Phase-synchronized stimulus presentation augments contingency knowledge and affective evaluation in a fear conditioning task.

Memory often combines information from different sensory modalities. Animal studies show that synchronized neuronal activity in the theta band (4-8 Hz) binds multimodal associations. Studies with human participants have likewise established that theta-phase synchronization augments the formation of declarative video-tone pair memories. Another form of associative learning, classical fear conditioning, models non-declarative, emotional memory - with distinct neuronal mechanisms. Typical fear conditioning tasks pair a conditioned stimulus (CS) in one modality with an aversive unconditioned stimulus (US) in another. The present study examines the effects of CS-US synchronization in the theta band on fear memory formation in humans.In a fear generalization procedure, we paired one of five visual gratings of varying orientation (CS) with an aversive auditory US. We modulated the luminance of the CS and the volume of the US at a rate of 4 Hz. To manipulate the synchrony between visual and auditory input during fear acquisition, one group (N = 20) received synchronous CS-US pairing, whereas the control group (N = 20) received the CS-US pairs out-of-phase.Phase synchronization improved CS-US contingency knowledge and facilitated CS discrimination in terms of rated valence and arousal, resulting in narrower generalization across the CS gratings compared to the out-of-phase group. In contrast, synchronization did not amplify conditioned responding in physiological arousal (skin conductance) and visuocortical engagement (steady-state visually evoked potentials) during acquisition, although both measures demonstrated tuning towards the CS+. Together, these data support a causal role of theta-phase synchronization in affective evaluation and contingency report during fear acquisition.Significance StatementDue to methodological limitations, examining the causal role of oscillatory synchrony in association formation has been challenging so far. Using repetitive, rhythmic sensory stimulation in a memory-related 4 Hz frequency, we examined the role of phase synchronization in fear conditioning. While synchronization improved the contingency knowledge and affective evaluation, physiological arousal and visuocortical activity were unaffected by the phase-modulation. Our results represent an initial step towards establishing the causal effects of theta phase synchronization in associative fear learning, thus improving our understanding of the neurophysiological mechanisms of fear-memory encoding.