Abstract

Slow-wave sleep cortical brain activity, conformed by slow-oscillations and sleep spindles, plays a key role in memory consolidation. The increase of the power of the slow-wave events, obtained by auditory sensory stimulation, positively correlates with memory consolidation performance. However, little is known about the experimental protocol maximizing this effect, which could be induced by the power of slow-oscillation, the number of sleep spindles, or the timing of both events' co-occurrence. Using a mean-field model of thalamocortical activity, we studied the effect of several stimulation protocols, varying the pulse shape, duration, amplitude, and frequency, as well as a target-phase using a closed-loop approach. We evaluated the effect of these parameters on slow-oscillations (SO) and sleep-spindles (SP), considering: (i) the power at the frequency bands of interest, (ii) the number of SO and SP, (iii) co-occurrences between SO and SP, and (iv) synchronization of SP with the up-peak of the SO. The first three targets are maximized using a decreasing ramp pulse with a pulse duration of 50 ms. Also, we observed a reduction in the number of SO when increasing the stimulus energy by rising its amplitude. To assess the target-phase parameter, we applied closed-loop stimulation at 0°, 45°, and 90° of the phase of the narrow-band filtered ongoing activity, at 0.85 Hz as central frequency. The 0° stimulation produces better results in the power and number of SO and SP than the rhythmic or random stimulation. On the other hand, stimulating at 45° or 90° change the timing distribution of spindles centers but with fewer co-occurrences than rhythmic and 0° phase. Finally, we propose the application of closed-loop stimulation at the rising zero-cross point using pulses with a decreasing ramp shape and 50 ms of duration for future experimental work.

Highlights

  • Humans spend about one-third time of their life sleeping

  • The evidence suggests that SP nested in the up phase of the slow oscillations (SO) may play a role in memory consolidation [15]

  • Following the discoveries from previous works of Ngo et al, the application of stimulus at a precise phase of the ongoing cortical activity [3] produces better behavioral results than rhythmic stimulation [36, 60]. Another result of the same authors shows that the application of more than two consecutive pulses does not improve physiological outcomes [61]. These results suggest the presence of mechanisms that prevent an over-driving of SO activity, which could be present in our case given a similar increase of I(SO) but lesser NSO/min. with stimulation types: random (STIM-R)

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Summary

Introduction

Humans spend about one-third time of their life sleeping. This behavior has paramount importance for the process of learning, as it contributes to the consolidation of memories [1, 2]. During the non-rapid eye movement (NREM) phase of sleep, the brain’s electrical activity is characterized by the occurrence of events recognizable on the cortical activity measured by electroencephalogram (EEG) registers. These events are the slow oscillations (SO), single highamplitude cortical oscillations lasting 0.8 to 2 seconds [3]; and the sleep spindles (SP), thalamocortical oscillation bursts lasting 0.5 to 2 seconds in the 9-16 Hz frequency band [4]. The characteristics of the EEG waveform depend on the contribution from multiple electrical current sources [6] Characteristics such as the amplitude and frequency involve the interaction of the cortex with other cerebral structures. Similar to in-vivo activity can be reproduced by computer models of the corticothalamic system [9, 10]

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