accumulation and exacerbates ADlike pathology. Furthermore, SR-B2 interacts with TLR4 and TLR6 to promote the activation of microglia by A, which induces the production of reactive oxygen species, IL-1 and other proinfl ammatory mediators as well as infl ammasome activation. These fi ndings indicate that SRs could be both benefi cial and detrimental in the progression of AD -benefi cial by promoting clearance of the neurotoxic A peptides, yet detrimental by contributing to disease progression and neurotoxicity through mediating the infl ammatory response to A. These dichotomous roles of SRs have led to their description as 'doubleedged swords'.SRs are also associated with atherosclerosis, a chronic infl ammatory disease characterized by the accumulation of modifi ed forms of lipoproteins as 'plaques' in the arterial wall. The failure of macrophages to process modifi ed lipoprotein effi ciently can lead to the formation of foam cells, thereby contributing to atherosclerosis. SR-A1, SR-A4, SR-B1, SR-B2, SR-D1, SR-E1, and SR-G1 can recognize OxLDL. Furthermore, upon exposure to modifi ed LDL, SR-B2 interacts with TLR4 and TLR6, resulting in NF-B activation and contributing to the infl ammatory response associated with atherosclerosis. The distinct role of each of these SRs in atherosclerosis is not clear; however, it is possible that the role of each SR depends on the level of its expression in a certain tissue or cell type. This interesting area of investigation remains understudied.Additionally, SRs are critically important in autoimmune diseases, such as SLE. Removal of apoptotic cells is a crucial process in immunity and in maintaining homeostasis in healthy tissues. Many cells, such as macrophages and dendritic cells, have the ability to clear apoptotic cells. A failure in the clearance of apoptotic cells can lead to their accumulation and facilitate the development of an 'anti-self' response to these cells, thereby contributing to autoimmune diseases. SLE is an example of this process, as patients with SLE have high levels of circulating apoptotic cells. SR-F1 binds to and phagocytoses apoptotic cells leading to their clearance, and, in mouse models, SR-F1 defi ciency impairs the engulfment of apoptotic cells leading to the development of a syndrome similar to SLE. Because of the limited available options to treat SLE, these fi ndings may have therapeutic implications for this disease. ConclusionsSRs are phagocytic and innate immune recognition receptors that play a crucial role as regulators of infl ammatory signaling. These receptors are involved in multiple physiological and pathological processes, including interactions with TLRs and delivery of ligands to different cellular compartments. Additionally, the roles of these receptors in many degenerative and autoimmune diseases, as well as their potential as targets for therapeutic interventions to treat various disorders, warrant further study.

Attention deficit hyperactivity disorder BLT Bright light therapy CCT Correlated colour temperature CIE Commission Internationale de l'Eclairage CRSWD Circadian rhythm sleep-wake disorders DLMO Dim-light melatonin onset EEG Electroencephalogram GHT Geniculohypothalamic tract IGL Intergeniculate leaflet ipRGC Intrinsically photosensitive retinal ganglion cell LED Light-emitting diode PRC Phase response curve RGC Retinal ganglion cell RHT Retinohypothalamic tract RN Raphe nuclei SAD Seasonal affective disorder SCN Suprachiasmatic nuclei SSRI Selective serotonin reuptake inhibitor SWA Slow wave activity UV Ultraviolet Somnologie 3 • 2019 147

For many studies, participants’ sleep-wake patterns are monitored and recorded prior to, during and following an experimental or clinical intervention using actigraphy, i.e. the recording of data generated by movements. Often, these data are merely inspected visually without computation of descriptive parameters, in part due to the lack of user-friendly software. To address this deficit, we developed a package for R Core Team [6], that allows computing several non-parametric measures from actigraphy data. Specifically, it computes the interdaily stability (IS), intradaily variability (IV) and relative amplitude (RA) of activity and gives the start times and average activity values of M10 (i.e. the ten hours with maximal activity) and L5 (i.e. the five hours with least activity). Two functions compute these ‘classical’ parameters and handle either single or multiple files. Two other functions additionally allow computing an L-value (i.e. the least activity value) for a user-defined time span termed ‘Lflex’ value. A plotting option is included in all functions. The package can be downloaded from the Comprehensive R Archives Network (CRAN).The package ‘nparACT’ for R serves the non-parametric analysis of actigraphy data.Computed parameters include interdaily stability (IS), intradaily variability (IV) and relative amplitude (RA) as well as start times and average activity during the 10 h with maximal and the 5 h with minimal activity (i.e. M10 and L5).

