Since the establishment of cognitive neuroscience, many researchers have been fascinated by the neural mechanism of memory. Animal studies and brain injury studies have suggested that the hippocampus is a critical region for memory-guided behaviors, which made the hippocampus become a focus of considerable interest. Researchers have begun to propose memory theory models based on the hippocampus, including "cognitive map", "index theory", "relationship theory" and so on. Integrating previous viewpoints, the current study come up with the idea that the function of the hippocampus is to organize memory index information into a relevant time-space framework, while detailed memory item is represented in the distributed neocortex, and the hippocampus needs to cooperate with the neocortex to complete various memories operate.
When thousands to tens of thousands of pyramidal neurons arranged in parallel are active simultaneously, a large number of transmembrane currents form local field potentials. The local field potential in the hippocampus often shows rhythmic neural oscillations in theta (4-12 Hz) and gamma (25-100 Hz) ranges (the frequency range differs slightly in different studies). These neural oscillations have been widely observed in both rodents and human hippocampus during memory and navigation tasks and were strongly correlated with behavioral performance. How the hippocampus uses neural oscillations as a computational component to achieve its memory functions is unclear.
The current study investigated how hippocampal neural oscillations support human memory-directed behavior employing epilepsy patients implanted with deep electrodes in the hippocampus as research subjects. Previous studies have shown that the hippocampus represents spatial memory. Therefore, in study 1，we explored how the interaction between hippocampal subregions and entorhinal support spatial memory retrieval. The results showed that the theta-gamma coupling of the hippocampus subregion CA1 and the entorhinal and the theta coherence between the two regions supported the correct memory retrieval; The same spatial memory task was used in Study 2 to explore how the hippocampus represents spatial information to support goal-directed navigation after memory retrieval. The results showed that theta oscillations (6-9 Hz) in the right hippocampus are predictive of goal distance, with theta power decreasing as approaching the goal. Further, this goal distance modulation showed a gradient along the longitude axis of the hippocampus, reflecting spatial hierarchical processing in the hippocampus. Most of the research on the hippocampus is theoretical research, and the application research is lacking. Study 3 intends to improve memory ability by modulating hippocampal neural oscillations through deep electrical stimulation. Previous studies have shown that the hippocampus is also involved in sequential representation, so Study 3 used sequential working memory tasks. The results showed that electrical stimulation of the anterior nucleus of the thalamus can improve working memory precision and increase hippocampal gamma (30-90 Hz) power. Furthermore, the increased in hippocampal gamma power is predictive of the improvement in working memory precision.
Various pieces of evidence show that the hippocampus is crucial in memory-guide behavior. However, since the hippocampus is located in a deep brain, it is difficult to study hippocampal signals using non-invasive electrophysiological methods. Some epilepsy patients implanted deep electrodes in the hippocampus-entorhinal cortex. Taking advantage of this valuable clinical opportunity, this study explores how hippocampal neural oscillations support spatial memory and temporal memory. The current study demonstrates the role of communication between hippocampal CA1 and entorhinal cortex in spatial memory retrieval, and first demonstrates hierarchical representation of goal distance along hippocampal long axis. Memory dysfunction caused by neurological diseases, brain injuries, and degenerative diseases has become a major burden on human society. Study 3 explored the possibility of improving memory performance through deep electrical stimulation of anterior nucleus of thalamus, which provided a valuable reference for therapeutic targets and electrical stimulation parameters.
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