Article Figures & Data
Figures
- Figure 1.
Schema for experiments 1 and 2. Timing of different phases for each experiment. In experiment 1, subjects arrived at the laboratory at 11:00 A.M. Following informed consent, participants performed the encoding portion of the word pair associates and virtual reality (VR) tasks, followed by setup of EEG electrodes. After a 2 h nap opportunity, participants completed the recall portions of the VR and word pair associates tasks, respectively. In experiment 2, participants arrived at the sleep laboratory at 9:00 P.M. for the accommodation night (no memory tasks or stimulation performed). On experimental nights (weeks 1 and 2), participants arrived at the sleep laboratory at 8:00 P.M. for EEG electrode setup, followed by word pair associates encoding at ∼9:00 P.M. Light’s out started at 11:00 P.M., and participants were awoken at ∼6:00 A.M. (e.g., after 7 h). A 1 week delay (washout) occurred between every session.
- Figure 2.
Closed-loop stimulation during a daytime nap enhances slow wave–spindle complexes, but does not enhance memory performance. A, Evoked responses from 12 subjects (mean ± SEM) shows that stimulation delivered during slow-wave UP states (red curves; dashed red line indicates the onset of acoustic pulse) enhances ongoing slow-wave oscillations (red) compared with sham stimulation (black). Spindle power is also increased in stimulation (red) compared with sham (black; inset). B, C, Memory performance, as assessed by postnap retention of word pairs (B), and spatial navigation performance, as measured by the number of speed improvements (C), do not exhibit a significant benefit from acoustic stimulation relative to sham (each line represents individual subject performance).
- Figure 3.
Acoustic stimulation during nap sleep enhances both fast- and slow-spindle amplitudes but is not related to memory performance. A, Fast-spindle (12–15 Hz) and slow-spindle (9–12 Hz) amplitude at electrode Cz time locked to the negative DOWN state of all off-line detected SO events (t = 0). Both fast- and slow-spindle amplitude showed significant increases in amplitude in the stimulation (red) condition relative to sham (black) stimulation. B, Scatter plots of retention versus peak fast-spindle amplitude (left) and the number of VR improvements versus peak fast-spindle amplitude (right) across individuals in sham and stimulation conditions (no significant correlations in either task).
- Figure 4.
Closed-loop stimulation during overnight sleep enhances slow-wave and spindle oscillations, but does not enhance verbal memory performance. A, Mean ± SEM EEG signal (at electrode Cz) averaged (across 19 subjects) time locked to the first auditory stimulus (t = 0 s) for the stimulation (red) and sham (black) conditions. The bottom panel indicates significant differences between conditions. Evoked responses from 19 subjects show that stimulation delivered during slow-wave UP states (red curves; dashed lines indicate onset of acoustic pulse) enhances ongoing slow-wave oscillations relative to sham stimulation (black). B, Memory performance, as assessed by the word pair associates task does not exhibit a significant benefit from acoustic stimulation relative to sham (mean, SEM). C, Correlation (and trend line) between the amount of SWS during the stimulation period and retention on the behavioral task. Correlations were not significant in either condition.
- Figure 5.
Acoustic stimulation enhances both fast- and slow-spindle amplitude but is not related to verbal memory consolidation. A, Fast-spindle (12–15 Hz) and slow-spindle (9–12 Hz) amplitude at electrode Cz time locked to the negative DOWN state of all detected SO events (t = 0). B, Scatter plot of retention versus peak fast-spindle amplitude across individuals in sham and stimulation conditions (not significant in either condition).
