Low-intensity ultrasound neuromodulation is a rapidly emerging technology due to its non-invasiveness and millimeter-scale precision. Despite numerous experimental settings demonstrating that ultrasonic waves can modulate the neural activity in different brain areas, the interaction between the ultrasonic source and the neuronal tissue is still not fully understood. Several underlying mechanisms have already been proposed to partially explain the interaction between ultrasound and neurons, including mechanosensitivity, flexoelectricity, membrane displacement, and thermodynamic effects. Understanding how these various mechanisms interact and affect the neuronal behavior may enable the optimization of stimulation protocols in silico, potentially improving neuromodulation therapy. This study focuses on the intramembrane cavitation mechanism, which occurs when ultrasonic pressure waves cause gas cavities to form between the phospholipid membrane leaflets. These gas cavities cause capacitive displacement currents, leading to membrane charge accumulation. To ascertain if the intramembrane cavitation mechanism can predict experimentally observed cell-type sensitivity and specificity, we focus on the predictions generated by cortical cell models; an example of such a model is shown in Fig. 1 (right) [1]. This mechanism has been implemented in the NICE model and is multi-scale optimized in the SONIC model, reducing the computation time by more than a factor of 1000 [2,3]. Although this model has not yet been extended to multi-compartmental brain cells with potentially strong axial coupling, it demonstrates that action potentials can be induced by ultrasound exposure. To enable multi-scale optimized simulations of multi-compartmental cells with strong intercompartmental coupling, the SECONIC model was introduced [4]. So far, simulations have only been conducted on models with homogeneous membrane dynamics and without branching morphologies [2-5]. In this study, the objective is to predict for the first time how a subset of morphologically realistic Blue Brain Project cortical pyramidal cells and interneurons [1] will react to ultrasonic insonication as shown in Fig. 1 (left). Examining the activation site, the importance of charge overtones, and comparison of the optimized model with experimental results, will help determine how various ultrasonic parameters affect cortical neuromodulation.