02190nas a2200277   4500000000100000000000100001008004100002260001500043653003000058653001700088100001700105700001500122700001700137700001500154700001700169700002100186700001500207700002100222700001900243700001500262700002000277245012100297856005500418520142500473022001401898       2026                            d  c2026-02-2510aAutism spectrum disorders10aNeuroscience1 aNisim Perets1 aLiya Kerem1 aNir Waiskopf1 aNoa Horesh1 aItay Goldman1 aJasmine Avichzer1 aDoron Bril1 aWilliam Tobelaim1 aMilcah Barashi1 aLiat David1 aAriel Tenenbaum00aPatient-derived brain organoids reveal divergent neuronal activity across subpopulations of autism spectrum disorder  uhttps://www.nature.com/articles/s41398-026-03890-13 aPatient-derived brain organoids have emerged as a powerful model for investigating the mechanisms underlying neurological and psychiatric disorders. They provide novel insights into autism spectrum disorder (ASD), a heterogeneous neurodevelopmental condition whose underlying mechanisms remain poorly understood. Recent advancements in generating electrophysiological functional 3D brain organoids enable the study of molecular and network-level neuronal activity. Here, we aimed to characterize the neurophysiological underpinnings of ASD by comparing electrophysiological properties of brain organoids derived from eleven individuals diagnosed with autism spectrum disorder, 10 with monogenic syndromic ASD across five genetic subtypes, and 1 with idiopathic ASD, to organoids derived from 4 neurotypical control individuals. We identified distinct differences in baseline activity (resting state) and evoked responses (synaptic plasticity and network dynamics) across ASD subgroups. To comprehensively assess these differences, we applied dimensionality reduction (principal component analysis, PCA) to integrate multiple electrophysiological features into a unified framework. Our findings reveal subtype-specific neurophysiological alterations in ASD brain organoids, offering mechanistic insights into ASD heterogeneity and potential applications for early diagnostics, drug screening, and therapeutic development.  a2158-3188