Objective:To investigate the relationship between the presence of a circadian body temperature rhythm and behaviorally assessed consciousness levels in patients with disorders of consciousness (DOC; i.e., vegetative state/unresponsive wakefulness syndrome or minimally conscious state).Methods:In a cross-sectional study, we investigated the presence of circadian temperature rhythms across 6 to 7 days using external skin temperature sensors in 18 patients with DOC. Beyond this, we examined the relationship between behaviorally assessed consciousness levels and circadian rhythmicity.Results:Analyses with Lomb-Scargle periodograms revealed significant circadian rhythmicity in all patients (range 23.5–26.3 hours). We found that especially scores on the arousal subscale of the Coma Recovery Scale–Revised were closely linked to the integrity of circadian variations in body temperature. Finally, we piloted whether bright light stimulation could boost circadian rhythmicity and found positive evidence in 2 out of 8 patients.Conclusion:The study provides evidence for an association between circadian body temperature rhythms and arousal as a necessary precondition for consciousness. Our findings also make a case for circadian rhythms as a target for treatment as well as the application of diagnostic and therapeutic means at times when cognitive performance is expected to peak.

Information processing has been suggested to depend on the current state of the brain as well as stimulus characteristics (e.g. salience). We compared processing of salient stimuli (subject's own names [SONs] and angry voice [AV] stimuli) to processing of unfamiliar names (UNs) and neutral voice (NV) stimuli across different vigilance stages (i.e. wakefulness as well as sleep stages N1 and N2) by means of event-related oscillatory responses during wakefulness and a subsequent afternoon nap. Our findings suggest that emotional prosody and self-relevance drew more attentional resources during wakefulness with specifically AV stimuli being processed more strongly. During N1, SONs were more arousing than UNs irrespective of prosody. Moreover, emotional and self-relevant stimuli evoked stronger responses also during N2 sleep suggesting a 'sentinel processing mode' of the brain during this state of naturally occurring unconsciousness. Finally, this initial preferential processing of salient stimuli during N2 sleep seems to be followed by an inhibitory sleep-protecting process, which is reflected by a K-complex-like response.

While it is a well-established finding that subjects' own names (SON) and familiar voices are salient during wakefulness, we here investigated processing of environmental stimuli during sleep including deep N3 and REM sleep. Besides the effects of sleep depth we investigated how sleep-specific EEG patterns (i.e. sleep spindles and slow oscillations [SOs]) relate to stimulus processing. Using 256-channel EEG we studied processing of auditory stimuli by means of event-related oscillatory responses (de-/synchronisation, ERD/ERS) and potentials (ERPs) in N = 17 healthy sleepers. We varied stimulus salience by manipulating subjective (SON vs. unfamiliar name) and paralinguistic emotional relevance (familiar vs. unfamiliar voice, FV/UFV). Results reveal that evaluation of voice familiarity continues during all NREM sleep stages and even REM sleep suggesting a 'sentinel processing mode' of the human brain in the absence of wake-like consciousness. Especially UFV stimuli elicit larger responses in a 1-15 Hz range suggesting they continue being salient. Beyond this, we find that sleep spindles and the negative slope of SOs attenuate information processing. However, unlike previously suggested they do not uniformly inhibit information processing, but inhibition seems to be scaled to stimulus salience.

