Nightmares share genetic risk factors with sleep and psychiatric traits.

Nightmares are vivid, extended, and emotionally negative or negative dreams that awaken the dreamer. While sporadic nightmares and bad dreams are common and generally harmless, frequent nightmares often reflect underlying pathologies of emotional regulation. Indeed, insomnia, depression, anxiety, or alcohol use have been associated with nightmares in epidemiological and clinical studies. However, the connection between nightmares and their comorbidities are poorly understood. Our goal was to examine the genetic risk factors for nightmares and estimate correlation or causality between nightmares and comorbidities. We performed a genome-wide association study (GWAS) in 45,255 individuals using a questionnaire-based assessment on the frequency of nightmares during the past month and genome-wide genotyping data. While the GWAS did not reveal individual risk variants, heritability was estimated at 5%. In addition, the genetic correlation analysis showed a robust correlation (rg > 0.4) of nightmares with anxiety (rg = 0.671, p = 7.507e-06), depressive (rg = 0.562, p = 1.282e-07) and posttraumatic stress disorders (rg = 0.4083, p = 0.0152), and personality trait neuroticism (rg = 0.667, p = 4.516e-07). Furthermore, Mendelian randomization suggested causality from insomnia to nightmares (beta = 0.027, p = 0.0002). Our findings suggest that nightmares share genetic background with psychiatric traits and that insomnia may increase an individual's liability to experience frequent nightmares. Given the significant correlations with psychiatric and psychological traits, it is essential to grow awareness of how nightmares affect health and disease and systematically collect information about nightmares, especially from clinical samples and larger cohorts.

Viral simulations in dreams: The effect of the COVID-19 pandemic on threatening dream content in a Finnish sample of diary dreams.

Previous research indicates that the COVID-19 pandemic has affected dreaming negatively. We compared 1132 dreams collected with prospective two-week dream diary during the pandemic to 166 dreams collected before the pandemic. We hypothesized that the pandemic would increase the number of threatening events, threats related to diseases, and the severity of threats. We also hypothesized that dreams that include direct references to the pandemic will include more threatening events, more disease-related threats, and more severe threats. In contradiction with our hypotheses, results showed no differences between pandemic and pre-pandemic samples in the number of threats, threats related to diseases, or severe threats. However, dreams with direct references to the pandemic had more threats, disease-related threats, and severe threats. Our results thus do not suggest a significant overall increase in nightmarish or threatening dream content during the pandemic but show a more profound effect on a minority of dreams.

COVID-19 on mind: Daily worry about the coronavirus is linked to negative affect experienced during mind-wandering and dreaming.

Despite a surge of studies on the effects of COVID-19 on our well-being, we know little about how the pandemic is reflected in people's spontaneous thoughts and experiences, such as mind-wandering (or daydreaming) during wakefulness and dreaming during sleep. We investigated whether and how COVID-19-related general concern, anxiety, and daily worry are associated with the daily fluctuation of the affective quality of mind-wandering and dreaming, and to what extent these associations can be explained by poor sleep quality. We used ecological momentary assessment by asking participants to rate the affect they experienced during mind-wandering and dreaming in daily logs over a 2-week period. Our preregistered analyses based on 1,755 dream logs from 172 individuals and 1,496 mind-wandering logs from 152 individuals showed that, on days when people reported higher levels of negative affect and lower levels of positive affect during mind-wandering, they experienced more worry. Only daily sleep quality was associated with affect experienced during dreaming at the within-person level: on nights with poorer sleep quality people reported experiencing more negative and less positive affect in dreams and were more likely to experience nightmares. However, at the between-person level, individuals who experienced more daily COVID-19 worry during the study period also reported experiencing more negative affect during mind-wandering and during dreaming. As such, the continuity between daily and nightly experiences seems to rely more on stable trait-like individual differences in affective processing. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Subjective experiences during dexmedetomidine- or propofol-induced unresponsiveness and non-rapid eye movement sleep in healthy male subjects.

