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Abstract: Objective: Abnormal perceptions and cognitions in schizophrenia might be related to abnormal resting states of the brain. Previous research found that a specific class (class D) of sub-second electroencephalography (EEG) microstates was shortened in schizophrenia. This shortening correlated with positive symptoms. We questioned if this reflected positive psychotic traits or present psychopathology. Methods: Resting-state EEGs of frequently hallucinating patients, indicating on- and offset of hallucinations by button press, were analyzed. Microstate class D duration was related to spontaneous within-subject fluctuations of auditory hallucinations. Results: Microstate D was significantly shorter in periods with hallucinations. Conclusions: Microstates of class D resemble topographies associated with error monitoring. Its premature termination may facilitate the misattribution of self-generated inner speech to external sources during hallucinations. Significance: These results suggest that microstate D represents a biological state marker for hallucinatory experiences. [Copyright &y& Elsevier]

Abstract: Phase locking or synchronization of brain areas is a key concept of information processing in the brain. Synchronous oscillations have been observed and investigated extensively in EEG during the past decades. EEG oscillations occur over a wide frequency range. In EEG, a prominent type of oscillations is alpha-band activity, present typically when a subject is awake, but at rest with closed eyes. The spectral power of alpha rhythms has recently been investigated in simultaneous EEG/fMRI recordings, establishing a wide-range cortico-thalamic network. However, spectral power and synchronization are different measures and little is known about the correlations between BOLD effects and EEG synchronization. Interestingly, the fMRI BOLD signal also displays synchronous oscillations across different brain regions. These oscillations delineate so-called resting state networks (RSNs) that resemble the correlation patterns of simultaneous EEG/fMRI recordings. However, the nature of these BOLD oscillations and their relations to EEG activity is still poorly understood. One hypothesis is that the subunits constituting a specific RSN may be coordinated by different EEG rhythms. In this study we report on evidence for this hypothesis. The BOLD correlates of global EEG synchronization (GFS) in the alpha frequency band are located in brain areas involved in specific RSNs, e.g. the ‘default mode network’. Furthermore, our results confirm the hypothesis that specific RSNs are organized by long-range synchronization at least in the alpha frequency band. Finally, we could localize specific areas where the GFS BOLD correlates and the associated RSN overlap. Thus, we claim that not only the spectral dynamics of EEG are important, but also their spatio-temporal organization. [Copyright &y& Elsevier]

Abnormalities of resting state EEG, both in time and frequency domains, were consistently reported in subjects with schizophrenia (SCZ) [2]. B Methods: b Our sample, recruited at five research sites as part of the add-on EEG study of the Italian Network for Research on Psychoses, consisted of 113 SCZ and 57 HC. Illness-related and functioning-related variables were measured at baseline in the whole group of SCZ, and after four-year follow-up in 61 SCZ. [Extracted from the article]

Abstract: Event-related potentials (ERPs) were used to trace changes in brain activity related to progress in second language learning. Twelve English-speaking exchange students learning German in Switzerland were recruited. ERPs to visually presented single words from the subjects'' native language (English), second language (German) and an unknown language (Romansh) were measured before (day 1) and after (day 2) 5 months of intense German language learning. When comparing ERPs to German words from day 1 and day 2, we found topographic differences between 396 and 540 ms. These differences could be interpreted as a latency shift indicating faster processing of German words on day 2. Source analysis indicated that the topographic differences were accounted for by shorter activation of left inferior frontal gyrus (IFG) on day 2. In ERPs to English words, we found Global Field Power differences between 472 and 644 ms. This may due to memory traces related to English words being less easily activated on day 2. Alternatively, it might reflect the fact that – with German words becoming familiar on day 2 – English words loose their oddball character and thus produce a weaker P300-like effect on day 2. In ERPs to Romansh words, no differences were observed. Our results reflect plasticity in the neuronal networks underlying second language acquisition. They indicate that with a higher level of second language proficiency, second language word processing is faster and requires shorter frontal activation. Thus, our results suggest that the reduced IFG activation found in previous fMRI studies might not reflect a generally lower activation but rather a shorter duration of activity. [Copyright &y& Elsevier]

Objective: In young, first-episode, never-treated schizophrenics compared with controls, (a) generally shorter durations of EEG microstates were reported (Koukkou et al., Brain Topogr 6 (1994) 251; Kinoshita et al., Psychiatry Res Neuroimaging 83 (1998) 58), and (b) specifically, shorter duration of a particular class of microstates (Koenig et al., Eur Arch Psychiatry Clin Neurosci 249 (1999) 205). We now examined whether older, chronic schizophrenic patients with positive symptomatology also show these characteristics.Methods: Multichannel resting EEG (62.2 s/subject) from two subject groups, 14 patients (36.1±10.2 years old) and 13 controls (35.1±8.2 years old), all males, was analyzed into microstates using a global approach for microstate analysis that clustered the microstates into 4 classes (Koenig et al., 1999).Results: (a) Hypothesis testing of general microstate shortening supported a trend (P=0.064). (b) Two-way repeated measure ANOVA (two subject groups×4 microstate classes) showed a significant group effect for microstate duration. Posthoc tests revealed that a microstate class with brain electric field orientation from left central to right central-posterior had significantly shorter microstates in patients than controls (68.5 vs. 76.1 ms, P=0.034).Conclusions: The results were in line with the results from young, never-treated, productive patients, thus suggesting that in schizophrenic information processing, one class of mental operations might intermittently cause deviant mental constructs because of premature termination of processing. [Copyright &y& Elsevier]

Purpose: The number of patients with childhood cancer (CC) in sub-Saharan Africa is expected to rise over the coming years. According to the WHO Initiative for Childhood Cancer, access to care is crucial and must be guided by the needs of patients and their families. Our study explored barriers to CC treatment from a patient's perspective to guide the health care providers., Methods: From February to September 2021, we conducted a multinational cross-sectional study with a sample from nine population-based cancer registries in nine sub-Saharan countries. Inclusion criteria comprised a cancer diagnosis according to the International Classification of Childhood Cancer, age 0-19 years, and year of diagnosis 2017-2019. A questionnaire was administered asking families about self-perceived barriers accessing surgery, radiotherapy, and chemotherapy. To assess associated factors, we conducted a multivariable regression analysis presenting the results as odds ratios (ORs)., Results: A total of 224 patients with CC was included. The fear of treatment effects and the perceived (poor) health of the child were named most frequently as barriers for all treatment modalities (78.9% and 75.5%, respectively). For chemotherapy, respondents who indicated themselves as rich had lower odds of perceiving the (poor) health of the child as a barrier (OR, 0.06 [95% CI, 0.01 to 0.36]). For radiotherapy, long waiting time and (limited) availability in the country were more commonly barriers (OR, 7.53 [95% CI, 3.38 to 16.78]; OR, 11.11 [95% CI, 2.04 to 60.46], respectively) than for chemotherapy., Conclusion: Despite known barriers such as the availability of therapy, our study additionally indicates the importance of the patients' and families' perceptions of the disease and its treatment. Further expanding measures of social support for affected families should be regarded as one of the main pillars to assure access to care.

