The evolution of gastrulation morphologies.

During gastrulation, early embryos specify and reorganise the topology of their germ layers. Surprisingly, this fundamental and early process does not appear to be rigidly constrained by evolutionary pressures; instead, the morphology of gastrulation is highly variable throughout the animal kingdom. Recent experimental results demonstrate that it is possible to generate different alternative gastrulation modes in single organisms, such as in early cnidarian, arthropod and vertebrate embryos. Here, we review the mechanisms that underlie the plasticity of vertebrate gastrulation both when experimentally manipulated and during evolution. Using the insights obtained from these experiments we discuss the effects of the increase in yolk volume on the morphology of gastrulation and provide new insights into two crucial innovations during amniote gastrulation: the transition from a ring-shaped mesoderm domain in anamniotes to a crescent-shaped domain in amniotes, and the evolution of the reptilian blastoporal plate/canal into the avian primitive streak.

Resolving morphogenesis into quantifiable cell behaviours.

Morphogenesis is extremely diverse, but its systematic quantification to determine the physical mechanisms that produce different phenotypes is possible by quantifying the underlying cell behaviours. These are limited and definable: they consist of cell proliferation, orientation of cell division, cell rearrangement, directional matrix production, cell addition/subtraction and cell size/shape change. Although minor variations in these categories are possible, in sum they capture all possible morphogenetic behaviours. This article summarises these processes, discusses their measurement, and highlights some salient examples.

Defining repetitive behaviours in frontotemporal dementia.

Repetitive behaviours are common manifestations of frontotemporal dementia (FTD). Patients with FTD exhibit various types of repetitive behaviours with unique behavioural and cognitive substrates, including compulsivity, lack of impulse control, stereotypy and hoarding. Other sources of repetitive behaviours, such as restrictive interests and insistence on sameness, may also be seen in FTD. Although repetitive behaviours are highly prevalent and potentially discriminatory in this population, their expression varies widely between patients, and the field lacks consensus about the classification of these behaviours. Terms used to describe repetitive behaviours in FTD are highly heterogeneous and may lack precise definitions. This lack of harmonization of the definitions for distinct forms of repetitive behaviour limits the ability to differentiate between pathological behaviours and impedes understanding of their underlying mechanisms. This review examines established definitions of well-characterized repetitive behaviours in other neuropsychiatric disorders and proposes operational definitions applicable to patients with FTD. Building on extant models of repetitive behaviours in non-human and lesion work and models of social behavioural changes in FTD, we describe the potential neurocognitive bases for the emergence of different types of repetitive behaviours in FTD and their potential perpetuation by a predisposition towards habit formation. Finally, examples of distinct therapeutic approaches for different forms of repetitive behaviours are highlighted, along with future directions to accurately classify, measure and treat these symptoms when they impair quality of life.

Effect of the mGlu2 positive allosteric modulator biphenyl-indanone A as a monotherapy and as adjunct to a low dose of L-DOPA in the MPTP-lesioned marmoset.

Activation of metabotropic glutamate 2 (mGlu2) receptors is a potential novel therapeutic approach for the treatment of parkinsonism. Thus, when administered as monotherapy or as adjunct to a low dose of L-3,4-dihydroxyphenylalanine (L-DOPA), the mGlu2 positive allosteric modulator (PAM) LY-487,379 alleviated parkinsonism in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-lesioned primates. Here, we sought to investigate the effect of biphenyl-indanone A (BINA), a highly selective mGlu2 PAM whose chemical scaffold is unrelated to LY-487,379, to determine if a structurally different mGlu2 PAM would also confer anti-parkinsonian benefit. In monotherapy experiments, MPTP-lesioned marmosets were injected with either vehicle, L-DOPA/benserazide (15/3.75 mg/kg, positive control) or BINA (0.1, 1, 10 mg/kg). In adjunct to a low L-DOPA dose experiments, MPTP-lesioned marmosets were injected with L-DOPA/benserazide (7.5/1.875 mg/kg) in combination with vehicle or BINA (0.1, 1, 10 mg/kg). Parkinsonism, dyskinesia and psychosis-like behaviours (PLBs) were then quantified. When administered alone, BINA 1 and 10 mg/kg decreased parkinsonism severity by ~22% (p < 0.01) and ~47% (p < 0.001), when compared with vehicle, which was comparable with the global effect of a high L-DOPA dose. When administered in combination with a low L-DOPA dose, BINA 1 and 10 mg/kg decreased global parkinsonism by ~38% (p < 0.001) and ~53% (p < 0.001). BINA 10 mg/kg decreased global dyskinesia by ~94% (p < 0.01) and global PLBs by ~92% (p < 0.01). Our results provide additional evidence that mGlu2 positive allosteric modulation elicits anti-parkinsonian effects. That this benefit is not related to a particular chemical scaffold suggests that it may be a class effect rather than the effect of a specific molecule.

