Human brain mechanisms of associative memory formation during spatial navigation

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Memory and navigation are essential cognitive functions of humans and animals. Associative memories interconnect previously unrelated items and human everyday life critically depends on the ability of forming and retrieving such associative memories. For example, when exploring a new city, we are able to rapidly encode the locations of important sights. How does it come that humans possess this ability of building associative memories between objects or events and their corresponding spatial contexts?The current project has been designed to answer this question using the rare opportunity of electrophysiological recordings from the human brain, which provide a temporal and spatial resolution that bridges the gap between electrophysiological studies in rodents and noninvasive neuroimaging studies in humans. These recordings are possible in neurosurgical epilepsy patients implanted with intracranial electrodes for diagnostic purposes. For this project, patients are asked to participate in object-location memory tasks that require patients to learn the locations of different objects within a virtual environment, while single-neuron activity and local field potentials are recorded from the hippocampus and adjacent brain areas. The hippocampus has been identified as a key region for memory and navigation in multiple previous studies, but the exact neuronal mechanisms of associative memory formation remain elusive. By connecting the behavioral data from the object-location memory tasks with the acquired neuronal data, unique insights into the underlying working principles of the human brain will be provided.More detailed, I will first identify single neurons in the hippocampus and adjacent brain regions that encode information about either objects or spatial locations within the virtual environment. Next, I will track the reactivation of these cell types throughout the task. I hypothesize that object-responsive cells and spatially-modulated cells reactivate synchronously during a specific electrophysiological network phenomenon termed ‘sharp wave-ripple’. Sharp wave-ripples are associated with increased excitability in the hippocampus, with increased synchronization between the hippocampus and connected brain regions, and have been established as a biomarker for memory processes. Reactivation of object-responsive and spatially-modulated cells during sharp wave-ripples may thus lead to common neural circuits encoding the entire object-location associations and may transfer these circuits from the hippocampus to the neocortex.In sum, the proposed research project will enable unique insights into the human brain mechanisms underlying associative memory formation. The resulting knowledge will be relevant both from a basic science perspective and from a clinical perspective, because mechanistic explanations for impaired associative memory performance in various neurological and psychiatric diseases (such as Alzheimer’s disease) may be derived.