BACKGROUND: Anaesthetic-induced unresponsiveness and non-rapid eye movement (NREM) sleep share common neural pathways and neurophysiological features. We hypothesised that these states bear resemblance also at the experiential level. METHODS: We compared, in a within-subject design, the prevalence and content of experiences in reports obtained after anaesthetic-induced unresponsiveness and NREM sleep. Healthy males (N=39) received dexmedetomidine (n=20) or propofol (n=19) in stepwise doses to induce unresponsiveness. Those rousable were interviewed and left unstimulated, and the procedure was repeated. Finally, the anaesthetic dose was increased 50%, and the participants were interviewed after recovery. The same participants (N=37) were also later interviewed after NREM sleep awakenings. RESULTS: Most subjects were rousable, with no difference between anaesthetic agents (P=0.480). Lower drug plasma concentrations were associated with being rousable for both dexmedetomidine (P=0.007) and propofol (P=0.002) but not with recall of experiences in either drug group (dexmedetomidine: P=0.543; propofol: P=0.460). Of the 76 and 73 interviews performed after anaesthetic-induced unresponsiveness and NREM sleep, 69.7% and 64.4% included experiences, respectively. Recall did not differ between anaesthetic-induced unresponsiveness and NREM sleep (P=0.581), or between dexmedetomidine and propofol in any of the three awakening rounds (P>0.05). Disconnected dream-like experiences (62.3% vs 51.1%; P=0.418) and memory incorporation of the research setting (88.7% vs 78.7%; P=0.204) were equally often present in anaesthesia and sleep interviews, respectively, whereas awareness, signifying connected consciousness, was rarely reported in either state. CONCLUSIONS: Anaesthetic-induced unresponsiveness and NREM sleep are characterised by disconnected conscious experiences with corresponding recall frequencies and content. CLINICAL TRIAL REGISTRATION: Clinical trial registration. This study was part of a larger study registered at ClinicalTrials.gov (NCT01889004).

Decreased Thalamic Activity Is a Correlate for Disconnectedness during Anesthesia with Propofol, Dexmedetomidine and Sevoflurane But Not S-Ketamine.

Establishing the neural mechanisms responsible for the altered global states of consciousness during anesthesia and dissociating these from other drug-related effects remains a challenge in consciousness research. We investigated differences in brain activity between connectedness and disconnectedness by administering various anesthetics at concentrations designed to render 50% of the subjects unresponsive. One hundred and sixty healthy male subjects were randomized to receive either propofol (1.7 µg/ml; n = 40), dexmedetomidine (1.5 ng/ml; n = 40), sevoflurane (0.9% end-tidal; n = 40), S-ketamine (0.75 µg/ml; n = 20), or saline placebo (n = 20) for 60 min using target-controlled infusions or vaporizer with end-tidal monitoring. Disconnectedness was defined as unresponsiveness to verbal commands probed at 2.5-min intervals and unawareness of external events in a postanesthesia interview. High-resolution positron emission tomography (PET) was used to quantify regional cerebral metabolic rates of glucose (CMRglu) utilization. Contrasting scans where the subjects were classified as connected and responsive versus disconnected and unresponsive revealed that for all anesthetics, except S-ketamine, the level of thalamic activity differed between these states. A conjunction analysis across the propofol, dexmedetomidine and sevoflurane groups confirmed the thalamus as the primary structure where reduced metabolic activity was related to disconnectedness. Widespread cortical metabolic suppression was observed when these subjects, classified as either connected or disconnected, were compared with the placebo group, suggesting that these findings may represent necessary but alone insufficient mechanisms for the change in the state of consciousness.SIGNIFICANCE STATEMENT Experimental anesthesia is commonly used in the search for measures of brain function which could distinguish between global states of consciousness. However, most previous studies have not been designed to separate effects related to consciousness from other effects related to drug exposure. We employed a novel study design to disentangle these effects by exposing subjects to predefined EC50 doses of four commonly used anesthetics or saline placebo. We demonstrate that state-related effects are remarkably limited compared with the widespread cortical effects related to drug exposure. In particular, decreased thalamic activity was associated with disconnectedness with all used anesthetics except for S-ketamine.

