Replicable Patterns of Causal Information Flow Between Hippocampus and Prefrontal Cortex During Spatial Navigation and Spatial-Verbal Memory Formation.

Interactions between the hippocampus and prefrontal cortex (PFC) play an essential role in both human spatial navigation and episodic memory, but the underlying causal flow of information between these regions across task domains is poorly understood. Here we use intracranial EEG recordings and spectrally resolved phase transfer entropy to investigate information flow during two different virtual spatial navigation and memory encoding/recall tasks and examine replicability of information flow patterns across spatial and verbal memory domains. Information theoretic analysis revealed a higher causal information flow from hippocampus to lateral PFC than in the reverse direction. Crucially, an asymmetric pattern of information flow was observed during memory encoding and recall periods of both spatial navigation tasks. Further analyses revealed frequency specificity of interactions characterized by greater bottom-up information flow from hippocampus to PFC in delta-theta band (0.5-8 Hz); in contrast, top-down information flow from PFC to hippocampus was stronger in beta band (12-30 Hz). Bayesian analysis revealed a high degree of replicability between the two spatial navigation tasks (Bayes factor > 5.46e+3) and across tasks spanning the spatial and verbal memory domains (Bayes factor > 7.32e+8). Our findings identify a domain-independent and replicable frequency-dependent feedback loop engaged during memory formation in the human brain.