Investigating mother-child inter-brain synchrony in a naturalistic paradigm: A functional near infrared spectroscopy (fNIRS) hyperscanning study.

Successful social interactions between mothers and children are hypothesised to play a significant role in a child's social, cognitive and language development. Earlier research has confirmed, through structured experimental paradigms, that these interactions could be underpinned by coordinated neural activity. Nevertheless, the extent of neural synchrony during real-life, ecologically valid interactions between mothers and their children remains largely unexplored. In this study, we investigated mother-child inter-brain synchrony using a naturalistic free-play paradigm. We also examined the relationship between neural synchrony, verbal communication patterns and personality traits to further understand the underpinnings of brain synchrony. Twelve children aged between 3 and 5 years old and their mothers participated in this study. Neural synchrony in mother-child dyads were measured bilaterally over frontal and temporal areas using functional Near Infra-red Spectroscopy (fNIRS) whilst the dyads were asked to play with child-friendly toys together (interactive condition) and separately (independent condition). Communication patterns were captured via video recordings and conversational turns were coded. Compared to the independent condition, mother-child dyads showed increased neural synchrony in the interactive condition across the prefrontal cortex and temporo-parietal junction. There was no significant relationship found between neural synchrony and turn-taking and between neural synchrony and the personality traits of each member of the dyad. Overall, we demonstrate the feasibility of measuring inter-brain synchrony between mothers and children in a naturalistic environment. These findings can inform future study designs to assess inter-brain synchrony between parents and pre-lingual children and/or children with communication needs.

Construction of a prognostic model for disulfidptosis-related long noncoding RNAs in R0 resected hepatocellular carcinoma and analysis of their impact on malignant behavior.

BACKGROUND: Disulfidptosis is an emerging form of cellular death resulting from the binding of intracellular disulfide bonds to actin cytoskeleton proteins. This study aimed to investigate the expression and prognostic significance of hub disulfidptosis-related lncRNAs (DRLRs) in R0 resected hepatocellular carcinoma (HCC) as well as their impact on the malignant behaviour of HCC cells. METHODS: A robust signature for R0 resected HCC was constructed using least absolute shrinkage and selection operator (LASSO) and multivariate Cox regression and was validated in an independent internal validation cohort to predict the prognosis of R0 HCC patients. Comprehensive bioinformatics analysis was performed on the hub DRLRs (KDM4A-AS1, MKLN1-AS, and TMCC1-AS1), followed by experimental validation using quantitative real-time polymerase chain reaction (qRT‒PCR) and cellular functional assays. RESULTS: The signature served as an independent prognostic factor applicable to R0 HCC patients across different age groups, tumour stages, and pathological characteristics. Gene Ontology (GO) and gene set enrichment analysis (GSEA) revealed hub pathways associated with this signature. The high-risk group presented an increased abundance of M0 macrophages and activated memory CD4 T cells as well as elevated macrophage and major histocompatibility complex (MHC) class I expression. High-risk R0 HCC patients also presented increased tumour immune dysfunction and exclusion scores (TIDEs), mutation frequencies, and tumour mutational burdens (TMBs). Drug sensitivity analysis revealed that high-risk patients were more responsive to drugs, including GDC0810 and osimertinib. High expression levels of the three hub DRLRs were detected in R0 HCC tissues and HCC cell lines. Functional assays revealed that the three hub DRLRs enhanced HCC cell proliferation, migration, and invasion. CONCLUSIONS: A signature was constructed on the basis of three DRLRs, providing novel insights for personalized precision therapy in R0 HCC patients.

Mental health problems and help-seeking behaviours of Syrian refugee adolescents: mediating role of self-stigma.

