AbstractThe medial temporal lobe (MTL) is a locus of episodic memory in the human brain. It is comprised of cytologically distinct subregions that, in concert, give rise to successful encoding and retrieval of context-dependent memories. However, the functional connections between these subregions are poorly understood. To determine functional connectivity among MTL subregions, we had 126 subjects fitted with indwelling electrodes perform a verbal memory task, and asked how encoding or retrieval correlated with interregional synchronization. Using phase-based measures of connectivity, we found that synchronous theta (4-8 Hz) activity underlies successful episodic memory, whereas high-frequencies exhibit desynchronization. Moreover, theta functional connectivity during encoding aligned with key anatomic connections, including critical links between the entorhinal cortex, dentate gyrus, and CA1 of the hippocampus. Retrieval-associated networks demonstrated enhanced involvement of the subiculum, reflecting a substantial reorganization of the encoding-associated network. We posit that coherent theta activity within the MTL marks periods of successful memory, but distinct patterns of connectivity dissociate key stages of memory processing.Significance StatementThe brain functions through the interaction of its distinct parts, but little is known about how such connectivity dynamics relate to learning and memory. We used a large dataset of 126 human subjects with intracranial electrodes to assess patterns of electrical connectivity within the medial temporal lobe – a key region for memory processing – as they performed a memory task. We discovered that unique networks of time-varying, low-frequency interactions correlate with memory encoding and retrieval, specifically in the theta band. Simultaneously, we observed elevated spectral power at high frequencies in these same regions. The result is a complete map of physiological dynamics within the MTL, highlighting how a reorganization of theta networks support distinct memory operations.
Functional wiring of the human medial temporal lobe