Maturation of auditory cortex neural responses during infancy and toddlerhood.

The infant auditory system rapidly matures across the first years of life, with a primary goal of obtaining ever-more-accurate real-time representations of the external world. Our understanding of how left and right auditory cortex neural processes develop during infancy, however, is meager, with few studies having the statistical power to detect potential hemisphere and sex differences in primary/secondary auditory cortex maturation. Using infant magnetoencephalography (MEG) and a cross-sectional study design, left and right auditory cortex P2m responses to pure tones were examined in 114 typically developing infants and toddlers (66 males, 2 to 24 months). Non-linear maturation of P2m latency was observed, with P2m latencies decreasing rapidly as a function of age during the first year of life, followed by slower changes between 12 and 24 months. Whereas in younger infants auditory tones were encoded more slowly in the left than right hemisphere, similar left and right P2m latencies were observed by ∼21 months of age due to faster maturation rate in the left than right hemisphere. No sex differences in the maturation of the P2m responses were observed. Finally, an earlier left than right hemisphere P2m latency predicted better language performance in older infants (12 to 24 months). Findings indicate the need to consider hemisphere when examining the maturation of auditory cortex neural activity in infants and toddlers and show that the pattern of left-right hemisphere P2m maturation is associated with language performance.

Differential Maturation of Auditory Cortex Activity in Young Children with Autism and Typical Development.

Maturation of auditory cortex neural encoding processes was assessed in children with typical development (TD) and autism. Children 6-9 years old were enrolled at Time 1 (T1), with follow-up data obtained ~ 18 months later at Time 2 (T2), and ~ 36 months later at Time 3 (T3). Findings suggested an initial period of rapid auditory cortex maturation in autism, earlier than TD (prior to and surrounding the T1 exam), followed by a period of faster maturation in TD than autism (T1-T3). As a result of group maturation differences, post-stimulus group differences were observed at T1 but not T3. In contrast, stronger pre-stimulus activity in autism than TD was found at all time points, indicating this brain measure is stable across time.

Peak Alpha Frequency and Thalamic Structure in Children with Typical Development and Autism Spectrum Disorder.

Associations between age, resting-state (RS) peak-alpha-frequency (PAF = frequency showing largest amplitude alpha activity), and thalamic volume (thalamus thought to modulate alpha activity) were examined to understand differences in RS alpha activity between children with autism spectrum disorder (ASD) and typically-developing children (TDC) noted in prior studies. RS MEG and structural-MRI data were obtained from 51 ASD and 70 TDC 6- to 18-year-old males. PAF and thalamic volume maturation were observed in TDC but not ASD. Although PAF was associated with right thalamic volume in TDC (R2 = 0.12, p = 0.01) but not ASD (R2 = 0.01, p = 0.35), this group difference was not large enough to reach significance. Findings thus showed unusual maturation of brain function and structure in ASD as well as an across-group thalamic contribution to alpha rhythms.

Abnormal Auditory Mismatch Fields in Children and Adolescents with 47,XYY Syndrome.

47,XYY syndrome (XYY) is one of the common forms of sex chromosome aneuploidy in males. XYY males tend to have tall stature, early speech, motor delays, social and behavioral challenges, and a high rate of language impairment. Recent studies indicate that 20-40% of males with XYY meet diagnostic criteria for autism spectrum disorder (ASD; the rate in the general population is 1-2%). Although many studies have examined the neural correlates of language impairment in ASD, few similar studies have been conducted on individuals with XYY. Studies using magnetoencephalography (MEG) in idiopathic ASD (ASD-I) have demonstrated delayed neurophysiological responses to changes in the auditory stream, revealed in the mismatch negativity or its magnetic counterpart, the mismatch field (MMF). This study investigated whether similar findings are observed in XYY-associated ASD and whether delayed processing is also present in individuals with XYY without ASD. MEG measured MMFs arising from the left and the right superior temporal gyrus during an auditory oddball paradigm with vowel stimuli (/a/ and /u/) in children/adolescents with XYY both with and without a diagnosis of ASD, as well as in those with ASD-I and in typically developing controls (TD). Ninety male participants (6-17 years old) were included in the final analyses (TD, n = 38, 11.50 ± 2.88 years; ASD-I, n = 21, 13.83 ± 3.25 years; XYY without ASD, n = 15, 12.65 ± 3.91 years; XYY with ASD, n = 16, 12.62 ± 3.19 years). The groups did not differ significantly in age (p > 0.05). There was a main effect of group on MMF latency (p < 0.001). Delayed MMF latencies were found in participants with XYY both with and without an ASD diagnosis, as well as in the ASD-I group compared to the TD group (ps < 0.001). Furthermore, participants with XYY (with and without ASD) showed a longer MMF latency than the ASD-I group (ps < 0.001). There was, however, no significant difference in MMF latency between individuals with XYY with ASD and those with XYY without ASD. Delayed MMF latencies were associated with severity of language impairment. Our findings suggest that auditory MMF latency delays are pronounced in this specific Y chromosome aneuploidy disorder, both with and without an ASD diagnosis, and thus may implicate the genes of the Y chromosome in mediating atypical MMF activity.

