A Multimodal Study of the Contributions of Conduction Velocity to the Auditory Evoked Neuromagnetic Response: Anomalies in Autism Spectrum Disorder.

This multimodal imaging study used magnetoencephalography, diffusion magnetic resonance imaging (MRI), and gamma-aminobutyric acid (GABA) magnetic resonance spectroscopy (MRS) to identify and contrast the multiple physiological mechanisms associated with auditory processing efficiency in typically developing (TD) children and children with autism spectrum disorder (ASD). Efficient transmission of auditory input between the ear and auditory cortex is necessary for rapid encoding of auditory sensory information. It was hypothesized that the M50 auditory evoked response latency would be modulated by white matter microstructure (indexed by diffusion MRI) and by tonic inhibition (indexed by GABA MRS). Participants were 77 children diagnosed with ASD and 40 TD controls aged 7-17 years. A model of M50 latency with auditory radiation fractional anisotropy and age as independent variables was able to predict 52% of M50 latency variance in TD children, but only 12% of variance in ASD. The ASD group exhibited altered patterns of M50 latency modulation characterized by both higher variance and deviation from the expected structure-function relationship established with the TD group. The TD M50 latency model was used to identify a subpopulation of ASD who are significant "outliers" to the TD model. The ASD outlier group exhibited unexpectedly long M50 latencies in conjunction with significantly lower GABA levels. These findings indicate the dependence of electrophysiologic sensory response latency on underlying microstructure (white matter) and neurochemistry (synaptic activity). This study demonstrates the use of biologically based measures to stratify ASD according to their brain-level "building blocks" as an alternative to their behavioral phenotype. LAY SUMMARY: Children with ASD often have a slower brain response when hearing sounds. This study used multiple brain imaging techniques to examine the structural and neurochemical factors which control the brain's response time to auditory tones in children with ASD and TD children. The relationship between brain imaging measures and brain response time was also used to identify ASD subgroups. Autism Res 2020, 13: 1730-1745. © 2020 International Society for Autism Research and Wiley Periodicals LLC.

Abnormal auditory mismatch fields are associated with communication impairment in both verbal and minimally verbal/nonverbal children who have autism spectrum disorder.

Abnormal auditory discrimination neural processes, indexed by mismatch fields (MMFs) recorded by magnetoencephalography (MEG), have been reported in verbal children with ASD. Association with clinical measures indicates that delayed MMF components are associated with poorer language and communication performance. At present, little is known about neural correlates of language and communication skills in extremely language impaired (minimally-verbal/non-verbal) children who have ASD: ASD-MVNV. It is hypothesized that MMF delays observed in language-impaired but nonetheless verbal children with ASD will be exacerbated in ASD-MVNV. The present study investigated this hypothesis, examining MMF responses bilaterally during an auditory oddball paradigm with vowel stimuli in ASD-MVNV, in a verbal ASD cohort without cognitive impairment and in typically developing (TD) children. The verbal ASD cohort without cognitive impairment was split into those demonstrating considerable language impairment (CELF core language index <85; "ASD-LI") versus those with less or no language impairment (CELF CLI >85; "ASD-V"). Eighty-four participants (8-12 years) were included in final analysis: ASD-MVNV: n = 9, 9.67 ± 1.41 years, ASD: n = 48, (ASD-V: n = 27, 10.55 ± 1.21 years, ASD-LI: n = 21, 10.67 ± 1.20 years) and TD: n = 27, 10.14 ± 1.38 years. Delayed MMF latencies were found bilaterally in ASD-MVNV compared to verbal ASD (both ASD-V and ASD-LI) and TD children. Delayed MMF responses were associated with diminished language and communication skills. Furthermore, whereas the TD children showed leftward lateralization of MMF amplitude, ASD-MVNV and verbal ASD (ASD-V and ASD-LI) showed abnormal rightward lateralization. Findings suggest delayed auditory discrimination processes and abnormal rightward laterality as objective markers of language/communication skills in both verbal and MVNV children who have ASD. Autism Res 2019, 12: 1225-1235. © 2019 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: Brain imaging showed abnormal auditory discrimination processes in minimally-verbal/non-verbal children (MVNV) who have autism spectrum disorder (ASD). Delays in auditory discrimination were associated with impaired language and communication skills. Findings suggest these auditory neural measures may be objective markers of language and communication skills in both verbal and, previously-understudied, MVNV children who have ASD.