Circulating oxylipin and bile acid profiles of dexmedetomidine, propofol, sevoflurane, and S-ketamine: a randomised controlled trial using tandem mass spectrometry.

Background: This exploratory study aimed to investigate whether dexmedetomidine, propofol, sevoflurane, and S-ketamine affect oxylipins and bile acids, which are functionally diverse molecules with possible connections to cellular bioenergetics, immune modulation, and organ protection. Methods: In this randomised, open-label, controlled, parallel group, Phase IV clinical drug trial, healthy male subjects (n=160) received equipotent doses (EC50 for verbal command) of dexmedetomidine (1.5 ng ml-1; n=40), propofol (1.7 µg ml-1; n=40), sevoflurane (0.9% end-tidal; n=40), S-ketamine (0.75 µg ml-1; n=20), or placebo (n=20). Blood samples for tandem mass spectrometry were obtained at baseline, after study drug administration at 60 and 130 min from baseline; 40 metabolites were analysed. Results: Statistically significant changes vs placebo were observed in 62.5%, 12.5%, 5.0%, and 2.5% of analytes in dexmedetomidine, propofol, sevoflurane, and S-ketamine groups, respectively. Data are presented as standard deviation score, 95% confidence interval, and P-value. Dexmedetomidine induced wide-ranging decreases in oxylipins and bile acids. Amongst others, 9,10-dihydroxyoctadecenoic acid (DiHOME) -1.19 (-1.6; -0.78), P<0.001 and 12,13-DiHOME -1.22 (-1.66; -0.77), P<0.001 were affected. Propofol elevated 9,10-DiHOME 2.29 (1.62; 2.96), P<0.001 and 12,13-DiHOME 2.13 (1.42; 2.84), P<0.001. Analytes were mostly unaffected by S-ketamine. Sevoflurane decreased tauroursodeoxycholic acid (TUDCA) -2.7 (-3.84; -1.55), P=0.015. Conclusions: Dexmedetomidine-induced oxylipin alterations may be connected to pathways associated with organ protection. In contrast to dexmedetomidine, propofol emulsion elevated DiHOMEs, oxylipins associated with acute respiratory distress syndrome, and mitochondrial dysfunction in high concentrations. Further research is needed to establish the behaviour of DIHOMEs during prolonged propofol/dexmedetomidine infusions and to verify the sevoflurane-induced reduction in TUDCA, a suggested neuroprotective agent. Clinical trial registration: NCT02624401.

Effects of dexmedetomidine, propofol, sevoflurane and S-ketamine on the human metabolome: A randomised trial using nuclear magnetic resonance spectroscopy.

BACKGROUND: Pharmacometabolomics uses large-scale data capturing methods to uncover drug-induced shifts in the metabolic profile. The specific effects of anaesthetics on the human metabolome are largely unknown. OBJECTIVE: We aimed to discover whether exposure to routinely used anaesthetics have an acute effect on the human metabolic profile. DESIGN: Randomised, open-label, controlled, parallel group, phase IV clinical drug trial. SETTING: The study was conducted at Turku PET Centre, University of Turku, Finland, 2016 to 2017. PARTICIPANTS: One hundred and sixty healthy male volunteers were recruited. The metabolomic data of 159 were evaluable. INTERVENTIONS: Volunteers were randomised to receive a 1-h exposure to equipotent doses (EC50 for verbal command) of dexmedetomidine (1.5 ng ml-1; n  = 40), propofol (1.7 µg ml-1; n  = 40), sevoflurane (0.9% end-tidal; n  = 39), S-ketamine (0.75 µg ml-1; n  = 20) or placebo (n = 20). MAIN OUTCOME MEASURES: Metabolite subgroups of apolipoproteins and lipoproteins, cholesterol, glycerides and phospholipids, fatty acids, glycolysis, amino acids, ketone bodies, creatinine and albumin and the inflammatory marker GlycA, were analysed with nuclear magnetic resonance spectroscopy from arterial blood samples collected at baseline, after anaesthetic administration and 70 min post-anaesthesia. RESULTS: All metabolite subgroups were affected. Statistically significant changes vs. placebo were observed in 11.0, 41.3, 0.65 and 3.9% of the 155 analytes in the dexmedetomidine, propofol, sevoflurane and S-ketamine groups, respectively. Dexmedetomidine increased glucose, decreased ketone bodies and affected lipoproteins and apolipoproteins. Propofol altered lipoproteins, fatty acids, glycerides and phospholipids and slightly increased inflammatory marker glycoprotein acetylation. Sevoflurane was relatively inert. S-ketamine increased glucose and lactate, whereasbranched chain amino acids and tyrosine decreased. CONCLUSION: A 1-h exposure to moderate doses of routinely used anaesthetics led to significant and characteristic alterations in the metabolic profile. Dexmedetomidine-induced alterations mirror a2-adrenoceptor agonism. Propofol emulsion altered the lipid profile. The inertness of sevoflurane might prove useful in vulnerable patients. S-ketamine induced amino acid alterations might be linked to its suggested antidepressive properties. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02624401.

