Neurons in the human medial temporal lobe track multiple temporal contexts during episodic memory processing

Abstract

Episodic memory requires associating items with temporal context, a process for which the medial temporal lobe (MTL) is critical. This study uses recordings from 27 human subjects who were undergoing surgical intervention for intractable epilepsy. These same data were also utilized in Umbach et al. (2020) . We identify 103 memory-sensitive neurons in the hippocampus and entorhinal cortex, whose firing rates predicted successful episodic memory encoding as subjects performed a verbal free recall task. These neurons exhibit important properties. First, as predicted from the temporal context model, they demonstrate reinstatement of firing patterns observed during encoding at the time of retrieval. The magnitude of reinstatement predicted the tendency of subjects to cluster retrieved memory items according to input serial position. Also, we found that spiking activity of these neurons was locked to the phase of hippocampal theta oscillations, but that the mean phase of spiking shifted between memory encoding versus retrieval. This unique observation is consistent with predictions of the “Separate Phases at Encoding And Retrieval (SPEAR)” model. Together, the properties we identify for memory-sensitive neurons characterize direct electrophysiological mechanisms for the representation of contextual information in the human MTL.

Acetylcholine modulates the temporal dynamics of human theta oscillations during memory

“…Theta oscillations are known to be important for coordinating spike timing, and this may explain why the theta disruption from scopolamine causes memory impairment. In animals and humans, item and context representations encoded by hippocampal neurons require coordination with local theta oscillations via phase precession (O'Keefe and Recce, 1993;Qasim et al, 2021) and phase locking (Rutishauser et al, 2010;Yoo et al, 2021). Based on this literature, our results suggest that the way in which cholinergic blockade impairs memory performance is by disrupting theta-related temporal dynamics, and thus disrupting the normally organized timing of singleneuron spiking.…”

The Hippocampal Horizon: Constructing and Segmenting Experience for Episodic Memory

“…In this way, a fundamental question is whether c-Fos + CA1 cells are indexing specific events within a spatially stable environment. If so, such activity may be comparable to the event cells recorded in humans (Zheng et al, 2021;Yoo et al, 2021). It is also notable that triple projecting ventral CA1 task-responsive neurons were preferentially recruited during SWRs (Ciocchi, Passecker, Malagon-Vina, Mikus & Klausberger, 2015).…”

“…Therefore, there is good evidence to support the distinction of event horizons which tend occur on longer timescales, relating to coarser-gained event boundaries (Ben-Yakov & Henson, 2018;Baldassano et al, 2017;Ben-Yakov & Dudai, 2011;Ben-Yakov et al, 2013;Zacks et al, 2010;Stawarczyk, Bezdek & Zacks, 2021). Further work will be needed to characterise event horizon activity in humans on the cellular level (Zheng et al, 2021;Yoo, Umbach, Lega, 2021) and investigate how aging and pathology impacts event boundaries and horizons (Reagh, Delarazan, Garber & Ranganath, 2020;Bailey et al, 2013).…”

“…This highlights that one's own volition on shorter timescales are an important factor to consider within the scheme of unfolding events. Thus, it is necessary to further establish whether theta organised hippocampal cellular activity exists in humans and in relation to event boundaries and event horizons (which preliminary evidence supports that it does, e.g., Qasim, Fried & Jacobs, 2021;Zheng et al, 2021;Yoo et al, 2021). For example, Zheng and colleagues (2021) asked patients to watch a continuous movie clip with no boundary, a movie clip with a soft boundary (cutting to new scene in the same movie) or with a hard boundary (cutting to a different movie; an event horizon).…”

Hippocampal Neuronal Activity Preceding Stimulus Predicts Later Memory Success

“…We categorized pre-SME neurons that were statistically defined by comparing the distribution of each neuron’s firing rate (FR) similar to previously applied methods ( Yoo et al, 2021 ). Neurons were classified as (1) “pre-SME” cells if the FR was higher in subsequently remembered words compared with subsequently forgotten words, (2) “anti-pre-SME” if the FR was higher to subsequently forgotten words relative to subsequently remembered words, or (3) “non-pre-SME,” if FR was not a significant response to recognition success.…”