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Poster E in Poster Session E: Thursday, August 6, 10:30 am – 12:15 pm, Kimmel Center, Shorin & Rosenthal Rooms

From Empirical to Simulated Brains: Using Digital Twin Models to Identify Therapeutic Targets in MCI

Jinyu Wang¹, Xiangyu Bai¹, Kim Cuong Tran Dang¹, Sarah Ostadabbas¹, Stephanie Noble¹, Psyche Loui¹; ¹Northeastern University

Presenter: Jinyu Wang

Brain stimulation techniques offer promising non-pharmacological interventions for improving cognitive function in mild cognitive impairment (MCI), yet optimal stimulation targets remain unclear. Here, we built a digital twin brain (DTB) model that integrates multimodal neuroimaging data to simulate individual brain dynamics and identify regions that promote recovery from MCI toward healthy states via virtual perturbation. We analyzed data from 30 MCI and 26 healthy participants by modeling regional dynamics with a Hopf oscillator coupled via structural connectivity, using probabilistic metastable substates (PMS) to capture functional dynamics, and optimizing the model to minimize discrepancies between simulated and empirical data. Systematic perturbation revealed that increasing excitability in default mode, memory-related, reward, and sensorimotor regions, and decreasing excitability in executive control, language, and sensory regions, shifted MCI brain dynamics toward healthy patterns. These findings provide causal insights into MCI neural mechanisms and may guide targeted brain stimulation therapies.

Topic Area: Development, Individual Differences & Clinical Populations