Multimodal Spatiotemporal Dynamics of Frontomedial Theta and BOLD Signal Reveal Functional Roles in Updating and...

Fear and extinction learning are fundamental processes shaping the regulation and expression of fear in both healthy individuals and patients with anxiety-related disorders. Pavlovian fear conditioning serves as a powerful model for these mechanisms; however, the precise spatiotemporal neural dynamics underlying fear and extinction learning in humans still remain unclear. Theta oscillations have been implicated in these learning processes, yet their precise relationship with blood-oxygen-level-dependent (BOLD) signals of corresponding brain networks remains poorly understood. This study employed simultaneous electroencephalography and functional magnetic resonance imaging (EEG-fMRI) in fifty healthy humans to investigate the role of frontomedial theta oscillations (4-8 Hz) in fear learning. Participants underwent a one-day differential fear conditioning paradigm with concurrent EEG and fMRI recordings. We assumed that individual theta power variations would correspond to distinct activation patterns in the fear and safety networks during fear acquisition and extinction training. To test this hypothesis, we extracted frontomedial theta power across three trial segments (0 to 2 s, 2 to 4 s, 4 to 5.5 s after the onset of conditioned stimuli, CS) and integrated these measures into whole-brain fMRI analyses. Results revealed a significant increase in differential (CS+ vs. CS-) theta power toward the end of the CS presentation during fear acquisition training, aligning with prior findings of theta ramping-up before unconditioned stimulus onset. EEG-driven fMRI analyses during fear acquisition showed distinct theta-BOLD co-activations in cuneal and precuneal cortices and motor areas at 2 to 4 s and 4 to 5.5 s trial segments. Notably, during extinction training, the theta activity of the mid-trial segment (2 to 4 s post-stimulus) was co-activated with the BOLD signal in vmPFC, suggesting a role of theta during extinction in safety memory formation. Our findings support the hypothesis that theta oscillations may contribute to the temporal encoding of threat expectation during fear learning, but also to memory updating through fear response suppression during extinction learning. Interestingly, theta modulation was linked to distinct brain regions in different temporal segments. Critically, our results integrate previous findings from different neuroimaging modalities and extend our understanding of the spatiotemporal neural dynamics underlying fear and extinction learning.