Changes in cross-frequency coupling following closed-loop auditory stimulation in non-rapid eye movement sleep

Abstract

Regional changes of non-rapid eye movement (NREM) sleep delta and sigma activity, and their temporal coupling have been related to experience-dependent plastic changes during previous wakefulness. These sleep-specific rhythms seem to be important for brain recovery and memory consolidation. Recently, it was demonstrated that by targeting slow waves in a particular region at a specific phase with closed-loop auditory stimulation, it is possible to locally manipulate slow-wave activity and interact with training-induced neuroplastic changes. In our study, we tested whether closed-loop auditory stimulation targeting the up-phase of slow waves might not only interact with the main sleep rhythms but also with their coupling within the circumscribed region. We demonstrate that while closed-loop auditory stimulation globally enhances delta, theta and sigma power, changes in cross-frequency coupling of these oscillations were more spatially restricted. Importantly, a significant increase in delta-sigma coupling was observed over the right parietal area, located directly posterior to the target electrode. These findings suggest that closed-loop auditory stimulation locally modulates coupling between delta phase and sigma power in a targeted region, which could be used to manipulate sleep-dependent neuroplasticity within the brain network of interest. A substantial body of evidence highlights the importance of non-rapid eye movement (NREM) sleep for experience-dependent neuroplasticity and associated improvements in behavioral performance after a bout of sleep 1,2. NREM sleep electroencephalographic (EEG) recordings are hallmarked by neocortical slow waves (1-4 Hz) and sleep spindles, the waxing and waning activity in the sigma frequency band (10-16 Hz). It is well established that slow waves orchestrate faster oscillations, with the up-phase of slow waves being associated with increased sigma band activity, and sigma oscillations, in turn, group gamma activity in their troughs 3,4. This precise crossfrequency phase-amplitude coupling is thought to organize communication across multiple brain areas and to facilitate coordinated information processing in brain networks during NREM sleep 5. Not only the magnitude and spatial distribution of slow waves and sigma activity 3,6-10 , but especially their temporal coupling seems to contribute to sleep-dependent benefits of behavioral performance 11,12. Similar to phase-amplitude coupling between slow waves and sigma, modulation of theta band activity (5-8 Hz) by the phase of slow waves has been described in several studies. Both in surface EEG and in intracranial (iEEG) recordings, theta power was increased during the transition to the down phase of slow waves, with the last trough of theta-burst coinciding with the slow-wave down-phase 5,13-15. Moreover, theta band activity in NREM sleep may play a role in sleep-dependent memory consolidation in humans. NREM theta oscillations were associated with the replay of the wake neuronal activity patterns during slow-wave sleep 16,17. Fur...

Closed-loop auditory stimulation method to modulate sleep slow waves and motor learning performance in rats

“…In support of this argument, we observed that the number of attempts in the down-phase group was lower than in the other groups at motor-training day 1, indicating that before any memory consolidation process took place, these animals already performed worse than their counterparts did. On the other hand, memory consolidation, a process at least partially mediated by spindles (Diekelmann & Born, 2010) in which specific synapses are strengthened, is also potentially sensitive to CLAS (Krugliakova et al, 2020; H.-Viet V. Papalambros et al, 2017). In fact, we did observe positive correlations between sigma -potentially a proxy for spindles (Holz et al, 2012) -during motor-training days 1-4 and success rate on motor-training day 4.…”

“…Our tool, thus, may be utilized to disentangle the exact effects of CLAS-modulated SWS on rodent cognition. Further, CLAS can be strategically combined with other tools, such as multiunit-activity recording, and provide crucial insight into the underlying neuronal mechanisms of auditory modulated slow waves and sigma (Krugliakova et al, 2020), and their functional role on learning and memory.…”

Effectiveness of Visual vs. Acoustic Closed-Loop Stimulation on EEG Power Density during NREM Sleep in Humans

“…Although EEG slow waves are a global cortical phenomenon during sleep [ 22 ], slow waves may be different in amplitude and phase across different brain regions. Slow oscillations during NREM sleep propagate from the medial frontal cortex to the medial temporal lobe [ 23 ] and can be regulated locally [ 24 , 25 ]; therefore, the effect following the stimuli presentation may be attributable to a particular brain region only [ 26 ]. It is not excluded, therefore, that the slight EEG fluctuations around baseline following the light stimulus ( Figure 4 ) may indeed represent visual-evoked potential (VEP) that would be more visible at the occipital region.…”

“…Following the acoustic stimulation, we received event-related responses containing spectral components (P200, N350, P450, N550, and P900) that are characteristic of stimulation-evoked K-complexes [ 21 ]. A convincing explanation of the closed-loop stimulation effects is that K-complexes externally evoked by stimulation time-locked to a particular phase of slow waves promote further synchronization of endogenous slow waves [ 8 , 26 ]. In our study, acoustic stimuli were delivered at the decay part of the slow wave up-phase in a relatively broad time range of the excitatory up-state of slow waves.…”

Sounding It Out: Auditory Stimulation and Overnight Memory Processing

“…The vast majority of auditory stimulation studies have used the closed-loop method; that is, utilising the ongoing EEG activity to deliver auditory stimuli in synchrony with the brain's endogenous rhythm [13,14,16,17,19,[21][22][23][24][25][26][27][28][29][30][31]32]. One study, however, used an open-loop protocol in which the ongoing EEG data had no bearing on the timing of stimulus delivery [33].…”