Monitoring the reality status of conscious experience is essential for a human being to interact successfully with the external world. Despite its importance for everyday functioning, reality monitoring can systematically become erroneous, for example, while dreaming or during hallucinatory experiences. To investigate brain processes associated with reality monitoring occurring online during an experience, i.e., perceptual reality monitoring, we assessed EEG microstates in healthy, young participants. In a within-subjects design, we compared the experience of reality when being confronted with dream-like bizarre elements versus realistic elements in an otherwise highly naturalistic real-world scenario in immersive virtual reality. Dream-like bizarreness induced changes in the subjective experience of reality and bizarreness, and led to an increase in the contribution of a specific microstate labelled C'. Microstate C' was related to the suspension of disbelief, i.e. the suppression of bizarre mismatches. Together with the functional interpretation of microstate C' as reported by previous studies, the findings of this study point to the importance of prefrontal meta-conscious control processes in perceptual reality monitoring., (© 2024 The Author(s). European Journal of Neuroscience published by Federation of European Neuroscience Societies and John Wiley & Sons Ltd.)

Purpose: This study presents a novel and comprehensive framework for evaluating magnetic resonance guided radiotherapy (MRgRT) workflow by integrating the Failure Modes and Effects Analysis (FMEA) approach with Time-Driven Activity-Based Costing (TDABC). We assess the workflow for safety, quality, and economic implications, providing a holistic understanding of the MRgRT implementation. The aim is to offer valuable insights to healthcare practitioners and administrators, facilitating informed decision-making regarding the 0.35T MRIdian MR-Linac system's clinical workflow., Methods: For FMEA, a multidisciplinary team followed the TG-100 methodology to assess the MRgRT workflow's potential failure modes. Following the mitigation of primary failure modes and workflow optimization, a treatment process was established for TDABC analysis. The TDABC was applied to both MRgRT and computed tomography guided RT (CTgRT) for typical five-fraction stereotactic body RT (SBRT) treatments, assessing total workflow and costs associated between the two treatment workflows., Results: A total of 279 failure modes were identified, with 31 categorized as high-risk, 55 as medium-risk, and the rest as low-risk. The top 20% risk priority numbers (RPN) were determined for each radiation oncology care team member. Total MRgRT and CTgRT costs were assessed. Implementing technological advancements, such as real-time multi leaf collimator (MLC) tracking with volumetric modulated arc therapy (VMAT), auto-segmentation, and increasing the Linac dose rate, led to significant cost savings for MRgRT., Conclusion: In this study, we integrated FMEA with TDABC to comprehensively evaluate the workflow and the associated costs of MRgRT compared to conventional CTgRT for five-fraction SBRT treatments. FMEA analysis identified critical failure modes, offering insights to enhance patient safety. TDABC analysis revealed that while MRgRT provides unique advantages, it may involve higher costs. Our findings underscore the importance of exploring cost-effective strategies and key technological advancements to ensure the widespread adoption and financial sustainability of MRgRT in clinical practice., (© 2024 The Author(s). Journal of Applied Clinical Medical Physics is published by Wiley Periodicals, Inc. on behalf of The American Association of Physicists in Medicine.)

Microstate analysis is a multivariate method that enables investigations of the temporal dynamics of large-scale neural networks in EEG recordings of human brain activity. To meet the enormously increasing interest in this approach, we provide a thoroughly updated version of the first open source EEGLAB toolbox for the standardized identification, visualization, and quantification of microstates in resting-state EEG data. The toolbox allows scientists to (i) identify individual, mean, and grand mean microstate maps using topographical clustering approaches, (ii) check data quality and detect outlier maps, (iii) visualize, sort, and label individual, mean, and grand mean microstate maps according to published maps, (iv) compare topographical similarities of group and grand mean microstate maps and quantify shared variances, (v) obtain the temporal dynamics of the microstate classes in individual EEGs, (vi) export quantifications of these temporal dynamics of the microstates for statistical tests, and finally, (vii) test for topographical differences between groups and conditions using topographic analysis of variance (TANOVA). Here, we introduce the toolbox in a step-by-step tutorial, using a sample dataset of 34 resting-state EEG recordings that are publicly available to follow along with this tutorial. The goals of this manuscript are (a) to provide a standardized, freely available toolbox for resting-state microstate analysis to the scientific community, (b) to allow researchers to use best practices for microstate analysis by following a step-by-step tutorial, and (c) to improve the methodological standards of microstate research by providing previously unavailable functions and recommendations on critical decisions required in microstate analyses., (© 2023. The Author(s).)

Developing motor and cognitive skills is needed to achieve expert (motor) performance or functional recovery from a neurological condition, e.g., after stroke. While extensive practice plays an essential role in the acquisition of good motor performance, it is still unknown whether certain person-specific traits may predetermine the rate of motor learning. In particular, learners' functional brain organisation might play an important role in appropriately performing motor tasks. In this paper, we aimed to study how two critical cognitive brain networks-the Attention Network (AN) and the Default Mode Network (DMN)-affect the posterior motor performance in a complex visuomotor task: virtual surfing. We hypothesised that the preactivation of the AN would affect how participants divert their attention towards external stimuli, resulting in robust motor performance. Conversely, the excessive involvement of the DMN-linked to internally diverted attention and mind-wandering-would be detrimental for posterior motor performance. We extracted seven widely accepted microstates-representing participants mind states at rest-out of the Electroencephalography (EEG) resting-state recordings of 36 healthy volunteers, prior to execution of the virtual surfing task. By correlating neural biomarkers (microstates) and motor behavioural metrics, we confirmed that the preactivation of the posterior DMN was correlated with poor posterior performance in the motor task. However, we only found a non-significant association between AN preactivation and the posterior motor performance. In this EEG study, we propose the preactivation of the posterior DMN-imaged using EEG microstates-as a neural trait related to poor posterior motor performance. Our findings suggest that the role of the executive control system is to preserve an homeostasis between the AN and the DMN. Therefore, neurofeedback-based downregulation of DMN preactivation could help optimise motor training., (© 2022. The Author(s).)

