Development of an objective index, neural activity score (NAS), reveals neural network ontogeny and treatment effects on microelectrode arrays

Microelectrode arrays (MEAs) are valuable tools for electrophysiological analysis, providing assessment of neural network health and development. Analysis can be complex, however, requiring intensive processing of large data sets consisting of many activity parameters, leading to information loss as studies subjectively report relatively few metrics in the interest of simplicity. In screening assays, many groups report simple overall activity (i.e. firing rate) but omit network connectivity changes (e.g. burst characteristics and synchrony) that may not be evident from basic parameters. Our goal was to develop an objective process to capture most of the valuable information gained from MEAs in neural development and toxicity studies. We implemented principal component analysis (PCA) to reduce the high dimensionality of MEA data. Upon analysis, we found the first principal component was strongly correlated to time, representing neural culture development; therefore, factor loadings were used to create a single index score-named neural activity score (NAS)-reflecting neural maturation. For validation, we applied NAS to studies analyzing various treatments. In all cases, NAS accurately recapitulated expected results, suggesting viability of NAS to measure network health and development. This approach may be adopted by other researchers using MEAs to analyze complicated treatment effects and multicellular interactions.