A foundation model for brain organoid network dynamics uncovers intrinsic computation and convergent disease phenotypes
Year: 2026
Type: preprint
Abstract: SUMMARY Brain organoids develop self-organizing neural networks that can be used to model neurodevelopment and disease. Here we introduce PULSE, a foundation model developed using over 900 hours of high-density microelectrode array recordings of in vitro and ex vivo neural tissue. We show that this single model can address two open questions: how disease-associated variants alter network development, and how naive circuits encode information. PULSE revealed accelerated network maturation in held-out human 16p11.2-deletion organoids. It also revealed a change in network coordination shared with SHANK3 deficiency. Because organoids develop without sensory input, they let us ask how circuits encode information before any representation is learned. Closed-loop control of a virtual inverted pendulum engaged existing spontaneous activity patterns rather than creating new ones. PULSE provides a common reference frame for neural circuits across genotypes, protocols and tasks.
Language: English
Subfield: Cognitive Neuroscience
Field: Neuroscience
Domain: Life Sciences
Open Access status: green
Funders: National Science Foundation, California Institute for Regenerative Medicine, University of California, Santa Cruz, National Institutes of Health, University of California, San Diego, Office of the President, University of California, National Institute of Mental Health, National Human Genome Research Institute
Awards: NSF2026: EAGER: The evolution and diversity of the human brain, EFRI BEGIN OI: Reinforcement Learning for Scalable Biocomputing, Deep phenotyping of human brain organoid models of autism spectrum disorder to unravel disease heterogeneity and develop biomarkers and treatments, Defining Neurovascular Metabolism in Neurodevelopmental and Neuropsychiatric Disorders, G5109076114, RECODE-ing the Logic of Ectodermal Organoid Patterning via Combinatorial Morphogen Treatments and Longitudinal Monitoring, G6423641252, Unraveling disease pathways for autism spectrum disorder with phenotyping of human brain organoids., Data Resource and Administrative Coordination Center for the Scalable and Systematic Neurobiology of Psychiatric and Neurodevelopmental Disorder Risk Genes Consortium, Center for Live Cell Genomics
OpenAlex ID: W7221618313