The current study aimed to investigate alterations of event-related potentials (ERPs) microstate during reward anticipation in subjects with schizophrenia (SCZ), and their association with hedonic experience and negative symptoms. EEG data were recorded in thirty SCZ and twenty-three healthy controls (HC) during the monetary incentive delay task in which reward, loss and neutral cues were presented. Microstate analysis and standardized low-resolution electromagnetic tomography (sLORETA) were applied to EEG data. Furthermore, analyses correlating a topographic index (the ERPs score), calculated to quantify brain activation in relationship to the microstate maps, and scales assessing hedonic experience and negative symptoms were performed. Alterations in the first (125.0-187.5 ms) and second (261.7-414.1 ms) anticipatory cue-related microstate classes were observed. In SCZ, reward cues were associated to shorter duration and earlier offset of the first microstate class as compared to the neutral condition. In the second microstate class, the area under the curve was smaller for both reward and loss anticipation cues in SCZ as compared to HC. Furthermore, significant correlations between ERPs scores and the anticipation of pleasure scores were detected, while no significant association was found with negative symptoms. sLORETA analysis showed that hypo-activation of the cingulate cortex, insula, orbitofrontal and parietal cortex was detected in SCZ as compared to HC. Abnormalities in ERPs could be traced already during the early stages of reward processing and were associated with the anticipation of pleasure, suggesting that these dysfunctions might impair effective evaluation of incoming pleasant experiences. Negative symptoms and anhedonia are partially independent results., (© 2023. The Author(s).)

Background: Most breastfeeding individuals take at least one prescription drug, yet limited data from lactation studies are available to inform the safety of these drugs during breastfeeding. As a result, healthcare providers (HCPs) rely on available information about safety of drugs used during pregnancy or on personal experiences to inform prescribing/counseling decisions for breastfeeding individuals. To improve risk communication regarding drugs used during lactation, the U.S. Food and Drug Administration published the Pregnancy and Lactation Labeling Rule (PLLR) in 2015, which added a narrative summary of available risk information to the lactation section of Prescribing Information (PI). Prior studies on labeling in PLLR format revealed that although HCPs found these details valuable, they regarded the narrative as too long to support decision-making during patient encounters., Objective: This qualitative study's objective was to assess the utility of adding a concise summary to the Lactation subsection of PI to complement the narrative and succinctly communicate to busy HCPs a drug's risks when used during lactation. The concise summary consisted of a bolded headline, bulleted descriptions of available study findings and potential adverse reactions, and recommendations for risk mitigation., Methods: Twenty-five online focus groups were conducted with five segments of HCPs to obtain their feedback on the concise summary and discuss their prescribing/counseling decisions for four fictitious prescription drugs including one vaccine., Results: HCPs utilized the concise summary to make initial prescribing/counseling decisions. Many also used the labeling narrative for a comprehensive benefit-risk assessment., Conclusion: The findings indicate a need to continue to improve communication about safety of drugs used during lactation, and that the concise summary may help facilitate this communication. The study also highlights the need to educate HCPs about PI limitations when clinical data are lacking and the need to encourage clinical studies to be conducted to support actionable recommendations about use of prescription drugs during lactation., (Published by Elsevier Inc.)

EEG microstates are brief, recurring periods of stable brain activity that reflect the activation of large-scale neural networks. The temporal characteristics of these microstates, including their average duration, number of occurrences, and percentage contribution have been shown to serve as biomarkers of mental and neurological disorders. However, little is known about how microstate characteristics of prototypical network types relate to each other. Normative intercorrelations among these parameters are necessary to help researchers better understand the functions and interactions of underlying networks, interpret and relate results, and generate new hypotheses. Here, we present a systematic analysis of intercorrelations between EEG microstate characteristics in a large sample representative of western working populations (n = 583). Notably, we find that microstate duration is a general characteristic that varies across microstate types. Further, microstate A and B show mutual reinforcement, indicating a relationship between auditory and visual sensory processing at rest. Microstate C appears to play a special role, as it is associated with longer durations of all other microstate types and increased global field power, suggesting a relationship of these parameters with the anterior default mode network. All findings could be confirmed using independent EEG recordings from a retest-session (n = 542)., (© 2023. The Author(s).)

Consciousness always requires some representational content; that is, one can only be conscious about something. However, the presence of conscious experience (awareness) alone does not determine whether its content is in line with the external and physical world. Dreams, apart from certain forms of hallucinations, typically consist of non-veridical percepts, which are not recognized as false, but rather considered real. This type of experiences have been described as a state of dissociation between phenomenal and reflective awareness. Interestingly, during the transition to sleep, reflective awareness seems to break down before phenomenal awareness as conscious experience does not immediately fade with reduced wakefulness but is rather characterized by the occurrence of uncontrolled thinking and perceptual images, together with a reduced ability to recognize the internal origin of the experience. Relative deactivation of the frontoparietal and preserved activity in parieto-occipital networks has been suggested to account for dream-like experiences during the transition to sleep. We tested this hypothesis by investigating subjective reports of conscious experience and large-scale brain networks using EEG microstates in 45 healthy young subjects during the transition to sleep. We observed an inverse relationship between cognitive effects and physiological activation; dream-like experiences were associated with an increased presence of a microstate with sources in the superior and middle frontal gyrus and precuneus. Additionally, the presence of a microstate associated with higher-order visual areas was decreased. The observed inverse relationship might therefore indicate a disengagement of cognitive control systems that is mediated by specific, inhibitory EEG microstates., (© 2022. The Author(s).)

Over the last decade, EEG resting-state microstate analysis has evolved from a niche existence to a widely used and well-accepted methodology. The rapidly increasing body of empirical findings started to yield overarching patterns of associations of biological and psychological states and traits with specific microstate classes. However, currently, this cross-referencing among apparently similar microstate classes of different studies is typically done by "eyeballing" of printed template maps by the individual authors, lacking a systematic procedure. To improve the reliability and validity of future findings, we present a tool to systematically collect the actual data of template maps from as many published studies as possible and present them in their entirety as a matrix of spatial similarity. The tool also allows importing novel template maps and systematically extracting the findings associated with specific microstate maps from ongoing or published studies. The tool also allows importing novel template maps and systematically extracting the findings associated with specific microstate maps in the literature. The analysis of 40 included sets of template maps indicated that: (i) there is a high degree of similarity of template maps across studies, (ii) similar template maps were associated with converging empirical findings, and (iii) representative meta-microstates can be extracted from the individual studies. We hope that this tool will be useful in coming to a more comprehensive, objective, and overarching representation of microstate findings., (© 2023. The Author(s).)

