Globally elevated excitation–inhibition ratio in children with autism spectrum disorder and below-average intelligence
Background: Altered neuronal excitation–inhibition (E–I) balance is strongly implicated in ASD. However, it is not
known whether the direction and degree of changes in the E–I ratio in individuals with ASD correlates with intellec-
tual disability often associated with this developmental disorder. The spectral slope of the aperiodic 1/f activity reflects
the E–I balance at the scale of large neuronal populations and may uncover its putative alternations in individuals
with ASD with and without intellectual disability.
Methods: Herein, we used magnetoencephalography (MEG) to test whether the 1/f slope would differentiate ASD
children with average and below–average (< 85) IQ. MEG was recorded at rest with eyes open/closed in 49 boys with
ASD aged 6–15 years with IQ ranging from 54 to 128, and in 49 age-matched typically developing (TD) boys. The cor-
tical source activity was estimated using the beamformer approach and individual brain models. We then extracted
the 1/f slope by fitting a linear function to the log–log-scale power spectra in the high-frequency range.
Results: The global 1/f slope averaged over all cortical sources demonstrated high rank-order stability between the
two conditions. Consistent with previous research, it was steeper in the eyes-closed than in the eyes-open condi-
tion and flattened with age. Regardless of condition, children with ASD and below-average IQ had flatter slopes than
either TD or ASD children with average or above-average IQ. These group differences could not be explained by differ-
ences in signal-to-noise ratio or periodic (alpha and beta) activity.
Limitations: Further research is needed to find out whether the observed changes in E–I ratios are characteristic of
children with below-average IQ of other diagnostic groups.
Conclusions: The atypically flattened spectral slope of aperiodic activity in children with ASD and below-average
IQ suggests a shift of the global E–I balance toward hyper-excitation. The spectral slope can provide an accessible
noninvasive biomarker of the E–I ratio for making objective judgments about treatment effectiveness in people with
ASD and comorbid intellectual disability.