Auditory mismatch impairments are characterized by core neural dysfunctions in schizophrenia.

Major theories on the neural basis of schizophrenic core symptoms highlight aberrant salience network activity (insula and anterior cingulate cortex), prefrontal hypoactivation, sensory processing deficits as well as an impaired connectivity between temporal and prefrontal cortices. The mismatch negativity is a potential biomarker of schizophrenia and its reduction might be a consequence of each of these mechanisms. In contrast to the previous electroencephalographic studies, functional magnetic resonance imaging may disentangle the involved brain networks at high spatial resolution and determine contributions from localized brain responses and functional connectivity to the schizophrenic impairments. Twenty-four patients and 24 matched control subjects underwent functional magnetic resonance imaging during an optimized auditory mismatch task. Haemodynamic responses and functional connectivity were compared between groups. These data sets further entered a diagnostic classification analysis to assess impairments on the individual patient level. In the control group, mismatch responses were detected in the auditory cortex, prefrontal cortex and the salience network (insula and anterior cingulate cortex). Furthermore, mismatch processing was associated with a deactivation of the visual system and the dorsal attention network indicating a shift of resources from the visual to the auditory domain. The patients exhibited reduced activation in all of the respective systems (right auditory cortex, prefrontal cortex, and the salience network) as well as reduced deactivation of the visual system and the dorsal attention network. Group differences were most prominent in the anterior cingulate cortex and adjacent prefrontal areas. The latter regions also exhibited a reduced functional connectivity with the auditory cortex in the patients. In the classification analysis, haemodynamic responses yielded a maximal accuracy of 83% based on four features; functional connectivity data performed similarly or worse for up to about 10 features. However, connectivity data yielded a better performance when including more than 10 features yielding up to 90% accuracy. Among others, the most discriminating features represented functional connections between the auditory cortex and the anterior cingulate cortex as well as adjacent prefrontal areas. Auditory mismatch impairments incorporate major neural dysfunctions in schizophrenia. Our data suggest synergistic effects of sensory processing deficits, aberrant salience attribution, prefrontal hypoactivation as well as a disrupted connectivity between temporal and prefrontal cortices. These deficits are associated with subsequent disturbances in modality-specific resource allocation. Capturing different schizophrenic core dysfunctions, functional magnetic resonance imaging during this optimized mismatch paradigm reveals processing impairments on the individual patient level, rendering it a potential biomarker of schizophrenia.

Delayed magnetic mismatch negativity field, but not auditory M100 response, in specific language impairment.

Recent studies show that electrophysiological markers of auditory processing such as the cortical 100 ms response (M100) and the mismatch field, derived from magnetoencephalography, might be used to identify children with autism spectrum disorders--M100 peak latency--and to stratify children with autism according to the degree of language impairment--mismatch field peak latency. The present study examined the latency of right superior temporal gyrus M100 and mismatch field in a cohort of children and young adolescents with specific language impairment (n=17), in comparison with age-matched and nonverbal intelligence quotient-matched typically developing controls (n=21). Neither group showed symptoms associated with autism. Although M100 latency (reflecting early auditory processing) did not distinguish controls from children with specific language impairment, the later 'change detection' mismatch field response was significantly delayed (by >50 ms) in the specific language impairment group. Linear discriminant analysis confirmed the role of mismatch field latency (92%) but not M100 latency (8%) in distinguishing groups. The present results lend support to the claim that a delayed M100 is specific to autism spectrum disorders (with relative independence of degree of language impairment) and that a delayed mismatch field reflects an abnormality more generally associated with language impairment, suggesting that mismatch field delay in the present specific language impairment group and previously reported in autistic children with language impairment may be indicative of a common neural system dysfunction.