EEG microstates represent functional brain networks observable in resting EEG recordings that remain stable for 40-120ms before rapidly switching into another network. It is assumed that microstate characteristics (i.e., durations, occurrences, percentage coverage, and transitions) may serve as neural markers of mental and neurological disorders and psychosocial traits. However, robust data on their retest-reliability are needed to provide the basis for this assumption. Furthermore, researchers currently use different methodological approaches that need to be compared regarding their consistency and suitability to produce reliable results. Based on an extensive dataset largely representative of western societies (2 days with two resting EEG measures each; day one: n = 583; day two: n = 542) we found good to excellent short-term retest-reliability of microstate durations, occurrences, and coverages (average ICCs = 0.874-0.920). There was good overall long-term retest-reliability of these microstate characteristics (average ICCs = 0.671-0.852), even when the interval between measures was longer than half a year, supporting the longstanding notion that microstate durations, occurrences, and coverages represent stable neural traits. Findings were robust across different EEG systems (64 vs. 30 electrodes), recording lengths (3 vs. 2 min), and cognitive states (before vs. after experiment). However, we found poor retest-reliability of transitions. There was good to excellent consistency of microstate characteristics across clustering procedures (except for transitions), and both procedures produced reliable results. Grand-mean fitting yielded more reliable results compared to individual fitting. Overall, these findings provide robust evidence for the reliability of the microstate approach., (© 2023. The Author(s).)

Electroencephalography (EEG) microstates are short successive periods of stable scalp field potentials representing spontaneous activation of brain resting-state networks. EEG microstates are assumed to mediate local activity patterns. To test this hypothesis, we correlated momentary global EEG microstate dynamics with the local temporo-spectral evolution of electrocorticography (ECoG) and stereotactic EEG (SEEG) depth electrode recordings. We hypothesized that these correlations involve the gamma band. We also hypothesized that the anatomical locations of these correlations would converge with those of previous studies using either combined functional magnetic resonance imaging (fMRI)-EEG or EEG source localization. We analyzed resting-state data (5 min) of simultaneous noninvasive scalp EEG and invasive ECoG and SEEG recordings of two participants. Data were recorded during the presurgical evaluation of pharmacoresistant epilepsy using subdural and intracranial electrodes. After standard preprocessing, we fitted a set of normative microstate template maps to the scalp EEG data. Using covariance mapping with EEG microstate timelines and ECoG/SEEG temporo-spectral evolutions as inputs, we identified systematic changes in the activation of ECoG/SEEG local field potentials in different frequency bands (theta, alpha, beta, and high-gamma) based on the presence of particular microstate classes. We found significant covariation of ECoG/SEEG spectral amplitudes with microstate timelines in all four frequency bands (p = 0.001, permutation test). The covariance patterns of the ECoG/SEEG electrodes during the different microstates of both participants were similar. To our knowledge, this is the first study to demonstrate distinct activation/deactivation patterns of frequency-domain ECoG local field potentials associated with simultaneous EEG microstates., (© 2023. The Author(s).)

The first Stakeholder Network Meeting of the EU Horizon 2020-funded ONTOX project was held on 13-14 March 2023, in Brussels, Belgium. The discussion centred around identifying specific challenges, barriers and drivers in relation to the implementation of non-animal new approach methodologies (NAMs) and probabilistic risk assessment (PRA), in order to help address the issues and rank them according to their associated level of difficulty. ONTOX aims to advance the assessment of chemical risk to humans, without the use of animal testing, by developing non-animal NAMs and PRA in line with 21st century toxicity testing principles. Stakeholder groups (regulatory authorities, companies, academia, non-governmental organisations) were identified and invited to participate in a meeting and a survey, by which their current position in relation to the implementation of NAMs and PRA was ascertained, as well as specific challenges and drivers highlighted. The survey analysis revealed areas of agreement and disagreement among stakeholders on topics such as capacity building, sustainability, regulatory acceptance, validation of adverse outcome pathways, acceptance of artificial intelligence (AI) in risk assessment, and guaranteeing consumer safety. The stakeholder network meeting resulted in the identification of barriers, drivers and specific challenges that need to be addressed. Breakout groups discussed topics such as hazard versus risk assessment, future reliance on AI and machine learning, regulatory requirements for industry and sustainability of the ONTOX Hub platform. The outputs from these discussions provided insights for overcoming barriers and leveraging drivers for implementing NAMs and PRA. It was concluded that there is a continued need for stakeholder engagement, including the organisation of a 'hackathon' to tackle challenges, to ensure the successful implementation of NAMs and PRA in chemical risk assessment.

A growing body of clinical and cognitive neuroscience studies have adapted a broadband EEG microstate approach to evaluate the electrical activity of large-scale cortical networks. However, the functional aspects of these microstates have not yet been systematically reviewed. Here, we present an overview of the existing literature and systematize the results to provide hints on the functional role of electrical brain microstates. Studies that evaluated and manipulated the temporal properties of resting-state microstates and utilized questionnaires, task-initiated thoughts, specific tasks before or between EEG session(s), pharmacological interventions, neuromodulation approaches, or localized sources of the extracted microstates were selected. Fifty studies that met the inclusion criteria were included. A new microstate labeling system has been proposed for a comprehensible comparison between the studies, where four classical microstates are referred to as A-D, and the others are labeled by the frequency of their appearance. Microstate A was associated with both auditory and visual processing and links to subjects' arousal/arousability. Microstate B showed associations with visual processing related to self, self-visualization, and autobiographical memory. Microstate C was related to processing personally significant information, self-reflection, and self-referential internal mentation rather than autonomic information processing. In contrast, microstate E was related to processing interoceptive and emotional information and to the salience network. Microstate D was associated with executive functioning. Microstate F is suggested to be a part of the Default Mode Network and plays a role in personally significant information processing, mental simulations, and theory of mind. Microstate G is potentially linked to the somatosensory network., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The sense of agency (SoA) is central to human experience. The comparator model, contrasting sensory prediction and action feedback, is influential but limited in explaining SoA. We investigated mechanisms beyond the comparator model, focusing on the processing of unpredictable stimuli, perimotor components of SoA, and their relation to schizotypy. ERPs were recorded from 18 healthy participants engaged in button-pressing tasks while perceiving tones with varying causal relationships with their actions. We investigated the processing of non-causally related tones, contrasted this to causally related tones, and examined perimotor correlates of subjective expectancy and experience of agency. We confirmed N100 attenuation for self-generated stimuli but found similar effects for expectancy-dependent processing of random tones. SoA also correlated with perimotor ERP components, modulated by schizotypy. Thus, neural processes preceding actions contribute to the formation of SoA and are associated with schizotypy. Unpredictable events also undergo sensory attenuation, implying additional mechanisms contributing to SoA., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

