A foundation model for brain organoid network dynamics uncovers intrinsic computation and convergent disease phenotypes

Authors

Schweiger, H. E., Robbins, A., Hernandez, S., Moreno-Ochando, A., Cline, I., Doganyigit, K., Mouzaya, M., Hussain, K., Pang, Z. P., Duan, J., Salama, S. R., Pollen, A. A., Bhaduri, A., Haussler, D., Teodorescu, M., Mostajo-Radji, M. A.

Abstract

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.

Preprint server: bioRxiv
The authors list and abstract were imported from bioRxiv on 14 Oct 2026.

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