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FUNCTIONAL NETWORK PROPERTIES OF FRESHLY RESECTED HUMAN CORTICAL TISSUES FROM FOCAL EPILEPSY

Alessio Di Clementeand 13 co-authors

International School of Advanced Studies (SISSA)

FENS Forum 2026 (2026)

Barcelona, Spain

Board PS05-09AM-386

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Date TBA

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Board: PS05-09AM-386

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PS05-09AM-386

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Abstract

Animal models have been, and continue to be, pivotal to understanding the physiology of single neurons and neuronal circuits, as well as developing novel therapeutic strategies. Nevertheless, they fail to capture human-specific dynamical time-scales and inter-individual variability. This contributes to the missing link in neuropharmacology, where most compounds selected at the preclinical level fail to translate to humans.

Here, we leverage a unique pipeline for the high-density functional mapping of freshly resected 350µm-thick human cortical tissue slices, obtained from resective surgery for focal epilepsy and/or tumor lesions. Utilizing 4096-channel high-density microelectrode arrays (HD-MEAs), we captured, in standard aCSF and under pharmacological stimulation, the spatiotemporal fingerprint of network-level electrical activity, as a proxy for intrinsic circuit integrity.

With few notable exceptions, slices showed only mild and sparse spontaneous spiking activity in standard aCSF. By contrast, under pharmacological stimulation, they alternated epileptic-like bursts of spiking activity with relatively silent periods. This behavior, typical of neocortical slices under pharmacological stimulation, is thought to arise from intrinsic network properties and may yield insights into the latter. Spatiotemporal dynamics of these bursts revealed functional properties exhibiting consistent inter-patient variability. Notably, a subset of these properties showed diagnosis-dependent modulation, potentially reflecting pathological network alterations.

These results suggest that inter-patient variability is not noise but a diagnosis-dependent signal, reflecting pathological network remodeling. This approach may represent a key step to move towards a personalized Seizure-on-a-Chip platform, enabling the close screening of patient-specific therapeutic response, relevant for both personalized medicine and general principles of human pathophysiology.

FUNCTIONAL NETWORK PROPERTIES OF FRESHLY RESECTED HUMAN CORTICAL TISSUES FROM FOCAL EPILEPSY

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