Increased neuronal signatures of targeted memory reactivation during slow-wave up states

Maurice Göldi, Eva Anna Maria van Poppel, Björn Rasch, Thomas Schreiner, Maurice Göldi, Eva Anna Maria van Poppel, Björn Rasch, Thomas Schreiner

Abstract

It is assumed that slow oscillatory up-states represent crucial time windows for memory reactivation and consolidation during sleep. We tested this assumption by utilizing closed-loop targeted memory reactivation: Participants were re-exposed to prior learned foreign vocabulary during up- and down-states of slow oscillations. While presenting memory cues during slow oscillatory up-states improved recall performance, down-state cueing did not result in a clear behavioral benefit. Still, no robust behavioral benefit of up- as compared to down-state cueing was observable. At the electrophysiological level however, successful memory reactivation during up-states was associated with a characteristic power increase in the theta and sleep spindle band. No oscillatory changes were observable for down-state cues. Our findings provide experimental support for the assumption that slow oscillatory up-states may represent privileged time windows for memory reactivation, while the interplay of slow oscillations, theta and sleep spindle activity promotes successful memory consolidation during sleep.

Conflict of interest statement

The authors declare no competing interests.

Figures

Figure 1
Figure 1
Closed-loop TMR algorithm evaluation. (a) Schematic overview of the slow-wave detection algorithm and the targeted areas for up-state TMR (blue) and down-states TMR (red). (b) The ERP-analyses revealed that up-state cues were located at the down-to-up transition of the cortical slow wave (beginning of slow oscillatory up-state), and that down-state cues were played at the up-to-down transition (beginning of slow oscillatory down-state). (c) Phase angle at stimulus release. The top row illustrates the angles averaged at subject level, the bottom row shows results on trial level (red and blue shading corresponds to targeted areas in a). The left column indicates the up-state phases, while the right column shows the down-state phase angles. All data is shown for electrode Fz.
Figure 2
Figure 2
Experimental Procedure and memory task results. (a) After studying 120 Dutch-German word pairs in the evening, participants slept for 3 hours. During NREM sleep, 40 Dutch words were presented during SO up-states and 40 Dutch words were presented during SO down-states using closed-loop TMR. 40 Dutch words were not replayed. A cued recall procedure was applied after sleep, testing the participant’s memory for the German translations. (b) Presenting prior learned words during SO up-states significantly enhanced memory performance compared to uncued words. Recall performance of words replayed during SO down-states did not differ from the two other categories. Retrieval performance is indicated as percentage of recalled German translations with performance before sleep set to 100%. Values are mean ± SEM **P ≤ 0.025. (c) Correlation between memory performance and relative time spent in REM sleep. Memory performance for words presented during down-states is positively correlated with time spent in REM sleep (r14 = 0.59, P = 0.017). There was no significant correlation for words presented during up-states (r14 = −0.16, P = 0.552), and a marginal significant negative correlation for uncued words (r14 = −0.49, P = 0.052).
Figure 3
Figure 3
Oscillatory results. Time-frequency contrasts between remembered and not-remembered words in the theta and sleep spindle band for (a) up-state and (c) down-state cues, averaged over all 31 significant spindle electrodes. Black bars (significant cluster in frequency band analysis) with white lines below and above the time-frequency plot show the number of significantly differing electrodes for the theta and sleep spindle band respectively. The full height of the bar corresponds to 100% (31) electrodes. Dashed boxes indicate the areas of significant difference between remembered and not remembered words. These time-windows were used to illustrate the topographical distributions (b,d,f) left column, top row spindle band, bottom row theta band; significant electrodes shown as filled black dots). (b,d,f) right column show the mean power within the significant clusters, averaged over the significant electrodes, all frequencies and time in the sleep spindle (top) and theta (bottom) band. For up-state cueing (a) remembered words show enhanced power in the theta (5–8 Hz) as well as the sleep spindle (11–15 Hz) range compared to not-remembered words. Averaged over time, channels and frequency band, within these clusters this difference was significant in the theta band (t15 = 2.69, P = 0.008; see b right column, bottom row) and in the spindle band (t15 = 2.50, P = 0.012; see b, right column, top row). For words presented during down-states (c) no significant difference emerged between remembered and forgotten words, neither in the sleep spindle nor the theta band. Consequently, averaged activity in those clusters observed in the analysis of SO up-states did not reveal any significant differences for down-state cues, neither in the theta (t15 = 0.68, P = 0.253) nor the spindle band (t15 = −0.42, P = 0.661). The difference between the two contrasts of up and down (e) showed enhanced power in the spindle band, but not in the theta band. Averaged activity in the spindle cluster (t15 = 2.41, P = 0.015; see f right column, top row) showed a significant difference, while theta activity (averaged over the duration of the SO up-state theta cluster) showed only a statistical trend (t15 = 1.44, P = 0.085; see f right column, bottom row). Mean ± SEM are indicated. **P < 0.01; *P < 0.05.

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