IFG) in response to inverted faces in the ASD group. These group differences were absent in response to upright faces. The magnitude of functional connectivity between the FFA and the IFG was significantly correlated with the severity of ASD, and FFA-IFG long-range functional connectivity increased with age in TD group, but not in the ASD group. Our findings suggest that both local and long-range functional connectivity are abnormally reduced in children with ASD when processing inverted faces, and that the pattern of abnormalities associated with the processing of inverted faces differs from the pattern of upright faces in ASD, likely due to the presumed greater reliance on top-down regulations necessary for efficient processing of inverted faces. LAY SUMMARY: We found alterations in the neurophysiological responses to inverted faces in children with ASD, that were not reflected in the evoked responses, and were not observed in the responses to upright faces. These alterations included reduced local functional connectivity in the fusiform face area (FFA), and decreased long-range alpha-band modulated functional connectivity between the FFA and the left IFG. The magnitude of long-range functional connectivity between the FFA and the inferior frontal gyrus was correlated with the severity of ASD., (© 2021 International Society for Autism Research, Wiley Periodicals LLC.)

The neurophysiology of face processing has been studied extensively in the context of social impairments associated with autism spectrum disorder (ASD), but the existing studies have concentrated mainly on univariate analyses of responses to upright faces, and, less frequently, inverted faces. The small number of existing studies on neurophysiological responses to inverted face in ASD have used univariate approaches, with divergent results. Here, we used a data-driven, classification-based, multivariate machine learning decoding approach to investigate the temporal and spatial properties of the neurophysiological evoked response for upright and inverted faces, relative to the neurophysiological evoked response for houses, a neutral stimulus. 21 (2 females) ASD and 29 (4 females) TD participants ages 7 to 19 took part in this study. Group level classification accuracies were obtained for each condition, using first the temporal domain of the evoked responses, and then the spatial distribution of the evoked responses on the cortical surface, each separately. We found that classification of responses to inverted neutral faces vs. houses was less accurate in ASD compared to TD, in both the temporal and spatial domains. In contrast, there were no group differences in the classification of evoked responses to upright neutral faces relative to houses. Using the classification in the temporal domain, lower decoding accuracies in ASD were found around 120 ms and 170 ms, corresponding the known components of the evoked responses to faces. Using the classification in the spatial domain, lower decoding accuracies in ASD were found in the right superior marginal gyrus (SMG), intra-parietal sulcus (IPS) and posterior superior temporal sulcus (pSTS), but not in core face processing areas. Importantly, individual classification accuracies from both the temporal and spatial classifiers correlated with ASD severity, confirming the relevance of the results to the ASD phenotype., (Copyright © 2020. Published by Elsevier Inc.)