Real-time classification of experience-related ensemble spiking patterns for closed-loop applications

Communication in neural circuits across the cortex is thought to be mediated by spontaneous temporally organized patterns of population activity lasting ~50 –200 ms. Closed-loop manipulations have the unique power to reveal direct and causal links between such patterns and their contribution to cognition. Current brain–computer interfaces, however, are not designed to interpret multi-neuronal spiking patterns at the millisecond timescale. To bridge this gap, we developed a system for classifying ensemble patterns in a closed-loop setting and demonstrated its application in the online identification of hippocampal neuronal replay sequences in the rat. Our system decodes multi-neuronal patterns at 10 ms resolution, identifies within 50 ms experience-related patterns with over 70% sensitivity and specificity, and classifies their content with 95% accuracy. This technology scales to high-count electrode arrays and will help to shed new light on the contribution of internally generated neural activity to coordinated neural assembly interactions and cognition.