BACKGROUND: Although common mental health problems have been widely studied with self-stigma, few studies have focused on the mediating effect of self-stigma in the relationship between mental health problems and help-seeking behaviours of refugee adolescents. Therefore, the purpose of the present study was to examine whether self-stigma mitigates the adverse effects of stress, anxiety, and depression symptoms on the help-seeking behaviours of Syrian adolescents living in Turkey. METHODS: The participants of this study included 488 Syrian refugee adolescents (boys, 63.73%; girls, 3627%) living in Turkey. Participants completed the Depression Anxiety Stress Scale and General Help-Seeking Scale and Self-Stigma of Seeking Psychology Help Scale. RESULTS: The findings revealed that stress (ß = 0.19, p < 0.01), anxiety (ß = 0.12, p < 0.05), and depression (ß = 0.17, p < 0.01) had significant and positive predictive effects on self-stigma, but not on help-seeking behaviours. Also, self-stigma (ß = -0.12, p < 0.01) had a significant negative predictive effect on help-seeking behaviours. With regard to the indirect effects, the findings showed that self-stigma fully mediated the associations between stress - help-seeking [effect = -0.05, 95% confidence interval (CI) -0.11 to -0.01], anxiety - help-seeking (effect = -0.04, 95% CI -0.09 to -0.01)], and depression - help-seeking (effect = -0.05, 95% CI -0.12 to -0.01). CONCLUSIONS: Our findings highlight the potential negative effects of self-stigma on the help-seeking behaviours of Syrian refugee adolescents, both directly and indirectly. These results can be used to develop and implement effective and efficient interventions to address the unmet mental health needs of refugee adolescents.

Social interactions generate complex selection patterns in virtual worlds.

Understanding the influence of social interactions on individual fitness is key to improving our predictions of phenotypic evolution. However, we often overlook the different components of selection regimes arising from interactions among organisms, including social, correlational, and indirect selection. This is due to the challenging sampling efforts required in natural populations to measure phenotypes expressed during interactions and individual fitness. Furthermore, behaviours are crucial in mediating social interactions, yet few studies have explicitly quantified these selection components on behavioural traits. In this study, we capitalize on an online multiplayer video game as a source of extensive data recording direct social interactions among prey, where prey collaborate to escape a predator in realistic ecological settings. We estimate natural and social selection and their contribution to total selection on behavioural traits mediating competition, cooperation, and predator-prey interactions. Behaviours of other prey in a group impact an individual's survival, and thus are under social selection. Depending on whether selection pressures on behaviours are synergistic or conflicting, social interactions enhance or mitigate the strength of natural selection, although natural selection remains the main driving force. Indirect selection through correlations among traits also contributed to the total selection. Thus, failing to account for the effects of social interactions and indirect selection would lead to a misestimation of the total selection acting on traits. Dissecting the contribution of each component to the total selection differential allowed us to investigate the causal mechanisms relating behaviour to fitness and quantify the importance of the behaviours of conspecifics as agents of selection. Our study emphasizes that social interactions generate complex selective regimes even in a relatively simple ecological environment.

Biophysical, thermo-physiological and perceptual determinants of cool-seeking behaviour during exercise in younger and older women.

Women continue to be under-represented in thermoregulatory research despite their undergoing unique physiological changes across the lifespan. This study investigated the biophysical, thermo-physiological, and perceptual determinants of cool-seeking behaviour during exercise in younger and older women. Eleven younger (25 ± 5 years; 1.7 ± 0.1 m; 63.1 ± 5.2 kg) and 11 older women (53 ± 6 years; 1.7 ± 0.1 m; 65.4 ± 13.9 kg) performed a 40-min incremental cycling test in a thermoneutral environment (22 ± 1.7°C; 36 ± 4% relative humidity). Throughout the test, participants freely adjusted the temperature of a cooling probe applied to their wrists to offset their thermal discomfort. We continuously recorded the probe-wrist interface temperature to quantify participants' cool-seeking behaviour. We also measured changes in participants' rate of metabolic heat production, core and mean skin temperatures, and skin wetness. Finally, we body-mapped participants' skin heat, cold and wetness sensitivity. Our results indicated that: (1) older and younger women exhibited similar onset and magnitude of cool-seeking behaviour, despite older women presented reduced autonomic heat-dissipation responses (i.e., whole-body sweat losses); (2) older women's thermal behaviour was less determined by changes in core temperature (this being a key driver in younger women), and more by changes in multiple thermo-physiological and biophysical parameters (i.e., physical skin wetness, temperature and heat production); (3) older women did not present lower regional skin thermal and wetness sensitivity than younger women. We conclude that predictions of female cool-seeking behaviours based on thermo-physiological variables should consider the effects of ageing. These findings are relevant for the design of wearable cooling systems and sports garments that meet the thermal needs of women across the lifespan.

