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Alzheimer’s disease (AD) affects more than 6 million Americans and costs the U.S. economy over $300 billion annually. To better understand the circuit-level deficits that underlie early cognitive decline in AD, Rodrigo Pena, Ph.D., an assistant professor in the Department of Biological Sciences, Charles E. Schmidt College of Science, was named a SEED funding recipient by the College of Engineering and Computer Science and the Institute for Sensing and Embedded Network Systems Engineering (I-SENSE) for the 2025-26 fiscal year. Together with researchers in the College of Engineering and Computer Science, the team received $22,500 to study, “Brain organoid-interfaced robotic hand to investigate learning and memory deficits in Alzheimer’s disease (AD).”��

“I am thrilled and deeply grateful,” expressed Pena. “Receiving this I-SENSE support is both a vote of confidence in our vision and a way to generate the preliminary data we need for large federal proposals. Personally, it is energizing to see 911�Թ� invest in truly multidisciplinary, high-risk/high-reward science.”��

Pena, along with Erik Engeberg, Ph.D., professor, 911�Թ� Department of Ocean and Mechanical Engineering, Minghan Wei, Ph.D., assistant professor, 911�Թ� Department of Electrical Engineering and Computer Science, and Ramin Pashaie, Ph.D., professor and I-SENSE Fellow, 911�Թ� Department of Electrical Engineering and Computer Science, aim to create the first closed loop “neurorobotic” test bed in which human cortical organoids, grown from both healthy and Alzheimer’s patients, control and receive sensory feedback from a dexterous robotic hand. By watching how these mini-brains learn—or fail to learn—tactile tasks, they can pinpoint the circuit-level deficits that underlie early cognitive decline in Alzheimer’s disease.��

“Current mouse models capture only fragments of the human disease,” noted Pena. “Our human-cell-based system provides a much more relevant platform to discover early biomarkers, understand disease mechanisms and rapidly screen candidate therapeutics.”��

Pena leads the computational neuroscience arm of the project. His group is tasked to build and calibrate large-scale Hodgkin-Huxley network models that mirror the electrophysiological signatures recorded from the organoids and fuse three data streams together, including MEA spikes/LFPs, optical coherence tomography (OCT) images and biochemical assays. They will also work to identify the ion-channel and synaptic parameters that best explain dysfunctions similar to AD. Finally, the team anticipates generating in-silico predictions that will guide the next round of robotic learning experiments, effectively closing the loop between experiment and model.��

Preparatory work is already underway. Pena has begun coding the first version of the study’s simulation framework. The SEED grant also supports a graduate student who joined the team in August. Once the organoid cultures are established, he expects wet-lab experiments to start in the spring.��

“Alzheimer’s disease is an interdisciplinary problem, and cross-departmental projects enable us to tackle AD issues that no single discipline can solve,” said Pena. “In our case, stem-cell biology, electrophysiology, robotics, optical imaging and computational modeling come together to answer fundamental questions about AD. This synergy accelerates discovery, makes our grant proposals more competitive and gives students exposure to a wider array of skills and career paths.”��

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