The neural underpinnings of selfhood encompass pre-reflective and reflective self-experience. The former refers to a basic, immediate experience of being a self, while the latter involves cognition and introspection. Although neural correlates of reflective self-experience have been studied, the pre-reflective remains underinvestigated. This research aims to bridge this gap by comparatively investigating ERP correlates of reading first- vs. third-person pronouns - approximating pre-reflective self-experience - and self- vs. other-related adjectives - approximating reflective self-experience - in 30 healthy participants. We found differential neural engagement between pre-reflective and reflective self-experience at 254-310 ms post-stimulus onset. Source estimation suggested that our sensor-level results could be plausibly explained by the involvement of cortical midline structures and default mode network in the general sense of self but selective recruitment of anterior cingulate and top-down dorsal attention network in the pre-reflective self. These findings offer a deeper understanding of the experiential self, especially pre-reflective, providing a foundation for investigating self-disorders., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Resting-state electroencephalography (EEG) microstates are brief periods (60-120 ms) of quasi-stable scalp field potentials, indicating simultaneous activity of large-scale networks. Microstates are assumed to reflect basic neuronal information processing. A common finding in psychosis spectrum disorders is that microstates classes C and D are altered. Whereas evidence in adults with schizophrenia is substantial, little is known about effects in underage patients, particularly in those at clinical high risk for psychosis (CHR) and first-episode psychosis (FEP). The present study used 74-channel EEG to investigate microstate effects in a large sample of patients with CHR (n = 100) and FEP (n = 33), clinical controls (CC, n = 18), as well as age-matched healthy controls (HC, n = 68). Subjects span an age range from 9 to 35 years, thus, covering underage patients as well as the most vulnerable period for the emergence of psychosis and its prodrome. Four EEG microstates classes were analyzed (A-D). In class D, CHR and FEP patients showed a decrease compared to HC, and CHR patients also to CC. An increase in class C was found in CHR and FEP compared to HC but not to CC. Results were independent of age and no differences were found between the psychosis spectrum groups. The findings suggest an age-independent decrease of microstate class D to be specific to the psychosis spectrum, whereas the increase in class C seems to reflect unspecific psychopathology. Overall, present data strengthens the role of microstate D as potential biomarker for psychosis, as early as in adolescence and already in CHR status., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

The recent developments in genomic sequencing have permitted the publication of many new complete genome sequences of Treponema pallidum pallidum , the bacterium responsible for syphilis, which has led to a new understanding of its phylogeny and diversity. However, few archived samples are available, because of the degradability of the bacterium and the difficulties in preservation. We present a complete genome obtained from a Formalin-Fixed Paraffin-Embedded (FFPE) organ sample from 1947, kept at the Strasbourg Faculty of Medicine. This is the preliminary, proof-of concept study of this collection/biobank of more than 1.5 million FFPE samples and the evaluation of the feasibility of genomic analyses. We demonstrate here that even degraded DNA from fragile bacteria can be recovered from 75-year-old FFPE samples and therefore propose that such collections as this one can function as sources of biological material for genetic studies of pathogens, cancer, or even the historical human population itself., Competing Interests: The authors declare no competing interests., (© 2023 The Author(s).)

Background: Sleep and neurodegeneration are assumed to be locked in a bi-directional vicious cycle. Improving sleep could break this cycle and help to prevent neurodegeneration. We tested multi-night phase-locked acoustic stimulation (PLAS) during slow wave sleep (SWS) as a non-invasive method to improve SWS, memory performance and plasma amyloid levels., Methods: 32 healthy older adults (agemean: 68.9) completed a between-subject sham-controlled three-night intervention, preceded by a sham-PLAS baseline night., Results: PLAS induced increases in sleep-associated spectral-power bands as well as a 24% increase in slow wave-coupled spindles, known to support memory consolidation. There was no significant group-difference in memory performance or amyloid-beta between the intervention and control group. However, the magnitude of PLAS-induced physiological responses were associated with memory performance up to 3 months post intervention and beneficial changes in plasma amyloid. Results were exclusive to the intervention group., Discussion: Multi-night PLAS is associated with long-lasting benefits in memory and metabolite clearance in older adults, rendering PLAS a promising tool to build upon and develop long-term protocols for the prevention of cognitive decline., (© The Author(s) 2023. Published by Oxford University Press on behalf of the British Geriatrics Society. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Postoperative delirium is a serious sequela of surgery and surgery-related anaesthesia. One recommended method to prevent postoperative delirium is using bi-frontal EEG recording. The single, processed index of depth of anaesthesia allows the anaesthetist to avoid episodes of suppression EEG and excessively deep anaesthesia. The study data presented here were based on multichannel (19 channels) EEG recordings during anaesthesia. This enabled the analysis of various parameters of global electrical brain activity. These parameters were used to compare microstate topographies under anaesthesia with those in healthy volunteers and to analyse changes in microstate quantifiers and EEG global state space descriptors with increasing exposure to anaesthesia. Seventy-three patients from the Surgery Depth of Anaesthesia and Cognitive Outcome study (SRCTN 36437985) received intraoperative multichannel EEG recordings. Altogether, 720 min of artefact-free EEG data, including 210 min (29.2%) of suppression EEG, were analysed. EEG microstate topographies, microstate quantifiers (duration, frequency of occurrence and global field power) and the state space descriptors sigma (overall EEG power), phi (generalized frequency) and omega (number of uncorrelated brain processes) were evaluated as a function of duration of exposure to anaesthesia, suppression EEG and subsequent development of postoperative delirium. The major analyses involved covariate-adjusted linear mixed-effects models. The older (71 ± 7 years), predominantly male (60%) patients received a median exposure of 210 (range: 75-675) min of anaesthesia. During seven postoperative days, 21 patients (29%) developed postoperative delirium. Microstate topographies under anaesthesia resembled topographies from healthy and much younger awake persons. With increasing duration of exposure to anaesthesia, single microstate quantifiers progressed differently in suppression or non-suppression EEG and in patients with or without subsequent postoperative delirium. The most pronounced changes occurred during enduring suppression EEG in patients with subsequent postoperative delirium: duration and frequency of occurrence of microstates C and D progressed in opposite directions, and the state space descriptors showed a pattern of declining uncorrelated brain processes (omega) combined with increasing EEG variance (sigma). With increasing exposure to general anaesthesia, multiple changes in the dynamics of microstates and global EEG parameters occurred. These changes varied partly between suppression and non-suppression EEG and between patients with or without subsequent postoperative delirium. Ongoing suppression EEG in patients with subsequent postoperative delirium was associated with reduced network complexity in combination with increased overall EEG power. Additionally, marked changes in quantifiers in microstate C and in microstate D occurred. These putatively adverse intraoperative trajectories in global electrical brain activity may be seen as preceding and ultimately predicting postoperative delirium., Competing Interests: The authors report no competing interests., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Guarantors of Brain.)

