GLIOBLASTOMA INVASION REORGANIZES NETWORK STRUCTURE AND INFORMATION FLOW IN <EM>IN VITRO </EM>NEURONAL NETWORKS

Glioblastoma is the most aggressive primary brain tumor and is frequently accompanied by severe neurological symptoms, including epilepsy and cognitive impairment. Although hyperexcitability associated with glioblastoma is often attributed to increased excitatory drive or local disinhibition, the neurological symptoms often persist following surgical resection, indicating that glioblastoma induces durable and self-sustaining changes in the surrounding neural circuitry. In this work, we investigated how invasion by glioblastoma reorganizes neuronal network dynamics using a compartmentalized in vitro platform. Neuron somata and glioblastoma were cultured in separate wells connected by axon-guiding microchannels, allowing observation of tumor–neuron interactions. The system was placed on top of high-density microelectrode arrays to permit simultaneous electrophysiological recordings from the network. We found that glioblastoma infiltration drives a collapse of modular network organization and the emergence of broadcasting hub neurons. These hubs played a functional role during population bursts: they were silent at burst onset and became active at later stages of the burst. Network reorganization was also accompanied by changes in information dynamics: glioblastoma confined information transfer predominantly to population bursts, while information integration shifted toward redundant processing. We used a spiking neural network model coupled to a glioblastoma-driven global modulatory variable to mechanistically interpret these findings. We showed that population dynamics can be recapitulated when hub neurons possess reduced baseline excitability combined with stronger coupling to glioblastoma-mediated signals. Our results suggest that glioblastoma reshapes neural activity not merely by homogeneously elevating excitability, but by reorganizing network structure and redistributing computational roles across neurons.