Pacheco Estefan, Daniel, Zucca, Riccardo, Arsiwalla, Xerxes2, Principe, Alessandro Zhang, Hui, Rocamora, Rodrigo, Axmacher, Nikolai, & Verschure, Paul F.M.J

Electrophysiological studies in rodents show that active navigation enhances 
hippocampal theta oscillations (4-12Hz), providing a temporal framework for stimulus-related neural codes. Here we show that active learning promotes a similar phase coding regime in humans, although in a lower frequency range (3-8Hz). We analyzed intracranial EEG from epilepsy patients who studied images under either volitional or passive learning conditions. Active learning increased memory performance and hippocampal theta oscillations and promoted a more accurate reactivation of stimulus-specific information during memory retrieval. Representational signals were clustered to opposite phases of the theta cycle during encoding and retrieval. Critically, during active but not passive learning, the temporal structure of intra-cycle reactivations in theta reflected the semantic similarity of stimuli, segregating conceptually similar items into more distant theta phases. Taken together, these results demonstrate a multi-layered mechanism by which active learning improves memory via a phylogenetically old phase coding scheme.

Keywords 
Active learning, self-directed learning, episodic memory, intracranial EEG, theta oscillations, neural phase coding, hippocampus
Significance statement 
While behavioral evidence shows that volitionally controlled learning benefits human memory, little is known about the neural mechanisms underlying this effect. Insights from spatial navigation research in rodents points to the relevance of hippocampal theta oscillations. However, the mechanisms through which theta might support the beneficial 28  effects of active learning in humans are currently unknown. Here, we demonstrate hippocampal theta oscillations increase during volitional learning, promoting a segregation of task-relevant representational signals according to their semantic content. Our results constitute a direct link to the animal literature on hippocampal theta oscillations and its relation to volition and memory processes.