Recurrence Quantification Analysis of Spontaneous Electrophysiological Activity during Development: Characterization of In Vitro Neuronal Networks Cultured on Multi Electrode Array Chips

The combination of a nonlinear time series analysis technique, Recurrence Quantification Analysis (RQA) based on Recurrence Plots (RPs), and traditional statistical analysis for neuronal electrophysiology is proposed in this paper as an innovative paradigm for studying the variation of spontaneous electrophysiological activity of in vitro Neuronal Networks (NNs) coupled to Multielectrode Array (MEA) chips. Recurrence, determinism, entropy, distance of activity patterns, and correlation in correspondence to spike and burst parameters (e.g., mean spiking rate, mean bursting rate, burst duration, spike in burst, etc.) have been computed to characterize and assess the daily changes of the neuronal electrophysiology during neuronal network development and maturation. The results show the similarities/differences between several channels and time periods as well as the evolution of the spontaneous activity in the MEA chip. RPs could be used for graphically exploring possible neuronal dynamic breaking/changing points, whereas RQA parameters are suited for locating them. The combination of RQA with traditional approaches improves the identification, description, and prediction of electrophysiological changes and it will be used to allow intercomparison between results obtained from different MEA chips. Results suggest the proposed processing paradigm as a valuable tool to analyze neuronal activity for screening purposes (e.g., toxicology, neurodevelopmental toxicology).