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

Abstract

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.

Figure 1

(A) Right-hemisphere M100 STG sensor waveforms for a typically developing and (B) age-matched ASD participant. Note similar sensor waveform morphology, but temporal shift (~20 msec) in participant with ASD. Dashed vertical line indicates stimulus onset (0 msec). Arrows indicate M100 peak. (C) Right-hemisphere source waveforms derived from BESA standard source model applied to the sensor data shown in (A) and (B). Note the similarity in M100 peak latency between the sensor and source waveforms. (D) Sagittal brain image displays STG dipole differentially oriented at peak M100 amplitude for both subjects.

Figure 2

Right-hemisphere M100 average latencies (error bars represent standard error of the mean) as a function of frequency for TD and ASD children. Although the right-hemisphere Group × Frequency interaction term was not significant, the ‘*’’ shows significant t-tests results (P < 0.05) at 300 and 500 Hz to allow comparison with other studies. Latency delay in children with ASD is most evident at 500 Hz.

Figure 3

Scatterplot of right-hemisphere 500 Hz M100 response latencies and age for TD and ASD children. Age was significantly associated with M100 latency only in controls.

Figure 4

ROC analysis of M100 response latency to a 500 Hz tone stimulus in the right hemisphere: sensitivity 75% and specificity of 81%. Positive predictive value (PPV) is 86%.