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.

Abnormal auditory mismatch fields in adults with autism spectrum disorder.

The auditory mismatch field (MMF) is a pre-attentive processing component, reflecting neural discrimination and inhibitory processing. Abnormal MMFs have been reported in children with autism spectrum disorder (ASD) along with an association with abnormal language comprehension; however, relatively little is known about MMF abnormalities to contrasting vowel stimuli in adults with ASD. To better understand the neurophysiological mechanisms underlying auditory language discrimination of vowel stimuli in individuals with ASD, magnetoencephalography was used to measure MMFs during an auditory oddball paradigm with vowel stimuli (/a/ and /u/) in adults with ASD. MMFs arising from left and right superior temporal gyrus are reported from nine high-functioning right handed males with ASD (22.22 ± 5.74yrs) and sixteen typically developing (TD) right handed males (27.25 ± 6.63yrs). The MMF was delayed in adults with ASD (188.90 ± 5.8 ms) as compared to the TD participants (173.08 ± 4.31 ms, p < 0.05). Replicating previous findings in children, the earlier M100 component to single stimulus tokens was also delayed in adults with ASD (108.59 ± 4.1 ms) compared to the TD participants (94.60 ± 3.0 ms, p < 0.05). However, there was no correlation between delayed M100 latency and MMF latency. Furthermore, whereas TD participants showed a leftward lateralization of MMF amplitude, participants with ASD showed an opposite (rightward) lateralization. Findings suggest that adults with ASD have hemispherically- and temporally- abnormal auditory discrimination processing in addition to and distinct from abnormal neurophysiological mechanisms in earlier cortical responses.

Delayed Auditory Evoked Responses in Autism Spectrum Disorder across the Life Span.

The M50 and M100 auditory evoked responses reflect early auditory processes in the primary/secondary auditory cortex. Although previous M50 and M100 studies have been conducted on individuals with autism spectrum disorder (ASD) and indicate disruption of encoding simple sensory information, analogous investigations of the neural correlates of auditory processing through development from children into adults are very limited. Magnetoencephalography was used to record signals arising from the left and right superior temporal gyrus during auditory presentation of tones to children/adolescents and adults with ASD as well as typically developing (TD) controls. One hundred and thirty-two participants (aged 6-42 years) were included into the final analyses (children/adolescents: TD, n = 36, 9.21 ± 1.6 years; ASD, n = 58, 10.07 ± 2.38 years; adults: TD, n = 19, 26.97 ± 1.29 years; ASD, n = 19, 23.80 ± 6.26 years). There were main effects of group on M50 and M100 latency (p < 0.001) over hemisphere and frequency. Delayed M50 and M100 latencies were found in participants with ASD compared to the TD group, and earlier M50 and M100 latencies were associated with increased age. Furthermore, there was a statistically significant association between language ability and both M50 and M100 latencies. Importantly, differences in M50 and M100 latencies between TD and ASD cohorts, often reported in children, persisted into adulthood, with no evidence supporting latency convergence.

Auditory Evoked M100 Response Latency is Delayed in Children with 16p11.2 Deletion but not 16p11.2 Duplication.

Individuals with the 16p11.2 BP4-BP5 copy number variant (CNV) exhibit a range of behavioral phenotypes that may include mild impairment in cognition and clinical diagnoses of autism spectrum disorder (ASD). To better understand auditory processing impairments in populations with this chromosomal variation, auditory evoked responses were examined in children with the 16p11.2 deletion, 16p11.2 duplication, and age-matched controls. Stimuli consisted of sinusoidal binaural tones presented passively while children underwent recording with magnetoencephalography (MEG). The primary indicator of auditory processing impairment was the latency of the ∼100-ms "M100" auditory response detected by MEG, with the 16p11.2 deletion population exhibiting profoundly delayed M100 latencies relative to controls. This delay remained even after controlling for potential confounds such as age and cognitive ability. No significant difference in M100 latency was observed between 16p11.2 duplication carriers and controls. Additionally, children meeting diagnostic criteria for ASD (16p11.2 deletion carriers) exhibited nonsignificant latency delays when compared with the corresponding CNV carriers not meeting criteria for ASD. Present results indicate that 16p11.2 deletion is associated with auditory processing delays analogous to (but substantially more pronounced than) those previously reported in "idiopathic" ASD.