'No Man is an Island': Effects of social seclusion on social dream content and REM sleep.

Based on the Social Simulation Theory of dreaming (SST), we studied the effects of voluntary social seclusion on dream content and sleep structure. Specifically, we studied the Compensation Hypothesis, which predicts social dream contents to increase during social seclusion, the Sociality Bias - a ratio between dream and wake interactions - and the Strengthening Hypothesis, which predicts an increase in familiar dream characters during seclusion. Additionally, we assessed changes in the proportion of REM sleep. Sleep data and dream reports from 18 participants were collected preceding (n = 94), during (n = 90) and after (n = 119) a seclusion retreat. Data were analysed using linear mixed-effects models. We failed to support the Compensation Hypothesis, with dreams evidencing fewer social interactions during seclusion. The Strengthening Hypothesis was supported, with more familiar characters present in seclusion dreams. Dream social interactions maintained the Sociality Bias even under seclusion. Additionally, REM sleep increased during seclusion, coinciding with previous literature and tentatively supporting the proposed attachment function for social REM sleep.

On no man's land: Subjective experiences during unresponsive and responsive sedative states induced by four different anesthetic agents.

To understand how anesthetics with different molecular mechanisms affect consciousness, we explored subjective experiences recalled after responsive and unresponsive sedation induced with equisedative doses of dexmedetomidine, propofol, sevoflurane, and S-ketamine in healthy male participants (N = 140). The anesthetics were administered in experimental setting using target-controlled infusion or vapouriser for one hour. Interviews conducted after anesthetic administration revealed that 46.9% (n = 46) of arousable participants (n = 98) reported experiences, most frequently dreaming or memory incorporation of the setting. Participants receiving dexmedetomidine reported experiences most often while S-ketamine induced the most multimodal experiences. Responsiveness at the end of anesthetic administration did not affect the prevalence or content of reported experiences. These results demonstrate that subjective experiences during responsive and unresponsive sedation are common and anesthetic agents with different molecular mechanisms of action may have different effects on the prevalence and complexity of the experiences, albeit in the present sample the differences between drugs were minute.

The dynamics of affect across the wake-sleep cycle: From waking mind-wandering to night-time dreaming.

Affective experiences occur across the wake-sleep cycle-from active wakefulness to resting wakefulness (i.e., mind-wandering) to sleep (i.e., dreaming). Yet, we know little about the dynamics of affect across these states. We compared the affective ratings of waking, mind-wandering, and dream episodes. Results showed that mind-wandering was more positively valenced than dreaming, and that both mind-wandering and dreaming were more negatively valenced than active wakefulness. We also compared participants' self-ratings of affect with external ratings of affect (i.e., analysis of affect in verbal reports). With self-ratings all episodes were predominated by positive affect. However, the affective valence of reports changed from positively valenced waking reports to affectively balanced mind-wandering reports to negatively valenced dream reports. These findings show that (1) the positivity bias characteristic to waking experiences decreases across the wake-sleep continuum, and (2) conclusions regarding affective experiences depend on whether self-ratings or verbal reports describing these experiences are analysed.

