Intensity-dependent tACS entrainment effects in a cortical microcircuit: a computational study

Abstract Transcranial alternating current stimulation (tACS) is a promising noninvasive technique for modulating disrupted neural oscillations in psychiatric disorders and enhancing cognitive functions. However, its efficacy remains debated, partly because neuronal morphology and other microscopic factors critically affect the response to external electric fields. To address this issue and investigate cellular- and network-level mechanisms underlying tACS-induced neural entrainment, we developed a cortical microcircuit model integrating realistic neuronal morphologies, synaptic connectivity, and intrinsic oscillatory dynamics. Using the NEURON simulation environment, we constructed a microcircuit comprising five distinct biophysical cortical neuron models. Neural responses to a range of tACS intensities were assessed with metrics based on cross-correlation, phase coherence, and phase-locking value. While tACS modulates spike timing without significantly altering firing rates, pyramidal neurons are particularly sensitive to external fields compared to interneurons. In addition, tACS can either disrupt or enhance synchronization depending on the endogenous oscillation and stimulation intensity. Our computational study reveals that tACS effects arise from a complex interplay between intrinsic neuronal properties and network dynamics. These findings underscore the importance of neuronal morphology in determining tACS responses and provide insights that may help optimize stimulation parameters for precise neuromodulation in both clinical and research settings.