Female thermal sensitivity and behaviour across the lifespan: A unique journey.

Women are a group of individuals that undergo unique anatomical, physiological and hormonal changes across the lifespan. For example, consider the impact of the menstrual cycle, pregnancy and menopause, all of which are accompanied by both short- and long-term effects on female body morphology (e.g., changes in breast size) and temperature regulation, heat tolerance, thermal sensitivity and comfort. However, empirical evidence on how skin thermal and wetness sensitivity might change across the lifespan of women, and the implications that this has for female-specific thermal behaviours, continues to be lacking. This paper is based on a symposium presentation given at Physiology 2023 in Harrogate, UK. It aims to review new evidence on anatomical and physiological mechanisms underpinning differences in skin thermal and wetness sensitivity amongst women varying in breast size and age, in addition to their role in driving female thermal behaviours. It is hoped that this brief overview will stimulate the development of testable hypotheses to increase our understanding of the behavioural thermal physiology of women across the lifespan and at a time of climate change.

Medically assisted reproduction and mental health in adolescence: evidence from the UK Millennium Cohort Study.

BACKGROUND: The number and proportion of children conceived through medically assisted reproduction (MAR) is steadily increasing yet the evidence on their mental health in adolescence is inconclusive. Two main mechanisms with opposite effects can explain differences in mental health outcomes by conception mode: while more advantaged parental characteristics could positively influence it, higher parental stress could have a negative influence. METHODS: Linear and logistic estimations on a longitudinal population-based birth cohort study of 9,897 individuals to investigate whether adolescents conceived through MAR are more likely than naturally conceived (NC) children to experience mental health problems at age 17, as reported by adolescents themselves and their parents. We test whether this association is confounded and/or mediated by parental background characteristics collected when the cohort member was around 9 months old (maternal age, maternal education level, ethnicity, income quintile), family structure variables measured in adolescence (number of siblings in the household at age 15, parental household structure at age 14) or maternal distress at age 14. RESULTS: Children conceived naturally and through MAR self-reported similar mental health outcomes. The only differences between MAR and NC adolescents are in the parental reports, with parents who conceived through MAR reporting their children had 3.82 (95% CI: 1.140 to 11.54) and 2.35 (95% CI: 1.145 to 4.838) higher odds of falling within the high category of SDQ total difficulties and emotional symptoms scales, respectively. The results did not change on adjustment for mediators, such as maternal distress, number of siblings in the household and parental household structure. CONCLUSIONS: The results reveal a lack of or small differences in MAR adolescents' mental health outcomes compared to children who were conceived naturally. While the results based on the parental reports could suggest that MAR adolescents are at higher risk of suffering from mental health problems, the differences are small and not supported by adolescents' own reports. The difference between MAR and NC adolescent's parental report might reflect differences in parental concern, their relationship or closeness and can help to reconcile the mixed findings of previous studies.

Understanding the relationship between social camouflaging in autism and safety behaviours in social anxiety in autistic and non-autistic adolescents.

BACKGROUND: Social camouflaging (hereafter camouflaging) in autism includes factors such as masking and compensating for one's neurodevelopmental differences, and to assimilate or 'fit in' with non-autistic peers. Efforts to hide one's authentic self and autism traits (masking) resemble impression management (IM) in safety behaviours identified in Clark and Wells' (1995) cognitive model of social anxiety (SA). This study explores the relationship between camouflaging in autism and safety behaviours in SA among autistic and non-autistic adolescents. METHODS: One hundred fifteen adolescents (14-19 years) with (n = 61; 36 female) and without (n = 54; 37 female) a clinical diagnosis of autism matched on age and SA symptom severity were recruited from clinics, schools and online. Adolescents completed online measures including autism traits, SA symptoms, camouflaging behaviours, SA-related safety behaviours and SA-related negative cognitions. Partial and bivariate Pearson's correlations and structural equation modelling were used to understand the relationship between camouflaging, safety behaviours, autism traits and SA in both groups. Exploratory factor analysis assessed item-level factor cross-loadings between camouflaging and safety behaviours. RESULTS: Across both groups, masking and IM were significantly associated with SA symptom severity, not autism traits, via SA-related social cognitions. Exploratory factor analysis indicated construct overlap across masking, assimilation, IM and avoidance behaviours and identified factors analogous to self-focused attention, social avoidance and mental rehearsal identified in the Clark and Wells' (1995) model of SA. CONCLUSIONS: This is the first study using group-matched design to identify that masking (factor in social camouflaging) and IM both relate to SA in autistic and non-autistic adolescents. Assessment and formulation of construct overlap between masking and IM may inform psychoeducation and adaptation of SA treatment for autistic adolescents.