Foundations of Human Consciousness: Imaging the Twilight Zone.

What happens in the brain when conscious awareness of the surrounding world fades? We manipulated consciousness in two experiments in a group of healthy males and measured brain activity with positron emission tomography. Measurements were made during wakefulness, escalating and constant levels of two anesthetic agents (experiment 1, n = 39), and during sleep-deprived wakefulness and non-rapid eye movement sleep (experiment 2, n = 37). In experiment 1, the subjects were randomized to receive either propofol or dexmedetomidine until unresponsiveness. In both experiments, forced awakenings were applied to achieve rapid recovery from an unresponsive to a responsive state, followed by immediate and detailed interviews of subjective experiences during the preceding unresponsive condition. Unresponsiveness rarely denoted unconsciousness, as the majority of the subjects had internally generated experiences. Unresponsive anesthetic states and verified sleep stages, where a subsequent report of mental content included no signs of awareness of the surrounding world, indicated a disconnected state. Functional brain imaging comparing responsive and connected versus unresponsive and disconnected states of consciousness during constant anesthetic exposure revealed that activity of the thalamus, cingulate cortices, and angular gyri are fundamental for human consciousness. These brain structures were affected independent from the pharmacologic agent, drug concentration, and direction of change in the state of consciousness. Analogous findings were obtained when consciousness was regulated by physiological sleep. State-specific findings were distinct and separable from the overall effects of the interventions, which included widespread depression of brain activity across cortical areas. These findings identify a central core brain network critical for human consciousness.SIGNIFICANCE STATEMENT Trying to understand the biological basis of human consciousness is currently one of the greatest challenges of neuroscience. While the loss and return of consciousness regulated by anesthetic drugs and physiological sleep are used as model systems in experimental studies on consciousness, previous research results have been confounded by drug effects, by confusing behavioral "unresponsiveness" and internally generated consciousness, and by comparing brain activity levels across states that differ in several other respects than only consciousness. Here, we present carefully designed studies that overcome many previous confounders and for the first time reveal the neural mechanisms underlying human consciousness and its disconnection from behavioral responsiveness, both during anesthesia and during normal sleep, and in the same study subjects.

Nightmare Distress Questionnaire: associated factors.

STUDY OBJECTIVES: The diagnosis of a nightmare disorder is based on clinically significant distress caused by the nightmares, eg, sleep or mood disturbances during the day. The question what factors might be associated with nightmare distress in addition to nightmares frequency is not well studied. METHODS: Overall, 1,474 persons (893 women, 581 men) completed an online survey. Nightmare distress was measured with the Nightmare Distress Questionnaire. RESULTS: The findings indicated that nightmare distress, measured by the Nightmare Distress Questionnaire, correlated with a variety of factors in addition to nightmare frequency: neuroticism, female sex, low education, extraversion, low agreeableness, and sensation seeking. Moreover, the percentage of replicative trauma-related nightmares was also associated with higher nightmare distress. CONCLUSIONS: A large variety of factors are associated with nightmare distress, a finding that is of clinical importance. The construct harm avoidance, however, was not helpful in explaining interindividual differences in nightmare distress. Furthermore, the relationship between nightmare distress and other factors, eg, education or agreeableness, is not yet understood.

Dreams and nightmares in healthy adults and in patients with sleep and neurological disorders.

Dreams are experiences that occur during sleep, while we are disconnected from the environment. Thanks to recent progress in neuroimaging techniques, it is now becoming possible to relate dream features to specific patterns of brain activity. Some conditions occurring in patients with neurological disorders, such as lucid dreams and parasomnias, not only have diagnostic value, but also offer a window into the dream process. They show that dreaming is reflected in physiological signals, behaviours, and brain activity patterns, and that the body can enact dream content. Yet, the dream body can also be distinct from the real body; in their dreams, patients with congenital paraplegia can walk, those with sleep apnoea rarely suffocate, and phantom limb pain can disappear. These conditions provide valuable models for future studies investigating the mechanisms that underlie oneiric experiences.

