Neurophysiological Evidence of Human Hippocampal Longitudinal Differentiation in Associative Memory

In humans, the hippocampus exhibits evident structural and connectivity differences along the longitudinal axis. Experiments in rodents and more recently in human subjects have stimulated several theories of functional longitudinal specialization. This question pertains directly to the management of neurosurgical patients, as nascent technologies permit more precise treatments that can selectively spare longitudinal regions. Given the critical importance of the hippocampus to episodic memory formation, the limited amount of direct electrophysiological evidence interrogating models of functional differentiation is striking. With this in mind, we investigated hippocampal longitudinal specialization in human intracranial EEG subjects as they performed an associative recognition episodic memory task. Utilizing the behavioral contrasts available in this task, we characterize the neurophysiological features that distinguish the anterior versus posterior hippocampal activity during recollection and familiarity–based memory retrieval, as well as novelty processing. We use subspace representations to characterize longitudinal differences in the temporal dynamics of key computational processes ascribed to the hippocampus, namely pattern separation and pattern completion. We place our findings in the context of existing models, adding to sparse literature using direct brain recordings to explicate the functional differentiation along the hippocampal longitudinal axis in humans.