Tables
Experiment 1 (N = 12) Experiment 2 (N = 19) Female (n, %) 6.0 50.0% 9.0 47.4% Age, years (mean, SEM) 23.3 0.8 23.3 0.9 Race (n, %) Caucasian/white 5.0 41.7% 8.0 42.1% African American/black 4.0 33.3% 2.0 10.5% Asian 3.0 25.0% 5.0 26.3% Biracial 0.0 0.0% 1.0 5.3% Not specified 0.0 0.0% 3.0 15.8% Hispanic/Latino (n, %) 0.0 0.0% 2.0 10.5% Education, years (mean, SEM) 15.8 0.3 14.7 0.4 SSS score visit 1 maximum score = 6 Pre (mean, SEM) 2.9 0.3 3.5 0.4 Post (mean, SEM) 2.2 0.3 2.6 0.2 SSS score visit 2 maximum score = 6 Pre (mean, SEM) 2.3 0.2 3.5 0.3 Post (mean, SEM) 2.2 0.3 2.5 0.3 PVT score visit 1 Pre (mean, SEM) 0.3 0.0 Post (mean, SEM) 0.3 0.0 PVT score visit 2 Pre (mean, SEM) 0.3 0.0 Post (mean, SEM) 0.3 0.0 MOCA score maximum score = 30 (mean, SEM) 27.9 0.4 28.6 0.3 Demographics table of subjects who participated in experiments 1 and 2.
Stim Sham p Value W 7.42% (1.85) 6.29% (1.73) 0.49 N1 20.92% (2.96) 20.92% (1.59) 0.53 N2 30.77% (4.04) 33.26% (4.19) 0.57 SWS 16.53% (2.73) 18.45% (2.03) 0.40 REM 22.57% (6.91) 21.01% (5.16) 0.78 MA 0.08% (0.08) 0.07% (0.06) 0.92 TST (mins) 83.0 (9.60) 79.3 (7.31) 0.69 Sleep during daytime nap study is characterized with the average time spent in each sleep stage (mean ± SEM). The percentage of time spent in each condition (W, wake; N1, stage 1; N2, stage 2; MA, movement artifact) was similar during the stimulation period, demonstrating that stimulation did not disrupt sleep or increase the overall time spent in non-REM sleep.
- Table 3.
Slow-oscillation characteristics during afternoon nap closed-loop stimulation (experiment 1)
Stim Sham p Value Number of SOs 166.67 (27.76) 154.58 (17.65) 0.52 SO amplitude (μV) 147.36 (13.04) 143.17 (9.89) 0.40 SO slope (μV/s) 278.68 (26.09) 275.92 (20.30) 0.83 Duration (s) 1.13 (0.01) 1.15 (0.01) 0.04 Mean ± SEM number of slow oscillations (identified off-line; see Materials and Methods) during the entire recording, amplitude (negative half-wave-to-peak), slope, and duration between stim and sham conditions. Duration of SO in the stimulation condition was significantly shorter compared with the sham condition, suggesting that the induced SO oscillation peaked at a higher frequency compared with the sham condition (∼1 Hz)
BF10 Error % Experiment 1 Word pair retention Stim-sham 0.302 0.019 VR speed improvements Stim-sham 0.299 0.019 Experiment 2 Word pair retention Stim-sham 0.249 0.012 Bayes factor (BF10) and proportional error of the BF for paired-samples t test of the hypothesis the memory performance scores in the stim and sham sessions are equal. A Bayes factor <1 indicates evidence in favor of the null hypothesis (e.g., stim = sham)
Stim Sham p Value W 1.55% (0.69) 4.11% (3.21) 0.44 N1 3.61% (1.00) 2.19% (0.64) 0.23 N2 44.50% (3.47) 39.33% (3.89) 0.33 SWS 39.69% (3.34) 40.85% (4.32) 0.83 REM 9.25% (1.35) 7.39% (1.48) 0.36 MA 1.39% (0.29) 0.89% (0.20) 0.17 Total sleep time (min) 394.4 (15.6) 398.5 (11.1) 0.83 Sleep characteristics during the 210 min stimulation period showing the average time spent in each sleep stage demonstrates that the percentage of time spent in each condition (W, wake; N1, stage 1; N2, stage 2; MA, muscle artifact) was similar during the stimulation period, suggesting that stimulation did not disrupt sleep or increase the overall time spent in NREM sleep.
- Table 6.
Characteristics of slow oscillations during overnight closed-loop stimulation (experiment 2).
