Evaluating Encoding Strategies for Closed-Loop Classification in Biological Neural Networks

Interfacing with Biological Neural Networks (BNNs) requires encoding information into stimulation patterns that can be effectively processed and that enable the underlying system to adapt. Nevertheless, the role of stimulation encoding remains poorly understood. In this work, we compare multiple encoding strategies, including rate-based, phase-based, burst-based, and time-to-first-spike temporal encodings, in a closed-loop neural classification task using cultured BNNs. We encode visual inputs as spatiotemporal stimulation patterns delivered via a Multi-Electrode Array (MEA) and evaluate classification performance for each encoding scheme. We find that burst-based temporal encoding yields the highest observed performance, achieving up to 95.6 % accuracy in a binary classification task, compared to substantially lower performance from rate- and phase-based approaches. We further show that performance is highly sensitive to the spatial distribution of stimulation, with suboptimal electrode selection significantly degrading accuracy. These findings indicate that effective interfacing with biological neural systems requires the joint optimization of temporal and spatial encoding strategies, and highlight temporal encoding as a key design dimension for bio-digital computing.