Transient and steady-state auditory gamma-band responses in first-degree relatives of people with autism spectrum disorder

Abstract

Background: Stimulus-related γ-band oscillations, which may be related to perceptual binding, are reduced in people with autism spectrum disorders (ASD). The purpose of this study was to examine auditory transient and steady-state γ-band findings in first-degree relatives of people with ASD to assess the potential familiality of these findings in ASD.

Methods: Magnetoencephalography (MEG) recordings in 21 parents who had a child with an autism spectrum disorder (pASD) and 20 healthy adult control subjects (HC) were obtained. Gamma-band phase locking factor (PLF), and evoked and induced power to 32, 40 and 48 Hz amplitude-modulated sounds were measured for transient and steady-state responses. Participants were also tested on a number of behavioral and cognitive assessments related to the broad autism phenotype (BAP).

Results: Reliable group differences were seen primarily for steady-state responses. In the left hemisphere, pASD subjects exhibited lower phase-locked steady-state power in all three conditions. Total γ-band power, including the non-phase-locked component, was also reduced in the pASD group. In addition, pASD subjects had significantly lower PLF than the HC group. Correlations were seen between MEG measures and BAP measures.

Conclusions: The reduction in steady-state γ-band responses in the pASD group is consistent with previous results for children with ASD. Steady-state responses may be more sensitive than transient responses to phase-locking errors in ASD. Together with the lower PLF and phase-locked power in first-degree relatives, correlations between γ-band measures and behavioral measures relevant to the BAP highlight the potential of γ-band deficits as a potential new autism endophenotype.

Figure 1

Phase-locking factor results. Phase-locking factor (PLF) group results (mean ± SE) for the left and right hemisphere dipole waveforms (shown in left and right columns respectively). Results for the transient and steady-state responses are shown in the top and bottom rows respectively.

Figure 2

Evoked power results. Baseline normalized evoked amplitude group results (mean ± SE) for the left and right hemisphere dipole waveforms (shown in left and right columns respectively). Results for the transient and steady-state responses are shown in the top and bottom rows respectively.

Figure 3

Scatter plots of correlation results. (A)Transient γ-band response (tGBR) phase-locking factor (PLF) and evoked power; (B) auditory steady-state response (ASSR) PLF and evoked power; (C) tGBR PLF and Autism-specturm Quotient (AQ) communication subscale; (D) ASSR PLF and AQ communication subscale; (E) tGBR evoked power and SRS; (F) ASSR evoked power and Social Responsiveness Scale (SRS). Black lines indicate linear regression line.

Figure 4

Data example. (A) Unfiltered time-domain average 248-sensor waveforms from single subject. (B) Unfiltered, averaged dipole waveform for right auditory cortex corresponding to data in A. (C) Waveform in B filtered using a 35 to 45 Hz bandpass to emphasize γ-band in time-domain (not part of data analysis). (D) Time-frequency representation of phase-locked, baseline-normalized evoked power from same waveform in (B). (E) Time-frequency representation of phase-locking factor (PLF) corresponding to data in (B).