The stability of long-term memories is enhanced by reactivation during sleep. Correlative evidence has linked memory reactivation with thalamocortical sleep spindles, although their functional role is not fully understood. Our initial study replicated this correlation and also demonstrated a novel rhythmicity to spindles, such that a spindle is more likely to occur approximately 3-6 s following a prior spindle. We leveraged this rhythmicity to test the role of spindles in memory by using real-time spindle tracking to present cues within versus just after the presumptive refractory period; as predicted, cues presented just after the refractory period led to better memory. Our findings demonstrate a precise temporal link between sleep spindles and memory reactivation. Moreover, they reveal a previously undescribed neural mechanism whereby spindles may segment sleep into two distinct substates: prime opportunities for reactivation and gaps that segregate reactivation events.

The mental context in which we experience an event plays a fundamental role in how we organize our memories of an event (e.g. in relation to other events) and, in turn, how we retrieve those memories later. Because we use contextual representations to retrieve information pertaining to our past, processes that alter our representations of context can enhance or diminish our capacity to retrieve particular memories. We designed a functional magnetic resonance imaging (fMRI) experiment to test the hypothesis that people can intentionally forget previously experienced events by changing their mental representations of contextual information associated with those events. We had human participants study two lists of words, manipulating whether they were told to forget (or remember) the first list prior to studying the second list. We used pattern classifiers to track neural patterns that reflected contextual information associated with the first list and found that, consistent with the notion of contextual change, the activation of the first-list contextual representation was lower following a forget instruction than a remember instruction. Further, the magnitude of this neural signature of contextual change was negatively correlated with participants’ abilities to later recall items from the first list.

Abstract:The stability of long-term memories is enhanced by reactivation during sleep. Correlative evidence has linked memory reactivation with thalamocortical sleep spindles, although their functional role is poorly understood. Our initial study replicated this correlation but also demonstrated a novel rhythmicity to spindles, such that spindles are less likely to occur immediately following other spindles. We leveraged this rhythmicity to test the role of spindles in memory by using real-time spindle tracking to present cues inside versus outside the presumptive refractory period; as predicted, cues presented outside the refractory period led to better memory. Our findings reveal a previously undescribed neural mechanism whereby spindles segment sleep into two distinct substates: prime opportunities for reactivation and gaps that segregate reactivation events. One Sentence Summary:The characteristic timing of sleep spindles regulates when memories can be reactivated during sleep. Main Text:Memories of daytime episodes are covertly reactivated during sleep, improving memory storage in the brain (1). Previous research has implicated three electrophysiological signals in memory processing during sleep. The slowest of these are sleep slow oscillations (SOs), brain rhythms at approximately 1 Hz prominent during deep sleep (2). A second signal is the sleep spindle, a burst of activity at 11-16 Hz lasting 0.5-3 s. Third, replay of newly formed memories is thought to occur in conjunction with high-frequency bursts of hippocampal and cortical activity called ripples (1,3,4). These three signals can occur with precise temporal interrelationships; spindles tend to occur most often during the up-state phase of SOs, and ripples tend to occur at spindle troughs (5-7). To the extent that these relationships are evidenced, memory consolidation appears to be more effective (8), suggesting a dual cross-frequency coupling mechanism by which initially hippocampal-dependent memories become stabilized in long-term neocortical networks over time (2). Pharmacological evidence suggests spindles promote memory consolidation in humans (9); however, the time course relating spindles to memory consolidation has not been well-characterized.Here, we investigated and manipulated temporal relationships between spindles and learningrelated auditory cues known to boost memory, relying on a technique called targeted memory reactivation (TMR) (10,11). In experiment 1 (N = 18; Fig 1A), subjects first over-learned novel associations between individual sounds and picture items (e.g., [meow]-Brad Pitt, [violin]-Eiffel Tower). Next, they learned unique locations for each item on a background grid. After an initial test, they took an afternoon nap with background white noise (~40 dB; Table S1 provides sleep stage information). Upon online indications of slow-wave sleep (SWS), we embedded half of the . CC-BY 4.0 International license peer-reviewed) is the author/funder. It is made available under a The copyright holder for this preprint (which was not ....