Research Review: A systematic review and meta-analysis of sex differences in narrow constructs of restricted and repetitive behaviours and interests in autistic children, adolescents, and adults.

BACKGROUND: Evidence that autism often manifests differently between males and females is growing, particularly in terms of social interaction and communication, but it is unclear if there are sex differences in restricted and repetitive behaviours and interests (RRBIs) when rigorously focusing on the narrow construct level (i.e., stereotyped behaviour, restricted interests, insistence on sameness, and/or sensory experiences). METHODS: We conducted a systematic review and four random effects meta-analyses investigating sex differences in narrow construct measures of RRBIs in autistic children, adolescents, and adults (Prospero registration ID: CRD42021254221). Study quality was appraised using the Newcastle-Ottawa Quality Assessment Scale. RESULTS: Forty-six studies were narratively synthesised and 25 of these were included in four random effects meta-analyses. Results found that autistic males had significantly higher levels of stereotyped behaviours (SMD = 0.21, 95% confidence interval (CI) [0.09, 0.33], p < .001) and restricted interests (SMD = 0.18, 95% CI [0.07, 0.29], p < .001) compared to autistic females. In contrast, there were no significant sex differences for sensory experiences (SMD = -0.09, 95% CI [-0.27, 0.09], p = .32) and insistence on sameness (SMD = 0.01, 95% CI [-0.03, 0.05], p = .68). The findings from the narrative synthesis were generally consistent with those from the meta-analyses and also found qualitative sex differences in the way RRBIs manifest. CONCLUSIONS: Our findings show significant differences in narrowly defined RRBIs in males and females. Practitioners need to be aware of such differences, which could be contributing to the under-recognition of autism in females and may not be captured by current diagnostic instruments.

Many faces of dominance: the manifestation of cohabiting companion dogs' rank in competitive and non-competitive scenarios.

There are indications that companion dogs of multi-dog households form a hierarchy, maintained by formal and agonistic dominance. Although it was found that the behaviour of dogs depends on their rank in several contexts, so far, the assessment of their rank itself has been based on owner-completed questionnaires. With this research we endeavoured to find associations between rank scores from the Dog Rank Assessment Questionnaire (DRA-Q) and cohabiting dogs' behaviour in a competitive test (Toy Possession test-32 dog pairs) and a non-competitive, citizen science scenario (Greeting test-20 dog pairs). Based on the grabbing the toy first and keeping the toy at the end variables, the dogs' rank score provided a reliable indication of the dominant and subordinate dogs' behaviour in the Toy Possession test. Similarly, the occurrence of dominant and submissive behaviours in the Greeting Test showed a good match with the agonistic and leadership subscores of the composite rank score from the DRA-Q. Our results provide a pioneering case for validating a questionnaire-based rank scoring method with biologically meaningful behavioural tests in the case of companion dogs. The finer analysis of the results highlighted that in the case of a multi-question scoring system, some components might provide more effective prediction of the dogs' rank-related behaviour in some situations, while other components are more relevant in others, with traits related to agonistic dominance having relevance across contexts.

Parental sleep-related practices and sleep in children aged 1-3 years: a systematic review.

