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Identification of neural oscillations and epileptiform changes in human brain organoids | bioRxiv

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Brain organoids represent a powerful tool for the study of human neurological diseases, particularly those impacting brain growth and structure. However, many diseases manifest with clear evidence of physiological and network abnormality in the absence of anatomical changes. This raises the question of whether organoids possess sufficient neural network complexity to model these conditions. Here, we explore the network level functions of brain organoids using calcium sensor imaging and extracellular recording approaches that together reveal the existence of complex network behaviors reminiscent of intact brain preparations. We demonstrate highly abnormal and epileptiform-like activity in organoids derived from MECP2 mutant patients compared to isogenic controls accompanied by modest transcriptomic differences revealed by single cell analyses. We also rescue key physiological activities with an unconventional neuromodulatory drug, Pifithrin- α . Together, these findings provide an essential foundation for the utilization of brain organoids to study intact and disordered human brain network formation and illustrate their utility in therapeutic discovery. ### Competing Interest Statement The authors have declared no competing interest.

Identification of neural oscillations and epileptiform changes in human brain organoids | bioRxiv Skip to main content New Results Identification of neural oscillations and epileptiform changes in human brain organoids Ranmal A. Samarasinghe , Osvaldo A. Miranda , Jessie E. Buth , Simon Mitchell , Isabella Ferando , Momoko Watanabe , Thomas F. Allison , Arinnae Kurdian , Namie N. Fotion , Michael J. Gandal , Peyman Golshani , Kathrin Plath , William E. Lowry , Jack M. Parent , Istvan Mody , View ORCID Profile Bennett G. Novitch doi: https://doi.org/10.1101/820183 Ranmal A. Samarasinghe 1 Depar

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