Frequency-tagged fMRI: A platform for fine-grained spatiotemporal analysis of cortical function

Frequency tagging with functional MRI (ft-fMRI) enables precise mapping of neural dynamics by synchronizing oscillatory stimuli to stimulus-driven blood-oxygen-level-dependent (BOLD) responses. We developed and validated a dual-frequency tagging protocol to dissociate fundamental, multiplexed, and nonlinear intermodulation frequency responses across the human visual cortex at high spatial resolution. Using 3T and 7T fMRI, we reliably detected frequency-tagged BOLD responses at the level of individual vertices, revealing fine-grained cortical topographies and robust temporal synchronization to driving frequencies. Multiplexed responses, encoding multiple frequencies simultaneously, and nonlinear intermodulation components, were spatially dissociable and exhibited reproducible dynamics within and across experimental sessions. These findings establish ft-fMRI as a powerful tool for investigating fine-grained cortical computations, previously inaccessible to traditional fMRI. By bridging the spatiotemporal resolution gap between electrophysiology and fMRI, ft-fMRI provides a versatile platform for studying perception, attention, and multisensory integration in health and disease.