Bridging language phenotypes, neural dynamics and gene regulation in autism

Autism Spectrum Disorders (ASDs) affect approximately 1% of the global population, with prevalence rising over recent decades. Although ASDs are heritable (~70%), translating genetic findings into effective therapeutics remains challenging due to the vast number of implicated risk genes (>700) and the limited influence of individual genes on disease expression. Their collective impact and convergent expression patterns of small-effect genes provide insights into ASD-related neurobiological mechanisms. Current interventions remain symptom-focused and do not address underlying neurodevelopmental mechanisms. Emerging approaches in functional genomics offer new insights into ASD pathogenesis by exploring gene expression diversity, yet clinical applications remain distant. Language deficits are among the most frequent and disabling features of ASD, profoundly affecting individuals' and families' quality of life. Recent evidence from neuroimaging and electrophysiology studies suggests disrupted neural oscillatory dynamics are linked to language deficits in ASD. Several ASD-associated genes have been implicated in biological pathways involved in the regulation of brain oscillatory dynamics, suggesting a potential mechanistic link between genetic variation, altered brain rhythms, and language impairment. We propose a neurophysiological imaging genetics framework that leverages neural oscillatory profiles as endophenotypes for targeted investigation and as functional readouts of gene expression. Within this framework, neuromodulation is proposed as an experimental approach to investigate and potentially modulate altered oscillatory dynamics associated with speech communication deficits in ASD, while integrating oscillation-related ASD candidate genes into a symptom-oriented model of functional genomics. This approach shows how integrating genetic variation, non-invasive neuroimaging, and behavioral phenotypes can advance our understanding of ASD and inform targeted, mechanism-based interventions.