OPTIMIZING CHRONIC SIGNAL STABILITY IN CORTICAL NEUROPROSTHETICS THROUGH OPTOELECTRICAL INVESTIGATION OF HOMEOSTATIC PLASTICITY IN HUMAN ORGANOTYPIC SLICES

One of the greatest challenges of cortical neuroprosthetics is the gradual decline in signal response due to homeostatic adaptation of the human neocortex. Current stimulation models are predominantly derived from animal studies, which are often not representative of the specific biophysical properties and synaptic scaling mechanisms of human neural networks. To address this, we utilize human organotypic brain slice cultures (HOBSCs) coupled with multi-electrode arrays (MEAs) to investigate the long-term stability of network activity under chronic stimulation. Our methodology integrates clinical relevance by comparing neuronal dynamics in standard artificial cerebrospinal fluid (aCSF) with human cerebrospinal fluid (hCSF). Preliminary results demonstrate that hCSF significantly modulates spontaneous firing patterns and enhances the signal-to-noise ratio, suggesting that the extracellular environment fundamentally reshapes network dynamics and is essential for accurate translational modeling. We have successfully established layer-specific input-output (I/O) curves using biphasic electrical stimulation across supra- and infragranular layers. While data collection is still ongoing, the current results support the hypothesis that stimulus-induced desensitization can be quantified and potentially modulated through adaptive pulse protocols. Combining human-specific electrophysiology with hybrid optogenetic stimulation in organotypic models offers an excellent framework for defining cortical excitability and the refinement of closed-loop neuroprosthetic systems to ensure long-term perceptual stability.