Faculty Affairs and Academic Programs
Jie Zheng
Medical; Health Sciences; Nursing
Cellular Precision Neural Interfaces for Midbrain Modulation and Memory Enhancement
This project aims to advance understanding of human memory by investigating the role of midbrain circuits, particularly the substantia nigra, in memory formation and modulation. Although models and animal studies implicate dopaminergic midbrain regions, progress in humans has been limited by conceptual gaps and technical challenges in recording deep-brain activity. Recent DBS studies provide rare access to these regions, but standard clinical probes capture only one or two neurons per session, limiting analysis. To overcome these barriers, we will develop a high-density neural recording platform to capture cellular-resolution activity from hundreds of substantia nigra neurons during intraoperative memory tasks. Our approach integrates four innovations: (1) leveraging DBS surgeries for direct human midbrain recordings; (2) using advanced high-density probes to map population dynamics; (3) employing naturalistic memory paradigms focused on event boundaries—points where the brain segments experience into episodes and reorganizes memory, often accompanied by dopaminergic peaks; and (4) testing how stimulation at these boundaries alters neural activity and memory outcomes. Expected outcomes include identifying real-time neural signatures of memory success, defining optimal stimulation windows, and demonstrating closed-loop neuromodulation feasibility. This work will generate foundational knowledge, establish a versatile technical platform, and position the PI at the forefront of a new research direction in cognitive neuroscience and neuromodulation. The platform’s adaptability will enable broader midbrain investigations and precision interventions for memory disorders.