Alpha band frontal connectivity is a state-specific electroencephalographic correlate of unresponsiveness during exposure to dexmedetomidine and propofol.

BACKGROUND: Coherent alpha electroencephalogram (EEG) rhythms in the frontal cortex have been correlated with the hypnotic effects of propofol and dexmedetomidine, but less is known about frontal connectivity as a state-specific correlate of unresponsiveness as compared with long-range connectivity. We aimed to distinguish dose- and state-dependent effects of dexmedetomidine and propofol on EEG connectivity. METHODS: Forty-seven healthy males received either dexmedetomidine (n=23) or propofol (n=24) as target-controlled infusion with stepwise increments until loss of responsiveness (LOR). We attempted to arouse participants during constant dosing (return of responsiveness [ROR]), and the target concentration was then increased 50% to achieve presumed loss of consciousness. We collected 64-channel EEG data and prefrontal-frontal and anterior-posterior functional connectivity in the alpha band (8-14 Hz) was measured using coherence and weighted phase lag index (wPLI). Directed connectivity was measured with directed phase lag index (dPLI). RESULTS: Prefrontal-frontal EEG-based connectivity discriminated the states at the different drug concentrations. At ROR, prefrontal-frontal connectivity reversed to the level observed before LOR, indicating that connectivity changes were related to unresponsiveness rather than drug concentration. Unresponsiveness was associated with emergence of frontal-to-prefrontal dominance (dPLI: -0.13 to -0.40) in contrast to baseline (dPLI: 0.01-0.02). Coherence, wPLI, and dPLI had similar capability to discriminate the states that differed in terms of responsiveness and drug concentration. In contrast, anterior-posterior connectivity in the alpha band did not differentiate LOR and ROR. CONCLUSIONS: Local prefrontal-frontal EEG-based connectivity reflects unresponsiveness induced by propofol or dexmedetomidine, suggesting its utility in monitoring the anaesthetised state with these agents. CLINICAL TRIAL REGISTRATION: NCT01889004.

The Dream Catcher experiment: blinded analyses failed to detect markers of dreaming consciousness in EEG spectral power.

The Dream Catcher test defines the criteria for a genuine discovery of the neural constituents of phenomenal consciousness. Passing the test implies that some patterns of purely brain-based data directly correspond to the subjective features of phenomenal experience, which would help to bridge the explanatory gap between consciousness and brain. Here, we conducted the Dream Catcher test for the first time in a step-wise and simplified form, capturing its core idea. The Dream Catcher experiment involved a Data Team, which measured participants' brain activity during sleep and collected dream reports, and a blinded Analysis Team, which was challenged to predict, based solely on brain measurements, whether or not a participant had a dream experience. Using a serial-awakening paradigm, the Data Team prepared 54 1-min polysomnograms of non-rapid eye movement sleep-27 of dreamful sleep and 27 of dreamless sleep (three of each condition from each of the nine participants)-redacting from them all associated participant and dream information. The Analysis Team attempted to classify each recording as either dreamless or dreamful using an unsupervised machine learning classifier, based on hypothesis-driven, extracted features of electroencephalography (EEG) spectral power and electrode location. The procedure was repeated over five iterations with a gradual removal of blindness. At no level of blindness did the Analysis Team perform significantly better than chance, suggesting that EEG spectral power could not be utilized to detect signatures specific to phenomenal consciousness in these data. This study marks the first step towards realizing the Dream Catcher test in practice.

Modulating dream experience: Noninvasive brain stimulation over the sensorimotor cortex reduces dream movement.

