(dys)Functional Information Transfer in ex vivo human brain tissue Samples: a multiscale investigation through in vitro and in silico approaches

The complexity of the human brain is poorly captured by animal tissue models or human pluripotent stem cells. While animal neurophysiology advanced basic Neuroscience, its translation to human brain disorders often fails. Organoids and stem cell cultures certainly match personalised genetic details, but unavoidably lack tissue cytoarchitectonics and microcircuitry realism. FITS uniquely combines cutting-edge electrophysiology, imaging, and in silico modelling with routine access to fresh human tissue samples, obtained from resective therapeutic neurosurgery. This novel route of investigation does recapitulate synaptic and network-level components of abnormal excitability and neurodegeneration, especially for hippocampal and cortical pathologies. Matching academic and clinical excellence, thanks to a unique geographical proximity between research labs and neurosurgery, FITS exploits advanced cell- and microcircuit-levels characterisation focusing on brain rhythms in health and diseases. By ultimately employing data to build accurate in silico twins of the microcircuits of interest, FITS closes a conceptual loop: from single-cell and (sub)cellular biophysical properties to (dys)functional network rhythms. Ultimately, the combined experimental and modelling characterisation will serve as a compact fingerprint, linking firing activity and electroresponsiveness across time-scales offering in future an (un)supervised identification of significant alterations associated to neurodegeneration such as neuronal dysplasia and epileptic activity. The electrophysiological data sets, the live and structural imaging data, and the models will lead to accurate computational descriptions of (dys)functional human cortical neurons and microcircuits, representing an additional perspective for personalised pharmacological screening and predictive medicine in a dish. FITS' multimodal combination of functional/structural data and in silico models will advance our knowledge and immensely boost scope and significance of neurophysiology, neurotechnologies, drug-screening, and mesoscopic Brain Digital Twin reconstructions