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

The activity of different brain networks in non-rapid eye movement (NREM) sleep is regulated locally in an experience-dependent manner, reflecting the extent of the network load during wakefulness. In particular, improved task performance after sleep correlates with the local post-learning power increase of neocortical slow waves and faster oscillations such as sleep spindles and their temporal coupling. Recently, it was demonstrated that by targeting slow waves in a particular region at a particular phase with closed-loop auditory stimulation it is possible to locally manipulate slow-wave activity and interact with training-induced neuroplastic changes. Based on this finding, we tested whether closed-loop auditory stimulation targeting the up-phase of slow-waves over the right sensorimotor area might affect power in delta, theta and sigma bands and coupling between these oscillations within the circumscribed region. We demonstrate that while closed-loop auditory stimulation globally enhances power in delta, theta and sigma bands, changes in cross-frequency coupling of these oscillations were more spatially restricted. In particular, stimulation induced a significant decrease of delta-theta coupling in frontal channels, within the area of the strongest baseline coupling between these frequency bands. In contrast, 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 memory formation within the brain network of interest.