Network-Wide Adaptive Burst Detection Depicts Neuronal Activity with Improved Accuracy

Inkeri A. Välkki, Kerstin Lenk, Jarno E. Mikkonen, Fikret E. Kapucu, Jari A. K. Hyttinen

Neuronal networks are often characterized by their spiking and bursting statistics. Previously, we introduced an adaptive burst analysis method which enhances the analysis power for neuronal networks with highly varying firing dynamics. The adaptation is based on single channels analyzing each element of a network separately. Such kind of analysis was adequate for the assessment of local behavior, where the analysis focuses on the neuronal activity in the vicinity of a single electrode. However, the assessment of the whole network may be hampered, if parts of the network are analyzed using different rules. Here, we test how using multiple channels and measurement time points affect adaptive burst detection. The main emphasis is, if network-wide adaptive burst detection can provide new insights into the assessment of network activity. Therefore, we propose a modification to the previously introduced inter-spike interval (ISI) histogram based cumulative moving average (CMA) algorithm to analyze multiple spike trains simultaneously. The network size can be freely defined, e.g., to include all the electrodes in a microelectrode array (MEA) recording. Additionally, the method can be applied on a series of measurements on the same network to pool the data for statistical analysis. Firstly, we apply both the original CMA-algorithm and our proposed network-wide CMA-algorithm on artificial spike trains to investigate how the modification changes the burst detection. Thereafter, we use the algorithms on MEA data of spontaneously active chemically manipulated in vitro rat cortical networks. Moreover, we compare the synchrony of the detected bursts introducing a new burst synchrony measure. Finally, we demonstrate how the bursting statistics can be used to classify networks by applying k-means clustering to the bursting statistics. The results show that the proposed network wide adaptive burst detection provides a method to unify the burst definition in the whole network and thus improves the assessment and classification of the neuronal activity, e.g., the effects of different pharmaceuticals. The results indicate that the novel method is adaptive enough to be usable on networks with different dynamics, and it is especially feasible when comparing the behavior of differently spiking networks, for example in developing networks.