Shaping overnight consolidation via slow-oscillation closed-loop targeted memory reactivation

Abstract

Sleep constitutes a privileged state for new memories to reactivate and consolidate. Previous work has demonstrated that consolidation can be bolstered experimentally either via delivery of reminder cues (targeted memory reactivation [TMR]) or via noninvasive brain stimulation geared toward enhancing endogenous sleep rhythms. Here, we combined both approaches, controlling the timing of TMR cues with respect to ongoing slow-oscillation (SO) phases. Prior to sleep, participants learned associations between unique words and a set of repeating images (e.g., car) while hearing a prototypical image sound (e.g., engine starting). Memory performance on an immediate test vs. a test the next morning quantified overnight memory consolidation. Importantly, two image sounds were designated as TMR cues, with one cue delivered at SO UP states and the other delivered at SO DOWN states. A novel sound was used as a TMR control condition. Behavioral results revealed a significant reduction of overnight forgetting for words associated with UP-state TMR compared with words associated with DOWN-state TMR. Electrophysiological results showed that UP-state cueing led to enhancement of the ongoing UP state and was followed by greater spindle power than DOWN-state cueing. Moreover, UP-state (and not DOWN-state) cueing led to reinstatement of target image representations. Together, these results unveil the behavioral and mechanistic effects of delivering reminder cues at specific phases of endogenous sleep rhythms and mark an important step for the endeavor to experimentally modulate memories during sleep.

The functions of sleep: A cognitive neuroscience perspective

“…Ngo and Staresina ( 39 ) take the novel step of pairing TMR with experimental augmentation of slow-wave sleep, another method of experimentally enhancing memory consolidation ( 40 ). By combining the two approaches, these authors show that delivering TMR cues during the depolarizing up states of slow oscillations both triggered strong reactivation of memory representations and led to enhanced memory consolidation as measured by improvement in performance.…”

“…By combining the two approaches, these authors show that delivering TMR cues during the depolarizing up states of slow oscillations both triggered strong reactivation of memory representations and led to enhanced memory consolidation as measured by improvement in performance. Ngo and Staresina ( 39 ) speculate that the relatively late increase in reinstatement they observe in the scalp electroencephalography (EEG; at about one second) might reflect a slower hippocampal contribution to memory reactivation. However, they note that intracranial EEG recordings would be necessary to test this conjecture.…”

Reap while you sleep: consolidation of memories differs by how they were sown

“…A recent meta-analysis of TMR studies found that the effect sizes for olfactory cuing was not significantly different than that for auditory cuing (Hu et al, 2020, Table 2C). Since most olfactory TMR studies involve multiple memories and most auditory studies involve single memories (but see Ngo & Staresina, 2022), this could be seen as evidence that the benefits of cuing are similar regardless of the number of reactivated memories. Alternatively, they may reflect some inherent difference between modalities.…”

“…Which factors determine the consequences of reactivation? The predominant factors promoting harmonious benefits among memories seem to be either study designs with no inherent competition among items (Klinzing et al, 2018;Ngo & Staresina, 2022;Rasch et al, 2007;Rihm et al, 2014;Seibold et al, 2018) or designs that implicitly or explicitly encourage subjects to integrate and group memories together. In Schechtman et al (2022b), this was encouraged explicitly by linking items via the creation of a narrative context.…”

“…Sleep spindles are brief bursts of neural activity (0.5 -2 s; 11-15 Hz) occurring between the thalamus and cortex that similarly coordinate hippocampal-neocortical interactions and overlap with hippocampal reactivation events (Antony et al, 2019;McCormick & Bal, 1997;Siapas & Wilson, 1998). Intriguingly, TMR efficacy can differ based on when cues are delivered with respect to the slow oscillation phase (Batterink et al, 2016;Ngo & Staresina, 2022; though see Goldi et al, 2019;Wang et al, 2022). Additionally, TMR cues delivered shortly after spindles, which are unlikely to produce other beneficial post-cue spindles due to the presence of a 3-6 second spindle refractory period, are less effective than those delivered outside of the refractory period (Antony, Piloto, et al, 2018;Wang et al, 2019).…”