Hippocampal Theta Oscillations Support Successful Associative Memory Formation

Abstract

Models of memory formation posit that recollection as compared to familiarity-based memory depends critically on the hippocampus, which binds features of an event to its context. For this reason, the contrast between study items that are later recollected versus those that are recognized on the basis of familiarity should reveal electrophysiological patterns in the hippocampus selectively involved in associative memory encoding. Extensive data from studies in rodents support a model in which theta oscillations fulfill this role, but results in humans results have not been as clear. Here, we employed an associative recognition memory procedure to identify hippocampal correlates of successful associative memory encoding and retrieval in patients undergoing intracranial EEG monitoring. We identified a dissociation between 2-5 Hz and 5-9 Hz theta oscillations, by which 2-5 Hz oscillations uniquely were linked with successful associative memory in both the anterior and posterior hippocampus. These oscillations exhibited a significant phase reset that also predicted successful associative encoding, distinguished recollected from familiar items at retrieval, and contributed to reinstatement of encoding-related patterns that distinguished these items. Our results provide direct electrophysiological evidence that 2-5 Hz hippocampal theta oscillations support the encoding and retrieval of memories based on recollection but not familiarity. 2. Significance Statement Extensive fMRI evidence suggests that the hippocampus plays a selective role in recollection rather than familiarity, during both encoding and retrieval. However, there is little or no electrophysiological evidence that speaks to whether the hippocampus is selectively involved in recollection. Here, we used intracranial EEG from human participants engaged in an associative recognition paradigm. The findings suggest that oscillatory power and phase reset in the hippocampus are selectively associated with recollection rather than familiarity-based memory judgements. Furthermore, reinstatement of oscillatory patterns in the hippocampus was stronger for successful recollection than familiarity. Collectively, the findings support a role for hippocampal theta oscillations in human episodic memory.

Theta rhythmicity governs human behavior and hippocampal signals during memory-dependent tasks

“…The data reported so far indicate that across trials, memory-relevant behavioral responses fall onto a consistent phase of a theta oscillation. The presence of such an oscillation, determined on the basis of one response per trial, implies phase consistency across trials in the neural oscillations in hippocampus presumed to underly memory formation and reinstatement, as previously shown by Kota et al 44 , and Fell et al 45 . We hypothesized that this phase consistency, induced by events in the trial, persists until the participant successfully encodes or retrieves the memory (expected to slightly precede the button press).…”

A Hypothesis for Theta Rhythm Frequency Control in CA1 Microcircuits

“…In rodents, it has been shown that social stimuli elicit high theta, and fearful stimuli elicit low theta (Tendler and Wagner, 2015 ), and type 2 theta oscillations have been shown to be associated with increased risk-taking behavior (Mikulovic et al, 2018 ). In humans, theta frequencies are lower overall (Jacobs, 2014 ), but it is still possible to distinguish high and low theta frequencies, with low theta supporting encoding and retrieval of memories (Kota et al, 2020 ). Clearly, what the particular theta frequency is has functional significance, and so how theta frequencies are controlled is functionally important to consider.…”

Interaction between theta-phase and spike-timing dependent plasticity simulates theta induced memory effects

“…Our model can account for data from both rodents and humans, which connects human episodic memory behaviour to synaptic modifications induced by non-neurophysiological stimulation in the animal brain. Our model provides an explanation to the findings in human electrophysiological studies, which show that hippocampal theta synchronization supports episodic encoding, especially when there is need to form arbitrary associations (Backus et al, 2016;Kota et al, 2020;Staudigl & Hanslmayr, 2013). Though those findings are correlational rather than causal, our model suggests that theta synchronization links to stronger synaptic weights between corresponding hippocampal neurons after encoding.…”

“…Indeed, hippocampal theta phase resetting has been found to occur after stimulus onset during memory encoding (Rutishauser et al, 2010). Further, Kota et al (2020) shows in an iEEG study that ongoing hippocampal theta oscillation phase was reset to support episodic encoding. Such phase reset indicates a mechanism for inputs to be more likely to undergo LTP (McCartney et al, 2004;Mormann et al, 2005;Rizzuto et al, 2003).…”