Clicking the brain into deep sleep. Commentary on Weigenand et al. ()

Abstract

This is a commentary on Weigenand, A., Mölle, M., Werner, F., Martinetz, T. & Marshall, L. (2016) Timing matters: open-loop stimulation does not improve overnight consolidation of word pairs in humans. Eur. J. Neurosci., 44, 2357-2368. The article can be viewed at wileyonlinelibrary.com.Slow-wave sleep (SWS) has been ascribed to play a key role in memory consolidation processes (Rasch & Born, 2013). One of the most salient features of SWS is the elevated occurrence of slow oscillations (< 1 Hz). Slow oscillations (SOs) are generated in thalamic and neocortical circuits and comprise alterations between periods of increased excitability (up-states) and hyperpolarized neural silence (down-states) (Contreras & Steriade, 1995). This alternating neural activity spreads throughout the neocortex and also affects other brain regions among others the hippocampus (Contreras et al., 1997). By orchestrating thalamic sleep spindles and hippocampal sharp-wave ripples (SWR), SOs are thought to coordinate the reactivation of memories during sleep, enabling the beneficial effects of sleep on memory formation (Diekelmann & Born, 2010).Given the assumed role of SOs in mediating the most prominent effects of sleep on cognitive functioning, several attempts have been made to potentiate them (Bellesi et al., 2014).Recently, Ngo et al. (2013) used brief click sounds to enhance SO activity. Critically, the phase of the ongoing oscillatory activity was taken into account to provide auditory stimulation in synchrony with spontaneous SOs. By analyzing the sleep EEG online, the researchers were able to forecast the occurrence of SOs up-states and delivered click sounds time-locked to their appearance. This procedure led to a 9% enhancement of SO power compared to a sham condition, facilitated the induction of SO trains and boosted fast sleep spindle power. Strikingly, memory consolidation processes also benefitted from this procedure. Enhancing SOs led to improved memory for word pairs, which were initially learned before sleep. While those results fit perfectly with the proposed involvement of SOs and sleep spindles in memory consolidation, it is still unclear which specific aspects of the 'closed loop' rationale drive the memory enhancement. The work by Weigenand et al. (2016) presented in Volume 44, Issue 6 of EJN is one of the first important steps to give these details a closer look. The authors tested whether a similar effect on oscillatory activity and behavioural outcomes would be achieved when applying click sounds in a quasi-phasedependent manner, a paradigm named "open loop" stimulation. Here, each first click was presented at a random phase of the endogenous present SOs, whereas the second and third click of a sequence were delivered with a fixed time-interval (~1000 ms). The rationale was, that the first click would induce a K-complex (KC), thus a single SO (Steriade & Amzica, 1998), whereas clicks 2 and 3 would be again presented during the up-states of the evoked SOs to enhance SO activity and, presumably, consolidation proce...