Background: Vascular diseases are often treated minimally invasively. The interventional material (stents, guidewires, etc.) used during such percutaneous interventions are visualized by some form of image guidance. Today, this image guidance is usually provided by 2D X-ray fluoroscopy, that is, a live 2D image. 3D X-ray fluoroscopy, that is, a live 3D image, could accelerate existing and enable new interventions. However, existing algorithms for the 3D reconstruction of interventional material require either too many X-ray projections and therefore dose, or are only capable of reconstructing single, curvilinear structures., Purpose: Using only two new X-ray projections per 3D reconstruction, we aim to reconstruct more complex arrangements of interventional material than was previously possible., Methods: This is achieved by improving a previously presented deep learning-based reconstruction pipeline, which assumes that the X-ray images are acquired by a continuously rotating biplane system, in two ways: (a) separation of the reconstruction of different object types, (b) motion compensation using spatial transformer networks., Results: Our pipeline achieves submillimeter accuracy on measured data of a stent and two guidewires inside an anthropomorphic phantom with respiratory motion. In an ablation study, we find that the aforementioned algorithmic changes improve our two figures of merit by 75 % (1.76 mm → 0.44 mm) and 59 % (1.15 mm → 0.47 mm) respectively. A comparison of our measured dose area product (DAP) rate to DAP rates of 2D fluoroscopy indicates a roughly similar dose burden., Conclusions: This dose efficiency combined with the ability to reconstruct complex arrangements of interventional material makes the presented algorithm a promising candidate to enable 3D fluoroscopy., (© 2023 The Authors. Medical Physics published by Wiley Periodicals LLC on behalf of American Association of Physicists in Medicine.)

This report reviews the image acquisition and reconstruction characteristics of C-arm Cone Beam Computed Tomography (C-arm CBCT) systems and provides guidance on quality control of C-arm systems with this volumetric imaging capability. The concepts of 3D image reconstruction, geometric calibration, image quality, and dosimetry covered in this report are also pertinent to CBCT for Image-Guided Radiation Therapy (IGRT). However, IGRT systems introduce a number of additional considerations, such as geometric alignment of the imaging at treatment isocenter, which are beyond the scope of the charge to the task group and the report. Section 1 provides an introduction to C-arm CBCT systems and reviews a variety of clinical applications. Section 2 briefly presents nomenclature specific or unique to these systems. A short review of C-arm fluoroscopy quality control (QC) in relation to 3D C-arm imaging is given in Section 3. Section 4 discusses system calibration, including geometric calibration and uniformity calibration. A review of the unique approaches and challenges to 3D reconstruction of data sets acquired by C-arm CBCT systems is give in Section 5. Sections 6 and 7 go in greater depth to address the performance assessment of C-arm CBCT units. First, Section 6 describes testing approaches and phantoms that may be used to evaluate image quality (spatial resolution and image noise and artifacts) and identifies several factors that affect image quality. Section 7 describes both free-in-air and in-phantom approaches to evaluating radiation dose indices. The methodologies described for assessing image quality and radiation dose may be used for annual constancy assessment and comparisons among different systems to help medical physicists determine when a system is not operating as expected. Baseline measurements taken either at installation or after a full preventative maintenance service call can also provide valuable data to help determine whether the performance of the system is acceptable. Collecting image quality and radiation dose data on existing phantoms used for CT image quality and radiation dose assessment, or on newly developed phantoms, will inform the development of performance criteria and standards. Phantom images are also useful for identifying and evaluating artifacts. In particular, comparing baseline data with those from current phantom images can reveal the need for system calibration before image artifacts are detected in clinical practice. Examples of artifacts are provided in Sections 4, 5, and 6., (© 2023 American Association of Physicists in Medicine.)

Slow-wave sleep (SWS) is a fundamental physiological process, and its modulation is of interest for basic science and clinical applications. However, automatised protocols for the suppression of SWS are lacking. We describe the development of a novel protocol for the automated detection (based on the whole head topography of frontal slow waves) and suppression of SWS (through closed-loop modulated randomised pulsed noise), and assessed the feasibility, efficacy and functional relevance compared to sham stimulation in 15 healthy young adults in a repeated-measure sleep laboratory study. Auditory compared to sham stimulation resulted in a highly significant reduction of SWS by 30% without affecting total sleep time. The reduction of SWS was associated with an increase in lighter non-rapid eye movement sleep and a shift of slow-wave activity towards the end of the night, indicative of a homeostatic response and functional relevance. Still, cumulative slow-wave activity across the night was significantly reduced by 23%. Undisturbed sleep led to an evening to morning reduction of wake electroencephalographic theta activity, thought to reflect synaptic downscaling during SWS, while suppression of SWS inhibited this dissipation. We provide evidence for the feasibility, efficacy, and functional relevance of a novel fully automated protocol for SWS suppression based on auditory closed-loop stimulation. Future work is needed to further test for functional relevance and potential clinical applications., (© 2023 The Authors. Journal of Sleep Research published by John Wiley & Sons Ltd on behalf of European Sleep Research Society.)