Recently, cortical correlates of specific dream contents have been reported, such as the activation of the sensorimotor cortex during dreamed hand clenching. Yet, despite a close resemblance of such activation patterns to those seen during the corresponding wakeful behaviour, the causal mechanisms underlying specific dream contents remain largely elusive. Here, we aimed to investigate the causal role of the sensorimotor cortex in generating movement and bodily sensations during REM sleep dreaming. Following bihemispheric transcranial direct current stimulation (tDCS) or sham stimulation, guided by functional mapping of the primary motor cortex, naive participants were awakened from REM sleep and responded to a questionnaire on bodily sensations in dreams. Electromyographic (EMG) and electroencephalographic (EEG) recordings were used to quantify physiological changes during the preceding REM period. We found that tDCS, compared to sham stimulation, significantly decreased reports of dream movement, especially of repetitive actions. Other types of bodily experiences, such as tactile or vestibular sensations, were not affected by tDCS, confirming the specificity of stimulation effects to movement sensations. In addition, tDCS reduced EEG interhemispheric coherence in parietal areas and affected the phasic EMG correlation between both arms. These findings show that a complex temporal reorganization of the motor network co-occurred with the reduction of dream movement, revealing a link between central and peripheral motor processes and movement sensations of the dream self. tDCS over the sensorimotor cortex interferes with dream movement during REM sleep, which is consistent with a causal contribution to dream experience and has broader implications for understanding the neural basis of self-experience in dreams.

The influence of dexmedetomidine and propofol on circulating cytokine levels in healthy subjects.

BACKGROUND: Surgery and diseases modify inflammatory responses and the immune system. Anesthetic agents also have effects on the human immune system but the responses they induce may be altered or masked by the surgical procedures or underlying illnesses. The aim of this study was to assess how single-drug dexmedetomidine and propofol anesthesia without any surgical intervention alter acute immunological biomarkers in healthy subjects. METHODS: Thirty-five healthy, young male subjects were anesthetized using increasing concentrations of dexmedetomidine (n = 18) or propofol (n = 17) until loss of responsiveness (LOR) was detected. The treatment allocation was randomized. Multi-parametric immunoassays for the detection of 48 cytokines, chemokines and growth factors were used. Concentrations were determined at baseline and at the highest drug concentration for each subject. RESULTS: The changes in the concentration of eotaxin (decrease after dexmedetomidine) and platelet-derived growth factor (PDGF, increase after propofol) were statistically significantly different between the groups. Significant changes were detected within both groups; the concentrations of monocyte chemotactic protein 1, chemokine ligand 27 and macrophage migration inhibitory factor were lower in both groups after the drug administration. Dexmedetomidine decreased the concentration of eotaxin, interleukin-18, interleukin-2Rα, stem cell factor, stem cell growth factor and vascular endothelial growth factor, and propofol decreased significantly the levels of hepatocyte growth factor, IFN-γ-induced protein 10 and monokine induced by IFN-γ, and increased the levels of interleukin-17, interleukin-5, interleukin-7 and PDGF. CONCLUSIONS: Dexmedetomidine seemed to have an immunosuppressive effect on the immune system whereas propofol seemed to induce mixed pro- and anti-inflammatory effects on the immune system. The choice of anesthetic agent could be relevant when treating patients with compromised immunological defense mechanisms. TRIAL REGISTRATION: Before subject enrollment, the study was registered in the European Clinical Trials database (EudraCT number 2013-001496-21, The Neural Mechanisms of Anesthesia and Human Consciousness) and in ClinicalTrials.gov (Principal Investigator: Harry Scheinin, number NCT01889004, The Neural Mechanisms of Anesthesia and Human Consciousness, Part 2, on the 23rd of June 2013).

Testing the Empathy Theory of Dreaming: The Relationships Between Dream Sharing and Trait and State Empathy.