The current systematic review sought to identify the relationship between the range of different parental sleep-related practices that had been explored in relations to child sleep outcomes in children aged 1-3 years. A systematic literature review was carried out in CINAHL, The Cochrane Library, PsycArticles, PsycInfo, PubMed and Web of Science, as well as relevant grey literature in August 2022 using the terms; population (children, aged 1-3 years), exposure (parental sleep-related practice) and outcome (child sleep). Any quantitative study published between 2010 and 2022 that explored the relationship between parental sleep-related practices and the sleep of children aged 1-3 years were included. The Mixed Methods Appraisal Tool was employed to quality appraise included studies and results were narratively synthesised. In all, 16 longitudinal and cross-sectional quantitative studies met inclusion criteria. Parental presence or physical involvement, as well as broader parental practices including using screens or devices at bedtime and night-time breastfeeding were all related to poorer child sleep outcomes. Consistent and relaxing routines, sleeping in a cot, and spending all night in their own sleep location were associated with better child sleep outcomes. Acknowledging the plethora of diverse parental sleep-related practices, which may have varying relationships with child sleep outcomes, could be usefully considered in theoretical models and to inform clinical practice. Issues of definitional and measurement ambiguity are highlighted and discussed.

Sleep-related safety behaviours predict insomnia symptoms 1 year later in a sample of university students.

Several studies have demonstrated the relevance of cognitive factors in the development of insomnia complaints, but very few have investigated how these factors influence the development of insomnia complaints over time. In this study we set out to investigate key factors associated with present insomnia severity and the development of insomnia complaints over time. We employed a two-wave longitudinal design where we measured insomnia severity, pre-sleep arousal, dysfunctional beliefs about sleep, sleep-related worry and safety-behaviours in a sample of students at baseline and 1 year later. At baseline, 353 respondents filled in the questionnaires and 79 completed these a year later. In the cross-sectional analyses, pre-sleep arousal and sleep-related worry were unique contributors to insomnia severity. Using baseline data to predict insomnia severity 1 year later, only sleep-related safety emerged as a predictor. These findings suggest that sleep-related worry and pre-sleep arousal are the primary factors influencing current severity. In terms of development and/or persistence, sleep safety may constitute a potentially underestimated factor.

Sleep timing behaviour, sleep duration and adherence to obesogenic dietary patterns from pre-school to school age: results from the Portuguese birth cohort Generation XXI.

In an obesogenic environment, short sleeping may increase opportunistic eating. The timing of sleep might also influence the drive to eat. This study investigated the prospective association of sleep timing and duration with diet in 5286 children from the Portuguese birth cohort Generation XXI, evaluated at 4 and 7 years of age. At 4 years, sleep duration was categorised into ≤10 and >10 h. Four sleep timing categories were generated based on the median split for sleep-onset and -offset times: 'Early Sleep-Early Wake'; 'Early Sleep-Late Wake'; 'Late Sleep-Early Wake'; 'Late Sleep-Late Wake'. At 7 years, diet was obtained by a food frequency questionnaire and three dietary patterns were included: 'Healthier', 'Energy-Dense Foods (EDF)' and 'Snacking'. The Healthy Eating Index was used to evaluate diet quality. Multinomial logistic regression models and generalised linear models were performed. Children who had a late sleep, independently of the time of waking up, had higher odds of following the 'EDF' pattern, compared with the 'Healthier'. Boys who had late sleep and/or late wake had also higher odds of following the 'Snacking' pattern and had poorer diet quality. In both sexes, a late sleep or late wake were associated with a lower diet quality, compared to the group 'Early Sleep-Early Wake', and independently of nap behaviour. In boys, shorter sleep duration was associated with a poorer diet. In conclusion, pre-schoolers with late bedtimes or wake-up times have worse dietary patterns and poorer diet quality at the age of 7 years, which seems to be independent of sleep duration.

Sleep should not be this difficult: An interpretive descriptive study of older adults' perspectives on behaviour change elements in Sleepwell and experiences with benzodiazepine discontinuation.

