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Human brain mechanisms of associative memory formation during spatial navigation

Subject Area Human Cognitive and Systems Neuroscience
Term from 2020 to 2023
Project identifier Deutsche Forschungsgemeinschaft (DFG) - Project number 447634521
 
Final Report Year 2024

Final Report Abstract

Memory and spatial navigation are essential cognitive abilities of humans and animals. In our daily lives, we often rely on being able to find our way safely in our environment and to link objects or events with their respective spatial position in the environment. For example, when exploring an unfamiliar city, we are capable of quickly memorizing the locations of important buildings. Where does this ability to form associative memories between objects or events and their associated places come from? The present project sought to answer this question using electrophysiological measurements from inside the human brain. These measurements are possible in neurosurgical epilepsy patients who are implanted with intracranial electrodes for diagnostic purposes. Such recordings lie at the scientific interface between electrophysiological animal studies and non-invasive imaging studies in humans, providing neural data with excellent spatial and temporal resolution. As part of this project, we asked the implanted patients to participate in computer-based tasks that required the patients to form associative memories between locations and objects in a virtual environment. At the same time, using the intracranial electrodes, we recorded local field potentials and single-cell activity from the patients’ hippocampus and neighboring brain areas, which have been implicated in memory processes and spatial navigation in multiple previous studies. During the project, I then identified neurons in the hippocampus and adjacent brain areas that represented information about objects and/or locations within the virtual environment. Subsequently, I examined the reactivation of these neurons. I observed that object-specific and locationspecific neurons became active together during the network phenomenon of “sharp waveripples” when the participants formed and recalled associative memories that they formed during the task. In line with previous studies, we found that sharp wave-ripples were associated with an increased excitability of the hippocampus and that they led to a stronger synchronization between the hippocampus and connected brain regions. We therefore propose that the reactivations of object-specific and location-specific neurons during sharp wave-ripples evoke and activate neural circuits that encompass the entire associative memory. Furthermore, the reactivations during sharp wave-ripples could lead to a transfer of the memories to the neocortex, as suggested by theoretical models of memory formation and consolidation. The results of this project thus contribute to a better understanding of the mechanisms of the human brain that underlie the formation of associative memories. Using these insights, it might be possible in the future to generate hypotheses on how associative memory deficits occur in various neurological and psychiatric disorders (e.g., Alzheimer's disease).

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