**4. Sleep and cognitive functions**

164 Neuroimaging – Cognitive and Clinical Neuroscience

reactivation of the hippocampus and medial prefrontal cortex during sleep, basing on previous findings, the authors assume an important role of hippocampal-cortical connectivity for sleep-dependent declarative memory consolidation (Gais et al., 2007). The last convincing evidence concerning the role for SWS in memory formation comes from a recent fMRI study where the effect of declarative memory reconsolidation on declarative memory consolidation during SWS and wake was investigated (Diekelmenn et al., 2011). By using an experimental protocol similar to that previously applied by Rasch et al. (2007), the authors aimed at reactivating memories in humans by presenting associated odor cues either during SWS or during wake. During wake, reactivation of memories was followed by an interference task to probe memory stability, and as expected (Brown & Robertson, 2007; Robertson, 2009), this reactivation resulted in destabilized memories. In contrast, reactivation during SWS immediately stabilized memories, thereby directly increasing their resistance to interference. Importantly, BOLD signal revealed quite different patterns of reactivation during SWS and wake. The reactivation during SWS was mainly seen in the hippocampus and posterior cortical regions, whereas reactivation during wake was primarily found in the prefrontal cortical areas, thus showing that reactivation of memory serves distinct functions depending on brain state: wake versus SWS (Diekelmann et al., 2011). It is to be noted that similar differences between effects of oscillating trans-cranial direct current stimulation on both EEG activity and memory processes was also shown during wake when compared to SWS, although these differences distinguished specifically verbal memory encoding from declarative memory consolidation (Kirov et al., 2009;

To our knowledge, only one neuroimaging study was able to provide convincing evidence for reactivation of brain regions during REM sleep in association with sleep-dependent consolidation of procedural memory (Maquet et al., 2000). In this study, three groups of subjects learned a serial reaction time task (SRTT) during wakefulness. To verify which brain regions are activated by SRTT, one group was scanned by using of PET either during training or during the subsequent rest wake period, and was not further examined. Subjects from a second group were trained on the task during two sessions in the afternoon, and then scanned during the night after training, both during wake and during various sleep stages. This group was retested at recall after sleep to verify that sleep-dependent learning had occurred. A third group was scanned at the same time points as the second group was, however, under absence of learning (no learning condition). Sleep architecture in the latter two groups was assessed by a routine PSG, and rCBF was measured across both three groups and all time points. Interestingly, although the third group improved implicit learning component of SRTT at recall after sleep, no any changes in sleep architecture between the learning and the non-learning conditions were found. However, as measured by the rCBF, a specific pattern of brain activation found in the first group during and after learning was reactivated only in the second group, and only during REM sleep. This pattern engaged a set of brain regions located in occipital and premotor cortices (Maquet et al., 2000). A later PET study by the same group (Laureys et al., 2001) confirmed that specific brain reactivation occurs during REM sleep in relation to procedural memory consolidation (Maquet et al., 2000). The authors showed that the left premotor cortex is functionally more correlated with the left posterior parietal cortex and bilateral pre-supplementary motor area during REM sleep in subjects previously trained to a reaction time task relative to untrained

Marshall et al., 2006; 2011).

The strongest evidence for the important role that sleep plays in a variety of cognitive functions comes from many observations of effects of sleep loss and sleep deprivation on cognition (Killgore, 2010; Walker, 2008). The exclusively important role of sleep for cognitive functions has been best demonstrated in a study showing that even one night of total sleep deprivation results in inability to learn facts, i.e. deficient encoding of episodic memories (Yoo et al., 2007b). The neuroimaging correlates of this impaired learning ability will be presented below in the respective section.
