The increasing amount of chemicals with human exposure, and the accumulating evidence for interspecies differences regarding adverse effects on the CNS, call for scalable in vitro neurotoxicity screening tools using human cells. Generating neuronal cells through differentiation from induced pluripotent stem cells (iPSCs) carries a great potential to overcome the inaccessibility of human primary tissue and accelerate cell-based assays. In combination with microelectrode array (MEA) readouts, neural activity in response to chemical compounds can be quantified allowing neurotoxicity screening beyond mere neuron-related cytotoxicity. However, the assessment of neuroactive effects in human-derived cell-based assays remains challenging due to cell type variability and poorly defined baseline physiology.