Transcranial direct current stimulation during sleep improves declarative memory

Abstract

In humans, weak transcranial direct current stimulation (tDCS) modulates excitability in the motor, visual, and prefrontal cortex. Periods rich in slow-wave sleep (SWS) not only facilitate the consolidation of declarative memories, but in humans, SWS is also accompanied by a pronounced endogenous transcortical DC potential shift of negative polarity over frontocortical areas. To experimentally induce widespread extracellular negative DC potentials, we applied anodal tDCS (0.26 mA) [correction] repeatedly (over 30 min) bilaterally at frontocortical electrode sites during a retention period rich in SWS. Retention of declarative memories (word pairs) and also nondeclarative memories (mirror tracing skills) learned previously was tested after this period and compared with retention performance after placebo stimulation as well as after retention intervals of wakefulness. Compared with placebo stimulation, anodal tDCS during SWS-rich sleep distinctly increased the retention of word pairs (p < 0.005). When applied during the wake retention interval, tDCS did not affect declarative memory. Procedural memory was also not affected by tDCS. Mood was improved both after tDCS during sleep and during wake intervals. tDCS increased sleep depth toward the end of the stimulation period, whereas the average power in the faster frequency bands (,alpha, and beta) was reduced. Acutely, anodal tDCS increased slow oscillatory activity <3 Hz. We conclude that effects of tDCS involve enhanced generation of slow oscillatory EEG activity considered to facilitate processes of neuronal plasticity. Shifts in extracellular ionic concentration in frontocortical tissue (expressed as negative DC potentials during SWS) may facilitate sleep-dependent consolidation of declarative memories.

Figure 1.

Procedure of the Sleep experiment. Time points of learning and recall of the memory tasks (PAL, MT), psychometric tests (d2, EWL, PANAS), tDCS, blood sampling (arrows), period of lights off (horizontal black bar), and sleep, represented by the schematized hypnogram, are indicated. W, Wake; 1-4, sleep stages 1-4; vertical black bar, REM sleep.

Figure 2.

Memory performance on the PAL and MT tasks across retention periods of sleep (left) and wakefulness (right) during which either tDCS (hatched bar) or placebo stimulation (white bar) was applied. Recall after the retention interval is expressed as difference from performance at learning in number of words (for PAL) and in milliseconds for draw time (for MT). ^**p < 0.01, for differences between the effects of tDCS and placebo stimulation. Error bars represent SEM.

Figure 3.

Time course of mean sleep stage for tDCS (solid line) and placebo (dotted line) conditions of the Sleep experiment. Average sleep stages were determined by associating values of 1, 2, 3, and 4 to sleep stages 1-4 and 0 and -1 to REM sleep and wakefulness, respectively. Significant differences between the time courses are indicated at the bottom. The gray area represents the stimulation interval.

Figure 4.

Average EEG power for periods of stage 2 sleep and SWS during the 30 min interval of tDCS (hatched bars) and a corresponding interval during the placebo condition (white bars) of the Sleep experiments. θ (4-8 Hz), lower α (8-10 Hz), and lower β (15-20 Hz) bands are averaged for frontal (F7, Fz, F8), central (C3, Cz, C4), and parietal (P3, Pz, P4) electrode locations. ^**p < 0.01; ^*p < 0.05; ^tp < 0.1, for differences between tDCS and placebo (stage 2 sleep, n = 14; SWS, n = 16). Error bars represent SEM.

Figure 5.

Average EEG power within the slow <3 Hz frequency band for the 60 15 sec stimulation periods of acute anodal polarization (solid line) and the 60 intermittent 15 sec periods (dotted line) in which stimulation was discontinued in the tDCS condition of the Sleep experiment. Data are shown for the mean of frontal (F7, Fz, F8) and parietal (P3, Pz, P4) electrode locations, where most consistent increases in power were observed during acute anodal stimulation. Significant differences between the spectra are indicated at the bottom of each diagram (n = 16). Error bars represent SEM.