Episodic memories are information-rich, often multisensory events that rely on binding different elements [1]. The elements that will constitute a memory episode are processed in specialized but distinct brain modules. The binding of these elements is most likely mediated by fast-acting long-term potentiation (LTP), which relies on the precise timing of neural activity [2]. Theta oscillations in the hippocampus orchestrate such timing as demonstrated by animal studies in vitro [3, 4] and in vivo [5, 6], suggesting a causal role of theta activity for the formation of complex memory episodes, but direct evidence from humans is missing. Here, we show that human episodic memory formation depends on phase synchrony between different sensory cortices at the theta frequency. By modulating the luminance of visual stimuli and the amplitude of auditory stimuli, we directly manipulated the degree of phase synchrony between visual and auditory cortices. Memory for sound-movie associations was significantly better when the stimuli were presented in phase compared to out of phase. This effect was specific to theta (4 Hz) and did not occur in slower (1.7 Hz) or faster (10.5 Hz) frequencies. These findings provide the first direct evidence that episodic memory formation in humans relies on a theta-specific synchronization mechanism.

Episodic memories are rich in sensory information and often contain integrated information from different sensory modalities. For instance, we can store memories of a recent concert with visual and auditory impressions being integrated in one episode. Theta oscillations have recently been implicated in playing a causal role synchronizing and effectively binding the different modalities together in memory. However, an open question is whether momentary fluctuations in theta synchronization predict the likelihood of associative memory formation for multisensory events. To address this question we entrained the visual and auditory cortex at theta frequency (4 Hz) and in a synchronous or asynchronous manner by modulating the luminance and volume of movies and sounds at 4 Hz, with a phase offset at 0° or 180°. EEG activity from human subjects (both sexes) was recorded while they memorized the association between a movie and a sound. Associative memory performance was significantly enhanced in the 0° compared with the 180° condition. Source-level analysis demonstrated that the physical stimuli effectively entrained their respective cortical areas with a corresponding phase offset. The findings suggested a successful replication of a previous study (Clouter et al., 2017). Importantly, the strength of entrainment during encoding correlated with the efficacy of associative memory such that small phase differences between visual and auditory cortex predicted a high likelihood of correct retrieval in a later recall test. These findings suggest that theta oscillations serve a specific function in the episodic memory system: binding the contents of different modalities into coherent memory episodes. How multisensory experiences are bound to form a coherent episodic memory representation is one of the fundamental questions in human episodic memory research. Evidence from animal literature suggests that the relative timing between an input and theta oscillations in the hippocampus is crucial for memory formation. We precisely controlled the timing between visual and auditory stimuli and the neural oscillations at 4 Hz using a multisensory entrainment paradigm. Human associative memory formation depends on coincident timing between sensory streams processed by the corresponding brain regions. We provide evidence for a significant role of relative timing of neural theta activity in human episodic memory on a single-trial level, which reveals a crucial mechanism underlying human episodic memory.

How multi-sensory experiences are bound to form a coherent episodic memory representation is one of the fundamental questions in human episodic memory research. Evidence from animal literature suggests that the relative timing between an input and theta oscillations in the hippocampus is crucial for memory formation. We precisely controlled the timing between visual and auditory stimuli and the neural oscillations at 4 Hz using a multisensory entrainment paradigm. Human associative memory formation depends on coincident timing between sensory streams processed by the corresponding brain regions. We provide evidence for a significant role of relative timing of neural theta activity in human episodic memory on a single trial level, which reveals a crucial mechanism underlying human episodic memory.

Abnormally increased beta bursts in cortical-basal ganglia-thalamic circuits are associated with rigidity and bradykinesia in patients with Parkinson's disease. Increased beta bursts detected in the motor cortex have also been associated with longer reaction times in healthy participants. Here we further hypothesize that suppressing beta bursts through neurofeedback training can improve motor performance in healthy subjects. We conducted a double-blind sham-controlled study on 20 human volunteers (10 females) using a sequential neurofeedback-behaviour task with the neurofeedback reflecting the occurrence of beta bursts over sensorimotor cortex quantified in real-time. The results show that neurofeedback training helps healthy participants learn to volitionally suppress beta bursts in the sensorimotor cortex, with training being accompanied by reduced reaction time in subsequent cued movements. These changes were only significant in the real feedback group but not in the sham group, confirming the effect of neurofeedback training over simple motor imagery. In addition, reaction times correlated with the rate and accumulated duration of beta bursts in the contralateral motor cortex before the Go cue, but not with averaged beta power. The reduced reaction times induced by neurofeedback training positively correlated with reduced beta bursts across all tested hemispheres. These results strengthen the link between the occurrence of beta bursts in the sensorimotor cortex before the Go cue and slowed movement initiation in healthy motor control. The results also highlight the potential benefit of neurofeedback training in facilitating voluntary suppression of beta bursts in order to speed up movement initiation. Significance This double-blind sham-controlled study suggested that neurofeedback training can facilitate volitional suppression of beta bursts in sensorimotor cortex in healthy motor control better 3 than sham feedback. The training was accompanied by reduced reaction time in subsequent cued movements, and the reduced reaction time positively correlated with the level of reduction in cortical beta bursts before the Go cue, but not with average beta power. These results provide further evidence of a causal link between sensorimotor beta bursts and movement initiation and suggest that neurofeedback training could potentially be used to train participants to speed up movement initiation.