Abnormal Auditory Mismatch Fields Arising from Superior Temporal Gyrus in Minimally Verbal / Non-Verbal Children

Background: Approximately 30 % of the autism spectrum disorder (ASD) population can be categorized as minimally-verbal/non-verbal (MVNV). Previously, abnormal auditory/language discrimination processes, indexed by abnormal mismatch negativity (MMN) potentials or their magnetic counterparts (MMNm or MMF), have been reported in higher-functioning (verbal) children with ASD along with an association with degree of language impairment; however, little is known about neural correlates of language ability in lower-functioning MVNV children with ASD.

Objectives: To understand the neurophysiological mechanisms underlying auditory language discrimination of vowel stimuli in MVNV children with ASD, magnetoencephalography (MEG) measured mismatch fields (MMFs) arising from left and right superior temporal gyrus during an auditory oddball paradigm in three cohorts: 1) MVNV children with ASD, 2) higher-functioning children with ASD (both with and without clinical language impairment) and 3) typically developing (TD) children.

Methods: Eighty-seven participants (aged 8-12yrs) were included in the final analysis (MVNV children with ASD; n=12, 10.13±1.49yrs, higher-functioning children with ASD; n=48, 10.61±1.20yrs (without language impairment, operationally defined as Clinical Evaluation of Language Fundamentals - fifth edition (CELF 5) core language index > 85): n=27, with language impairment (CELF-5 CLI < 85): n=21), TD children, n=27, 10.14±1.38yrs). MEG data were obtained in a magnetically shielded room using a 275-channel whole-cortex CTF magnetometer (CTF MEG, Coquitlam, Canada). Vowel stimuli /a/ and /u/ of 300ms duration were presented binaurally at 45dB SL with each token as the standard (85%) or deviant (15%) stimulus, respectively; stimulus onset asynchrony was 700ms. MMF was defined from subtraction of the standard response from the corresponding deviant. To assess language ability, The Vineland Adaptive Behavior Scales, second edition communication scores were used. Linear mixed model were used for statistical analysis. 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.

Results: There were no group differences of age (p>.05).There were statistically significant main effects of group on MMF latency and MMF amplitude (p’s<.01) with no effect of Hemisphere and no interactions. Significantly delayed MMF latencies were found in MVNV children with ASD (247.5 +/- 3.9 ms;p’s<.01) compared to higher-functioning children with ASD (with (215.9+/-2.9ms) and without (210.1+/-2.6ms) language impairment) and TD children (189.2+/-2.6ms), and these delayed MMF responses were negatively associated with language ability (r=-.52;p<.01). Furthermore, while TD children showed a leftward lateralization of MMF amplitude (LI=0.14+/- .05;p’s<.01), MVNV children showed the abnormal rightward lateralization (LI=-.19 +/- .07) as did higher functioning children with ASD both with (LI=-.14 +/- .05) and without (LI=-.10 +/- .05) language impairment.

Conclusions: Findings suggest that delayed auditory discrimination processes and abnormal rightward laterality could be effective and objective markers associated with language ability both in higher functioning and, importantly, in MVNV children with ASD.