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. While ASDs are strongly heritable (~70%),translating genetic findings into effective therapeutics remains challenging due to thevast number of implicated risk genes (>700) and their limited influence in diseaseexpression. Current interventions remain symptom-focused and do not explicitlyaddress underlying neurodevelopmental mechanisms. Emerging approaches infunctional genomics offer new insights into ASD pathogenesis by exploring thediversity of gene expression, yet clinical applications remain distant. Language deficitsare among the most frequent and disabling features of ASD, profoundly affecting theindividual’s and family’s quality of life. Recent evidence from neuroimaging andelectrophysiology studies suggest that disrupted and atypical neural oscillations –rhythmic brain activity patterns – dynamics are linked to language deficits in ASD.Importantly, several ASD-associated genes modulate brain oscillatory dynamics,pointing to a potential mechanistic link between genetic variation, altered brainrhythms, and language impairment. In this perspective article, we propose an imaginggenetics framework that leverages neural oscillatory profiles as both endophenotypesrelevant for targeted treatment and functional readouts of gene expression.Specifically, we advocate the use of neuromodulation to target and treat alteredoscillatory dynamics underlying speech communication deficits in ASD, and theintegration of oscillation-related ASD candidate genes into a new, symptom-orientedmodel of functional genomics. This approach illustrates how bridging genetic variation,non-invasive neuroimaging, and behavioral phenotypes can advance ourunderstanding of ASD and inform the development of targeted, mechanism-basedinterventions.