Background Healthy circadian rhythmicity has been suggested to relate to a better state of brain‐injured patients and to support the emergence of consciousness in patient groups characterized by a relative instability thereof such as patients with disorders of consciousness (DOC). Methods Going beyond earlier studies, a systems‐level perspective was adopted and, using multilevel modelling, the joint predictive value of three indices of circadian rhythm integrity derived from skin temperature variations, melatoninsulfate secretion, and physical activity (wrist actigraphy) patterns was evaluated for the behaviourally assessed state [Coma Recovery Scale ‐ Revised (CRS‐R) score] of DOC patients [13 unresponsive wakefulness syndrome; seven minimally conscious (exit) state]. Additionally, it was assessed in a subset of 16 patients whether patients’ behavioural repertoire (CRS‐R score) varied (i) with time of day or (ii) offset from the body temperature maximum (BTmax), i.e. when cognitive performance is expected to peak. Results The results reveal that better integrity of circadian melatoninsulfate and temperature rhythms relate to a richer behavioural repertoire. Moreover, higher CRS‐R scores are, by trend, related to assessments taking place at a later daytime or deviating less from the pre‐specified time of occurrence of BTmax. Conclusions In conclusion, the results suggest that therapeutic approaches aimed at improving circadian rhythms in brain‐injured patients are promising and should be implemented in hospitals or nursing homes. Beyond this, it might be helpful to schedule diagnostic procedures and therapies around the (pre‐assessed) BTmax (≈4 pm in healthy individuals) as this is when patients should be most responsive.

31While it is a well-established finding that subject's own names (SON) or familiar voices are salient 32 during wakefulness, we here investigated processing of environmental stimuli during sleep including deep 33 N3 and REM sleep. Besides the effects of sleep depth we investigated how sleep-specific EEG patterns 34 (i.e. sleep spindles and slow oscillations [SOs]) relate to stimulus processing. Using 256-channel EEG we 35 studied processing of auditory stimuli by means of event-related oscillatory responses (de-/ 36 synchronisation, ERD/ERS) and potentials (ERPs) in N = 17 healthy sleepers. We varied stimulus 37 salience by manipulating subjective (SON vs. unfamiliar name) and paralinguistic emotional relevance38 (familiar vs. unfamiliar voice, FV/UFV). Results reveal that evaluation of voice familiarity continues 39 during all NREM sleep stages and even REM sleep suggesting a 'sentinel processing mode' of the human 40 brain in the absence of wake-like consciousness. Especially UFV stimuli elicit larger responses in a 1-15 41Hz range suggesting they continue being salient. Beyond this, we find that sleep spindles and the negative 42 slope of SOs attenuate information processing. However, unlike previously suggested they do not 43 uniformly inhibit information processing, but inhibition seems to be scaled to stimulus salience. 44 45 46 Keywords: sleep, sleep spindles, slow oscillations, high-density electroencephalography, auditory 47 stimulation 48 3 1. Introduction 49 Cognitive processing and task performance are well-known to vary with time of day (Dijk et al., 50 1992; Santhi et al., 2016; Wyatt et al., 1999). Behaviourally, these variations can readily be observed with 51 major changes in performance paralleling the sleep-wake cycle. Beyond these within-state studies that 52 investigated wakefulness only, we lately studied cognitive processing during the fading of consciousness, 53 which we here define as behavioural responsiveness, that is across vigilance stages from waking to light 54 NREM sleep (Blume et al., 2016). Specifically, during a nap we compared processing of subjectively 55 relevant vs. irrelevant stimuli (i.e. subject's own names [SONs] vs. unfamiliar names [UNs]) during 56 wakefulness and non-rapid eye movement (NREM) sleep stages N1 and N2. Besides subjective relevance 57 we additionally varied the emotional prosody of stimuli (i.e. stimuli spoken by an angry vs. a neutral 58 voice [AV vs. NV]). Interestingly, we found evidence for preferential processing of salient stimuli (i.e. 59SONs and AV stimuli) not only during wakefulness, but also during light NREM sleep, with these 60 findings suggesting not only continued processing of external stimuli, but a 'sentinel processing mode' of 61 the brain during states of decreased consciousness and naturally occurring unconsciousness, that is N1 62 and N2 sleep, respectively. Moreover, this initial preferential processing of salient stimuli seemed to be 63 accompanied by a subsequent inhibitory sleep-protecting process during N2 sleep that was refle...