Using multimodal imaging, we investigated the extent and functional correlates of myocardial fibroblast activation in patients with aortic stenosis (AS) scheduled for transcatheter aortic valve replacement (TAVR). AS may cause myocardial fibrosis, which is associated with disease progression and may limit response to TAVR. Novel radiopharmaceuticals identify upregulation of fibroblast activation protein (FAP) as a cellular substrate of cardiac profibrotic activity. Methods: Twenty-three AS patients underwent 68 Ga-FAP inhibitor 46 ( 68 Ga-FAPI) PET, cardiac MRI, and echocardiography within 1-3 d before TAVR. Imaging parameters were correlated and then were integrated with clinical and blood biomarkers. Control cohorts of subjects without a history of cardiac disease and with ( n = 5) and without ( n = 9) arterial hypertension were compared with matched AS subgroups. Results: Myocardial FAP volume varied significantly among AS subjects (range, 1.54-138 cm 3 , mean ± SD, 42.2 ± 35.6 cm 3 ) and was significantly higher than in controls with (7.42 ± 8.56 cm 3 , P = 0.007) and without (2.90 ± 6.67 cm 3 ; P < 0.001) hypertension. FAP volume correlated with N-terminal prohormone of brain natriuretic peptide ( r = 0.58, P = 0.005), left ventricular ejection fraction ( r = -0.58, P = 0.02), mass ( r = 0.47, P = 0.03), and global longitudinal strain ( r = 0.55, P = 0.01) but not with cardiac MRI T1 (spin-lattice relaxation time) and extracellular volume ( P = not statistically significant). In-hospital improvement in left ventricular ejection fraction after TAVR correlated with pre-TAVR FAP volume ( r = 0.440, P = 0.035), N-terminal prohormone of brain natriuretic peptide, and strain but not with other imaging parameters. Conclusion: FAP-targeted PET identifies varying degrees of left ventricular fibroblast activation in TAVR candidates with advanced AS. 68 Ga-FAPI signal does not match other imaging parameters, generating the hypothesis that it may become useful as a tool for personalized selection of optimal TAVR candidates., (© 2023 by the Society of Nuclear Medicine and Molecular Imaging.)

Background: The purpose of this study was to evaluate if kilohertz frequency alternating current (KHFAC) stimulation of peripheral nerve could serve as a treatment for lumbar radiculopathy. Prior work shows that KHFAC stimulation can treat sciatica resulting from chronic sciatic nerve constriction. Here, we evaluate if KHFAC stimulation is also beneficial in a more physiologic model of low back pain which mimics nucleus pulposus (NP) impingement of a lumbar dorsal root ganglion (DRG)., Methods: To mimic a lumbar radiculopathy, autologous tail NP was harvested and placed upon the right L5 nerve root and DRG. During the same surgery, a cuff electrode was implanted around the sciatic nerve with wires routed to a headcap for delivery of KHFAC stimulation. Male Lewis rats (3 mo., n = 18) were separated into 3 groups: NP injury + KHFAC stimulation (n = 7), NP injury + sham cuff (n = 6), and sham injury + sham cuff (n = 5). Prior to surgery and for 2 weeks following surgery, animal tactile sensitivity, gait, and static weight bearing were evaluated., Results: KHFAC stimulation of the sciatic nerve decreased behavioral evidence of pain and disability. Without KHFAC stimulation, injured animals had heightened tactile sensitivity compared to baseline (p < 0.05), with tactile allodynia reversed during KHFAC stimulation (p < 0.01). Midfoot flexion during locomotion was decreased after injury but improved with KHFAC stimulation (p < 0.05). Animals also placed more weight on their injured limb when KHFAC stimulation was applied (p < 0.05). Electrophysiology measurements at end point showed decreased, but not blocked, compound nerve action potentials with KHFAC stimulation (p < 0.05)., Conclusions: KHFAC stimulation decreases hypersensitivity but does not cause additional gait compensations. This supports the idea that KHFAC stimulation applied to a peripheral nerve may be able to treat chronic pain resulting from sciatic nerve root inflammation., (© 2023. The Author(s).)

The ability to organize self-generated thought into coherent, meaningful semantic representations is a central aspect of human cognition and undergoes regular alterations throughout the day. To investigate whether changes in semantic processing might explain the loss of coherence, logic, and voluntary control over thinking typically accompanying the transition to sleep, we recorded N400 evoked potentials from 44 healthy subjects. Auditory word pairs with varying semantic distance were presented while they were allowed to fall asleep. Using semantic distance and wakefulness level as regressors, we found that semantic distance reliably elicited an N400, and lower wakefulness levels were associated with increased frontal negativity within a similar time range. Additionally, and contrary to our initial hypothesis, the results showed an interaction of semantic distance and wakefulness that is best interpreted as an increased N400 effect with decreasing wakefulness. While these results do not rule out a possible role of semantic processes in the generation of diminished logic and thought control during the transition to sleep, we discuss the possibility of additional brain mechanisms that usually constrain the inner stream of consciousness during wakefulness., Competing Interests: Declaration of competing interest None., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Different electrophysiological (EEG) indices have been investigated as possible biomarkers of schizophrenia. However, these indices have a very limited use in clinical practice, as their associations with clinical and functional outcomes remain unclear. This study aimed to investigate the associations of multiple EEG markers with clinical variables and functional outcomes in subjects with schizophrenia (SCZs)., Methods: Resting-state EEGs (frequency bands and microstates) and auditory event-related potentials (MMN-P3a and N100-P3b) were recorded in 113 SCZs and 57 healthy controls (HCs) at baseline. Illness- and functioning-related variables were assessed both at baseline and at 4-year follow-up in 61 SCZs. We generated a machine-learning classifier for each EEG parameter (frequency bands, microstates, N100-P300 task, and MMN-P3a task) to identify potential markers discriminating SCZs from HCs, and a global classifier. Associations of the classifiers' decision scores with illness- and functioning-related variables at baseline and follow-up were then investigated., Results: The global classifier discriminated SCZs from HCs with an accuracy of 75.4% and its decision scores significantly correlated with negative symptoms, depression, neurocognition, and real-life functioning at 4-year follow-up., Conclusions: These results suggest that a combination of multiple EEG alterations is associated with poor functional outcomes and its clinical and cognitive determinants in SCZs. These findings need replication, possibly looking at different illness stages in order to implement EEG as a possible tool for the prediction of poor functional outcome.

