More complex neuronal culture analyses can be done using HDMEAs such as burst pattern tracking (Gandolfo et al., 2010) and functional connectivity estimation (Maccione et al., 2012). By plating low-density cultures, it is feasible to not only optically visualize the network of stained neurons, but also to estimate the functional connections and to obtain detailed functional maps at cellular resolution (Maccione et al., 2012), see Figures 8C,D. Maccione et al. processed and analyzed the HDMEA signals by ad hoc developed spatio-temporal filtering and by applying a cross-correlation based method.