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Background Individuals with either deletion or duplication of the BP4–BP5 segment of chromosome 16p11.2 have varied behavioral phenotypes that may include autistic features, mild to moderate intellectual disability, and/or language impairment. However, the neurophysiological correlates of auditory language discrimination processing in individuals with 16p11.2 deletion and 16p11.2 duplication have not been investigated. Methods Magnetoencephalography was used to measure magnetic mismatch fields (MMFs) arising from the left and right superior temporal gyrus during an auditory oddball paradigm with vowel stimuli (/a/ and /u/) in children and adolescents with 16p11.2 deletion or 16p11.2 duplication and in typically developing peers. One hundred twenty-eight participants ranging from 7 to 17 years of age were included in the final analysis (typically developing: n = 61, 12.08 ± 2.50 years of age; 16p11.2 deletion: n = 45, 11.28 ± 2.51 years of age; and 16p11.2 duplication: n = 22, 10.73 ± 2.49 years of age). Results Delayed MMF latencies were found in both 16p11.2 deletion and 16p11.2 duplication groups compared with typically developing subjects. In addition, these delayed MMF latencies were associated with language and cognitive ability, with prolonged latency predicting greater impairment. Conclusions Our findings suggest that auditory MMF response delays are associated with clinical severity of language and cognitive impairment in individuals with either 16p11.2 deletion or 16p11.2 duplication, indicating a correlate of their shared/overlapping behavioral phenotype (and not a correlate of gene dosage).

Several electrophysiological parameters, including the auditory evoked response component M50/M100 latencies and the phase synchrony of transient and steady-state gamma-band oscillations have been implicated as atypical (to various extents) in autism spectrum disorder (ASD). Furthermore, some hypotheses suggest that an underlying neurobiological mechanism for these observations might be atypical local circuit function indexed by atypical levels of inhibitory neurotransmitter, GABA. This study was a randomized, placebo-controlled, double-blind, escalating-dose, acute investigation conducted in 25 14–18 year-old adolescents with ASD. The study assessed the sensitivity of magnetoencephalography (MEG) and MEGAPRESS “GABA” magnetic resonance spectroscopy (MRS) to monitor dose-dependent acute effects, as well as seeking to define properties of the pre-drug “baseline” electrophysiological and GABA signatures that might predict responsiveness to the GABA-B agonist, arbaclofen (STX-209). Overall, GABA levels and gamma-band oscillatory activity showed no acute changes at either low (15 mg) or high (30 mg) dose. Evoked M50 response latency measures tended to shorten (normalize), but there was heterogeneity across the group in M50 latency response, with only a subset of participants (n = 6) showing significant M50 latency shortening, and only at the 15 mg dose. Findings thus suggest that MEG M50 latency measures show acute effects of arbaclofen administration in select individuals, perhaps reflecting effective target engagement. Whether these subjects have a greater trend towards clinical benefit remains to be established. Finally, findings also provide preliminary support for the use of objective electrophysiological measures upon which to base inclusion for optimal enrichment of populations to be included in full-scale clinical trials of arbaclofen.