Neuromagnetic oscillations predict evoked-response latency delays and core language deficits in autism spectrum disorders.

Previous studies have observed evoked response latency as well as gamma band superior temporal gyrus (STG) auditory abnormalities in individuals with autism spectrum disorders (ASD). A limitation of these studies is that associations between these two abnormalities, as well as the full extent of oscillatory phenomena in ASD in terms of frequency and time, have not been examined. Subjects were presented pure tones at 200, 300, 500, and 1,000 Hz while magnetoencephalography assessed activity in STG auditory areas in a sample of 105 children with ASD and 36 typically developing controls (TD). Findings revealed a profile such that auditory STG processes in ASD were characterized by pre-stimulus abnormalities across multiple frequencies, then early high-frequency abnormalities followed by low-frequency abnormalities. Increased pre-stimulus activity was a 'core' abnormality, with pre-stimulus activity predicting post-stimulus neural abnormalities, group membership, and clinical symptoms (CELF-4 Core Language Index). Deficits in synaptic integration in the auditory cortex are associated with oscillatory abnormalities in ASD as well as patient symptoms. Increased pre-stimulus activity in ASD likely demonstrates a fundamental signal-to-noise deficit in individuals with ASD, with elevations in oscillatory activity suggesting an inability to maintain an appropriate 'neural tone' and an inability to rapidly return to a resting state prior to the next stimulus.

Auditory magnetic mismatch field latency: a biomarker for language impairment in autism.

BACKGROUND: Auditory processing abnormalities are frequently observed in autism spectrum disorders (ASD), and these abnormalities may have sequelae in terms of clinical language impairment (LI). The present study assessed associations between language impairment and the amplitude and latency of the superior temporal gyrus magnetic mismatch field (MMF) in response to changes in an auditory stream of tones or vowels. METHODS: Fifty-one children with ASD, and 27 neurotypical control subjects, all aged 6 to 15 years, underwent neuropsychological evaluation, including tests of language function, as well as magnetoencephalographic recording during presentation of tones and vowels. The MMF was identified in the difference waveform obtained from subtraction of responses to standard from deviant stimuli. RESULTS: Magnetic mismatch field latency was significantly prolonged (p < .001) in children with ASD, compared with neurotypical control subjects. Furthermore, this delay was most pronounced (∼50 msec) in children with concomitant LI, with significant differences in latency between children with ASD with LI and those without (p < .01). Receiver operator characteristic analysis indicated a sensitivity of 82.4% and specificity of 71.2% for diagnosing LI based on MMF latency. CONCLUSIONS: Neural correlates of auditory change detection (the MMF) are significantly delayed in children with ASD, and especially those with concomitant LI, suggesting a neurobiological basis as well as a clinical biomarker for LI in ASD.

MEG detection of delayed auditory evoked responses in autism spectrum disorders: towards an imaging biomarker for autism.

Motivated by auditory and speech deficits in autism spectrum disorders (ASD), the frequency dependence of superior temporal gyrus (STG) 50 msec (M50) and 100 msec (M100) neuromagnetic auditory evoked field responses in children with ASD and typically developing controls were evaluated. Whole-cortex magnetoencephalography (MEG) was obtained from 17 typically developing children and 25 children with ASD. Subjects were presented tones with frequencies of 200, 300, 500, and 1,000 Hz, and left and right STG M50 and M100 STG activity was examined. No M50 latency or amplitude Group differences were observed. In the right hemisphere, a Group x Frequency ANOVA on M100 latency produced a main effect for Group (P=0.01), with an average M100 latency delay of 11 msec in children with ASD. In addition, only in the control group was the expected association of earlier M100 latencies in older than younger children observed. Group latency differences remained significant when hierarchical regression analyses partialed out M100 variance associated with age, IQ, and language ability (all P-values <0.05). Examining the right-hemisphere 500 Hz condition (where the largest latency differences were observed), a sensitivity of 75%, a specificity of 81%, and a positive predictive value (PPV) of 86% was obtained at a threshold of 116 msec. The M100 latency delay indicates disruption of encoding simple sensory information. Given similar findings in language impaired and non-language impaired ASD subjects, a right-hemisphere M100 latency delay appears to be an electrophysiological endophenotype for autism.