Much research finds that lying takes longer than truth-telling. Yet, the source of this response time difference remains elusive. Here, we assessed the spatiotemporal evolution of electrical brain activity during honesty and dishonesty in 150 participants using a sophisticated electrical neuroimaging approach-the microstate approach. This uniquely positioned us to identify and contrast the entire chain of mental processes involved during honesty and dishonesty. Specifically, we find that the response time difference is the result of an additional late-occurring mental process, unique to dishonest decisions, interrupting the antecedent mental processing. We suggest that this process inhibits the activation of the truth, thus permitting the execution of the lie. These results advance our understanding of dishonesty and clarify existing theories about the role of increased cognitive load. More broadly, we demonstrate the vast potential of our approach to illuminate the temporal organization of mental processes involved in decision-making., (© The Author(s) 2023. Published by Oxford University Press.)

Elevated urine bis(monoacylglycerol)phosphate (BMP) levels have been found in gain-of-kinase function LRRK2 G2019S mutation carriers. Here, we have expanded urine BMP analysis to other Parkinson's disease (PD) associated mutations and found them to be consistently elevated in carriers of LRRK2 G2019S and R1441G/C as well as VPS35 D620N mutations. Urine BMP levels are promising biomarkers for patient stratification and potentially target engagement in clinical trials of emerging targeted PD therapies., (© 2023. The Author(s).)

Aims: Peripartum cardiomyopathy (PPCM) is a rare heart disease, occurring in previously heart-healthy women during the last month of pregnancy or the first months after delivery due to left ventricular (LV) systolic dysfunction. A common pathomechanistic pathway of PPCM includes increased oxidative stress and the subsequent generation of a cleaved prolactin fragment (16 kDa PRL), which promotes the onset of heart failure (HF) in a microRNA (miR)-146a-dependent manner. Inhibition of prolactin secretion with the dopamine D2 receptor (D2R) agonist bromocriptine combined with standard HF therapy supports cardiac recovery. This study examined whether treatment with the more selective D2R agonist cabergoline prevents HF development in an experimental PPCM mouse model and might be used as an alternative treatment regime for PPCM., Methods and Results: Postpartum (PP) female PPCM-prone mice with a cardiomyocyte restricted STAT3-deficiency (αMHC-Cre tg/+ ; Stat3 fl/fl ; CKO) were treated over two consecutive nursing periods with cabergoline (CKO Cab, 0.5 mg/kg/day) and were compared with bromocriptine treated CKO (CKO Br) and postpartum-matched WT and CKO mice. Cabergoline treatment in CKO PP mice preserved cardiac function [fractional shortening (FS): CKO Cab: 34.5 ± 9.4% vs. CKO: 22.1 ± 9%, P < 0.05] and prevented the development of cardiac hypertrophy, fibrosis, and inflammation as effective as bromocriptine therapy (FS: CKO Br: 33.4 ± 5.6%). The myocardial up-regulation of the PPCM biomarkers plasminogen inhibitor activator 1 (PAI-1) and miR-146a were prevented by both cabergoline and bromocriptine therapy. A small cohort of three PPCM patients from the German PPCM Registry was treated with cabergoline (1 mg per week for 2 weeks, followed by 0.5 mg per week for another 6 weeks) due to a temporary unavailability of bromocriptine. All PPCM patients initially presented with a severely reduced LV ejection fraction (LVEF: 26 ± 2%). However, at 6 months of follow-up, LV function (LVEF: 56 ± 2%) fully recovered in all three PPCM patients, and no adverse events were detected., Conclusions: In the experimental PPCM mouse model, the selective D2R agonist cabergoline prevents the onset of postpartum HF similar to bromocriptine. In PPCM patients, cabergoline treatment was safe and effective as all patients fully recovered. Cabergoline might serve as a promising alternative to bromocriptine. However, these findings are based on experimental data and a small case series and thus have to be interpreted with caution and should be validated in a larger clinical trial., (© 2022 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Our knowledge about the human resting state is predominantly based on either electroencephalographic (EEG) or functional magnetic resonance imaging (fMRI) methods. While EEG recordings can be performed in seated posture in quiet conditions, the fMRI environment presents a substantial contrast with supine and restricted posture in a narrow tube that is filled with acoustic scanner noise (ASN) at a chainsaw-like volume level. However, the influence of these diverging conditions on resting-state brain activation is neither well studied nor broadly discussed. In order to promote data as a source of sharper hypotheses for future studies, we investigated alterations in EEG-frequency-band power (delta, theta, alpha, beta, gamma) and spatial power distribution as well as cortical vigilance measures in different postures and ASN surroundings over the course of time. Participants (N = 18) underwent three consecutive resting-state EEG recordings with a fixed posture and ASN setting sequence; seated, supine, and supine with ASN (supnoise) using an MRI simulator. The results showed that compared to seated, supnoise, the last instance within the posture sequence, was characterized by lower power and altered spatial power distribution in all assessed frequency bands. This might also have been an effect of time alone. In delta, theta, alpha, and beta, the power of supnoise was also reduced compared to supine, as well as the corresponding distribution maps. The vigilance analysis revealed that in supine and supnoise, the highest and lowest vigilance stages were more dominant compared to the seated and earliest posture condition within the sequence. Hence, our results demonstrate that the differences in recording settings and progress of time are related to changes in cortical arousal and vigilance regulation, findings that should be taken into account more profoundly for hypothesis generation as well as analytic strategies in future resting-state studies., (© 2022. The Author(s).)

Brain-state-dependent stimulation during slow-wave sleep is a promising tool for the treatment of psychiatric and neurodegenerative diseases. A widely used slow-wave prediction algorithm required for brain-state-dependent stimulation is based on a specific amplitude threshold in the electroencephalogram. However, due to decreased slow-wave amplitudes in aging and psychiatric conditions, this approach might miss many slow-waves because they do not fulfill the amplitude criterion. Here, we compared slow-wave peaks predicted via an amplitude-based versus a multidimensional approach using a topographical template of slow-wave peaks in 21 young and 21 older healthy adults. We validate predictions against the gold-standard of offline detected peaks. Multidimensionally predicted peaks resemble the gold-standard regarding spatiotemporal dynamics but exhibit lower peak amplitudes. Amplitude-based prediction, by contrast, is less sensitive, less precise and - especially in the older group - predicts peaks that differ from the gold-standard regarding spatiotemporal dynamics. Our results suggest that amplitude-based slow-wave peak prediction might not always be the ideal choice. This is particularly the case in populations with reduced slow-wave amplitudes, like older adults or psychiatric patients. We recommend the use of multidimensional prediction, especially in studies targeted at populations other than young and healthy individuals., (© 2022 The Authors. Journal of Sleep Research published by John Wiley & Sons Ltd on behalf of European Sleep Research Society.)