Delayed M50 / M100 Latency Arising from Superior Temporal Gyrus in Minimally Verbal / Nonverbal Children

Background: Abnormal auditory M50 and M100 responses, which reflect early auditory processing, have been reported in children with autism spectrum disorder (ASD) along with an association with abnormal language comprehension; however, most prior research has focused on higher functioning individuals and so rather little is known about neural activity during auditory processing in lower-functioning (e.g. minimally verbal / non-verbal (MVNV)) children.

Objectives: To understand the neurophysiological mechanisms underlying early auditory processing in MVNV children, magnetoencephalography (MEG) measured M50 and M100 arising from left and right superior temporal gyri during tone stimuli in four cohorts: 1) MVNV children with ASD, 2) lower Intellegence Quotient (IQ) Intellectual Disability/ Developmental Disability (ID/DD, non-ASD) clinical controls (of mixed genetic etiology), 3) high functioning children with ASD and 4) typically developing (TD) children.

Methods: One hundred and sixteen participants (aged 8-12 yrs) were included in the final analysis (MVNV children with ASD; n=17, 9.83±1.27 yrs, lower IQ ID/DD (non-ASD) clinical controls; n=6, 10.54±0.62 yrs, higher functioning children with ASD; n=59, 10.67±1.30 yrs, TD children, n=34, 10.18±1.36 yrs). MEG data were obtained in a magnetically shielded room using a 275-channel whole-cortex CTF magnetometer (CTF MEG, Coquitlam, Canada). Sinusoidal tones (300 ms duration; 10 ms ramps) with a pseudo-randomized 600-2000ms inter-trial interval were presented binaurally at 45dB SL. Responses were averaged, filtered and source-modeled to allow identification of M50 and M100 components bilaterally. To assess language and cognitive abilities, The Vineland Adaptive Behavior Scale, second edition (VABS-2) communication scores, Differential Ability Scale - II and Leiter International Performance Scale, third Edition Nonverbal IQ were used. The study was approved by the Children’s Hospital of Philadelphia IRB and all participants’ families gave written informed consent, in accordance with the principles of the Declaration of Helsinki. As indicated by institutional policy, where competent to do so, children over the age of seven additionally gave verbal assent. Analyses used linear mixed models (LMM's) with subject as a random effect.

Results: There were no group differences of age (p> .05). There were statistically significant main effects of group on M50 latency and M100 latency (p’s< .001) with no effect of Hemisphere and no interactions (p’s> .05). Significantly delayed M100 latencies were found in MVNV children with ASD (169.28+/-7.47ms) and in the low IQ ID/DD clinical control children (174.38+/-12.40ms) compared to TD (128.79+/-5.47ms; p< .01) as well as higher functioning children with ASD (150.50+/-4.06ms; p< .05). Delayed M50 latencies were also found in MVNV children with ASD (93.15+/-2.47ms) and the low IQ ID/DD children (93.75+/-4.09ms) compared to TD children (80.05+/-1.76ms;p’s< .01). These delayed latencies were negatively correlated with language and communication ability (M50: r= -.45; M100: r= -.27;p’s < .01).

Conclusions: Findings suggest that the delays in early auditory cortex neural activity in minimally verbal/non-verbal children with ASD were exacerbated compared to higher functioning children with ASD and could thus be effective objective markers in MVNV children with ASD, associated with language impairment as well as general cognitive ability (as evidenced by the delayed latencies also in the non-ASD, low-IQ clinical control cohort).