Sleep spindle refractoriness segregates periods of memory reactivation

Abstract

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 ....

Targeted Memory Reactivation during Sleep Elicits Neural Signals Related to Learning Content

“…We averaged RMS values across specified time windows for each subject and calculated differences across conditions using within-subject t-tests. Our specified precue window was Ϫ2000 to 0, based on a previous study (Antony et al, 2018b). Our a priori postcue window was 1000 to 1500 ms (Antony et al, 2018a), although we eventually widened this window to 1000 to 4500 ms after observing that left/right decoding accuracy stayed above chance up to 4.5 s after cue onset.…”

“…Therefore, we anticipated that postcue spindles would positively predict lateralized evidence of retrieval during sleep, as well as subsequent memory during the postnap test. Furthermore, prior work has shown that spindles have a refractory period of 3-6 s, during which TMR cues are less effective (Antony et al, 2018b); as such, we expected that precue spindles would negatively predict both lateralized evidence of retrieval and subsequent memory.…”

Electrophysiological signatures of memory reactivation in humans

“…Accordingly, an intimate relationship between TMR and sleep spindles has been established. Promoting memory reactivation via TMR has been demonstrated to cause a robust surge in sleep spindle activity [120,[126][127][128][129][130]. In addition, a growing number of TMR studies also point towards a critical role of theta with regards to memory reactivation during sleep.…”

How odor cues help to optimize learning during sleep in a real life-setting

“…Interestingly, memory cueing during night is not restricted to the olfactory modality, as auditory cues, even the auditory presentation of previously learned words during SWS, also work 13,19,20 . However, continuous stimulation with auditory cues can be problematic because of a certain refractoriness pattern: Auditory stimulus presentation needs to be below a certain temporal duration 33 and spaced in time within the SWS stage in order to prevent the disappearance of the beneficial effect of cueing. The latter strongly reminds of well-known spacing effects 15,[34][35][36] or retroactive interference effects during learning 16 .…”