Electrophysiologically-defined excitation-inhibition autism neurosubtypes

Abstract

AbstractExcitation-inhibition (E:I) imbalance has long been considered one of the primary neurobiological theories explaining autism. However, the theory has been bolstered heavily by research on high-penetrance genetic mechanisms which are only found in a small proportion of the autism population. Thus, how well does E:I imbalance explain idiopathic autism? Here we find that idiopathic autistic males can be split into two distinct E:I-defined ‘neurosubtypes’. These E:I neurosubtypes can be identified in EEG data via an E:I-sensitive metric known as the Hurst exponent (H). Half of autistic individuals fall into the first E:I neurosubtype and can be described as having elevated E:I ratio relative to typically-developing (TD) comparison group. The remaining other half of autistic males fall into a second E:I neurosubtype with the opposite pattern of reduced E:I ratio relative to TD. Finally, E:I neurosubtypes show differential relationships between H and behavioral and demographic variables consisting of age, intelligence, and autism symptomatology. This work suggests that different types of E:I imbalance can manifest in idiopathic autistic males. Such differential E:I biomarkers may be indicative of distinctive etiological or compensatory mechanisms and differential underlying micro- and macroscale neural organization with differential phenotypic impact.