Virtual white matter: a novel system for cross-dish neural interaction and modulation

<i>Objective</i>. Biological neural networks (BNNs) are characterized by complex interregional connectivity, allowing for seamless communication between different brain regions.<i>In vitro</i>models traditionally consist of single-dish neural cultures that cannot recapitulate the dynamics of interregional interactions and little effort has been made to interconnect multiple BNNs to process information through a hybrid interconnection of the biological and digital systems.<i>Approach</i>. We introduce virtual white matter (VWM), a novel platform enabling real-time functional digital connectivity between neural cultures in separate microelectrode array dishes. By detecting neural activity in one dish and providing precisely timed electrical stimulation to another, VWM recreates bidirectional inter-regional neural communication. The study introduces the conceptual framework, technical implementation, and proof-of-concept validation of the VWM system.<i>Main Results.</i>VWM represents a significant advancement<i>in vitro</i>modeling and data processing by enabling controlled interactions between heterogeneous neural cultures, such as different brain regions or cell types. The platform successfully enables the investigation of dynamic network behaviors and integration with both biological and artificial neural networks.<i>Significance</i>. VWM will push forward biocomputing, wetware computing, and organic intelligence by establishing a reliable form of interconnection between these systems. Furthermore, VWM has the potential to be applied in fields like therapeutic interventions that use directed neural plasticity to promote recovery from brain injury or disease responses. VWM enables complex<i>in vitro</i>models to be built with the same neural connectivity as in the human brain. VWM is versatile, placing it at the core of a transformational tool for experimental neuroscience, biocomputing, and translational research to bridge biological and digital systems.