Functional Connectivity of Electrically Stimulated HiPSCs-Derived Neuronal Networks

Electrical stimulation is a powerful tool for modulating neuronal activity, but its effects on human induced Pluripotent Stem Cell (hiPSC) derived networks remain not fully deepened. In this study, we investigated whether and how external stimulation impacts functional connectivity of hiPSC-derived neuronal network coupled to Micro-Electrode Arrays (MEAs). In particular, we analyzed two network types: purely excitatory (100E) and excitatory-inhibitory (75E25I) networks, recording spontaneous activity before and after effective stimulation. Our results showed that stimulation tends to increase the networks' modularity and clustering, suggesting a reinforcement of local connectivity without altering the global one. Notably, the fully excitatory configuration exhibited higher modularity, whereas the configuration with an inhibition contribution showed greater integration and efficiency. These results highlight the potential of electrical stimulation to refine neuronal organization, with implications for neuromodulation and disease modelling.Clinical Relevance -This study highlights how electrical stimulation can refine the functional connectivity of hiPSC-derived neuronal networks, promoting local connectivity. These insights could support the development of targeted stimulation protocols for neurological disorders and personalized therapeutic interventions.