Benzodiazepine receptor agonists are often used for insomnia in older adults contrary to current evidence. The harms outweigh the benefits, which are limited. Cognitive behavioural therapy for insomnia is the first-line recommended treatment. Sleepwell was created as a repository of evidence-based resources to promote cognitive behavioural therapy for insomnia and limit benzodiazepine receptor agonist use. This qualitative study uses an interpretive description design and reflexive thematic analysis to explore older adults' perspectives on behavioural change techniques used in Sleepwell resources. It also explores challenges and opportunities towards benzodiazepine receptor agonist discontinuation and cognitive behavioural therapy for insomnia use. Participants were recruited from the Sleepwell arm of a randomized controlled trial. Data were collected from 15 older adults using semi-structured interviews. Two main themes were developed: (1) sleep should not be this difficult; and (2) whether you know it, or learn it, drugs are bad. Two sub-themes were created within the first theme: (1) justification of benzodiazepine receptor agonist use to achieve sleep goals; (2) efforts of committing to cognitive behavioural therapy for insomnia. Several behavioural change techniques (e.g. information about consequences, anticipated regret, salience of consequences) were enablers of benzodiazepine receptor agonist-related behaviour change. For committing to cognitive behavioural therapy for insomnia, several behavioural change techniques (e.g. self-monitoring of behaviour, distraction, stimulus substitution) were beneficial, but social support, which was perceived as useful, was absent. Older adults experienced tension with benzodiazepine receptor agonist use and deprescribing, despite knowing or learning the potential consequences of benzodiazepine receptor agonists. Cognitive behavioural therapy for insomnia implementation was challenging. Embedded behavioural change techniques in the Sleepwell booklets were identified as helpful, but more (e.g. social support) are needed to optimize cognitive behavioural therapy for insomnia use.

Do changes in beliefs and behaviours moderate improvement in insomnia after acquired brain injury?

Key mechanisms of change in cognitive behavioural therapy for insomnia in the general population encompass changing sleep-related beliefs and behaviours. In a population with acquired brain injury, cognitive behavioural therapy for insomnia is effective as well, but little is known about the mechanisms of change. The aim of this study was to evaluate how changing sleep-related beliefs and behaviours were associated with improvement in insomnia following blended cognitive behavioural therapy for insomnia in a population with acquired brain injury. A secondary analysis was performed on data of a randomized-controlled trial, including 24 participants that received blended cognitive behavioural therapy for insomnia, and 24 participants that received treatment as usual. Results showed that following blended cognitive behavioural therapy for insomnia, significantly more participants improved on dysfunctional beliefs and sleep-related behaviours and this was associated to improvement in insomnia severity. For sleep-related behaviours, the association between improvement on behaviour and improvement on insomnia was significantly moderated by blended cognitive behavioural therapy for insomnia. However, the relation between dysfunctional beliefs and insomnia was not moderated by type of treatment. Similar results were found for acquired brain injury-adapted versions of the questionnaires in which up to half of the items were excluded as they could be regarded as not dysfunctional for people with acquired brain injury. These results show that improvement on insomnia severity is related to improvement in dysfunctional beliefs and behaviours, and cognitive behavioural therapy for insomnia efficacy may be moderated by the improvement in behaviours in particular. A focus on these behaviours can enhance treatment efficacy, but caution is needed regarding the behaviours that may reflect adequate coping with the consequences of the acquired brain injury.

REM sleep behaviour disorder (RBD): Personal perspectives and research priorities.

The formal identification and naming of rapid eye movement (REM) sleep behaviour disorder (RBD) in 1985-1987 is described; the historical background of RBD from 1966 to 1985 is briefly discussed; and RBD milestones are presented. Current knowledge on RBD is identified with reference to recent comprehensive reviews, allowing for a focus on research priorities for RBD: factors and predictors of neurodegenerative phenoconversion from isolated RBD and patient enrolment in neuroprotective trials; isolated RBD clinical research cohorts; epidemiology of RBD; traumatic brain injury, post-traumatic stress disorder, RBD and neurodegeneration; depression, RBD and synucleinopathy; evolution of prodromal RBD to neurodegeneration; gut microbiome dysbiosis and colonic synuclein histopathology in isolated RBD; other alpha-synuclein research in isolated RBD; narcolepsy-RBD; dreams and nightmares in RBD; phasic REM sleep in isolated RBD; RBD, periodic limb movements, periodic limb movement disorder pseudo-RBD; other neurophysiology research in RBD; cardiac scintigraphy (123I-MIBG) in isolated RBD; brain magnetic resonance imaging biomarkers in isolated RBD; microRNAs as biomarkers in isolated RBD; actigraphic, other automated digital monitoring and machine learning research in RBD; prognostic counselling and ethical considerations in isolated RBD; and REM sleep basic science research. RBD research is flourishing, and is strategically situated at an ever-expanding crossroads of clinical (sleep) medicine, neurology, psychiatry and neuroscience.