In general, dreams are a novel but realistic simulation of waking social life, with a mixture of characters, motivations, scenarios, and positive and negative emotions. We propose that the sharing of dreams has an empathic effect on the dreamer and on significant others who hear and engage with the telling of the dream. Study 1 tests three correlations that are predicted by the theory of dream sharing and empathy: that trait empathy will be correlated with frequency of telling dreams to others, with frequency of listening to others' dreams, and with trait attitude toward dreams (ATD) (for which higher scores indicate positive attitude). 160 participants completed online the Toronto Empathy Questionnaire and the Mannheim Dream Questionnaire. Pearson partial correlations were conducted, with age and sex partialled out. Trait empathy was found to be significantly associated with the frequency of listening to the dreams of others, frequency of telling one's own dreams to others, and attitude toward dreams. Study 2 tests the effects of discussing dreams on state empathy, using an adapted version of the Shen (2010) state empathy scale, for 27 pairs of dream sharers and discussers. Dream discussion followed the stages of the Ullman (1996) dream appreciation technique. State empathy of the dream discusser toward the dream sharer was found to increase significantly as a result of the dream discussion, with a medium effect size, whereas the dream sharer had a small decrease in empathy toward the discusser. A proposed mechanism for these associations and effects is taken from the robust findings in the literature that engagement with literary fiction can induce empathy toward others. We suggest that the dream acts as a piece of fiction that can be explored by the dreamer together with other people, and can thus induce empathy about the life circumstances of the dreamer. We discuss the speculation that the story-like characteristics of adult human dreams may have been selected for in human evolution, including in sexual selection, as part of the selection for emotional intelligence, empathy, and social bonding.

Pattern matters: Snakes exhibiting triangular and diamond-shaped skin patterns modulate electrophysiological activity in human visual cortex.

The neural and perceptual mechanisms that support the efficient visual detection of snakes in humans are still not fully understood. According to the Snake Detection Theory, selection pressures posed by snakes on early primates have shaped the development of the visual system. Previous studies in humans have investigated early visual electrophysiological activity in response to snake images vs. various alternative dangerous or non-dangerous stimuli. These studies have shown that the Early Posterior Negativity (EPN) component is selectively elicited by snake or snake-like images. Recent findings yielded the complementary/alternative hypothesis that early humans (and possibly other primates) evolved an aversion especially for potentially harmful triangular shapes, such as teeth, claws or spikes. In the present study we investigated the effect of triangular and diamond-shaped patterns in snake skins on the ERP correlates of visual processing in humans. In the first experiment, we employed pictures of snakes displaying either triangular/diamond-shaped patterns or no particular pattern on their skins, and pictures of frogs as control. Participants observed a random visual presentation of these pictures. Consistent with previous studies, snakes elicited an enhanced negativity between 225 and 300 ms (EPN) compared to frogs. However, snakes featuring triangular/diamond-shaped patterns on their skin produced an enhanced EPN compared to the snakes that did not display such patterns. In a second experiment we used pictures displaying only skin patterns of snakes and frogs. Results from the second experiment confirmed the results of the first experiment, suggesting that triangular snake-skin patterns modulate the activity in human visual cortex. Taken together, our results constitute an important contribution to the snake detection theory.

Single-subject analysis of N400 event-related potential component with five different methods.

There are several different approaches to analyze event-related potentials (ERPs) at single-subject level, and the aim of the current study is to provide information for choosing a method based on its ability to detect ERP effects and factors influencing the results. We used data from 79 healthy participants with EEG referenced to mastoid average and investigated the detection rate of auditory N400 effect in single-subject analysis using five methods: visual inspection of participant-wise averaged ERPs, analysis of variance (ANOVA) for amplitude averages in a time window, cluster-based non-parametric testing, a novel Bayesian approach and Studentized continuous wavelet transform (t-CWT). Visual inspection by three independent raters yielded N400 effect detection in 85% of the participants in at least one paradigm (active responding or passive listening), whereas ANOVA identified the effect in 68%, the cluster-method in 59%, the Bayesian method in 89%, and different versions of t-CWT in 22-59% of the participants. Thus, the Bayesian method was the most liberal and also showed the greatest concordance between the experimental paradigms (active/passive). ANOVA detected significant effect only in cases with converging evidence from other methods. The t-CWT and cluster-based method were the most conservative methods. As we show in the current study, different analysis methods provide results that do not completely overlap. The method of choice for determining the presence of an ERP component at single-subject level thus remains unresolved. Relying on a single statistical method may not be sufficient for drawing conclusions on single-subject ERPs.