Efri begin OI: integrating human-derived neural networks and AI for information processing in brain organoids

The University of Texas at San Antonio received a $1,998,582 Project Grant award from the National Science Foundation's Engineering program (CFDA 47.041), effective October 1, 2025 through September 30, 2029. This Emerging Frontiers Research Initiative (EFRI) award supports the development of biotechnology to grow and integrate human-derived brain organoids with artificial intelligence systems for advanced information processing. The research team will convert blood cells into human induced pluripotent stem cells (hiPSCs) and differentiate them into neurons that replicate neocortex-like network configurations. The primary deliverables include engineered brain organoid systems programmed to solve complex associative problems, comparative performance analyses against state-of-the-art neuromorphic computer chips, and foundational research establishing a new interdisciplinary field at the intersection of computer science, neuroscience, and neuroengineering.

The project also encompasses social and ethical implications research examining the use of biological tissue in artificial intelligence applications. A sub-awardee, Università degli Studi di Modena e Reggio Emilia in Italy, collaborates on microelectrode array (MEA) recording methodologies, computational neuroscience modeling, and electrophysiological data analysis to assess network activity in the organoid systems. This collaborative research aims to demonstrate how brain organoids can achieve computational learning and memory functions with superior energy efficiency compared to silicon-based approaches, potentially addressing significant challenges in machine learning scalability and adaptability.

Abstract

Artificial intelligence (AI) is poised to dramatically alter our world; however, one of the biggest challenges to progress in AI is the high energy consumption of the hardware and the lack of flexibility for adapting to new environments or problems. By contrast, the human nervous system has evolved to become flexible, nimble, and energy-efficient. This award will support the development of biotechnology to grow cellular brain organoids capable of replicating the network and activity observed in the brain. These organoids will be integrated into an engineered system and, using insights from cognitive science, programmed to solve increasingly complex associative problems. The research team will evaluate how this bioengineering technology compares to state-of-the-art computer chips that mimic brain function. The team will also study the social and ethical implications of using biological tissue to address AI challenges. This project aims to foster a new field at the interface of computer science, neuroscience, and neuroengineering. There is increasing interest in engineering systems that incorporate organoids - self-organized 3D cellular structures in vitro that resemble organs. In the context of the societal need to develop machine learning (ML) and AI for increasingly complex tasks under low-energy consumption demands, brain organoids offer considerable promise. Brain organoids may recapitulate fundamental computational learning and memory functions not achievable with silicon-based approaches. Research supported through this award will use cellular reprogramming tools to convert blood cells into human induced pluripotent stem cells (HIPSCS), with subsequent differentiation into neurons. These will be used to build brain organoids that integrate excitatory and inhibitory neurons in a configuration similar to that found in the neocortex. The motivating hypothesis is that the self-organization of these cortical-like brain organoids can be harnessed to perform computational, learning and memory tasks. However, for brain organoids to be viable for ML/AI applications, IT is essential to demonstrate that they can be reliably produced and programed using biological mechanisms of learning and memory. The proposed research will establish a framework to characterize, validate, and ?program? Brain organoids. Ethical considerations will be embedded throughout the project to enable in-depth analyses of emerging societal and ethical questions surrounding the use of brain organoids in ML/AI. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the foundation's intellectual merit and broader impacts review criteria.- subawards are planned for this award.