During systems-level consolidation, mnemonic representations initially reliant on the hippocampus are thought to migrate to neocortical sites for more permanent storage, with an eminent role of sleep for facilitating this information transfer. Mechanistically, consolidation processes have been hypothesized to rely on systematic interactions between the three cardinal neuronal oscillations characterizing non-rapid-eye-movement sleep: Under global control of de- and hyperpolarizing slow oscillations (SOs), sleep spindles may cluster hippocampal ripples for a precisely timed transfer of local information to the neocortex. Here we used direct intracranial electroencephalogram (iEEG) recordings from human epilepsy patients during natural sleep to test the assumption that SOs, spindles and ripples are functionally coupled in the hippocampus. Employing cross-frequency phase-amplitude coupling analyses, we first show that spindles are modulated by the up-state of SOs. Critically, spindles were found to in turn cluster ripples in their troughs, providing fine-tuned temporal frames for the hypothesized transfer of hippocampal memory traces.

Brain oscillations are one of the core mechanisms underlying episodic memory. However, while some studies highlight the role of synchronized oscillatory activity, others highlight the role of desynchronized activity. We here describe a framework to resolve this conundrum and integrate these two opposing oscillatory behaviors. Specifically, we argue that the synchronization and desynchronization reflect a division of labor between a hippocampal and a neocortical system, respectively. We describe a novel oscillatory framework that integrates synchronization and desynchronization mechanisms to explain how the two systems interact in the service of episodic memory.

SummaryHow are brief encounters transformed into lasting memories? Previous research has established the role of non-rapid eye movement (NREM) sleep, along with its electrophysiological signatures of slow oscillations (SOs) and spindles, for memory consolidation [1, 2, 3, 4]. In related work, experimental manipulations have demonstrated that NREM sleep provides a window of opportunity to selectively strengthen particular memory traces via the delivery of auditory cues [5, 6, 7, 8, 9, 10], a procedure known as targeted memory reactivation (TMR). It has remained unclear, however, whether TMR triggers the brain’s endogenous consolidation mechanisms (linked to SOs and/or spindles) and whether those mechanisms in turn mediate effective processing of mnemonic information. We devised a novel paradigm in which associative memories (adjective-object and adjective-scene pairs) were selectively cued during a post-learning nap, successfully stabilizing next-day retention relative to non-cued memories. First, we found that, compared to novel control adjectives, memory cues evoked an increase in fast spindles. Critically, during the time window of cue-induced spindle activity, the memory category linked to the verbal cue (object or scene) could be reliably decoded, with the fidelity of this decoding predicting the behavioral consolidation benefits of TMR. These results provide correlative evidence for an information processing role of sleep spindles in service of memory consolidation.

Recent neuroimaging studies have successfully identified encoding mechanisms that support different forms of subsequent episodic recognition memory. In our everyday lives, however, much of our episodic memory retrieval is accomplished by means of free recall, i.e., retrieval without an external recognition cue. In this study, we used functional magnetic resonance imaging to investigate the encoding mechanisms that support later free recall and their relationship to those that support different forms of later recognition memory. First, in agreement with previous work, we found that activation in the left inferior frontal gyrus and hippocampus correlated with later associative/relational recognition. In these regions, activation was further enhanced for items later freely recalled, pointing to shared underlying relational encoding mechanisms whose magnitude of activation differentiates later successful free recall from successful associative recognition. Critically, we also found evidence for free recall-specific encoding mechanisms that did not, in our paradigm, support later associative recognition compared with item recognition. These free recall-specific effects were observed in left mid/dorsolateral prefrontal (DLPFC) and bilateral posterior parietal cortices (PPC). We speculate that the higher-level working memory operations associated with DLPFC and attention to internal mnemonic representations perhaps mediated via PPC may serve to embed an item into a rich associative network during encoding that facilitates later access to the item. Finally, activation in the perirhinal cortex correlated with successful associative binding regardless of the form of later memory, i.e., recognition or free recall, providing novel evidence for the role of the perirhinal cortex in episodic intra-item encoding.