No benefit of auditory closed-loop stimulation on memory for semantically-incongruent associations.

Auditory closed-loop stimulation has gained traction in recent years as a means of enhancing slow oscillatory activity and, consequently, sleep-associated memory consolidation. Previous studies on this topic have primarily focused on the consolidation of semantically-congruent associations. In this study, we investigated the effect of auditory closed-loop stimulation on the overnight retention of semantically-incongruent associations. Twelve healthy males (age: M = 20.06, SD = 2.02 years) participated in two experimental conditions (simulation and sham). In the stimulation condition, clicks were delivered in phase with slow oscillation up-states, whereas in the sham condition no auditory stimuli were applied. Corroborating earlier work, stimulation (vs. sham) enhanced the slow oscillation rhythm, phase-coupled spindle activity and slow oscillation power. However, there was no benefit of stimulation on overnight memory retention. These findings suggest that closed-loop stimulation does not benefit semantically-incongruent associations.

Phase-locked auditory stimulation of theta oscillations during rapid eye movement sleep.

Auditory closed-loop stimulation is a non-invasive technique that has been widely used to augment slow oscillations during non-rapid eye movement sleep. Based on the principles of closed-loop stimulation, we developed a novel protocol for manipulating theta activity (3-7 Hz) in rapid eye movement (REM) sleep. Sixteen healthy young adults were studied in two overnight conditions: Stimulation and Sham. In the Stimulation condition, 1 s of 5 Hz amplitude-modulated white noise was delivered upon detection of two supra-threshold theta cycles throughout REM sleep. In the Sham condition, corresponding time points were marked but no stimulation was delivered. Auditory stimulation entrained EEG activity to 5 Hz and evoked a brief (~0.5 s) increase in theta power. Interestingly, this initial theta surge was immediately followed by a prolonged (~3 s) period of theta suppression. Stimulation also induced a prolonged (~2 s) increase in beta power. Our results provide the first demonstration that the REM sleep theta rhythm can be manipulated in a targeted manner via auditory stimulation. Accordingly, auditory stimulation might offer a fruitful avenue for investigating REM sleep electrophysiology and its relationship to behavior.

Memory Consolidation Is Linked to Spindle-Mediated Information Processing during Sleep.

How 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 [1-4]. 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 [5-10], 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.

Schema-conformant memories are preferentially consolidated during REM sleep.

Memory consolidation is most commonly described by the standard model, which proposes an initial binding role for the hippocampus which diminishes over time as intracortical connections are strengthened. Recent evidence suggests that slow wave sleep (SWS) plays an essential role in this process. Existing animal and human studies have suggested that memories which fit tightly into an existing knowledge framework or schema might use an alternative consolidation route in which the medial prefrontal cortex takes on the binding role. In this study we sought to investigate the role of sleep in this process using a novel melodic memory task. Participants were asked to remember 32 melodies, half of which conformed to a tonal schema present in all enculturated listeners, and half of which did not fit with this schema. After a 24-h consolidation interval, participants were asked to remember a further 32 melodies, before being given a recognition test in which melodies from both sessions were presented alongside some previously unheard foils. Participants remembered schema-conformant melodies better than non-conformant ones. This was much more strongly the case for consolidated melodies, suggesting that consolidation over a 24-h period preferentially consolidated schema-conformant items. Overnight sleep was monitored between the sessions, and the extent of the consolidation benefit for schema-conformant items was associated with both the amount of REM sleep obtained and EEG theta power in frontal and central regions during REM sleep. Overall our data suggest that REM sleep plays a crucial role in the rapid consolidation of schema-conformant items. This finding is consistent with previous results from animal studies and the SLIMM model of Van Kesteren, Ruiter, Fernández, and Henson (2012), and suggest that REM sleep, rather than SWS, may be involved in an alternative pathway of consolidation for schema-conformant memories.

Overnight consolidation aids the transfer of statistical knowledge from the medial temporal lobe to the striatum.

Sleep is important for abstraction of the underlying principles (or gist) which bind together conceptually related stimuli, but little is known about the neural correlates of this process. Here, we investigate this issue using overnight sleep monitoring and functional magnetic resonance imaging (fMRI). Participants were exposed to a statistically structured sequence of auditory tones then tested immediately for recognition of short sequences which conformed to the learned statistical pattern. Subsequently, after consolidation over either 30 min or 24h, they performed a delayed test session in which brain activity was monitored with fMRI. Behaviorally, there was greater improvement across 24h than across 30 min, and this was predicted by the amount of slow wave sleep (SWS) obtained. Functionally, we observed weaker parahippocampal responses and stronger striatal responses after sleep. Like the behavioral result, these differences in functional response were predicted by the amount of SWS obtained. Furthermore, connectivity between striatum and parahippocampus was weaker after sleep, whereas connectivity between putamen and planum temporale was stronger. Taken together, these findings suggest that abstraction is associated with a gradual shift from the hippocampal to the striatal memory system and that this may be mediated by SWS.