Stim Sham p Value Number of SOs (stimulation period) 529.37 (74.71) 477.05 (60.75) 0.59 Number of SOs (entire night) 1356.37 (111.47) 1338.89 (106.62) 0.87 SO amplitude (μV) 141.93 (9.16) 128.62 (10.06) 0.24 SO slope (μV/s) 277.64 (21.97) 244.02 (20.80) 0.14 Duration (s) 1.18 (0.01) 1.14 (0.07) 0.49 Mean ± SEM number of slow oscillations (SOs identified off-line; see Materials and Methods) during SWS epochs of the stimulation period and the entire night, amplitude (negative half-wave to positive-peak), slope, and duration between stim and sham conditions.
- Table 7.
Comparison of previous studies using acoustic stimulation to boost slow oscillations and spindle and their effects on memory
Study Study design Behavioral results EEG results Ngo et al., 2013 N = 11 healthy young adults (mean ± SD age, 24.2 ± 2.98 years) Stimulation protocol Hedges gav = 1.07
Retention (presleep − postsleep):
Stim: 22.2 ± 2.3 words
Sham: 13.0 ± 2.5 wordsIncrease in slow-wave and spindle power Closed-loop
Two-pulse stimulation
overnight sleep (7 h)Memory tests 120 semantically related word pairs Cox et al., 2014b N = 12 healthy adults (age range, 18–23 years; 11 females) Stimulation protocol No behavioral effect observed Increased slow-wave amplitude and spindle band power with sounds targeted at up-state Closed-loop
One-pulse stimulation
Evening nap (2 h)Memory tests Sound stimulus memory task Ong et al., 2016 N = 16 healthy young adults (mean ± SD age, 22 ± 1.4 years) Stimulation protocol Hedges gav = 0.41Retention (presleep − postsleep):Sham: −1.72 ± 4.16 SDsStim: 0.0 ± 3.76 SDs Increased slow-wave amplitude, theta, and fast-spindle activity Closed-loopFive consecutive pulsesAfternoon nap (1.5 h) Memory tests 40 semantically related word pairs Weigenand et al., 2016 N = 26 healthy young adults (mean age, 22.2 years; age range, 18– 28 years) Stimulation protocol No behavioral effect observed Increase in slow-wave and increase in spindle power with first pulse Open-loopThree consecutive pulse stimulationOvernight sleep (7 h) Memory tests 120 semantically related word pairs1 Leminen et al., 2017 N = 15 healthy adults (mean age, 30.5 years; range, 23–42 years) Stimulation protocol Hedges gav = 0.65Retention (presleep – postsleep):Stim: 21.1 ± 7.7 SDsSham: 15.6 ± 8.1 SDsNo behavioral effect on face–name memory, finger tapping, or picture memory (tasks 2–4) Increase in slow-wave and spindle power Closed-loopSingle-pulse stimulationOvernight sleep (7 h) Memory tests 120 semantically related word pairs2 Face–name association testFinger-tapping testPicture recognition task Papalambros et al., 2017 N = 13 healthy older adults (mean age, 75.2 years; age range, 60–84 years) Stimulation protocol Hedges gav = 0.77Retention (presleep – postsleep):Stim: 9.2 ± 7.93 SDsSham: 3.1 ± 6.85 SDs Increase in slow-wave and spindle power Closed-loopFive-pulse, phase-locked loop stimulationOvernight sleep (8 h) Memory tests 88 semantically related word pairs Ngo et al., 2019 N = 24 healthy young adults (mean ± SD age, 23.9 ± 3.42 years) Stimulation protocol No behavioral effect observed Acute increase in slow-wave and spindle power, but no effect on total overnight slow-wave and spindle power Closed-loopSeven-click spindle stimulationOvernight sleep (7 h) Memory tests 120 semantically related word pairs1 For each study, the brief description of the subject pool, stimulation and memory protocols, effect size (Hedges gav) of the behavioral effect (if applicable), and overall electrophysiological findings are provided.
↵1 Same word lists used in Ngo et al., 2013.
↵2 Translated from list used in Ngo et al., 2013.
In this issue
